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Sample records for optimally treated hiv

  1. Optimizing ribavirin dose in HIV/hepatitis C (HCV co-infected individuals treated for HCV

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    J Farley

    2012-11-01

    Full Text Available Hepatitis C (HCV and HIV share common transmission pathways and the acquisition of both viruses are relatively common. Concurrent treatment for HCV with highly active anti-retroviral therapy (HAART should be considered in HIV co-infected individuals to decrease the progression of liver damage. Adverse effects and less satisfactory treatment outcomes are often concerns when treating co-infected individuals. Although, direct acting antivirals (DAAs may increase SVR, they may not be possible because of drug-drug interactions. he objective of this study is to investigate the difference in response rates of HCV treatment in HIV co-infected inmates with varying doses of ribavirin. Retrospective medical chart reviews of 52 HCV/HIV co-infected inmates who underwent HCV therapy between 2003 and 2010. All received standard doses of pegylated interferon alpha 2a or 2b and 800–1600 mg of ribavirin depending on weight. The recommended dosage for genotypes 2 and 3 is 800 mg/day. For other genotypes, if weight is<75 kg, the recommended ribavirin dose is 1000 mg/day or 1200 mg/day if>75 kg. Efficacy was defined as attaining sustained virological response (SVR six months post treatment. Univariate analyses was performed using SPSS-18; Chi-square test with p-value<0.05 was defined significant. 52 co-infected (3 females & 49 males were identified. Mean age was 40±7 years. Caucasians accounted for 84.6%; First Nations for 13.5% and Asians 1.9%. 36 were concurrently on HAART. The genotype distribution was: geno 1, 66.0%; geno 2, 7.5%; geno 3, 26.4%. SVR by ribavirin dosage ratio (actual dosage/recommended dosage:=1.0; 41.2% (14/34,>1.0; 58.8% (20/34. Doses greater than 1.5 times were associated with higher adverse events and lower SVR. Suboptimal doses of weight-based ribavirin may be contributing to a lower treatment response in HCV/HIV co-infectants. In our experience, the optimal dose of ribavirin is between 1 and 1.2 times the current recommended dose. We

  2. Cerebral FDG-PET scanning abnormalities in optimally treated HIV patients

    DEFF Research Database (Denmark)

    Andersen, Åse Bengård; Law, Ian; Krabbe, Karen Suarez

    2010-01-01

    The long-term neurological consequences of HIV infection and treatment are not yet completely understood. In this study we examined the prevalence of cerebral metabolic abnormalities among a cohort of neurologically intact HIV patients with fully suppressed HIV viral loads. Concomitant analyses o...

  3. Cerebral FDG-PET scanning abnormalities in optimally treated HIV patients

    DEFF Research Database (Denmark)

    Andersen, Ase B; Law, Ian; Krabbe, Karen S

    2010-01-01

    BACKGROUND: The long-term neurological consequences of HIV infection and treatment are not yet completely understood. In this study we examined the prevalence of cerebral metabolic abnormalities among a cohort of neurologically intact HIV patients with fully suppressed HIV viral loads. Concomitan...

  4. Optimizing HIV drug therapy

    OpenAIRE

    Calmy, Alexandra

    2010-01-01

    The spectrum of drugs used in HIV-infected patients has dramatically changed since triple antiretroviral combinations were introduced, albeit at the expense of some severe adverse events, in 1996. Long term complications of antiretroviral drug exposure, such as HIV lipodystrophy, as well as organ-specific disease of heart and bone are, therefore, a critical issue when designing antiretroviral regimens. Because it is difficult to predict the occurrence of lipodystrophy, and because there is no...

  5. Cost-effectiveness of optimized background therapy plus maraviroc for previously treated patients with R5 HIV-1 infection from the perspective of the Spanish health care system.

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    Moreno, Santiago; González, Juan; Lekander, Ingrid; Martí, Belén; Oyagüez, Itziar; Sánchez-de la Rosa, Rainel; Casado, Miguel Angel

    2010-12-01

    The aim of this work was to evaluate the cost-effectiveness, from the perspective of the Spanish health care system, of optimized background therapy (OBT) plus maraviroc 300 mg BID versus OBT plus placebo in previously treated patients with R5 HIV-1 infection. A lifetime cohort model was developed, based on 24- and 48-week pooled results from the Maraviroc Versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) studies 1 and 2, to reflect the Spanish health care system's perspective. Treatment duration was based on clinical trial follow-up from MOTIVATE 1 and 2. Clinical data, cohort characteristics, success probability, CD4 increase rate, CD4 cell status link to disease states, and adverse-event probability were taken from the MOTIVATE trials and other published literature. Other input parameters were taken from published sources. Antiretroviral (ARV) costs were derived from local sources. Non-ARV drug costs were obtained from published literature and a cost database. All costs were calculated as year-2009 euros. The annual discount rate was set at 3.0%. The main outcomes were cost per life-year gained (LYG) and cost per quality-adjusted life-year (QALY) gained. Uncertainty was assessed with one-way and probabilistic sensitivity analyses. In the model analysis, adding maraviroc to OBT was associated with an increase of 0.952 LYG and 0.909 QALY. Total costs were €275,970 for maraviroc plus OBT and €254,655 for placebo plus OBT (difference: €21,315). The incremental cost per LYG was €22,398 and the incremental cost per QALY gained was €23,457. The model appeared to be robust for variations in key parameters. Results from the probabilistic sensitivity analyses indicated that the probability of the cost per QALY being below €30,000 was 99%. Despite the limitations of the model, our analysis suggested that OBT plus maraviroc 300 mg BID is a clinically valuable option, and cost-effective from the perspective of the

  6. Self-reported fatigue common among optimally treated HIV patients: no correlation with cerebral FDG-PET scanning abnormalities

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    Andersen, Ase B; Law, Ian; Ostrowski, Sisse R;

    2006-01-01

    patients (n = 95), known to be HIV positive for 5 years, on anti-retroviral therapy for a minimum of 3 years and with CD4 counts above 0.2 x 10(9) cells/l, completed a validated fatigue inventory, and plasma was analysed for pro-inflammatory markers including tumour necrosis factor-alpha, interleukin 6...... and soluble urokinase receptor (suPAR) levels. The distribution of the regional cerebral metabolic rate of glucose was measured in a sub-group of patients suffering from severe fatigue (n = 9) and a group with no fatigue (n = 7) using fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET......) scanning. RESULTS: Fifteen percent suffered from severe fatigue, but no association with pro-inflammatory markers was found. About 50% of the FDG-PET-scanned patients showed minor abnormalities in the relative cerebral metabolic rate of glucose. These abnormalities were not associated with fatigue...

  7. Optimization in HIV screening problems

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    Lev Abolnikov

    2003-01-01

    Full Text Available In this article, the authors use both deterministic and stochastic approaches to the analysis of some optimization problems that arise in the group (“pool” HIV screening practice. Two kinds of testing policies are considered. For the first kind, group-individual testing, the optimal size of the group that should be selected for testing is found. For more general group-subgroup testing procedure the authors develop a numerical algorithm for finding the sequence of successively selected subgroups that minimizes the total cost of testing. Assuming that both arriving and testing processes have a random nature, the authors suggest a stochastic model in which the optimal size of the group in the group-individual testing procedure is found by using methods of queueing theory.

  8. Nigerian dental students' willingness to treat HIV-positive patients.

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    Azodo, Clement Chinedu; Ehigiator, Osarobo; Oboro, Helen Oziofu; Ehizele, Adebola Oluyemisi; Umoh, Agnes; Ezeja, Ejike Bartholomew; Omili, Michael; Ehigiator, Laura

    2010-04-01

    Dental care of HIV-positive individuals plays a vital role in improving their nutritional intake, medication tolerance and effectiveness, treatment success rate, and quality of life. It is therefore important to ensure optimal dental care of this group of people, especially since more of them, with or without knowledge of their serologic status, are now utilizing dental services. The objective of this study was to assess Nigerian dental students' willingness to treat HIV-positive individuals. A descriptive cross-sectional survey of all seventy-six final-year dental students of the University of Benin, Nigeria, was conducted in December 2007 using a self-administered questionnaire that elicited information on the students' demography, self-rated knowledge on HIV/AIDS, attitude towards homosexuals, infection control practices, occupational risk perception, and willingness to provide care for HIV-positive individuals. The response rate was 76.3 percent. Over 77 percent of the respondents were in the twenty-five to thirty years age group. The male-female ratio was approximately 1.6:1. HIV-related knowledge was reported as high by only 31 percent of the respondents. Eighty-one percent showed great interest in HIV-related information, while about half (53.4 percent) exhibited significant worry about occupational contagion. Forty-eight (82.7 percent) desired more knowledge about safety precautions during treatment of HIV patients. Fifty respondents (86.2 percent) reported good infection control practices. About three-fourths (74.2 percent) rated the risk of HIV contagion from patients high, while only one-fourth (25.8 percent) reported having an unsympathetic attitude towards homosexuals. Almost all respondents (98.3 percent) agreed that oral care for HIV-positive individuals improves their quality of life, but only 58.8 percent expressed a willingness to treat HIV-positive patients and only 46.5 percent said they will render volunteer dental services in HIV centers. HIV

  9. T20QoL: an observational multicenter cohort study to evaluate the quality of life in HIV-patients treated with enfuvirtide (ENF, T-20 in combination with an optimized background therapy

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    R Bucciardini

    2008-09-01

    Full Text Available R Bucciardini1, M Massella1, A Corpolongo2, P Narciso2, V Fragola1, M Mirra1, S Donnini1, O Viganò3, S Costarelli4, V Tozzi21Istituto Superiore di Sanità, Rome, Italy; 2IRCCS L. Spallanzani, Rome, Italy; 3Ospedale L. Sacco, Milan, Italy; 4Spedali Civili di Brescia, Brescia, ItalyAim: To evaluate the impact of health-related quality of life (HRQoL enfuvirtide-based (ENF-based salvage regimens of treatment-experienced HIV patients, in an observational multicenter cohort study.Methods: HRQoL was measured in a cohort of 16 patients over a 6-month follow-up using 2 instruments: the ISSQoL (Istituto Superiore di Sanità Quality of Life, a recently validated HIV-specific questionnaire; the EQ-5D (EuroQol, a generic widely used instrument. ENF was given at standard dosage along with an optimized background regimen.Results: Most of HRQoL dimensions showed improvement in ENF-treated patients at the post-baseline time points. Social functioning was the only dimension showing a negative effect. Monthly care costs of antiretroviral drugs for HIV patients taking ENF plus an optimized background regimen were approximately €2,348 per patient-month (range €382– €2,940.Conclusion: Our results show that the addition of ENF to an optimized background salvage-HAART may positively affect HRQoL not only in clinical trials but also in a sample population of patients used in a routine clinical practice.Keywords: enfuvirtide, HRQoL, HIV

  10. Oxidative Imbalance in HIV-1 Infected Patients Treated with Antiretroviral Therapy

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    Antonella Mandas

    2009-01-01

    Full Text Available It is generally accepted that oxidative stress is involved in HIV infection. However, the role in oxidative balance of Highly Active Antiretroviral Therapy (HAART is still debated. In our study we assessed serum oxidant and antioxidant levels in an HIV-1-infected population treated with HAART, and compared them with those of untreated HIV-1 patients and HIV-1-negative subjects. The study included 116 HIV-1-infected patients (86 HAART-treated and 30 untreated, and 46 HIV-negative controls. Serum oxidant levels were significantly higher in the HIV-1 treated group as compared to untreated and control groups. In addition, a decrease of serum total antioxidant status was observed in the HIV-1 treated group. To be noted is that patients who rigorously follow antiretroviral therapy (optimal HAART adherence have significantly higher oxidative status than those who do not closely follow the therapy (poor HAART adherence. Analysis of variance revealed no significant further increase in oxidative status in HIV-1-infected patients taking antiretroviral and other drugs with the exception of psychiatric drugs (e.g. anxiolytics or antidepressants. Taken together, our results indicate that HAART may affect oxidative stress in HIV-1-infected patients and suggest that antiretroviral therapy plays an important role in the synergy of HIV infection and oxidative stress.

  11. Optimal control of HIV/AIDS dynamic: Education and treatment

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    Sule, Amiru; Abdullah, Farah Aini

    2014-07-01

    A mathematical model which describes the transmission dynamics of HIV/AIDS is developed. The optimal control representing education and treatment for this model is explored. The existence of optimal Control is established analytically by the use of optimal control theory. Numerical simulations suggest that education and treatment for the infected has a positive impact on HIV/AIDS control.

  12. Post-treatment control or treated controllers? Viral remission in treated and untreated primary HIV infection

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    Martin, Genevieve E.; Gossez, Morgane; Williams, James P.; Stöhr, Wolfgang; Meyerowitz, Jodi; Leitman, Ellen M.; Goulder, Philip; Porter, Kholoud; Fidler, Sarah; Frater, John

    2017-01-01

    Objective(s): An HIV cure will impose aviraemia that is sustained following the withdrawal of antiretroviral therapy (ART). Understanding the efficacy of novel interventions aimed at curing HIV requires characterization of both natural viral control and the effect of ART on viral control after treatment interruption. Design: Analysis of transient viral control in recent seroconverters in the Short Pulse AntiRetroviral Therapy at Acute Seroconversion trial. Methods: We compared untreated and treated HIV seroconverters (n = 292) and identified periods of control (plasma HIV RNA therapy) in 7.9% of ART-naive participants, and in 12.0% overall. HIV DNA was measured by qPCR, and HIV-specific CD8+ responses were measured by enzyme-linked immunosorbent spot assay (ELISpot). T-cell activation and exhaustion were measured by flow cytometry. Results: At baseline, future controllers had lower HIV DNA, lower plasma HIV RNA, higher CD4+ : CD8+ ratios (all P < 0.001) and higher CD4+ cell counts (P < 0.05) than noncontrollers. Among controllers, the only difference between the untreated and those who received ART was higher baseline HIV RNA in the latter (P = 0.003), supporting an added ART effect. Conclusion: Consideration of spontaneous remission in untreated individuals will be critical to avoid overestimating the effect size of new interventions used in HIV cure studies. PMID:28060012

  13. Fluctuating anaemia in treated HIV patients: could be a PICA?

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    Ajana, Faiza; Pasquet, Armelle; Auffret, Marine; Gautier, Sophie

    2013-01-01

    HIV infected patients are frequently exposed to anaemia, due to antiretroviral agents and/or prophylactic treatment of opportunistic infections. Anemia due to PICA, unusually evoked in our western countries, could be a more frequent situation than imagined. We report two cases of fluctuating anemia with no HIV or iatrogenic origin, observed in two HIV infected women, 47 years old and 33 years old respectively, coming from Africa and treated with antiretroviral agents. The anemia was explained by a culturally sanctioned practice of kaolin ingestion, in the broader context of PICA and resolved after the withdrawal of kaolin ingestion. PICA, and in particular kaolin ingestion, must be investigated when HIV infected patients came from Africa and presented significative unexplained anemia.

  14. The changing face of HIV/AIDS in treated patients.

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    Llibre, Josep M; Falco, Vicenç; Tural, Cristina; Negredo, Eugenia; Pineda, Juan A; Muñoz, Jose; Ortega, Enrique; Videla, Sebastia; Sirera, Guillem; Martinez, Esteban; Miralles, Celia; Iribarren, Josean; Galindo, Maria J; Domingo, Pere; d'Arminio-Monforte, Antonella; Miro, Jose M; Clotet, Bonaventura

    2009-07-01

    The spectrum of complications emerging in successfully treated HIV-infected patients has dramatically changed since the advent of HAART. Typical AIDS-defining illnesses have been substituted by new comorbid conditions that threaten even those patients who maintain virologic suppression. Proper management of cardiovascular risk, and early diagnosis of AIDS-related and, particularly, non-AIDS-related malignancies (including papilomavirus-related neoplasms) must be introduced into the routine of care. Hot areas of investigation include HIV-associated neurocognitive disorders, hepatitis B and C coinfection, non-alcoholic fatty liver disease, progressive multifocal leukoencephalopathy and tuberculosis. Bone and kidney long-term toxicities and lipoatrophy remain as issues of paramount importance. The identification and early treatment of immune reconstitution disease is also of major interest, specially in those patients starting their antiretroviral treatment with severe CD4 cell depletion. The present review focuses on these twelve areas of increasing interest for physicians currently facing successfully treated HIV+ patients.

  15. Traditional Chinese Herbal Medicines for Treating HIV Infections and AIDS

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    Wen Zou

    2012-01-01

    Full Text Available To assess the effects of TCHM on patients with HIV infection and AIDS, we reviewed eleven randomized placebo-controlled trials involving 998 patients. Due to the limited number of RCTs for included trials and the small sample size of each study, we are not able to draw firm conclusions concerning TCHM therapy in treating patients with HIV infection and AIDS. However, some high-quality clinical studies do exist. Studies of diarrhea and oral candidiasis, which are challenging symptoms of AIDS, were demonstrated to have positive effects. Study of peripheral leukocytes, which are a side effect of antiretroviral drugs, suggested that an integrated treatment approach may be of benefit. The overall methodological quality of the trials was adequate; however, randomization methods should be clearly described and fully reported in these trials according to the Consolidated Standards of Reporting Trials (CONSORT.

  16. Optimal investment in a portfolio of HIV prevention programs.

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    Zaric, G S; Brandeau, M L

    2001-01-01

    In this article, the authors determine the optimal allocation of HIV prevention funds and investigate the impact of different allocation methods on health outcomes. The authors present a resource allocation model that can be used to determine the allocation of HIV prevention funds that maximizes quality-adjusted life years (or life years) gained or HIV infections averted in a population over a specified time horizon. They apply the model to determine the allocation of a limited budget among 3 types of HIV prevention programs in a population of injection drug users and nonusers: needle exchange programs, methadone maintenance treatment, and condom availability programs. For each prevention program, the authors estimate a production function that relates the amount invested to the associated change in risky behavior. The authors determine the optimal allocation of funds for both objective functions for a high-prevalence population and a low-prevalence population. They also consider the allocation of funds under several common rules of thumb that are used to allocate HIV prevention resources. It is shown that simpler allocation methods (e.g., allocation based on HIV incidence or notions of equity among population groups) may lead to alloctions that do not yield the maximum health benefit. The optimal allocation of HIV prevention funds in a population depends on HIV prevalence and incidence, the objective function, the production functions for the prevention programs, and other factors. Consideration of cost, equity, and social and political norms may be important when allocating HIV prevention funds. The model presented in this article can help decision makers determine the health consequences of different allocations of funds.

  17. Raltegravir with optimized background therapy for resistant HIV-1 infection

    DEFF Research Database (Denmark)

    Steigbigel, Roy T; Cooper, David A; Kumar, Princy N;

    2008-01-01

    for the length of follow-up, cancers were detected in 3.5% of raltegravir recipients and in 1.7% of placebo recipients. The overall frequencies of drug-related adverse events were similar in the raltegravir and placebo groups. CONCLUSIONS: In HIV-infected patients with limited treatment options, raltegravir plus......BACKGROUND: Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs. METHODS: We conducted two identical trials in different geographic regions to evaluate the safety and efficacy...... of raltegravir, as compared with placebo, in combination with optimized background therapy, in patients infected with HIV-1 that has triple-class drug resistance in whom antiretroviral therapy had failed. Patients were randomly assigned to raltegravir or placebo in a 2:1 ratio. RESULTS: In the combined studies...

  18. HIV treatment optimism and sexual risk behaviors among HIV positive African American men who have sex with men.

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    Peterson, John L; Miner, Michael H; Brennan, David J; Rosser, B R Simon

    2012-04-01

    The association between HIV treatment optimism--beliefs about susceptibility to transmit HIV, motivation to use condoms, and severity of HIV--and sexual risk behavior was examined among HIV-positive African American men who have sex with men (MSM). Participants were 174 men recruited in four major metropolitan areas of the United States to participate in a weekend HIV risk reduction intervention. Baseline results revealed that beliefs in less susceptibility to transmit HIV and less motivation to use condoms were significantly associated with more unprotected anal intercourse among serodiscordant casual partners. Less motivation to use condoms also predicted more unprotected insertive and receptive anal sex and was more important than susceptibility beliefs in predicting these behaviors. Suggestions are offered of ways to better inform HIV-positive African American MSM about their misperceptions about HIV treatment and how their level of optimism about HIV treatment may diminish or encourage condom use.

  19. Increased brain-predicted aging in treated HIV disease

    NARCIS (Netherlands)

    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J; Kalsbeek, A.

    2017-01-01

    OBJECTIVE: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. METHODS: A la

  20. Optimization of a Pressure-Treating Process

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    Josean Velez

    2011-01-01

    Full Text Available A company that pressure-treats wood wants to minimize its annual cost without using more than 250 days of operation per year. In addition, they want to find the corresponding value of time, batches and cost for each category. We develop an expression in terms of boards per batch to model the total cost of the treatment process. We then take the derivative and use Newton's Method to find the number of boards per batch that minimizes total cost.

  1. Optimal antiviral switching to minimize resistance risk in HIV therapy.

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    Rutao Luo

    Full Text Available The development of resistant strains of HIV is the most significant barrier to effective long-term treatment of HIV infection. The most common causes of resistance development are patient noncompliance and pre-existence of resistant strains. In this paper, methods of antiviral regimen switching are developed that minimize the risk of pre-existing resistant virus emerging during therapy switches necessitated by virological failure. Two distinct cases are considered; a single previous virological failure and multiple virological failures. These methods use optimal control approaches on experimentally verified mathematical models of HIV strain competition and statistical models of resistance risk. It is shown that, theoretically, order-of-magnitude reduction in risk can be achieved, and multiple previous virological failures enable greater success of these methods in reducing the risk of subsequent treatment failures.

  2. Increased brain-predicted aging in treated HIV disease

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    Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.

    2017-01-01

    Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081

  3. A model for HIV/AIDS pandemic with optimal control

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    Sule, Amiru; Abdullah, Farah Aini

    2015-05-01

    Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is pandemic. It has affected nearly 60 million people since the detection of the disease in 1981 to date. In this paper basic deterministic HIV/AIDS model with mass action incidence function are developed. Stability analysis is carried out. And the disease free equilibrium of the basic model was found to be locally asymptotically stable whenever the threshold parameter (RO) value is less than one, and unstable otherwise. The model is extended by introducing two optimal control strategies namely, CD4 counts and treatment for the infective using optimal control theory. Numerical simulation was carried out in order to illustrate the analytic results.

  4. Optimism, well-being, and perceived stigma in individuals living with HIV.

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    Ammirati, Rachel J; Lamis, Dorian A; Campos, Peter E; Farber, Eugene W

    2015-01-01

    Given the significant psychological challenges posed by HIV-related stigma for individuals living with HIV, investigating psychological resource factors for coping with HIV-related stigma is important. Optimism, which refers to generalized expectations regarding favorable outcomes, has been associated with enhanced psychological adaptation to health conditions, including HIV. Therefore, this cross-sectional study investigated associations among optimism, psychological well-being, and HIV stigma in a sample of 116 adults living with HIV and seeking mental health services. Consistent with study hypotheses, optimism was positively associated with psychological well-being, and psychological well-being was negatively associated with HIV-related stigma. Moreover, results of a full structural equation model suggested a mediation pattern such that as optimism increases, psychological well-being increases, and perceived HIV-related stigma decreases. The implications of these findings for clinical interventions and future research are discussed.

  5. Optimizing antibiotic selection in treating COPD exacerbations

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    Attiya Siddiqi

    2008-03-01

    Full Text Available Attiya Siddiqi, Sanjay SethiDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Veterans Affairs Western New York Health Care System and University of Buffalo, State University of New York, Buffalo, New York, USAAbstract: Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations.Keywords: COPD, exacerbation, bronchitis, antibiotics

  6. Efavirenz Plasma Concentrations and HIV Viral Load in HIV/AIDS-tuberculosis Infection Patients Treated with Rifampicin.

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    Mariana, Nina; Purwantyastuti; Instiaty; Rusli, Adria

    2016-01-01

    to determine the effect of a rifampicin-containing tuberculosis regimen on efavirenz plasma concentrations and viral load in HIV/AIDS-Tuberculosis infection patients who received efavirenz-based antiretroviral therapy. plasma efavirenz concentrations and HIV viral load were measured in HIV/AIDS patients treated with 600 mg efavirenz-based antiretroviral for 3 to 6 months and in HIV/AIDS-Tuberculosis infection patients treated with similar antiretroviral regimen plus rifampicin-containing antituberculosis in Sulianti Saroso Infectious disease Hospital, Jakarta. Plasma efavirenz concentration in both groups were compared using Mann-Whitney test, while proportion of patients with viral load >40 copy/mL were analyzed with chi-square test. forty five patients (27 with HIV/AIDS and 18 with HIV/AIDS-Tuberculosis infections) were recruited during the period of February to May 2015. The median efavirenz plasma concentration obtained from HIV/AIDS group was 0,680 mg/L(range 0,24 to 5,67 mg/L and that obtained from HIV/AIDS-Tuberculosis group was 0.685 mg/L (0.12 -2.23 mg/L) which was not significantly different statistically. The proportion of patients with viral load 40 copies/mL after 3-6 months of ARV treatment in the HIV/AIDS group was 51.9%, and in the HIV/AIDS-Tuberculosis group was 72.2%, which was not significantly different statistically (Chi Square test, p=0.291). plasma efavirenz concentration in HIV/AIDS-tuberculosis patients receiving antiretroviral and rifampicin is not significantly different from that on HIV/AIDS patients without tuberculosis. Proportion of patients with viral load of >40 copy/mL is higher in HIV/AIDS-tuberculosis patients receiving rifampicin compared to HIV/AIDS patients that not receive rifampicin. However, this difference did not reach statistical significance. Confirmatory studies with bigger sample size are needed to clarify the influence of rifampicin on plasma level of efavirenzand and on viral load.

  7. Treating curable sexually transmitted infections to prevent HIV in Africa - Still an effective control strategy?

    NARCIS (Netherlands)

    White, Richard G.; Orroth, Kate K.; Glynn, Judith R.; Freeman, Esther E.; Bakker, Roel; Habbema, J. Dik F.; Terris-Prestholt, Fern; Kumaranayake, Lilani; Buve, Anne; Hayes, Richard J.

    2008-01-01

    Background: Evidence regarding the effectiveness of sexually transmitted infection (STI) treatment for HIV prevention in Africa is equivocal, leading some policy makers to question whether it should continue to be promoted for HIV control. We explore whether treating curable STIs remains a cost-effe

  8. Plasma lipidomic profiling of treated HIV-positive individuals and the implications for cardiovascular risk prediction.

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    Wong, Gerard; Trevillyan, Janine M; Fatou, Benoit; Cinel, Michelle; Weir, Jacquelyn M; Hoy, Jennifer F; Meikle, Peter J

    2014-01-01

    The increased risk of coronary artery disease in human immunodeficiency virus (HIV) positive patients is collectively contributed to by the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In this study, we investigate the characterisation of the plasma lipid profiles of treated HIV patients and the relationship of 316 plasma lipid species across multiple lipid classes with the risk of future cardiovascular events in HIV-positive patients. In a retrospective case-control study, we analysed plasma lipid profiles of 113 subjects. Cases (n = 23) were HIV-positive individuals with a stored blood sample available 12 months prior to their diagnosis of coronary artery disease (CAD). They were age and sex matched to HIV-positive individuals without a diagnosis of CAD (n = 45) and with healthy HIV-negative volunteers (n = 45). Association of plasma lipid species and classes with HIV infection and cardiovascular risk in HIV were determined. In multiple logistic regression, we identified 83 lipids species and 7 lipid classes significantly associated with HIV infection and a further identified 74 lipid species and 8 lipid classes significantly associated with future cardiovascular events in HIV-positive subjects. Risk prediction models incorporating lipid species attained an area under the receiver operator characteristic curve (AUC) of 0.78 (0.775, 0.785)) and outperformed all other tested markers and risk scores in the identification of HIV-positive subjects with increased risk of cardiovascular events. Our results demonstrate that HIV-positive patients have significant differences in their plasma lipid profiles compared with healthy HIV-negative controls and that numerous lipid species were significantly associated with elevated cardiovascular risk. This suggests a potential novel application for plasma lipids in cardiovascular risk screening of HIV-positive patients.

  9. Brain viral burden, neuroinflammation and neurodegeneration in HAART-treated HIV positive injecting drug users.

    Science.gov (United States)

    Smith, Donald B; Simmonds, Peter; Bell, Jeanne E

    2014-02-01

    The long-term impact of chronic human immunodeficiency virus (HIV) infection on brain status in injecting drug users (IDU) treated with highly active antiretroviral therapy (HAART) is unknown. Viral persistence in the brain with ongoing neuroinflammation may predispose to Alzheimer-like neurodegeneration. In this study, we investigated the brains of ten HAART-treated individuals (six IDU and four non-DU), compared with ten HIV negative controls (six IDU and four non-DU). HIV DNA levels in brain tissue were correlated with plasma and lymphoid tissue viral loads, cognitive status, microglial activation and Tau protein and amyloid deposition. Brain HIV proviral DNA levels were low in most cases but higher in HIV encephalitis (n = 2) and correlated significantly with levels in lymphoid tissue (p = 0.0075), but not with those in plasma. HIV positive subjects expressed more Tau protein and amyloid than HIV negative controls (highest in a 58 year old), as did IDU, but brain viral loads showed no relation to Tau and amyloid. Microglial activation linked significantly to HIV positivity (p = 0.001) and opiate abuse accentuated these microglial changes (p = 0.05). This study confirms that HIV DNA persists in brains despite HAART and that opiate abuse adds to the risk of brain damage in HIV positive subjects. Novel findings in this study show that (1) plasma levels are not a good surrogate indicator of brain status, (2) viral burden in brain and lymphoid tissues is related, and (3) while Tau and amyloid deposition is increased in HIV positive IDU, this is not specifically related to increased HIV burden within the brain.

  10. An Epigenetic Clock Measures Accelerated Aging in Treated HIV Infection.

    Science.gov (United States)

    Boulias, Konstantinos; Lieberman, Judy; Greer, Eric Lieberman

    2016-04-21

    In this issue of Molecular Cell, Gross et al. (2016) find a CpG DNA methylation signature in blood cells of patients with chronic well-controlled HIV infection that correlates with accelerated aging.

  11. Education about treating patients with HIV infections/AIDS: the student perspective.

    Science.gov (United States)

    Seacat, Jason P; Inglehart, Marita Rohr

    2003-06-01

    This study investigated dental and dental hygiene students' a) perceptions of their education about treating patients with HIV infections/AIDS, b) knowledge of universal precautions, c) attitudes towards treating these patients and patients perceived to be at risk for HIV infections, and d) evaluations of potential curricular activities such as discussion groups with HIV-infected patients. Data were collected with self-administered questionnaires from 315 dental and 89 dental hygiene students. On average, dental students reported having learned about this topic in fever courses than dental hygiene students. However, dental students answered significantly more knowledge questions about universal precautions correctly than did dental hygiene students. This knowledge increased over the program course. Male students had significantly stronger negative attitudes towards patients at risk for or with HIV infections/AIDS than female students. Overall, dental and dental hygiene students responded positively to the suggested methods for including more material about patients with HIV infections/AIDS such as case studies, discussion groups, and closely supervised clinical experiences. This study shows that dental and dental hygiene students are interested in learning more about treating patients with HIV infections/AIDS. It also adds information to previous research on factors involved in the dental healthcare providers' decisions to treat patients at risk for or with HIV infections/AIDS. The implications of these findings for curriculum development efforts are discussed.

  12. Fecal Bacterial Communities in treated HIV infected individuals on two antiretroviral regimens

    Science.gov (United States)

    Pinto-Cardoso, Sandra; Lozupone, Catherine; Briceño, Olivia; Alva-Hernández, Selma; Téllez, Norma; Adriana, Aguilar; Murakami-Ogasawara, Akio; Reyes-Terán, Gustavo

    2017-01-01

    Intestinal microbiome changes that occur in HIV positive individuals on different antiretroviral therapy (ART) regimens are important to understand, as they are potentially linked with chronic inflammation and microbiome-linked comorbidities that occur at increased incidence in this population. We conducted a cross-sectional study comparing the fecal microbiomes of HIV-uninfected (HIV SN) to HIV-infected individuals on long-term ART (HIV+ LTART) from Mexico using 16S ribosomal RNA (16sRNA) targeted sequencing. These individuals were on two ART regimens based on either Non-Nucleoside Reverse Transcriptase Inhibitors (EFV) or ritonavir-boosted Protease Inhibitors (PI) with the same backbone of Nucleoside Reverse Transcriptase Inhibitors. Microbiome diversity was reduced in treated HIV infection compared to HIV SN (p < 0.05). Several operational taxonomic units (OTUs) related to the Ruminococcaceae family including Faecalibacterium prausnitzii were depleted in EFV and PI compared to HIV SN and negatively correlated with intestinal gut dysfunction as measured by the intestinal fatty binding protein (p < 0.05). This is the first report to address the fecal bacterial communities in HIV-infected individuals on two ARV regimens from Mexico. PMID:28262770

  13. Self-reported HIV testing practice among physicians treating tuberculosis in Australia and New Zealand.

    Science.gov (United States)

    Emerson, C R; Goldberg, H; Vollmer-Conna, U; Post, J J

    2010-05-01

    Not all people with tuberculosis have their HIV status ascertained despite the interaction between these infections. We investigated the self-reported HIV testing practice among physicians treating tuberculosis in Australia and New Zealand and used logistic regression to assess factors associated with a routine offer of HIV testing in cases of tuberculosis. Of 290 subjects, 61% always recommended an HIV test for a 38-year-old married man with smear-positive pulmonary tuberculosis. A lower proportion (40%) always tested a 78-year-old man or a female patient (58%), and more always HIV tested a South African case (85%), a patient with oral candidiasis (87%) or an unmarried male patient (66%). No scenario was associated with a universal offer of HIV testing. Clinician factors such as specialty (odds ratio [OR] 3.09), jurisdiction of practice (OR 4.09) and number of HIV tests requested in the past five years (OR 0.29) predicted the self-reported frequency of always HIV testing tuberculosis patients. At least 48% of respondents reported that epidemiological or clinical factors influenced their decision to offer testing. Strategies to increase HIV testing in cases of tuberculosis need to consider clinician factors.

  14. Treating depression in HIV-positive patients affects adherence

    African Journals Online (AJOL)

    2012-09-02

    19,20-22 maintain CD4 cell counts; prevent clinical ... affecting ART adherence in HIV-positive patients,32-35 ... 99.5%, and of those who received psychotherapy increased .... children (chi2=5.022; p=0.285); past history.

  15. Treating depression in HIV-positive patients affects adherence

    OpenAIRE

    M Y H Moosa; F Y Jeenah

    2012-01-01

    Aim. To determine changes in adherence to antiretroviral therapy (ART) in HIV-positive patients with depression, following treatment with an antidepressant or psychotherapy. Methods. The study was prospective, randomised and controlled. Consenting volunteers aged ≥18 years and stable on ART for ≥6 months were included in the study. Sociodemographic data were obtained, and a clinical diagnostic evaluation and the Hamilton Depression rating scale (HAMD) were performed on all subjects at en...

  16. Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults

    OpenAIRE

    Newcomb, Michael E.; Bedoya, C. Andres; Blashill, Aaron J.; Lerner, Jonathan A.; O’Cleirigh, Conall; Pinkston, Megan M.; Safren, Steven A.

    2015-01-01

    There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depres...

  17. Enhancement of NMDA receptor-mediated excitatory postsynaptic currents by gp120-treated macrophages: Implications for HIV-1-associated neuropathology

    OpenAIRE

    Yang, Jianming; Hu, Dehui; Xia, Jianxun; Liu, Jianuo; Zhang, Gang; Gendelman, Howard E; Nawal M. Boukli; Xiong, Huangui

    2013-01-01

    A plethora of prior studies has linked HIV-1-infected and immune activated brain mononuclear phagocytes (MP; blood borne macrophages and microglia) to neuronal dysfunction. These are modulated by N-methyl-D-aspartate receptor (NMDAR) antagonists and supporting their relevance for HIV-1-associated nervous system disease. The role of NMDAR subsets in HIV-1-induced neuronal injury, nonetheless, is poorly understood. To this end, we investigated conditioned media from HIV-1gp120-treated human mon...

  18. Free Final-Time Optimal Control for HIV Viral Dynamics

    CERN Document Server

    Pachpute, Gaurav

    2011-01-01

    In this paper, we examine a well-established model for HIV wild-type infection. The algorithm for steepest descent method for fixed final-time is stated and a modified method for free final-time is presented. The first type of cost functional considered, seeks to minimize the total time of therapy. An easy implementation for this problem suggests that it can be effective in the early stages of treatment as well as for individual-based studies, due to the "hit first and hit hard" nature of optimal control. An LQR based cost functional is also presented and the solution is found using steepest descent method. It suggests that the optimal therapy must remain high until the patient shows signs of recovery after which, the therapy gradually decreases. This is in line with the biomedical philosophy. Solution to a modified problem which includes a weight for total time is approximated using the modified algorithm. It shows a considerable drop in the total period. We conclude that, a decreased and optimized therapy p...

  19. Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection

    Science.gov (United States)

    Altfeld, Marcus; Rosenberg, Eric S.; Shankarappa, Raj; Mukherjee, Joia S.; Hecht, Frederick M.; Eldridge, Robert L.; Addo, Marylyn M.; Poon, Samuel H.; Phillips, Mary N.; Robbins, Gregory K.; Sax, Paul E.; Boswell, Steve; Kahn, James O.; Brander, Christian; Goulder, Philip J.R.; Levy, Jay A.; Mullins, James I.; Walker, Bruce D.

    2001-01-01

    Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection. PMID:11148221

  20. Optimal HIV testing and earlier care: the way forward in Europe

    DEFF Research Database (Denmark)

    Coenen, T; Lundgren, J; Lazarus, Jeff;

    2008-01-01

    representing advocacy, clinical and policy areas of the HIV field, was convened in an effort to gain a common understanding on the role of HIV testing and counselling in optimizing diagnosis and the need for earlier care. Key topics discussed at the conference and described in the following articles include......The articles in this supplement were developed from a recent pan-European conference entitled 'HIV in Europe 2007: Working together for optimal testing and earlier care', which took place on 26-27 November in Brussels, Belgium. The conference, organized by a multidisciplinary group of experts......: current barriers to HIV testing across Europe, trends in the epidemiology of HIV in the region, problems associated with undiagnosed infection and the psychosocial barriers impacting on testing. The supplement also provides a summary of the World Health Organization's recommendations for HIV testing...

  1. Treating depression in HIV-positive patients affects adherence

    Directory of Open Access Journals (Sweden)

    M Y H Moosa

    2012-09-01

    Full Text Available Aim. To determine changes in adherence to antiretroviral therapy (ART in HIV-positive patients with depression, following treatment with an antidepressant or psychotherapy. Methods. The study was prospective, randomised and controlled. Consenting volunteers aged ≥18 years and stable on ART for ≥6 months were included in the study. Sociodemographic data were obtained, and a clinical diagnostic evaluation and the Hamilton Depression rating scale (HAMD were performed on all subjects at entry to and at the end of the study. Participants found to be depressed were randomly assigned antidepressant treatment (20 mg citalopram or interpersonal psychotherapy (IPT (5 sessions. Medication was dispensed at each visit and patients were asked to return all unused medication to determine ART adherence. The study was approved by the University of the Witwatersrand. Results. Sixty-two HIV-positive persons receiving ART participated; 30 were not depressed (control group and 32 were depressed (patient group. No significant differences in demographic characteristics existed between the control and patient groups. Mean ART adherence at the start of the study was 99.5% (standard error (SE ±0.46 and 92.1% (SE ±1.69 in the control and patients groups, respectively. Mean ART adherence at the end of the study changed marginally in the control group (99.7%; SE ±0.46 and increased significantly in the patient group (99.5%; SE± 0.13 (p>0.05. The mean ART adherence rate of patients who received pharmacotherapy increased from 92.8% to 99.5%, and of those who received psychotherapy increased from 91.1% to 99.6% (p>0.05. There was no significant association between the increased adherence in the patient group and baseline demographic and clinical characteristics, irrespective of antidepressant therapy or IPT (p>0.05. Conclusion. Successful treatment of depression with an antidepressant or psychotherapy was associated with improved ART adherence, independent of the type

  2. Immunologic Biomarkers, Morbidity, and Mortality in Treated HIV Infection.

    Science.gov (United States)

    Hunt, Peter W; Lee, Sulggi A; Siedner, Mark J

    2016-10-01

    Despite marked improvements in the modern treatment era, human immunodeficiency virus (HIV)-infected individuals, particularly those who initiated antiretroviral therapy (ART) at advanced disease stages, continue to have increased age-related morbidity and mortality, compared with the general population. Immune activation and inflammation persist despite suppressive ART and predict many of these morbidities. The goal of this review is to examine the evidence suggesting a link between the persistent inflammatory state and morbidity and mortality in this setting, to describe the impact of early ART initiation on these factors, and to highlight important unanswered questions for the field. We also advance a hypothesis to explain why some morbidities-and their root inflammatory drivers-may be prevented more than others by early ART initiation.

  3. Family Resiliency, Uncertainty, Optimism, and the Quality of Life of Individuals with HIV/AIDS

    Science.gov (United States)

    Frain, Michael P.; Berven, Norman L.; Chan, Fong; Tschopp, Molly K.

    2008-01-01

    The purpose of the study is to contribute to the understanding of quality of life as it is experienced by a community-based, nonclinical sample of individuals with HIV/AIDS by applying family resiliency theory and cognitive appraisal concepts of uncertainty and optimism. Through the use of a Web-based survey, 125 individuals with HIV/AIDS…

  4. HIV treatment optimism and its predictors among young adults in southern Malawi.

    Science.gov (United States)

    Yeatman, Sara; Dovel, Kathryn; Conroy, Amy; Namadingo, Hazel

    2013-08-01

    This study measures HIV treatment optimism and its predictors in a representative sample of young adults in southern Malawi. In 2010, 1275 women and 470 men between the ages of 16 and 26 were asked about their exposure to people on antiretroviral therapy (ART), sexual risk behavior, HIV status, and beliefs about ART. We used confirmatory factor analysis to develop a 4-item scale of the belief that HIV is a less serious health threat due to ART (reduced-severity optimism) and used a single measure to capture belief in the reduced infectivity of HIV due to ART (reduced-susceptibility optimism). Overall, respondents reported low levels of HIV treatment optimism. Being female and using ART were the largest predictors of both types of treatment optimism. We found a nonlinear relationship between exposure to people on ART and reduced-severity optimism. People who knew someone on ART but did not discuss it with them had lower levels of reduced-severity optimism than people who did not know anyone on ART and people who regularly discussed treatment with someone on ART. In multivariate regression models, HIV treatment optimism was positively associated with all measures of sexual risk behavior among men, but negatively associated with unprotected sex with a nonprimary partner among women. Our findings suggest that the spread of ART in Malawi has not led to widespread HIV treatment optimism. This may reflect the relatively recent spread of ART, the generalized nature of the HIV epidemic, or the fact that access to ART is complicated by structural limitations that delay treatment and limited availability of second-line medicines.

  5. Local tumor control and toxicity in HIV-associated anal carcinoma treated with radiotherapy in the era of antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Lütolf Urs M

    2006-08-01

    Full Text Available Abstract Purpose To investigate the outcome of HIV-seropositive patients under highly active antiretroviral treatment (HAART with anal cancer treated with radiotherapy (RT alone or in combination with standard chemotherapy (CT. Patients and methods Clinical outcome of 81 HIV-seronegative patients (1988 – 2003 and 10 consecutive HIV-seropositive patients under HAART (1997 – 2003 that were treated with 3-D conformal RT of 59.4 Gy and standard 5-fluorouracil and mitomycin-C were retrospectively analysed. 10 TNM-stage and age matched HIV-seronegative patients (1992 – 2003 were compared with the 10 HIV-seropositive patients. Pattern of care, local disease control (LC, overall survival (OS, cancer-specific survival (CSS, and toxicity were assessed. Results RT with or without CT resulted in complete response in 100 % of HIV-seropositive patients. LC was impaired compared to matched HIV-seronegative patients after a median follow-up of 44 months (p = 0.03. OS at 5 years was 70 % in HIV-seropositive patients receiving HAART and 69 % in the matched controls. Colostomy-free survival was 70 % (HIV+ and 100 % (matched HIV- and 78 % (all HIV-. No HIV-seropositive patient received an interstitial brachytherapy boost compared to 42 % of all HIV-seronegative patients and adherence to chemotherapy seemed to be difficult in HIV-seropositive patients. Acute hematological toxicity reaching 50 % was high in HIV-seropositive patients receiving MMC compared with 0 % in matched HIV-seronegative patients (p = 0.05 or 12 % in all HIV-seronegative patients. The rate of long-term side effects was low in HIV-seropositive patients. Conclusion Despite high response rates to organ preserving treatment with RT with or without CT, local tumor failure seems to be high in HIV-positive patients receiving HAART. HIV-seropositive patients are subject to treatment bias, being less likely treated with interstitial brachytherapy boost probably due to HIV-infection, and they are at

  6. Optimizing the HIV/AIDS informed consent process in India

    Directory of Open Access Journals (Sweden)

    Shrotri A

    2004-08-01

    Full Text Available Abstract Background While the basic ethical issues regarding consent may be universal to all countries, the consent procedures required by international review boards which include detailed scientific and legal information, may not be optimal when administered within certain populations. The time and the technicalities of the process itself intimidate individuals in societies where literacy and awareness about medical and legal rights is low. Methods In this study, we examined pregnant women's understanding of group education and counseling (GEC about HIV/AIDS provided within an antenatal clinic in Maharashtra, India. We then enhanced the GEC process with the use of culturally appropriate visual aids and assessed the subsequent changes in women's understanding of informed consent issues. Results We found the use of visual aids during group counseling sessions increased women's overall understanding of key issues regarding informed consent from 38% to 72%. Moreover, if these same visuals were reinforced during individual counseling, improvements in women's overall comprehension rose to 96%. Conclusions This study demonstrates that complex constructs such as informed consent can be conveyed in populations with little education and within busy government hospital settings, and that the standard model may not be sufficient to ensure true informed consent.

  7. Optimizing nitrate removal in woodchip beds treating aquaculture effluents

    DEFF Research Database (Denmark)

    von Ahnen, Mathis; Pedersen, Per Bovbjerg; Hoffmann, Carl Christian

    2016-01-01

    Nitrate is typically removed from aquaculture effluents using heterotrophic denitrification reactors. Heterotrophic denitrification reactors, however, require a constant input of readily available organic carbon (C) sources which limits their application in many aquaculture systems for practical...... the potential of optimizing woodchip reactors for treating aquaculture effluent. A central composite design (CCD) was applied to assess the effects of simultaneously changing the empty bed contact time (EBCTs of 5.0-15.0 h; corresponding to theoretical hydraulic retention times of 3.3-9.9 h) and bicarbonate...... (HCO3 -) inlet concentration (0.50-1.59 g HCO3 -/l) on the removal rate of NO3 -N, and additional organic and inorganic nutrients, in effluent deriving from an experimental recirculating aquaculture system (RAS).Volumetric NO3 -N removal rates ranged from 5.20 ± 0.02 to 8.96 ± 0.19 g/m3/day and were...

  8. Modeling and optimization of rotary kiln treating EAF dust

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Electric arc furnace (EAF) dust from steel industries is listed by the United Sates EPA as a hazardous waste under the regulations of the Resource Conservation and Recovery Act due to the presence of lead, cadmium and chlorine. The disposal of the approximately 650000 t of EAF dust per year in the U.S. and Canada is an expensive and unresolved problem for the majority of steel companies. The Waelz process has been considered as the best process for treating the EAF dust. A process model, combined thermodynamic modeling with heat transfer calculations, has been developed to simulate the chemical reactions, mass and heat transfer and heat balance in the kiln. The injection of air into the slag and the temperature profile along the kiln have been modeled. The effect of (CaO+MgO)/SiO2 on the solidus temperature of slag has also been predicted and discussed. Some optimized results have been presented.

  9. Allocating HIV prevention funds in the United States: recommendations from an optimization model.

    Directory of Open Access Journals (Sweden)

    Arielle Lasry

    Full Text Available The Centers for Disease Control and Prevention (CDC had an annual budget of approximately $327 million to fund health departments and community-based organizations for core HIV testing and prevention programs domestically between 2001 and 2006. Annual HIV incidence has been relatively stable since the year 2000 and was estimated at 48,600 cases in 2006 and 48,100 in 2009. Using estimates on HIV incidence, prevalence, prevention program costs and benefits, and current spending, we created an HIV resource allocation model that can generate a mathematically optimal allocation of the Division of HIV/AIDS Prevention's extramural budget for HIV testing, and counseling and education programs. The model's data inputs and methods were reviewed by subject matter experts internal and external to the CDC via an extensive validation process. The model projects the HIV epidemic for the United States under different allocation strategies under a fixed budget. Our objective is to support national HIV prevention planning efforts and inform the decision-making process for HIV resource allocation. Model results can be summarized into three main recommendations. First, more funds should be allocated to testing and these should further target men who have sex with men and injecting drug users. Second, counseling and education interventions ought to provide a greater focus on HIV positive persons who are aware of their status. And lastly, interventions should target those at high risk for transmitting or acquiring HIV, rather than lower-risk members of the general population. The main conclusions of the HIV resource allocation model have played a role in the introduction of new programs and provide valuable guidance to target resources and improve the impact of HIV prevention efforts in the United States.

  10. Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Lundgren, Jens D; Ridolfo, Annalisa

    2014-01-01

    Poisson regression was used to assess the relationship between current platelet counts and the incidence of non-AIDS-defining (pancreatitis, end-stage liver/renal disease, cancer, cardiovascular disease) and AIDS-defining events.RESULTS: There were 62 898 person-years of follow-up (PYFU) among 12 279...... the pathophysiological processes underlying thrombocytopenia are associated with the development of cancer during treated HIV disease....

  11. Incidence of syphilis seroconversion among HIV-infected persons in Asia: results from the TREAT Asia HIV Observational Database

    Science.gov (United States)

    Ahn, Jin Young; Boettiger, David; Kiertiburanakul, Sasisopin; Merati, Tuti Parwati; Huy, Bui Vu; Wong, Wing Wai; Ditangco, Rossana; Lee, Man Po; Oka, Shinichi; Durier, Nicolas; Choi, Jun Yong

    2016-01-01

    Introduction Outbreaks of syphilis have been described among HIV-infected men who have sex with men (MSM) in Western communities, whereas reports in Asian countries are limited. We aimed to characterize the incidence and temporal trends of syphilis among HIV-infected MSM compared with HIV-infected non-MSM in Asian countries. Methods Patients enrolled in the TREAT Asia HIV Observational Database cohort and with a negative non-treponemal test since enrolment were analyzed. Incidence of syphilis seroconversion, defined as a positive non-treponemal test after previously testing negative, was evaluated among patients at sites performing non-treponemal tests at least annually. Factors associated with syphilis seroconversion were investigated at sites doing non-treponemal testing in all new patients and subsequently testing routinely or when patients were suspected of having syphilis. Results We included 1010 patients from five sites that performed non-treponemal tests in all new patients; those included had negative non-treponemal test results during enrolment and subsequent follow-ups. Among them, 657 patients were from three sites conducting regular non-treponemal testing. The incidence of syphilis seroconversion was 5.38/100 person-years (PY). Incidence was higher in MSM than non-MSM (7.64/100 PY vs. 2.44/100 PY, p<0.001). Among MSM, the incidence rate ratio (IRR) for every additional year from 2009 was 1.19 (p=0.051). MSM status (IRR 3.48, 95% confidence interval (CI) 1.88–6.47), past syphilis diagnosis (IRR 5.15, 95% CI 3.69–7.17) and younger age (IRR 0.84 for every additional 10 years, 95% CI 0.706–0.997) were significantly associated with syphilis seroconversion. Conclusions We observed a higher incidence of syphilis seroconversion among HIV-infected MSM and a trend to increasing annual incidence. Regular screening for syphilis and targeted interventions to limit transmission are needed in this population. PMID:27774955

  12. Incidence of syphilis seroconversion among HIV-infected persons in Asia: results from the TREAT Asia HIV Observational Database

    Directory of Open Access Journals (Sweden)

    Jin Young Ahn

    2016-10-01

    Full Text Available Introduction: Outbreaks of syphilis have been described among HIV-infected men who have sex with men (MSM in Western communities, whereas reports in Asian countries are limited. We aimed to characterize the incidence and temporal trends of syphilis among HIV-infected MSM compared with HIV-infected non-MSM in Asian countries. Methods: Patients enrolled in the TREAT Asia HIV Observational Database cohort and with a negative non-treponemal test since enrolment were analyzed. Incidence of syphilis seroconversion, defined as a positive non-treponemal test after previously testing negative, was evaluated among patients at sites performing non-treponemal tests at least annually. Factors associated with syphilis seroconversion were investigated at sites doing non-treponemal testing in all new patients and subsequently testing routinely or when patients were suspected of having syphilis. Results: We included 1010 patients from five sites that performed non-treponemal tests in all new patients; those included had negative non-treponemal test results during enrolment and subsequent follow-ups. Among them, 657 patients were from three sites conducting regular non-treponemal testing. The incidence of syphilis seroconversion was 5.38/100 person-years (PY. Incidence was higher in MSM than non-MSM (7.64/100 PY vs. 2.44/100 PY, p<0.001. Among MSM, the incidence rate ratio (IRR for every additional year from 2009 was 1.19 (p=0.051. MSM status (IRR 3.48, 95% confidence interval (CI 1.88–6.47, past syphilis diagnosis (IRR 5.15, 95% CI 3.69–7.17 and younger age (IRR 0.84 for every additional 10 years, 95% CI 0.706–0.997 were significantly associated with syphilis seroconversion. Conclusions: We observed a higher incidence of syphilis seroconversion among HIV-infected MSM and a trend to increasing annual incidence. Regular screening for syphilis and targeted interventions to limit transmission are needed in this population.

  13. Assessment of atherosclerosis using carotid ultrasonography in a cohort of HIV-positive patients treated with protease inhibitors.

    Science.gov (United States)

    Seminari, E; Pan, A; Voltini, G; Carnevale, G; Maserati, R; Minoli, L; Meneghetti, G; Tinelli, C; Testa, S

    2002-06-01

    Lipid disorders associated with the use of protease inhibitors (PI) may be a risk factor for premature atherosclerosis development. The aim of this study is to evaluate the extent of carotid intima media thickness (IMT) among HIV-positive patients treated with PI containing regimens compared to PI-naïve and HIV-negative subjects. We analysed plasma lipid levels and carotid IMT in 28 HIV-positive patients treated with protease inhibitors (PIs) for a mean of 28.7 months (range 18-43) and in two control groups constituted, respectively, by 15 HIV-positive naïve patients and 16 HIV-negative subjects, that were matched for age, risk factors for HIV infection, cigarette smoke use and CD4+ cell count. PI-treated patients had higher triglyceride, HDL and apo B levels than controls. Carotid IMT was significantly increased in PI-treated patients compared to naïve or HIV-negative subjects. A correlation between cholesterol HDL, triglyceride and ApoB levels and IMT was observed among the entire cohort. Plasma lipid alterations were associated with an increased IMT and intima media thickening was more pronounced in PI-treated patients than in the two control groups. Periodical evaluation of blood lipid profile and, if required, the use of lipid-lowering agents is advisable. Moreover, physicians should address concurrent risk factor for atherosclerosis that can be modified, including smoking, hypertension, obesity and sedentary life-style.

  14. Pumping Optimization Model for Pump and Treat Systems - 15091

    Energy Technology Data Exchange (ETDEWEB)

    Baker, S.; Ivarson, Kristine A.; Karanovic, M.; Miller, Charles W.; Tonkin, M.

    2015-01-15

    Pump and Treat systems are being utilized to remediate contaminated groundwater in the Hanford 100 Areas adjacent to the Columbia River in Eastern Washington. Design of the systems was supported by a three-dimensional (3D) fate and transport model. This model provided sophisticated simulation capabilities but requires many hours to calculate results for each simulation considered. Many simulations are required to optimize system performance, so a two-dimensional (2D) model was created to reduce run time. The 2D model was developed as a equivalent-property version of the 3D model that derives boundary conditions and aquifer properties from the 3D model. It produces predictions that are very close to the 3D model predictions, allowing it to be used for comparative remedy analyses. Any potential system modifications identified by using the 2D version are verified for use by running the 3D model to confirm performance. The 2D model was incorporated into a comprehensive analysis system (the Pumping Optimization Model, POM) to simplify analysis of multiple simulations. It allows rapid turnaround by utilizing a graphical user interface that: 1 allows operators to create hypothetical scenarios for system operation, 2 feeds the input to the 2D fate and transport model, and 3 displays the scenario results to evaluate performance improvement. All of the above is accomplished within the user interface. Complex analyses can be completed within a few hours and multiple simulations can be compared side-by-side. The POM utilizes standard office computing equipment and established groundwater modeling software.

  15. Strategies to uncover undiagnosed HIV infection among heterosexuals at high risk and link them to HIV care with high retention: a "seek, test, treat, and retain" study.

    Science.gov (United States)

    Gwadz, Marya; Cleland, Charles M; Hagan, Holly; Jenness, Samuel; Kutnick, Alexandra; Leonard, Noelle R; Applegate, Elizabeth; Ritchie, Amanda S; Banfield, Angela; Belkin, Mindy; Cross, Bridget; Del Olmo, Montserrat; Ha, Katharine; Martinez, Belkis Y; McCright-Gill, Talaya; Swain, Quentin L; Perlman, David C; Kurth, Ann E

    2015-05-10

    Over 50,000 individuals become infected with HIV annually in the U.S., and over a quarter of HIV infected individuals are heterosexuals. Undiagnosed HIV infection, as well as a lack of retention in care among those diagnosed, are both primary factors contributing to ongoing HIV incidence. Further, there are racial/ethnic disparities in undiagnosed HIV and engagement in care, with African Americans/Blacks and Latinos remaining undiagnosed longer and less engaged in care than Whites, signaling the need for culturally targeted intervention approaches to seek and test those with undiagnosed HIV infection, and link them to care with high retention. The study has two components: one to seek out and test heterosexuals at high risk for HIV infection, and another to link those found infected to HIV care with high retention. We will recruit sexually active African American/Black and Latino adults who have opposite sex partners, negative or unknown HIV status, and reside in locations with high poverty and HIV prevalence. The "Seek and Test" component will compare the efficacy and cost effectiveness of two strategies to uncover undiagnosed HIV infection: venue-based sampling and respondent-driven sampling (RDS). Among those recruited by RDS and found to have HIV infection, a "Treat and Retain" component will assess the efficacy of a peer-driven intervention compared to a control arm with respect to time to an HIV care appointment and health indicators using a cluster randomized controlled trial design to minimize contamination. RDS initial seeds will be randomly assigned to the intervention or control arm at a 1:1 ratio and all recruits will be assigned to the same arm as the recruiter. Participants will be followed for 12 months with outcomes assessed using medical records and biomarkers, such as HIV viral load. Heterosexuals do not test for HIV as frequently as and are diagnosed later than other risk groups. The study has the potential to contribute an efficient, innovative

  16. HIV-positive patients treated for multidrug-resistant tuberculosis: clinical outcomes in the HAART era.

    Science.gov (United States)

    Palacios, E; Franke, M; Muñoz, M; Hurtado, R; Dallman, R; Chalco, K; Guerra, D; Mestanza, L; Llaro, K; Bonilla, C; Sebastian, J; Bayona, J; Lygizos, M; Lyzigos, M; Anger, H; Shin, S

    2012-01-01

    Multidrug-resistant tuberculosis (MDR-TB) and the human immunodeficiency virus (HIV) pose two of the greatest threats to global tuberculosis (TB) control. Given expanding global access to antiretroviral therapy (ART) and second-line TB drugs, more data are needed on experiences treating MDR-TB and HIV co-infection in resource-poor settings. To describe the clinical characteristics, management, outcomes, and factors associated with survival among HIV-positive individuals receiving treatment for MDR-TB. This was a retrospective case series of 52 HIV-positive individuals receiving treatment for MDR-TB in Lima, Peru. We used Cox proportional hazards regression models to identify risk factors for mortality. A total of 31 (57%) of the cohort died on treatment, with the majority of deaths due to MDR-TB. Low baseline weight predicted a three-fold increased rate of death (aHR 3.1, 95%CI 1.5-6.7), while individuals receiving highly active ART experienced a significantly lower rate of death compared to those who were not (aHR 0.4, 95%CI 0.2-0.9). Early ART is likely a key component of effective MDR-TB management in co-infected individuals.

  17. Optimal Use of Raltegravir (Isentress® in the Treatment of HIV-Infected Adults – Canadian Consensus Guidelines

    Directory of Open Access Journals (Sweden)

    Anita Rachlis

    2009-01-01

    Full Text Available BACKGROUND AND OBJECTIVES: A meeting of a Canadian group with significant experience and knowledge in HIV management, consisting of five physicians, a pharmacist and an AIDS researcher, was convened. Their goal was to develop guidance for Canadian HIV-treating physicians on the appropriate use of raltegravir (MK-0518, Isentress®, Merck Frosst Canada Inc in HIV-infected adults.

  18. Moderator effect of CYP2B6 genotype in HIV-1 patients with tuberculosis treated with rifampicin and efavirenz

    Directory of Open Access Journals (Sweden)

    C De la Calle

    2012-11-01

    Full Text Available Efavirenz (EFV is the preferred non-nucleoside reverse transcriptase inhibitor component of the ARV regimen in HIV-TB patients. Concomitant use of EFV with rifampicin (RIF, an important component of first-line tuberculosis treatment, induces various hepatic cytochrome P450 enzymes and is known to decrease EFV plasma concentrations in healthy volunteers and HIV-1 patients and EFV plasma concentrations below 1,000 µg/mL have been associated with an increased risk of virological failure [1]. Moreover, previous studies have shown that inter-individual variability in EFV plasma concentrations are associated with the presence of allelic variants in CYP2B6 gene. Carriers of the T allele of polymorphism 516 G>T are reported to be associated with slower EFV oral clearance. The aim of our study was to determine the influence of CYP2B6 genotype in EFV levels in HIV patients with TB treated with RIF. Four HIV patients who started ARV treatment concomitantly with TB treatment were analyzed. These patients started a regimen based on EFV at doses higher than standard due to RIF interaction. Viral load, CD4+ cell count and plasma levels of EFV in plasma were measured at each visit, and genotyping for CYP2B6 (516G>T polymorphism were performed. The self-reported rates of adherence to HAART were very high. One patient, who had TT genotype, required progressive dose reduction by toxic levels (Cmin: 20 µg/mL and effects on the central nervous system. Dose was adjusted to 600 mg qd despite treatment with RIF, and he required even lower doses after completion of TB treatment, 400 mg qd. Two other patients with non-mutated genotype (GG required dose escalation up to 1000 mg qd to achieve minimum recommended EFV concentrations between 1 and 4 µg/mL. All of them achieved virological suppression at six months. The fourth patient, who had non-mutated genotype, required dose increases for several months until dose adjustment. He needed 1600 mg qd during treatment with

  19. A narrative review of cost-effectiveness analysis of people living with HIV treated with HAART: from interventions to outcomes

    Directory of Open Access Journals (Sweden)

    Tse WF

    2015-08-01

    Full Text Available Wah Fung Tse,1 Weimin Yang,2 Wenlong Huang1,3 1School of International Pharmaceutical Business, China Pharmaceutical University, 2Editorial Department of Journal of Nanjing University of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, 3Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China Background: Since its introduction in 1996, highly active antiretroviral therapy (HAART, which involves the combination of antiretroviral drugs, has resulted in significant improvements in the morbidity, mortality, and life expectancy of HIV-infected patients. Numerous studies of the cost-effectiveness of HAART from different perspectives in HIV have been reported.Aim: To investigate the economic outcomes and relevance of HAART for people living with HIV.Materials and methods: A narrative literature review was conducted on 22 peer-reviewed full economic evaluations of people living with HIV treated with different HAART regimens and published in English between January 2005 and December 2014. Information regarding study details, such as interventions, outcomes, and modeling methods, was extracted. The high heterogeneity of the included studies rendered a meta-analysis inappropriate; therefore, we conducted a comparative analysis of studies grouped according to the similarity of the different intervention types and outcomes.Results: Most of the economic evaluations of HAART focused on comparisons between the specific HAART regimens and others from the following perspectives: injecting drug users versus noninjecting drug users, HIV-infected adults without AIDS versus those with AIDS, regimens based on developed world guidelines versus those based on developing world guidelines, self-administered HAART versus directly observed HAART, and “ideal” versus “typical” regimens.Conclusion: In general, HAART is more cost-effective than other therapeutic

  20. Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461.

    Directory of Open Access Journals (Sweden)

    James I Mullins

    Full Text Available The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first "mechanism validation" phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced. We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038 and 124 (p = 0.002 days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01, and to a lesser extent T to C and C to T mutations (p = 0.09, as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.

  1. Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461.

    Science.gov (United States)

    Mullins, James I; Heath, Laura; Hughes, James P; Kicha, Jessica; Styrchak, Sheila; Wong, Kim G; Rao, Ushnal; Hansen, Alexis; Harris, Kevin S; Laurent, Jean-Pierre; Li, Deyu; Simpson, Jeffrey H; Essigmann, John M; Loeb, Lawrence A; Parkins, Jeffrey

    2011-01-14

    The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first "mechanism validation" phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample) of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced). We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038) and 124 (p = 0.002) days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01), and to a lesser extent T to C and C to T mutations (p = 0.09), as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.

  2. Optima: A Model for HIV Epidemic Analysis, Program Prioritization, and Resource Optimization.

    Science.gov (United States)

    Kerr, Cliff C; Stuart, Robyn M; Gray, Richard T; Shattock, Andrew J; Fraser-Hurt, Nicole; Benedikt, Clemens; Haacker, Markus; Berdnikov, Maxim; Mahmood, Ahmed Mohamed; Jaber, Seham Abdalla; Gorgens, Marelize; Wilson, David P

    2015-07-01

    Optima is a software package for modeling HIV epidemics and interventions that we developed to address practical policy and program problems encountered by funders, governments, health planners, and program implementers. Optima's key feature is its ability to perform resource optimization to meet strategic HIV objectives, including HIV-related financial commitment projections and health economic assessments. Specifically, Optima allows users to choose a set of objectives (such as minimizing new infections, minimizing HIV-related deaths, and/or minimizing long-term financial commitments) and then determine the optimal resource allocation (and thus program coverage levels) for meeting those objectives. These optimizations are based on the following: calibrations to epidemiological data; assumptions about the costs of program implementation and the corresponding coverage levels; and the effects of these programs on clinical, behavioral, and other epidemiological outcomes. Optima is flexible for which population groups (specified by behavioral, epidemiological, and/or geographical factors) and which HIV programs are modeled, the amount of input data used, and the types of outputs generated. Here, we introduce this model and compare it with existing HIV models that have been used previously to inform decisions about HIV program funding and coverage targets. Optima has already been used in more than 20 countries, and there is increasing demand from stakeholders to have a tool that can perform evidence-based HIV epidemic analyses, revise and prioritize national strategies based on available resources, set program coverage targets, amend subnational program implementation plans, and inform the investment strategies of governments and their funding partners.

  3. Cancers in the TREAT Asia HIV Observational Database (TAHOD: a retrospective analysis of risk factors

    Directory of Open Access Journals (Sweden)

    Petoumenos Kathy

    2010-12-01

    Full Text Available Abstract Background This retrospective survey describes types of cancers diagnosed in HIV-infected subjects in Asia, and assesses risk factors for cancer in HIV-infected subjects using contemporaneous HIV-infected controls without cancer. Methods TREAT Asia HIV Observational Database (TAHOD sites retrospectively reviewed clinic medical records to determine cancer diagnoses since 2000. For each diagnosis, the following data were recorded: date, type, stage, method of diagnosis, demographic data, medical history, and HIV-related information. For risk factor analyses, two HIV-infected control subjects without cancer diagnoses were also selected. Cancers were grouped as AIDS-defining cancers (ADCs, and non-ADCs. Non-ADCs were further categorized as being infection related (NADC-IR and unrelated (NADC-IUR. Results A total of 617 patients were included in this study: 215 cancer cases and 402 controls from 13 sites. The majority of cancer cases were male (71%. The mean age (SD for cases was 39 (10.6, 46 (11.5 and 44 (13.7 for ADCs, NADC-IURs and NADCs-IR, respectively. The majority (66% of cancers were ADCs (16% Kaposi sarcoma, 40% non-Hodgkin's lymphoma, and 9% cervical cancer. The most common NADCs were lung (6%, breast (5% and hepatocellular carcinoma and Hodgkin's lymphoma (2% each. There were also three (1.4% cases of leiomyosarcoma reported in this study. In multivariate analyses, individuals with CD4 counts above 200 cells/mm3 were approximately 80% less likely to be diagnosed with an ADC (p Conclusions The spectrum of cancer diagnoses in the Asia region currently does not appear dissimilar to that observed in non-Asian HIV populations. One interesting finding was the cases of leiomyosarcoma, a smooth-muscle tumour, usually seen in children and young adults with AIDS, yet overall quite rare. Further detailed studies are required to better describe the range of cancers in this region, and to help guide the development of screening programmes.

  4. Pilot Project to Optimize Superfund-financed Pump and Treat Systems: Summary Report and Lessons Learned

    Science.gov (United States)

    This report summarizes Phase II (site optimization) of the Nationwide Fund-lead Pump and Treat Optimization Project. This phase included conducting Remediation System Evaluations (RSEs) at each of the 20 sites selected in Phase I.

  5. Open- and closed-loop multiobjective optimal strategies for HIV therapy using NSGA-II.

    Science.gov (United States)

    Heris, S Mostapha Kalami; Khaloozadeh, Hamid

    2011-06-01

    In this paper, multiobjective open- and closed-loop optimal treatment strategies for HIV/AIDS are presented. It is assumed that highly active antiretroviral therapy is available for treatment of HIV infection. Amount of drug usage and the quality of treatment are defined as two objectives of a biobjective optimization problem, and Nondominated Sorting Genetic Algorithm II is used to solve this problem. Open- and closed-loop control strategies are used to produce optimal control inputs, and the Pareto frontiers obtained from these two strategies are compared. Pareto frontier, resulted from the optimization process, suggests a set of treatment strategies, which all are optimal from a perspective, and can be used in different medical and economic conditions. Robustness of closed-loop system in the presence of measurement noises is analyzed, assuming various levels of noise.

  6. Optimism, community attachment and serostatus disclosure among HIV-positive men who have sex with men.

    Science.gov (United States)

    Murphy, Patrick J; Hevey, David; O'Dea, Siobhán; Ní Rathaille, Neans; Mulcahy, Fiona

    2015-01-01

    This study investigated the relationship between HIV health optimism (HHO) (the belief that health will remain good after HIV infection due to treatment efficacy), HIV-positive community attachment (HCA), gay community attachment (GCA) and serostatus disclosure to casual sex partners by HIV-positive men who have sex with men (MSM). Cross-sectional questionnaire data were gathered from 97 HIV-positive MSM attending an HIV treatment clinic in Dublin, Ireland. Based on self-reported disclosure to casual partners, participants were classified according to their pattern of disclosure (consistent, inconsistent or non-disclosers). Multinomial logistic regression was used to assess HHO, HCA and GCA as predictors of participants' pattern of disclosure. Classification as a non-discloser (compared to a consistent discloser) was associated with higher HHO, less HCA and greater GCA. Classification as an inconsistent discloser (compared to a consistent discloser) was associated with higher GCA. The study provided novel quantitative evidence for associations between the constructs of interest. The results suggest that (1) HHO is associated with reduced disclosure, suggesting optimism may preclude individuals reaping the benefits of serostatus disclosure and (2) HCA and GCA represent competing attachments with conflicting effects on disclosure behaviour. Limitations and areas for future research are discussed.

  7. Optimizing Antiretroviral Therapy in Children and Adolescents with HIV Infection

    NARCIS (Netherlands)

    N.Y. Rakhmanina (Natella)

    2010-01-01

    textabstractHIV infection became a newly recognized disease in the mid 1980s. High morbidity and mortality associated with it prompted the urgent development of new therapeutic agents and combination therapies. Throughout the next 20 years the hopes for cure have risen and fallen, and the vaccine re

  8. Optimizing Antiretroviral Therapy in Children and Adolescents with HIV Infection

    NARCIS (Netherlands)

    N.Y. Rakhmanina (Natella)

    2010-01-01

    textabstractHIV infection became a newly recognized disease in the mid 1980s. High morbidity and mortality associated with it prompted the urgent development of new therapeutic agents and combination therapies. Throughout the next 20 years the hopes for cure have risen and fallen, and the vaccine

  9. Optimizing HIV-1 protease production in Escherichia coli as fusion protein

    Directory of Open Access Journals (Sweden)

    Piubelli Luciano

    2011-06-01

    Full Text Available Abstract Background Human immunodeficiency virus (HIV is the etiological agent in AIDS and related diseases. The aspartyl protease encoded by the 5' portion of the pol gene is responsible for proteolytic processing of the gag-pol polyprotein precursor to yield the mature capsid protein and the reverse transcriptase and integrase enzymes. The HIV protease (HIV-1Pr is considered an attractive target for designing inhibitors which could be used to tackle AIDS and therefore it is still the object of a number of investigations. Results A recombinant human immunodeficiency virus type 1 protease (HIV-1Pr was overexpressed in Escherichia coli cells as a fusion protein with bacterial periplasmic protein dithiol oxidase (DsbA or glutathione S-transferase (GST, also containing a six-histidine tag sequence. Protein expression was optimized by designing a suitable HIV-1Pr cDNA (for E. coli expression and to avoid autoproteolysis and by screening six different E. coli strains and five growth media. The best expression yields were achieved in E. coli BL21-Codon Plus(DE3-RIL host and in TB or M9 medium to which 1% (w/v glucose was added to minimize basal expression. Among the different parameters assayed, the presence of a buffer system (based on phosphate salts and a growth temperature of 37°C after adding IPTG played the main role in enhancing protease expression (up to 10 mg of chimeric DsbA:HIV-1Pr/L fermentation broth. GST:HIVPr was in part (50% produced as soluble protein while the overexpressed DsbA:HIV-1Pr chimeric protein largely accumulated in inclusion bodies as unprocessed fusion protein. A simple refolding procedure was developed on HiTrap Chelating column that yielded a refolded DsbA:HIV-1Pr with a > 80% recovery. Finally, enterokinase digestion of resolubilized DsbA:HIV-1Pr gave more than 2 mg of HIV-1Pr per liter of fermentation broth with a purity ≤ 80%, while PreScission protease cleavage of soluble GST:HIVPr yielded ~ 0.15 mg of pure HIV-1

  10. News of Biomedical Advances in HIV: Relationship to Treatment Optimism and Expected Risk Behavior in US MSM.

    Science.gov (United States)

    Zimmerman, Rick S; Kirschbaum, Allison L

    2017-03-14

    HIV treatment optimism and the ways in which news of HIV biomedical advances in HIV is presented to the most at-risk communities interact in ways that affect risk behavior and the incidence of HIV. The goal of the current study was to understand the relationships among HIV treatment optimism, knowledge of HIV biomedical advances, and current and expected increased risk behavior as a result of reading hypothetical news stories of further advances. Most of an online-recruited sample of MSM were quite knowledgeable about current biomedical advances. After reading three hypothetical news stories, 15-24% of those not living with HIV and 26-52% of those living with HIV reported their condom use would decrease if the story they read were true. Results suggest the importance of more cautious reporting on HIV biomedical advances, and for targeting individuals with greater treatment optimism and those living with HIV via organizations where they are most likely to receive their information about HIV.

  11. Squamous cell carcinoma of the anal canal treated with chemoradiotherapy in a patient with HIV.

    Science.gov (United States)

    Sugimoto, Aya; Nakazuru, Shoichi; Sakakibara, Yuko; Nishio, Kumiko; Yamada, Takuya; Ishida, Hisashi; Yajima, Keishiro; Uehira, Tomoko; Mori, Kiyoshi; Mita, Eiji

    2016-01-01

    Since the introduction of combination antiretroviral therapy (ART), the life expectancy has increased for patients infected with human immunodeficiency virus (HIV). This has been associated with reductions in the incidences of some AIDS-defining malignancies, such as Kaposi sarcoma and non-Hodgkin lymphoma, but has coincided with an increased incidence of non-AIDS-defining malignancies, such as anal cancer. However, anal cancers are rare in patients with HIV in Japan. We report the case of an HIV-infected patient with anal cancer treated with chemoradiotherapy. A 37-year-old man receiving ART for HIV infection presented with a 1-month history of left inguinal lymphadenopathy and anal pain. Magnetic resonance imaging and computed tomography revealed a 56-mm mass, left inguinal lymphadenopathy, and left external iliac lymphadenopathy. The mass had infiltrated from the anal canal to the right levator ani and corpus spongiosum. Colonoscopy revealed a tumor with an ulcer in the anal canal. Histological examination of the tumor biopsy specimens confirmed the diagnosis of squamous cell carcinoma. The patient was diagnosed with anal cancer (T4N2M1 stage IV), and he received 5-fluorouracil (1000mg/m(2) on days 1-4 and 29-32) plus mitomycin C (10mg/m(2) on days 1 and 29) and concurrent radiotherapy (total dose, 59.4Gy in 33 fractions) along with ART. The treatment-related adverse events were grade 4 leukopenia and neutropenia, grade 3 thrombocytopenia, and grade 2 radiation dermatitis. Moreover, CD4 suppression was observed:the CD4 count decreased from 190 cells/μl before chemoradiotherapy to 138 cells/μl after 3 months, but increased to 210 cells/μl after 1 year. Because of the grade 4 leukopenia and neutropenia, the dose of 5-fluorouracil was reduced to 800mg/m(2) on days 29-32. A complete response was confirmed on magnetic resonance imaging, and colonoscopy confirmed the disappearance of the anal cancer. The patient is living with no signs of recurrence at 2 years

  12. Are you willing to treat patients with HIV/AIDS? An anonymous survey among staff and students of dental institution.

    Science.gov (United States)

    Vijayalaxmi, Nimma; Reddy, Lavanya; Swapna, Lingam Amara; Reddy, Sudhakara; Ramesh, T; Padmareddy, M

    2014-09-01

    India is one of the largest and most populated country in the world, with over one billion inhabitants. Of this number, it is estimated that around 23.9 lakh people are currently suffering with HIV. People living with HIV/AIDS (PLWHA) require increasingly competent and compassionate health care, including oral health care. The present study was conducted with the objective of evaluating the response of dental health care professionals (staff and students) in willingness to provide treatment to HIV/AIDS patients and whether the training and education provided to them is sufficient to handle such patients, or whether there is necessity for advanced curriculum to be implemented. An anonymous survey with the permission from ethical committee of dental institution was conducted with the use self-administered questionnaire eliciting information on self-rated HIV/AIDS knowledge, attitudes, infection control practices, occupational risk perception and willingness to treat HIV/AIDS patients. An increase in level of knowledge was observed with the increase in year of study from first BDS to post graduation and MDS staff. It was observed that interns and post graduate students were willing to treat patients with HIV/AIDS. Staff of the institution showed greater concern to undergo training to provide efficient treatment to patients with HIV/AIDS. It was concluded that there was a positive attitude and willingness of staff and students to treat a patient suffering with HIV/AIDS. Also, there was willingness and interest of the staff and students of the dental institution to participate in training programmes to provide better and more efficient treatment to HIV/AIDS patients.

  13. hepatitis b and hiv co-infection in south africa: just treat it!

    African Journals Online (AJOL)

    2009-03-16

    Mar 16, 2009 ... THE SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE. 10. BIOLOGY ... transmission routes of hepatitis B and HIV are similar, but hepatitis B is more efficient. ... HIV/HBV co-infected people have higher HBV viral loads,.

  14. The frequency and outcome of neuropathies among HIV/AIDS adults treated at a tertiary hospital in Kaduna State, Nigeria.

    Science.gov (United States)

    Obiako, O R; Ogoina, D; Abubakar, S A; Muktar, H M; Sheikh, T L; Tabi-Ajayi, E; Kehinde, J A; Iwuozo, E U; Musa, B O P

    2014-12-01

    Highly active antiretroviral therapy (HAART) has been shown to reduce AIDS- defining illnesses, including neuropathies. However, it has been postulated that an increase in age -, HIV- and HAART- related neurological complications will occur as HIV-infected persons live longer. This study investigated the frequency and outcome of neuropathies in relation to CD4+ cell count and HAART status of hospitalised HIV/AIDS patients in Shika. Consecutive adult (e"15 years) non pregnant HIV- infected patients treated at Ahmadu Bello University Teaching Hospital Shika-Zaria from January 2006 to May 2013 with neuropathies were studied. Non HIV-infected patients with neurological disorders and HIV-infected patients without neuropathies were excluded. Of 5240 HIV/AIDS patients seen , 11% (566) presented with neuropathy at median CD4+ cell counts of 200 cells / ul, with yearly reduction of the frequency of patients with neuropathy from 3.9% in 2006 to 0.06% in 2013. Male: female ratio was 2:1 and respective mean years were 41.9±10.1: 45.3±17.4 (pneuropathies. However, late presentation, low CD4+ cell counts and failure of patients to start HAART early were responsible for AIDS-related mortality thus highlighting the importance of early HIV screening and treatment.

  15. Hyperdopaminergic tone in HIV-1 protein treated rats and cocaine sensitization

    Science.gov (United States)

    Ferris, Mark J.; Frederick-Duus, Danielle; Fadel, Jim; Mactutus, Charles F; Booze, Rosemarie M.

    2013-01-01

    In the United States, one-third of infected individuals contracted Human Immunodeficiency Virus-1 (HIV-1) via injecting drugs with contaminated needles or through risky behaviors associated with drug use. Research demonstrates concomitant administration of psychostimulants and HIV-1-proteins damage neurons to a greater extent than viral proteins or the drug alone. To model the onset of HIV-1-infection in relation to a history of drug use, the current research compared behavior and extracellular dopamine and metabolite levels following Tat1–86 infusions in animals with and without a history of cocaine (Coc) experience (10 mg/kg; i.p.; 1 injection/day × 9 days). Animals receiving a behaviorally sensitizing regimen of Coc demonstrated a decrease in extracellular dopamine concentration in the nucleus accumbens, consistent with evidence describing up-regulation of dopamine transporter uptake. Contrary to this effect, Tat1–86 microinfusion into the nucleus accumbens following the sensitizing regimen of Coc caused a significant increase in extracellular dopamine levels (nM) within 48 h with no difference in percent of baseline response to Coc. After 72 h, Tat + Coc treated animals demonstrated a blunted effect on potassium-stimulated extracellular dopamine release (percent of baseline) with a corresponding decrease in expression of behavioral sensitization to Coc challenge. A persistent decrease in extracellular dopamine metabolite levels was found across all time-points in Tat-treated animals, regardless of experience with Coc. The current study provides evidence for divergent neurochemical and behavioral outcomes following Tat-treatment; contingent upon experience with Coc. PMID:20796175

  16. Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults.

    Science.gov (United States)

    Newcomb, Michael E; Bedoya, C Andres; Blashill, Aaron J; Lerner, Jonathan A; O'Cleirigh, Conall; Pinkston, Megan M; Safren, Steven A

    2015-11-01

    There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting.

  17. HIV DNA loads, plasma residual viraemia and risk of virological rebound in heavily treated, virologically suppressed HIV-infected patients.

    Science.gov (United States)

    Gianotti, N; Canducci, F; Galli, L; Cossarini, F; Salpietro, S; Poli, A; Nozza, S; Spagnuolo, V; Clementi, M; Sampaolo, M; Ceresola, E R; Racca, S; Lazzarin, A; Castagna, A

    2015-01-01

    In this single-centre, retrospective study, we analyzed data of 194 patients receiving antiretroviral therapy with <50 human immunodeficiency virus (HIV) RNA copies/mL in plasma and 318 HIV RNA/DNA paired samples. By kinetic polymerase chain reaction (kPCR) molecular system analysis, 104 (54%) subjects had undetectable HIV RNA and 90 (46%) had residual viraemia. Median (interquartile range) HIV DNA load was 780 (380-1930) copies/10(6) peripheral blood lymphocytes (PBL), and HIV DNA loads were independently associated with residual viraemia (p 0.002). Virological rebound occurred in 29/194 (15%) patients over a median (interquartile range) follow-up of 17.5 (13.5-31.5) months. Residual viraemia (p 0.002), but not HIV DNA load, was independently associated with virological rebound.

  18. In the interests of time: improving HIV allocative efficiency modelling via optimal time-varying allocations

    Directory of Open Access Journals (Sweden)

    Andrew J Shattock

    2016-02-01

    Full Text Available Introduction: International investment in the response to HIV and AIDS has plateaued and its future level is uncertain. With many countries committed to ending the epidemic, it is essential to allocate available resources efficiently over different response periods to maximize impact. The objective of this study is to propose a technique to determine the optimal allocation of funds over time across a set of HIV programmes to achieve desirable health outcomes. Methods: We developed a technique to determine the optimal time-varying allocation of funds (1 when the future annual HIV budget is pre-defined and (2 when the total budget over a period is pre-defined, but the year-on-year budget is to be optimally determined. We use this methodology with Optima, an HIV transmission model that uses non-linear relationships between programme spending and associated programmatic outcomes to quantify the expected epidemiological impact of spending. We apply these methods to data collected from Zambia to determine the optimal distribution of resources to fund the right programmes, for the right people, at the right time. Results and discussion: Considering realistic implementation and ethical constraints, we estimate that the optimal time-varying redistribution of the 2014 Zambian HIV budget between 2015 and 2025 will lead to a 7.6% (7.3% to 7.8% decrease in cumulative new HIV infections compared with a baseline scenario where programme allocations remain at 2014 levels. This compares to a 5.1% (4.6% to 5.6% reduction in new infections using an optimal allocation with constant programme spending that recommends unrealistic programmatic changes. Contrasting priorities for programme funding arise when assessing outcomes for a five-year funding period over 5-, 10- and 20-year time horizons. Conclusions: Countries increasingly face the need to do more with the resources available. The methodology presented here can aid decision-makers in planning as to when to

  19. Leptin and adiponectin, but not IL18, are related with insulin resistance in treated HIV-1-infected patients with lipodystrophy.

    Science.gov (United States)

    Veloso, Sergi; Escoté, Xavier; Ceperuelo-Mallafré, Victòria; López-Dupla, Miguel; Peraire, Joaquim; Viladés, Consuelo; Domingo, Pere; Castro, Antoni; Olona, Montserrat; Sirvent, Joan-Josep; Leal, Manuel; Vendrell, Joan; Richart, Cristóbal; Vidal, Francesc

    2012-05-01

    Leptin, adiponectin and IL18 are adipokines related with obesity, insulin resistance and dyslipidemia in the general population. Treated HIV-1-infected patients with lipodystrophy may develop insulin resistance and proatherogenic dyslipidemia. We assessed the relationship between plasma adipokine levels, adipokine genetics, lipodystrophy and metabolic disturbances. Plasma leptin, adiponectin and IL18 levels were assessed in 446 individuals: 282 HIV-1-infected patients treated with antiretroviral drugs (132 with lipodystrophy and 150 without) and 164 uninfected controls (UC). The LEP2410A>G, LEPRQ223R, ADIPQ276G>T, ADIPOR2-Intron5A>G and IL18-607C>A polymorphisms were validated by sequencing. Leptin levels were higher in UC than in HIV-1-infected, either with or without lipodystrophy (plipodystrophy compared with those without lipodystrophy (p=0.006). In patients with lipodystrophy, leptin had a positive correlation with insulin and with HOMA-IR. Adiponectin levels were non-significantly different in UC and HIV-1-infected patients. Patients with lipodystrophy had lower adiponectin levels than non-lipodystrophy subjects (plipodystrophy, adiponectin was negatively correlated with insulin, HOMA-IR and triglycerides. Plasma IL18 levels were higher in HIV-1-infected patients compared with UC (plipodystrophy. In patients with lipodystrophy there was a negative correlation between IL18 levels and LDLc. Genetic analyses indicated no significant associations with lipodystrophy nor with insulin resistance or with lipid abnormalities. In conclusion, HIV-1-infected patients have reduced plasma leptin levels. This reduction is magnified in patients with lipodystrophy whose adiponectin levels were lower than that of non-lipodystrophy subjects. Plasma IL18 levels are increased in infected patients irrespective of the presence of lipodystrophy. The polymorphisms assessed are not associated with lipodystrophy or metabolic disturbances in treated HIV-1-infected patients.

  20. Feature Selection Combined with Neural Network Structure Optimization for HIV-1 Protease Cleavage Site Prediction

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    Hui Liu

    2015-01-01

    Full Text Available It is crucial to understand the specificity of HIV-1 protease for designing HIV-1 protease inhibitors. In this paper, a new feature selection method combined with neural network structure optimization is proposed to analyze the specificity of HIV-1 protease and find the important positions in an octapeptide that determined its cleavability. Two kinds of newly proposed features based on Amino Acid Index database plus traditional orthogonal encoding features are used in this paper, taking both physiochemical and sequence information into consideration. Results of feature selection prove that p2, p1, p1′, and p2′ are the most important positions. Two feature fusion methods are used in this paper: combination fusion and decision fusion aiming to get comprehensive feature representation and improve prediction performance. Decision fusion of subsets that getting after feature selection obtains excellent prediction performance, which proves feature selection combined with decision fusion is an effective and useful method for the task of HIV-1 protease cleavage site prediction. The results and analysis in this paper can provide useful instruction and help designing HIV-1 protease inhibitor in the future.

  1. Pump-and-treat optimization using analytic element method flow models

    Science.gov (United States)

    Matott, L. Shawn; Rabideau, Alan J.; Craig, James R.

    2006-05-01

    Plume containment using pump-and-treat (PAT) technology continues to be a popular remediation technique for sites with extensive groundwater contamination. As such, optimization of PAT systems, where cost is minimized subject to various remediation constraints, is the focus of an important and growing body of research. While previous pump-and-treat optimization (PATO) studies have used discretized (finite element or finite difference) flow models, the present study examines the use of analytic element method (AEM) flow models. In a series of numerical experiments, two PATO problems adapted from the literature are optimized using a multi-algorithmic optimization software package coupled with an AEM flow model. The experiments apply several different optimization algorithms and explore the use of various pump-and-treat cost and constraint formulations. The results demonstrate that AEM models can be used to optimize the number, locations and pumping rates of wells in a pump-and-treat containment system. Furthermore, the results illustrate that a total outflux constraint placed along the plume boundary can be used to enforce plume containment. Such constraints are shown to be efficient and reliable alternatives to conventional particle tracking and gradient control techniques. Finally, the particle swarm optimization (PSO) technique is identified as an effective algorithm for solving pump-and-treat optimization problems. A parallel version of the PSO algorithm is shown to have linear speedup, suggesting that the algorithm is suitable for application to problems that are computationally demanding and involve large numbers of wells.

  2. Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence.

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    Hind Satti

    Full Text Available BACKGROUND: Few studies have examined outcomes for children treated for multidrug-resistant tuberculosis (MDR-TB, including those receiving concomitant treatment for MDR-TB and HIV co-infection. In Lesotho, where the adult HIV seroprevalence is estimated to be 24%, we sought to measure outcomes and adverse events in a cohort of children treated for MDR-TB using a community-based treatment delivery model. METHODS: We reviewed retrospectively the clinical charts of children ≤15 years of age treated for culture-confirmed or suspected MDR-TB between July 2007 and January 2011. RESULTS: Nineteen children, ages two to 15, received treatment. At baseline, 74% of patients were co-infected with HIV, 63% were malnourished, 84% had severe radiographic findings, and 21% had extrapulmonary disease. Five (26% children had culture-confirmed MDR-TB, ten (53% did not have culture results available, and four (21% subsequently had results indicating drug-susceptible TB. All children with HIV co-infection who were not already on antiretroviral therapy (ART were initiated on ART a median of two weeks after the start of the MDR-TB regimen. Among the 17 patients with final outcomes, 15 (88% patients were cured or completed treatment, two (12% patients died, and none defaulted or were lost to follow-up. The majority of patients (95% experienced adverse events; only two required permanent discontinuation of the offending agent, and only one required suspension of MDR-TB treatment for more than one week. CONCLUSIONS: Pediatric MDR-TB and MDR-TB/HIV co-infection can be successfully treated using a combination of social support, close monitoring by community health workers and clinicians, and inpatient care when needed. In this cohort, adverse events were well tolerated and treatment outcomes were comparable to those reported in children with drug-susceptible TB and no HIV infection.

  3. Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8 through Somatic Variation and Structure-Based Design

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Young D.; Georgiev, Ivelin S.; Ofek, Gilad; Zhang, Baoshan; Asokan, Mangaiarkarasi; Bailer, Robert T.; Bao, Amy; Caruso, William; Chen, Xuejun; Choe, Misook; Druz, Aliaksandr; Ko, Sung-Youl; Louder, Mark K.; McKee, Krisha; O' Dell, Sijy; Pegu, Amarendra; Rudicell, Rebecca S.; Shi, Wei; Wang, Keyun; Yang, Yongping; Alger, Mandy; Bender, Michael F.; Carlton, Kevin; Cooper, Jonathan W.; Blinn, Julie; Eudailey, Joshua; Lloyd, Krissey; Parks, Robert; Alam, S. Munir; Haynes, Barton F.; Padte, Neal N.; Yu, Jian; Ho, David D.; Huang, Jinghe; Connors, Mark; Schwartz, Richard M.; Mascola, John R.; Kwong, Peter D.; Sundquist, W. I.

    2016-04-06

    ABSTRACT

    Extraordinary antibodies capable of near pan-neutralization of HIV-1 have been identified. One of the broadest is antibody 10E8, which recognizes the membrane-proximal external region (MPER) of the HIV-1 envelope and neutralizes >95% of circulating HIV-1 strains. If delivered passively, 10E8 might serve to prevent or treat HIV-1 infection. Antibody 10E8, however, is markedly less soluble than other antibodies. Here, we describe the use of both structural biology and somatic variation to develop optimized versions of 10E8 with increased solubility. From the structure of 10E8, we identified a prominent hydrophobic patch; reversion of four hydrophobic residues in this patch to their hydrophilic germ line counterparts resulted in an ~10-fold decrease in turbidity. We also used somatic variants of 10E8, identified previously by next-generation sequencing, to optimize heavy and light chains; this process yielded several improved variants. Of these, variant 10E8v4 with 26 changes versus the parent 10E8 was the most soluble, with a paratope we showed crystallographically to be virtually identical to that of 10E8, a potency on a panel of 200 HIV-1 isolates also similar to that of 10E8, and a half-life in rhesus macaques of ~10 days. An anomaly in 10E8v4 size exclusion chromatography that appeared to be related to conformational isomerization was resolved by engineering an interchain disulfide. Thus, by combining a structure-based approach with natural variation in potency and solubility from the 10E8 lineage, we successfully created variants of 10E8 which retained the potency and extraordinary neutralization breadth of the parent 10E8 but with substantially increased solubility.

    IMPORTANCE Antibody 10E8 could be used to prevent HIV-1 infection, if manufactured and delivered economically. It suffers, however, from issues of solubility, which impede manufacturing. We hypothesized that the physical characteristic of 10E8 could be

  4. A different approach of optimal control on an HIV immunology model

    Directory of Open Access Journals (Sweden)

    Masoud Roshanfekr

    2014-03-01

    Full Text Available A system of ordinary differential equation, which describes the interaction of HIV and T cells in the immune system, is utilized, and optimal representing drug treatment strategies of this model are explored. Control model, in the sense of an optimal control problem shows the strategy of chemotherapy treatment setting through a dynamic treatment. In this model, the optimal control pair represents the percentage effect the chemotherapy on the CD4+T cells and virus production. An objective function characterized based on maximizing T cells and minimizing the systemic cost of the chemotherapy. The optimal control could characterize by using Pontryagin’s Maximum Principle. Then by using an embedding method, we transfer the problem in to a modified problem in measure space. This transformation is an injection; one-one mapping, so the optimal pair and its image under the transformation could be identified. New problem could be solved by a linear programming problem.

  5. Cystatin B and HIV regulate the STAT-1 signaling circuit in HIV-infected and INF-β-treated human macrophages.

    Science.gov (United States)

    Rivera, L E; Kraiselburd, E; Meléndez, L M

    2016-10-01

    Cystatin B is a cysteine protease inhibitor that induces HIV replication in monocyte-derived macrophages (MDM). This protein interacts with signal transducer and activator of transcription (STAT-1) factor and inhibits the interferon (IFN-β) response in Vero cells by preventing STAT-1 translocation to the nucleus. Cystatin B also decreases the levels of tyrosine-phosphorylated STAT-1 (STAT-1PY). However, the mechanisms of cystatin B regulation on STAT-1 phosphorylation in MDM are unknown. We hypothesized that cystatin B inhibits IFN-β antiviral responses and induces HIV replication in macrophage reservoirs through the inhibition of STAT-1 phosphorylation. Macrophages were transfected with cystatin B siRNA prior to interferon-β treatment or infected with HIV-ADA to determine the effect of cystatin B modulation in STAT-1 localization and activation using immunofluorescence and proximity ligation assays. Cystatin B decreased STAT-1PY and its transportation to the nucleus, while HIV infection retained unphosphorylated STAT (USTAT-1) in the nucleus avoiding its exit to the cytoplasm for eventual phosphorylation. In IFN-β-treated MDM, cystatin B inhibited the nuclear translocation of both, USTAT-1 and STAT-1PY. These results demonstrate that cystatin B interferes with the STAT-1 signaling and IFN-β-antiviral responses perpetuating HIV in macrophage reservoirs.

  6. Subsidized optimal ART for HIV-positive temporary residents of Australia improves virological outcomes: results from the Australian HIV Observational Database Temporary Residents Access Study

    Directory of Open Access Journals (Sweden)

    Kathy Petoumenos

    2015-02-01

    Full Text Available Introduction: HIV-positive (HIV+ temporary residents living in Australia legally are unable to access government subsidized antiretroviral treatment (ART which is provided via Medicare to Australian citizens and permanent residents. Currently, there is no information systematically being collected on non-Medicare eligible HIV+ patients in Australia. The objectives of this study are to describe the population recruited to the Australian HIV Observational Database (AHOD Temporary Residents Access Study (ATRAS and to determine the short- and long-term outcomes of receiving (subsidized optimal ART and the impact on onwards HIV transmission. Methods: ATRAS was established in 2011. Eligible patients were recruited via the AHOD network. Key HIV-related characteristics were recorded at baseline and prospectively. Additional visa-related information was also recorded at baseline, and updated annually. Descriptive statistics were used to describe the ATRAS cohort in terms of visa status by key demographic characteristics, including sex, region of birth, and HIV disease status. CD4 cell count (mean and SD and the proportion with undetectable (<50 copies/ml HIV viral load are reported at baseline, 6 and 12 months of follow-up. We also estimate the proportion reduction of onward HIV transmission based on the reduction in proportion of people with detectable HIV viral load. Results: A total of 180 patients were recruited to ATRAS by June 2012, and by July 2013 39 patients no longer required ART via ATRAS, 35 of whom became eligible for Medicare-funded medication. At enrolment, 63% of ATRAS patients were receiving ART from alternative sources, 47% had an undetectable HIV viral load (<50 copies/ml and the median CD4 cell count was 343 cells/µl (IQR: 222–479. At 12 months of follow-up, 85% had an undetectable viral load. We estimated a 75% reduction in the risk of onward HIV transmission with the improved rate of undetectable viral load. Conclusions: The

  7. Early-developed hand osteoarthritis in treated HIV-positive patients: Four cases.

    Science.gov (United States)

    Larcher, Romaric; Mauboussin, Jean-Marc; Rouanet, Isabelle; Sotto, Albert

    2015-10-01

    We describe four cases of hand osteoarthritis in patients with HIV infection under antiretroviral treatment. A 36-year-old HIV-infected man came for consultation in 2007 with hand osteoarthritis. He was diagnosed HIV positive by sexual transmission in 1997. A 52-year-old HIV-infected woman came for consultation with hand osteoarthritis started in 2006. She was diagnosed HIV positive in 1986 by sexual transmission. A 57-year-old man presented hand osteoarthritis. This former IV drug user was diagnosed HIV positive in 1989. A 61-year-old HIV-infected man presented with hand osteoarthritis started in 2010. He had been contaminated with HIV in 1990 by sexual transmission. For all patients, there were neither clinical nor biological manifestations suggesting inflammatory arthritis. X-rays showed signs of hand osteoarthritis. CD4 cell count was over 500/mm(3) and the viral load was below 20 copies/mL under treatments. These four cases show osteoarthritis in HIV-infected patients. Hand osteoarthritis did not seem to be linked to aging or to an antiretroviral treatment's side effect, but rather to the HIV infection itself, and it may pass through a metabolic syndrome. We described a possible association between early-developed hand osteoarthritis and HIV-infected patients. Clinicians should consider osteoarthritis when they are confronted with HIV-infected patients with chronic hand pain.

  8. The effects of untreated and treated HIV infection on bone disease.

    LENUS (Irish Health Repository)

    Cotter, Aoife G

    2013-11-20

    Low bone mineral density (BMD) is common in those with HIV, associated with higher bone turnover and a higher prevalence of fractures. This review explores low BMD in HIV, focusing on underlying mechanisms and relationships between low BMD and HIV infection, immune dysfunction, and antiretroviral therapy (ART).

  9. Optimization of electrocoagulation process to treat biologically pretreated bagasse effluent

    Directory of Open Access Journals (Sweden)

    Thirugnanasambandham K.

    2014-01-01

    Full Text Available The main objective of the present study was to investigate the efficiency of electrocoagulation process as a post-treatment to treat biologically pretreated bagasse effluent using iron electrodes. The removal of chemical oxygen demand (COD and total suspended solids (TSS were studied under different operating conditions such as amount of dilution, initial pH, applied current and electrolyte dose by using response surface methodology (RSM coupled with four-factor three-level Box-Behnken experimental design (BBD. The experimental results were analyzed by Pareto analysis of variance (ANOVA and second order polynomial mathematical models were developed with high correlation of efficiency (R2 for COD, TSS removal and electrical energy consumption (EEC. The individual and combined effect of variables on responses was studied using three dimensional response surface plots. Under the optimum operating conditions, such as amount of dilution at 30 %, initial pH of 6.5, applied current of 8 mA cm-2 and electrolyte dose of 740 mg l-1 shows the higher removal efficiency of COD (98 % and TSS (93 % with EEC of 2.40 Wh, which were confirmed by validation experiments.

  10. Humanized mice recapitulate key features of HIV-1 infection: a novel concept using long-acting anti-retroviral drugs for treating HIV-1.

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    Marc Nischang

    Full Text Available BACKGROUND: Humanized mice generate a lymphoid system of human origin subsequent to transplantation of human CD34+ cells and thus are highly susceptible to HIV infection. Here we examined the efficacy of antiretroviral treatment (ART when added to food pellets, and of long-acting (LA antiretroviral compounds, either as monotherapy or in combination. These studies shall be inspiring for establishing a gold standard of ART, which is easy to administer and well supported by the mice, and for subsequent studies such as latency. Furthermore, they should disclose whether viral breakthrough and emergence of resistance occurs similar as in HIV-infected patients when ART is insufficient. METHODS/PRINCIPAL FINDINGS: NOD/shi-scid/γ(cnull (NOG mice were used in all experimentations. We first performed pharmacokinetic studies of the drugs used, either added to food pellets (AZT, TDF, 3TC, RTV or in a LA formulation that permitted once weekly subcutaneous administration (TMC278: non-nucleoside reverse transcriptase inhibitor, TMC181: protease inhibitor. A combination of 3TC, TDF and TMC278-LA or 3TC, TDF, TMC278-LA and TMC181-LA suppressed the viral load to undetectable levels in 15/19 (79% and 14/14 (100% mice, respectively. In successfully treated mice, subsequent monotherapy with TMC278-LA resulted in viral breakthrough; in contrast, the two LA compounds together prevented viral breakthrough. Resistance mutations matched the mutations most commonly observed in HIV patients failing therapy. Importantly, viral rebound after interruption of ART, presence of HIV DNA in successfully treated mice and in vitro reactivation of early HIV transcripts point to an existing latent HIV reservoir. CONCLUSIONS/SIGNIFICANCE: This report is a unique description of multiple aspects of HIV infection in humanized mice that comprised efficacy testing of various treatment regimens, including LA compounds, resistance mutation analysis as well as viral rebound after treatment

  11. Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma.

    Science.gov (United States)

    Soulie, Cathia; Grudé, Maxime; Descamps, Diane; Amiel, Corinne; Morand-Joubert, Laurence; Raymond, Stéphanie; Pallier, Coralie; Bellecave, Pantxika; Reigadas, Sandrine; Trabaud, Mary-Anne; Delaugerre, Constance; Montes, Brigitte; Barin, Francis; Ferré, Virginie; Jeulin, Hélène; Alloui, Chakib; Yerly, Sabine; Signori-Schmuck, Anne; Guigon, Aurélie; Fafi-Kremer, Samira; Haïm-Boukobza, Stéphanie; Mirand, Audrey; Maillard, Anne; Vallet, Sophie; Roussel, Catherine; Assoumou, Lambert; Calvez, Vincent; Flandre, Philippe; Marcelin, Anne-Geneviève

    2017-08-01

    HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log 10 copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations. Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les hépatites virales Action Coordonnée 11 (ANRS AC11) genotype interpretation algorithm. Among the 227 studied patients with VL > 1.7 log 10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7-4.7) log 10 copies/mL] and 32 had discordant VL in plasma (VL  1.7 log 10 copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients. Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed.

  12. Clinical uncertainties, health service challenges, and ethical complexities of HIV "test-and-treat": a systematic review.

    Science.gov (United States)

    Kulkarni, Sonali P; Shah, Kavita R; Sarma, Karthik V; Mahajan, Anish P

    2013-06-01

    Despite the HIV "test-and-treat" strategy's promise, questions about its clinical rationale, operational feasibility, and ethical appropriateness have led to vigorous debate in the global HIV community. We performed a systematic review of the literature published between January 2009 and May 2012 using PubMed, SCOPUS, Global Health, Web of Science, BIOSIS, Cochrane CENTRAL, EBSCO Africa-Wide Information, and EBSCO CINAHL Plus databases to summarize clinical uncertainties, health service challenges, and ethical complexities that may affect the test-and-treat strategy's success. A thoughtful approach to research and implementation to address clinical and health service questions and meaningful community engagement regarding ethical complexities may bring us closer to safe, feasible, and effective test-and-treat implementation.

  13. Interfacial Cavity Filling To Optimize CD4-Mimetic Miniprotein Interactions with HIV-1 Surface Glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Morellato-Castillo, Laurence; Acharya, Priyamvada; Combes, Olivier; Michiels, Johan; Descours, Anne; Ramos, Oscar H.P.; Yang, Yongping; Vanham, Guido; Ariën, Kevin K.; Kwong, Peter D.; Martin, Loïc; Kessler, Pascal [ITM-Antwerp; (CEA-CNRS); (NIH)

    2013-08-05

    Ligand affinities can be optimized by interfacial cavity filling. A hollow (Phe43 cavity) between HIV-1 surface glycoprotein (gp120) and cluster of differentiation 4 (CD4) receptor extends beyond residue phenylalanine 43 of CD4 and cannot be fully accessed by natural amino acids. To increase HIV-1 gp120 affinity for a family of CD4-mimetic miniproteins (miniCD4s), we targeted the gp120 Phe43 cavity with 11 non-natural phenylalanine derivatives, introduced into a miniCD4 named M48 (1). The best derivative, named M48U12 (13), bound HIV-1 YU2 gp120 with 8 pM affinity and showed potent HIV-1 neutralization. It contained a methylcyclohexyl derivative of 4-aminophenylalanine, and its cocrystal structure with gp120 revealed the cyclohexane ring buried within the gp120 hydrophobic core but able to assume multiple orientations in the binding pocket, and the aniline nitrogen potentially providing a focus for further improvement. Altogether, the results provide a framework for filling the interfacial Phe43 cavity to enhance miniCD4 affinity.

  14. Lyme neuroborreliosis in HIV-1 positive men successfully treated with oral doxycycline: a case series and literature review

    Directory of Open Access Journals (Sweden)

    Gisslén Magnus

    2011-09-01

    Full Text Available Abstract Introduction Lyme neuroborreliosis is the most common bacterial central nervous system infection in the temperate parts of the northern hemisphere. Even though human immunodeficiency virus (HIV -1 infection is common in Lyme borreliosis endemic areas, only five cases of co-infection have previously been published. Four of these cases presented with typical Lyme neuroborreliosis symptoms such as meningoradiculitis and facial palsy, while a fifth case had more severe symptoms of encephalomyelitis. All five were treated with intravenous cephalosporins and clinical outcome was good for all but the fifth case Case presentations We present four patients with concomitant presence of HIV-1 infection and Lyme neuroborreliosis diagnosed in Western Sweden. Patient 1 was a 60-year-old Caucasian man with radicular pain and cognitive impairment. Patient 2 was a 39-year-old Caucasian man with headaches, leg weakness, and pontine infarction. Patient 3 was a 62-year-old Caucasian man with headaches, tremor, vertigo, and normal-pressure hydrocephalus. Patient 4 was a 50-year-old Caucasian man with radicular pain and peripheral facial palsy. Patients one, two, and three all had subnormal levels of CD4 cells, indicating impaired immunity. All patients were treated with oral doxycycline with good clinical outcome and normalization of CSF pleocytosis. Conclusion Given the low HIV-1 prevalence and medium incidence of Lyme neuroborreliosis in Western Sweden where these four cases were diagnosed, co-infection with HIV-1 and Borrelia is probably more common than previously thought. The three patients that were the most immunocompromised suffered from more severe and rather atypical neurological symptoms than are usually described among patients with Lyme neuroborreliosis. It is therefore important for doctors treating HIV patients to consider Lyme neuroborreliosis in a patient presenting with atypical neurological symptoms. All four patients were treated with

  15. Impaired cellular immune response to tetanus toxoid but not to cytomegalovirus in effectively HAART-treated HIV-infected children.

    Science.gov (United States)

    Alsina, Laia; Noguera-Julian, Antoni; Fortuny, Clàudia

    2013-05-07

    Despite of highly active antiretroviral therapy, the response to vaccines in HIV-infected children is poor and short-lived, probably due to a defect in cellular immune responses. We compared the cellular immune response (assessed in terms of IFN-γ production) to tetanus toxoid and to cytomegalovirus in a series of 13 HIV-perinatally-infected children and adolescents with optimal immunovirological response to first line antiretroviral therapy, implemented during chronic infection. A stronger cellular response to cytomegalovirus (11 out of 13 patients) was observed, as compared to tetanus toxoid (1 out of 13; p=0.003). These results suggest that the repeated exposition to CMV, as opposed to the past exposition to TT, is able to maintain an effective antigen-specific immune response in stable HIV-infected pediatric patients and strengthen current recommendations on immunization practices in these children.

  16. Optimizing Prevention of HIV and Unplanned Pregnancy in Discordant African Couples.

    Science.gov (United States)

    Wall, Kristin M; Kilembe, William; Vwalika, Bellington; Haddad, Lisa B; Khu, Naw Htee; Brill, Ilene; Onwubiko, Udodirim; Chomba, Elwyn; Tichacek, Amanda; Allen, Susan

    2017-08-01

    Dual method use, which combines condoms with a more effective modern contraceptive to optimize prevention of HIV and unplanned pregnancy, is underutilized in high-risk heterosexual couples. Heterosexual HIV-discordant Zambian couples were enrolled from couples' voluntary HIV counseling and testing services into an open cohort with 3-monthly follow-up (1994-2012). Relative to dual method use, defined as consistent condom use plus modern contraception, we examine predictors of (1) condom-only use (suboptimal pregnancy prevention) or (2) modern contraceptive use with inconsistent condom use (effective pregnancy prevention and suboptimal HIV prevention). Among 3,049 couples, dual method use occurred in 28% of intervals in M+F- and 23% in M-F+, p < 0.01; condom-only use in 56% in M+F- and 61% in M-F+, p < 0.01; and modern contraceptive use with inconsistent condom use in 16% regardless of serostatus. Predictors (p < 0.05) of condom-only use included the man being HIV+ (adjusted hazard ratio, aHR = 1.15); baseline oral contraceptive pill (aHR = 0.76), injectable (aHR = 0.48), or implant (aHR = 0.60) use; woman's age (aHR = 1.04 per 5 years) and lifetime number of sex partners (aHR = 1.01); postpartum periods (aHR = 1.25); and HIV stage of the index partner III/IV versus I (aHR = 1.10). Predictors (p < 0.05) of modern contraceptive use with inconsistent condom use included woman's age (aHR = 0.94 per 5 years) and HIV+ male circumcision (aHR = 1.51), while time-varying implant use was associated with more consistent condom use (aHR = 0.80). Three-quarters of follow-up intervals did not include dual method use. This highlights the need for counseling to reduce unintended pregnancy and HIV transmission and enable safer conception.

  17. Plasma Selenium Concentrations Are Sufficient and Associated with Protease Inhibitor Use in Treated HIV-Infected Adults123

    Science.gov (United States)

    Hileman, Corrilynn O; Dirajlal-Fargo, Sahera; Lam, Suet Kam; Kumar, Jessica; Lacher, Craig; Combs, Gerald F; McComsey, Grace A

    2015-01-01

    Background: Selenium is an essential constituent of selenoproteins, which play a substantial role in antioxidant defense and inflammatory cascades. Selenium deficiency is associated with disease states characterized by inflammation, including cardiovascular disease (CVD). Although HIV infection has been associated with low selenium, the role of selenium status in HIV-related CVD is unclear. Objectives: We sought to assess associations between plasma selenium and markers of inflammation, immune activation, and subclinical vascular disease in HIV-infected adults on contemporary antiretroviral therapy (ART) and to determine if statin therapy modifies selenium status. Methods: In the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN trial, HIV-infected adults on stable ART were randomly assigned 1:1 to rosuvastatin or placebo. Plasma selenium concentrations were determined at entry, week 24, and week 48. Spearman correlation and linear regression analyses were used to assess relations between baseline selenium, HIV-related factors and markers of inflammation, immune activation, and subclinical vascular disease. Changes in selenium over 24 and 48 wk were compared between groups. Results: One hundred forty-seven HIV-infected adults were included. All participants were on ART. Median current CD4+ count was 613, and 76% had HIV-1 RNA ≤48 copies/mL (range: contemporary ART. The association between current PI use and higher selenium may have implications for ART allocation, especially in resource-limited countries. Also, it appears that statin therapy may increase selenium concentrations; however, larger studies are necessary to confirm this finding. This trial was registered at clinicaltrials.gov as NCT01218802. PMID:26269240

  18. Carotid intima-media thickness in HIV patients treated with antiretroviral therapy

    DEFF Research Database (Denmark)

    Lebech, Anne-Mette; Wiinberg, Niels; Kristoffersen, Ulrik Sloth

    2007-01-01

    INTRODUCTION: Increased cardiovascular risk in HIV patients in antiretroviral therapy (ART) may be due to HIV infection, direct effect of ART or dyslipidaemia induced by ART. Our aim was to study the relative importance of HIV, ART and dyslipidaemia on atherosclerosis, assessed by the comparison...... of carotid artery intima-media thickness (IMT) in non-smoking HIV patients with high or low serum cholesterol levels as well as in healthy volunteers. METHODS: HIV patients in ART with normal cholesterol (or=6 x 5 mmol l(-1); n=12) as well as healthy controls (n=14) were included. All were non...... on these observations, one could speculate whether selective lowering of LDL cholesterol will be successful in reducing cardiovascular risk in non-smoking HIV patients....

  19. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection.

    Science.gov (United States)

    Wagh, Kshitij; Bhattacharya, Tanmoy; Williamson, Carolyn; Robles, Alex; Bayne, Madeleine; Garrity, Jetta; Rist, Michael; Rademeyer, Cecilia; Yoon, Hyejin; Lapedes, Alan; Gao, Hongmei; Greene, Kelli; Louder, Mark K; Kong, Rui; Karim, Salim Abdool; Burton, Dennis R; Barouch, Dan H; Nussenzweig, Michel C; Mascola, John R; Morris, Lynn; Montefiori, David C; Korber, Bette; Seaman, Michael S

    2016-03-01

    The identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct epitopes on the viral envelope (Env) will likely be required to overcome the extraordinary diversity of HIV-1, a key outstanding question is which bnAbs, and how many, will be needed to achieve optimal clinical benefit. We assessed the neutralizing activity of 15 bnAbs targeting four distinct epitopes of Env, including the CD4-binding site (CD4bs), the V1/V2-glycan region, the V3-glycan region, and the gp41 membrane proximal external region (MPER), against a panel of 200 acute/early clade C HIV-1 Env pseudoviruses. A mathematical model was developed that predicted neutralization by a subset of experimentally evaluated bnAb combinations with high accuracy. Using this model, we performed a comprehensive and systematic comparison of the predicted neutralizing activity of over 1,600 possible double, triple, and quadruple bnAb combinations. The most promising bnAb combinations were identified based not only on breadth and potency of neutralization, but also other relevant measures, such as the extent of complete neutralization and instantaneous inhibitory potential (IIP). By this set of criteria, triple and quadruple combinations of bnAbs were identified that were significantly more effective than the best double combinations, and further improved the probability of having multiple bnAbs simultaneously active against a given virus, a requirement that may be critical for countering escape in vivo. These results provide a rationale for advancing bnAb combinations with the best in vitro predictors of success into clinical trials for both the prevention and treatment of HIV-1 infection.

  20. T-lymphocyte subset dynamics in well-treated HIV-infected men during a bout of exhausting exercise.

    Science.gov (United States)

    Dirksen, Carsten; Hansen, Birgitte R; Kolte, Lilian; Haugaard, Steen B; Andersen, Ove

    2015-01-01

    In healthy individuals the substantial lymphocytosis during a bout of exhausting exercise constitutes primarily mature T cells from the peripheral lymphoid organs but naïve T cells are also recruited. This study investigated whether the defective CD4 + T-lymphocyte count in peripheral blood during rest in human immunodeficiency virus (HIV)-infected patients would also be observed following a maximal output ergometer bicycle test. At rest, in 45 well-treated HIV-infected patients, mature and naïve CD4 + T-lymphocyte counts were decreased whereas the less immune active CD8 + T lymphocytes were increased compared with 10 healthy control subjects. In response to exercise mature and naïve CD4 + T lymphocytes increased less and mature and naïve CD8 + T lymphocytes increased most in HIV-infected patients. In conclusion, defective resting mature and naïve CD4 + T lymphocytes in well-treated HIV-infected patients are also reflected in defective acutely mobilized active immune cells following exhausting exercise. The CD4 + T-lymphocyte count is highly sensitive to physical activity.

  1. Assessment of the antiviral capacity of primary natural killer cells by optimized in vitro quantification of HIV-1 replication.

    Science.gov (United States)

    He, Xuan; Simoneau, Camille R; Granoff, Mitchell E; Lunemann, Sebastian; Dugast, Anne-Sophie; Shao, Yiming; Altfeld, Marcus; Körner, Christian

    2016-07-01

    Despite a growing number of studies investigating the impact of natural killer (NK) cells on HIV-1 pathogenesis, the exact mechanism by which NK cells recognize HIV-1-infected cells and exert immunological pressure on HIV-1 remains unknown. Previously several groups including ours have introduced autologous HIV-1-infected CD4(+) T cells as suitable target cells to study NK-cell function in response to HIV-1 infection in vitro. Here, we re-evaluated and optimized a standardized in vitro assay that allows assessing the antiviral capacity of NK cells. This includes the implementation of HIV-1 RNA copy numbers as readout for NK-cell-mediated inhibition of HIV-1 replication and the investigation of inter-assay variation in comparison to previous methods, such as HIV-1 p24 Gag production and frequency of p24(+) CD4(+) T cells. Furthermore, we investigated the possibility to hasten the duration of the assay and provide concepts for downstream applications. Autologous CD4(+) T cells and NK cells were obtained from peripheral blood of HIV-negative healthy individuals and were separately enriched through negative selection. CD4(+) T cells were infected with the HIV-1 strain JR-CSF at an MOI of 0.01. Infected CD4(+) T cells were then co-cultured with primary NK cells at various effector:target ratios for up to 14days. Supernatants obtained from media exchanged at days 4, 7, 11 and 14 were used for quantification of HIV-1 p24 Gag and HIV-1 RNA copy numbers. In addition, frequency of infected CD4(+) T cells was determined by flow cytometric detection of intracellular p24 Gag. The assay displayed minimal inter-assay variation when utilizing viral RNA quantification or p24 Gag concentration for the assessment of viral replication. Viral RNA quantification was more rigorous to display magnitude and kinetics of NK-cell-mediated inhibition of HIV-1 replication, longitudinally and between tested individuals. The results of this study demonstrate that NK-cell-mediated inhibition of

  2. Radiological patterns in HIV-associated pulmonary tuberculosis: Comparison between HAART-treated and non-HAART-treated patients

    Energy Technology Data Exchange (ETDEWEB)

    Busi Rizzi, E. E-mail: radiologia@inmi.it; Schinina, V.; Palmieri, F.; Girardi, E.; Bibbolino, C

    2003-06-01

    AIM: To evaluate whether highly active antiretroviral therapy (HAART) modifies radiographic appearances of pulmonary tuberculosis (TB), in terms of patterns and their relative frequencies, among patients with human immunodeficiency virus (HIV) infection. MATERIALS AND METHODS: Chest radiographs were obtained in 209 HIV-infected patients with culture confirmed pulmonary TB. Computed tomography (CT) images were also reviewed for 42 patients whose chest radiographs were normal or showed questionable abnormalities. Imaging was evaluated for the presence and distribution of consolidation, cavitation, interstitial changes, pleural disease, adenopathy, and were classified as a primary or post-primary pattern. RESULTS: A post-primary pattern was more frequent after 1996 when HAART came into clinical use. Forty-four percent (77/176) of patients not on HAART had a post-primary pattern in comparison with 82% (27/33) of patients receiving HAART (p<0.001). A primary pattern was significantly more frequent (p<0.001), in patients with more severe immunosuppression (CD4 lymphocyte less than 200/mm{sup 3}). CONCLUSION: HIV patients receiving HAART with pulmonary TB, had a post-primary pattern more frequently than those not receiving this treatment. This observation is consistent with the partial restoration of cell-mediated immunity that can be induced by HAART.

  3. Optimization of HAART with genetic algorithms and agent-based models of HIV infection.

    Science.gov (United States)

    Castiglione, F; Pappalardo, F; Bernaschi, M; Motta, S

    2007-12-15

    Highly Active AntiRetroviral Therapies (HAART) can prolong life significantly to people infected by HIV since, although unable to eradicate the virus, they are quite effective in maintaining control of the infection. However, since HAART have several undesirable side effects, it is considered useful to suspend the therapy according to a suitable schedule of Structured Therapeutic Interruptions (STI). In the present article we describe an application of genetic algorithms (GA) aimed at finding the optimal schedule for a HAART simulated with an agent-based model (ABM) of the immune system that reproduces the most significant features of the response of an organism to the HIV-1 infection. The genetic algorithm helps in finding an optimal therapeutic schedule that maximizes immune restoration, minimizes the viral count and, through appropriate interruptions of the therapy, minimizes the dose of drug administered to the simulated patient. To validate the efficacy of the therapy that the genetic algorithm indicates as optimal, we ran simulations of opportunistic diseases and found that the selected therapy shows the best survival curve among the different simulated control groups. A version of the C-ImmSim simulator is available at http://www.iac.cnr.it/~filippo/c-ImmSim.html

  4. Recurrence of cervical intraepithelial neoplasia grades 2 or 3 in HIV-infected women treated by large loop excision of the transformation zone (LLETZ

    Directory of Open Access Journals (Sweden)

    Fábio Russomano

    Full Text Available CONTEXT AND OBJECTIVE: Women infected by HIV are more likely to have cervical cancer and its precursors. Treatment of the precursor lesions can prevent this neoplasia. The aim of this study was to assess the likelihood of recurrent cervical intraepithelial neoplasia grades 2 or 3 (CIN 2-3 in HIV-infected women, compared with HIV-negative women, all treated by large loop excision of the transformation zone (LLETZ. DESIGN AND SETTING: A cohort study in Instituto Fernandes Figueira, Fundação Oswaldo Cruz (IFF-Fiocruz, Rio de Janeiro. METHOD: 55 HIV-positive and 212 HIV-negative women were followed up after LLETZ for CIN 2-3 (range: 6-133 months. RESULTS: The incidence of recurrent CIN 2-3 was 30.06/10,000 woman-months in the HIV-positive group and 4.88/10,000 woman-months in the HIV-negative group (relative risk, RR = 6.16; 95% confidence interval, CI: 2.07-18.34. The likelihood of recurrence reached 26% at the 62nd month of follow-up among the HIV-positive women, and remained stable at almost 0.6% at the 93rd month of follow-up among the HIV-negative women. We were unable to demonstrate other prognostic factors relating to CIN recurrence, but the use of highly active antiretroviral therapy (HAART may decrease the risk of this occurrence among HIV patients. CONCLUSION: After LLETZ there is a higher risk of recurrence of CIN 2-3 among HIV-positive women than among HIV-negative women. This higher risk was not influenced by margin status or grade of cervical disease treated. The use of HAART may decrease the risk of this occurrence in HIV patients.

  5. Nutritional assessment and lipid profile in HIV-infected children and adolescents treated with highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Marina Hjertquist Tremeschin

    2011-06-01

    Full Text Available INTRODUCTION: HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART regimens that include a protease inhibitor (PI can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336, and 136 (63 - 271 versus control group: 54.5 (20 - 162; p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273 versus 67.5 (33 - 117; p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58 and 36 (23 - 43; control 49.5 (34 - 69; p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.

  6. Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI-treated patients.

    Directory of Open Access Journals (Sweden)

    André F A Santos

    Full Text Available BACKGROUND: Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H is poorly understood. METHODS AND FINDINGS: We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naïve and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher's exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. CONCLUSIONS: This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions.

  7. Optimization of struvite precipitation in synthetic biologically treated swine wastewater - Determination of the optimal process parameters

    OpenAIRE

    Capdevielle, Aurélie; Sýkorová, Eva; Biscans, Béatrice; Béline, Fabrice; Daumer, Marie-Line

    2013-01-01

    International audience; A sustainable way to recover phosphorus (P) in swine wastewater involves a preliminary step of P dissolution followed by the separation of particulate organic matter. The next two steps are firstly the precipitation of struvite crystals done by adding a crystallization reagent (magnesia) and secondly the filtration of the crystals. A design of experiments with five process parameters was set up to optimize the size of the struvite crystals in a synthetic swine wastewat...

  8. The association between substance use and sub-optimal HIV treatment engagement among HIV-infected female sex workers in Lilongwe, Malawi.

    Science.gov (United States)

    Lancaster, Kathryn E; Lungu, Thandie; Mmodzi, Pearson; Hosseinipour, Mina C; Chadwick, Katy; Powers, Kimberly A; Pence, Brian W; Go, Vivian F; Hoffman, Irving F; Miller, William C

    2017-02-01

    Female sex workers (FSW) have a high prevalence of substance use and HIV, but the impact of substance use on HIV treatment engagement is not well established. We evaluated the association between alcohol and marijuana use and sub-optimal HIV treatment engagement outcomes among HIV-infected FSW in Lilongwe, Malawi. We enroled FSW using venue-based recruitment into a cross-sectional evaluation assessing substance use and HIV treatment engagement. Seropositive FSW, identified through HIV rapid testing, received rapid CD4 count and viral load testing. We used Poisson regression with robust variance estimates to ascertain associations of alcohol and marijuana use with sub-optimal HIV treatment outcomes: (1) lack of ART use among previously diagnosed, ART-eligible FSW and (2) viral nonsuppression among FSW on ART. Of previously diagnosed, ART-eligible FSW (n = 96), 29% were not using ART. Patterns of hazardous drinking were identified in 30%, harmful drinking in 10%, and alcohol dependence in 12%. ART-eligible FSW with harmful drinking or alcohol dependency were 1.9 (95% CI: 1.0, 3.8) times as likely to not use ART compared to FSW without harmful or dependent drinking. Among those on ART, 14% were virally nonsuppressed. The prevalence ratio for viral nonsuppression was 2.0 (95% CI: 0.6, 6.5) for harmful drinkers and alcohol-dependent FSW. Over 30% of ART-eligible FSW reported using marijuana. Marijuana-using FSW were 1.9 (95% CI: 0.8, 4.6) times as likely to not use ART compared to FSW who were not using marijuana. Given the high prevalence of alcohol use and its association with lack of ART use, ART uptake and alcohol reduction strategies should be tailored for alcohol-using FSW in Malawi.

  9. All-cause mortality in treated HIV-infected adults with CD4 ≥500/mm3 compared with the general population

    DEFF Research Database (Denmark)

    Lewden, Charlotte; Bouteloup, Vincent; De Wit, Stéphane;

    2012-01-01

    Using data from a large European collaborative study, we aimed to identify the circumstances in which treated HIV-infected individuals will experience similar mortality rates to those of the general population....

  10. Envelope-specific antibodies and antibody-derived molecules for treating and curing HIV infection

    Science.gov (United States)

    Ferrari, Guido; Haynes, Barton F.; Koenig, Scott; Nordstrom, Jeffrey L.; Margolis, David M.; Tomaras, Georgia D.

    2017-01-01

    HIV-1 is a retrovirus that integrates into host chromatin and can remain transcriptionally quiescent in a pool of immune cells. This characteristic enables HIV-1 to evade both host immune responses and antiretroviral drugs, leading to persistent infection. Upon reactivation of proviral gene expression, HIV-1 envelope (HIV-1 Env) glycoproteins are expressed on the cell surface, transforming latently infected cells into targets for HIV-1 Env-specific monoclonal antibodies (mAbs), which can engage immune effector cells to kill productively infected CD4+ T cells and thus limit the spread of progeny virus. Recent innovations in antibody engineering have resulted in novel immunotherapeutics such as bispecific dual-affinity re-targeting (DART) molecules and other bi- and trispecific antibody designs that can recognize HIV-1 Env and recruit cytotoxic effector cells to kill CD4+ T cells latently infected with HIV‑1. Here, we review these immunotherapies, which are designed with the goal of curing HIV-1 infection. PMID:27725635

  11. Comfort Levels Among Predoctoral Dental and Dental Hygiene Students in Treating Patients at High-Risk for HIV/AIDS.

    Science.gov (United States)

    Natto, Zuhair S; Aladmawy, Majdi; Rogers, Thomas C

    2015-06-01

    The purpose of this article is to discuss the impact of the training program for predoctoral dental and hygiene students at Loma Linda University School of Dentistry (LLUSD) with regard to issues related to treating patients with a high risk of having HIV/AIDS. LLUSD offers a training program for fourth-year dental hygiene and predoctoral dental students that addresses the oral health care needs of persons with HIV disease. The training occurs in small groups 2 days per week at a community clinic serving HIV-positive individuals. Three academic quarters are required to train all fourth-year students each year. Evaluation of program effectiveness is conducted by means of pre- and post-session surveys. Dental hygiene and dental students completed the pre-survey during the spring quarter of their third year in public health dentistry courses. The same students completed the post-session survey at the end of their weekly training sessions during the fourth year. The overall change in all areas related to the students' comfort level in treating patients in the 3 defined categories is in a positive direction (p-valuedental hygiene students compared with predoctoral dental students. A comparison of pre- and post-session surveys reveals a significant improvement in students' perception of and comfort level with treating patients who are homosexual/bisexual or intravenous drug users, or who have a history of blood transfusion in both student groups upon completion of the HIV and the Dentist training program at LLUSD. Copyright © 2015 The American Dental Hygienists’ Association.

  12. Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease

    DEFF Research Database (Denmark)

    Borges, Álvaro H; Weitz, Jeffrey I; Collins, Gary;

    2014-01-01

    OBJECTIVE: The objective of this study is to determine the relationship between inflammatory interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)] and coagulation (D-dimer) biomarkers and the presence and type of anaemia among HIV-positive individuals. DESIGN: A cross-sectional st......OBJECTIVE: The objective of this study is to determine the relationship between inflammatory interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)] and coagulation (D-dimer) biomarkers and the presence and type of anaemia among HIV-positive individuals. DESIGN: A cross......-sectional study. METHODS: Combination antiretroviral therapy (cART)-treated adults participating in an international HIV trial with haemoglobin and mean corpuscular volume (MCV) measurements at entry were categorized by presence of anaemia (haemoglobin ≤14 g/dl in men and ≤12 g/dl in women) and, for those...... with anaemia, by type [microcytic (MCV 100 fl)]. We analysed the association between inflammation (IL-6 and hsCRP) and coagulation (D-dimer) and haemoglobin, controlling for demographics (age, race and sex), BMI, HIV plasma RNA levels, CD4⁺ T-cell counts (nadir...

  13. Evaluation of 'see-see and treat' strategy and role of HIV on cervical cancer prevention in Uganda

    Directory of Open Access Journals (Sweden)

    Sandin Sven

    2010-05-01

    Full Text Available Abstract Background There is scant information on whether Human Immunodeficiency Virus (HIV seropositivity has an influence on the outcome of treatment of precancerous cervical lesions using cryotherapy. We studied the prevalence of cervical abnormalities detectable by visual inspection and cervical lesions diagnosed by colposcopy according to HIV serostatus and described the outcomes of cryotherapy treatment. Methods Trained nurses examined women not previously screened for cervical cancer using visual inspection with acetic acid (VIA and Lugol's iodine (VILI in two family planning/post natal clinics in Kampala, Uganda, from February 2007 to August 2008. Women with abnormal visual inspection findings were referred for colposcopic evaluation and HIV testing. Women with precancerous cervical lesions detected at colposcopy were treated mainly by cryotherapy, and were evaluated for treatment outcome after 3 months by a second colposcopy. Results Of the 5 105 women screened, 834 presented a positive screening test and were referred for colposcopy. Of these 625 (75% returned for the colposcopic evaluation and were tested for HIV. For the 608 (97.5% women in the age range 20-60 years, colposcopy revealed 169 women with cervical lesions: 128 had inflammation, 19 had low grade squamous intraepithelial lesion (LGSIL, 13 had high grade squamous intraepithelial lesion (HGSIL, 9 had invasive cervical cancer and 2 had inconclusive findings. Detection rates per 1 000 women screened were higher among the older women (41-60 years compared to women aged 20-40 years. They were accordingly 55% and 20% for inflammation, 10% and 2% for LGSIL, 5% and 2% for HGSIL, 6% and 1% for invasive cervical cancer. Of the 608 women, 103 (16% were HIV positive. HIV positivity was associated with higher likelihood of inflammation (RR = 1.7; 95% CI: 1.2-2.4. Conclusions Detection rates were higher among older women 41-60 years. Visual inspection of the cervix uteri with acetic acid

  14. Optimizing hydraulic retention times in denitrifying woodchip bioreactors treating recirculating aquaculture system wastewater

    Science.gov (United States)

    The performance of wood-based denitrifying bioreactors to treat high-nitrate wastewaters from aquaculture systems has not previously been demonstrated. Four pilot-scale woodchip bioreactors (approximately 1:10 scale) were constructed and operated for 268 d to determine the optimal range of design hy...

  15. Why don't we treat chronic hepatitis C in HIV patients? Results from a cohort of HIV-HCV coinfected patients from the southeast of Spain

    Directory of Open Access Journals (Sweden)

    C Smilg Nicolás

    2012-11-01

    Full Text Available Purpose of the study: To know the different reasons why we decide not to treat or to delay the antiviral treatment against HCV in HIV coinfected patients. Methods: Prospective cohort of HIV and HCV coinfected patients, followed in the Infectious Diseases Department of the Santa Lucia Universitary Hospital (Cartagena, Spain between 1/12/2011 and 28/02/2012 in which we made transitory elastography. We evaluated the main reasons that moved us to decide not to treat or to delay the antiviral treatment against HCV: social-familiar-laboral reasons; neuro-psychiatric severe diseases; patient decision; low grade hepatic fibrosis; previous failure to pegylated interferon (IFN and ribavirin (RBV in no-1 genotype patients; delay in the approval of the triple therapy with INF-RBV and a protease inhibitor (boceprevir or telaprevir by the Regional Sanitary Authority; active alcohol abuse; active diseases that contraindicate the antiviral treatment, incomplete study of HCV (VL of HCV, genotype, ILB28, abdominal ecography; previous intolerance against IFN-RBV and severe thrombocytopenia (<50×109/L. Summary of results: The cohort included 109 patients, being 27 of them females (25% and 82 males (75%, with a median of age of 45.8 years (SD: 6.2. In 98 patients (90% we decided not to treat or to delay the antiviral treatment against HCV for one or more of the following reasons: 37 (34% presented low grade hepatic fibrosis (<9.5 kpascal or F0-F2; 19 (17% had neuro-psychiatric diseases; 18 (16.5% were waiting for the approval of triple therapy by the Regional Sanitary Authority; 10 (9.2% did not want to be treated; 10 (9.2% had failure to IFN-RBV in no-1 genotype; 6 (5.5% had social-familiar-laboral reasons; 6 (5.5% presented active severe diseases; 4 (3.7% were waiting to complete HCV study; 3 (2.8% presented active alcohol abuse; 3 (2.8% had previous intolerance against IFN-RBV treatment and 2 (2% had severe thrombocytopenia. Conclusions: In our cohort of HIV

  16. Optimization of Multicomponent Behavioral and Biobehavioral Interventions for the Prevention and Treatment of HIV/AIDS.

    Science.gov (United States)

    Collins, Linda M; Kugler, Kari C; Gwadz, Marya Viorst

    2016-01-01

    To move society toward an AIDS-free generation, behavioral interventions for prevention and treatment of HIV/AIDS must be not only effective, but also cost-effective, efficient, and readily scalable. The purpose of this article is to introduce to the HIV/AIDS research community the multiphase optimization strategy (MOST), a new methodological framework inspired by engineering principles and designed to develop behavioral interventions that have these important characteristics. Many behavioral interventions comprise multiple components. In MOST, randomized experimentation is conducted to assess the individual performance of each intervention component, and whether its presence/absence/setting has an impact on the performance of other components. This information is used to engineer an intervention that meets a specific optimization criterion, defined a priori in terms of effectiveness, cost, cost-effectiveness, and/or scalability. MOST will enable intervention science to develop a coherent knowledge base about what works and does not work. Ultimately this will improve behavioral interventions systematically and incrementally.

  17. Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America

    DEFF Research Database (Denmark)

    May, Margaret T; Hogg, Robert S; Justice, Amy C

    2012-01-01

    HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear....

  18. Treating High-grade Lesions to Prevent Anal Cancer in HIV-infected People

    Science.gov (United States)

    This study, called the ANCHOR trial, will investigate whether screening and prevention methods similar to those used to prevent cervical cancer can help prevent anal cancer in HIV-infected men and women.

  19. Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.

    Directory of Open Access Journals (Sweden)

    Timothy B Hallett

    2011-11-01

    Full Text Available BACKGROUND: Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed. METHODS AND FINDINGS: We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is 70% effective. CONCLUSIONS: Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention. Please see later in the article for the Editors' Summary.

  20. Final Cost and Performance Report Application of Flow and Transport Optimization Codes to Groundwater Pump and Treat Systems

    Science.gov (United States)

    2004-01-01

    and treat; Remediation System Evaluation ( RSE ); Remedial Process Optimization (RPO) 16. SECURITY CLASSIFICATION OF: 19a. NAME OF RESPONSIBLE...Demolition Explosive RPO Remedial Process Optimization RSE Remediation System Evaluation SVE soil vapor extraction TCE Trichloroethylene TIO...standards in less time). Remediation System Evaluation ( RSE ) or Remedial Process Optimization (RPO) provides a broad assessment of optimization

  1. OPERA: use of pegylated interferon plus ribavirin for treating HCV-HIV coinfection in interferon-naive patients.

    Science.gov (United States)

    Carosi, Giampiero; Bruno, Raffaele; Cariti, Giuseppe; Nasta, Paola; Gulminetti, Roberto; Galli, Massimo; Angarano, Gioacchino; Verucchi, Gabriella; Pontali, Emanuele; Capetti, Amedeo; Raise, Enzo; Ravasio, Veronica; Maida, Ivana; Iannacone, Claudio; Caputo, Antonietta; Puoti, Massimo

    2014-01-01

    The Optimized Pegylated interferons Efficacy and anti-Retroviral Approach (OPERA) study aimed to assess the efficacy and safety profile of treatment with pegylated interferons (PEG-IFNs) in interferon-naive patients with chronic HCV and HIV infection in routine clinical practice. This was a multicentre, prospective observational cohort study conducted at 98 Italian referral centres for the treatment of chronic HCV and HIV coinfection. Adult subjects (n=1,523) with a confirmed diagnosis of HCV and stable HIV coinfection were followed between April 2005 and March 2011; of these, 1,284 were interferon-naive and were the focus of this analysis. Patients received PEG-IFN-α2a or -α2b plus ribavirin combination therapy. The choice of treatment and dose was at the investigator's discretion, according to the summary of product characteristics and current guidelines. The primary efficacy end point was sustained virological response (SVR). Secondary end points included rates of rapid viral response, early viral response and response at end of treatment. SVR was achieved by 40.0% of patients; the highest SVR rate was observed in patients with HCV genotypes 2 and 3. More genotype 2 and 3 than genotype 1 and 4 patients achieved rapid and early viral responses, and end of treatment responses. Higher SVR rates were also associated with ≥80% anti-HCV treatment compliance and lower baseline HCV levels. The OPERA study results show that PEG-IFN plus ribavirin is an effective treatment for HCV-HIV coinfection in interferon-naive patients. Independent predictors of SVR include HCV genotype, undetectable baseline HIV RNA and baseline HCV RNA<500,000 IU/ml.

  2. Sunitinib Malate in Treating HIV-Positive Patients With Cancer Receiving Antiretroviral Therapy

    Science.gov (United States)

    2014-03-14

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Langerhans Cell Histiocytosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Aggressive NK-cell Leukemia; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Malignancies; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Clear Cell Renal Cell Carcinoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV Infection; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Light Chain Deposition Disease; Mast Cell Leukemia; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Osteolytic Lesions of Multiple Myeloma; Peripheral T-cell Lymphoma; Plasma Cell Neoplasm; Polycythemia Vera; Post

  3. A Method for treating Damage Related Criteria in Optimal Topology Design of Continuum Structures

    DEFF Research Database (Denmark)

    Bendsøe, Martin P; Diaz, Alejandro

    1997-01-01

    In this paper we present a formulation of the well-known structural topology optimization problem that accounts for the presence of loads capable of causing permanent damage to the structure. Damage is represented in the form of an internal variable model which is standard in continuum damage...... mechanics. Here we employ an interpretation of this model as an optimum remodeling problem for maximal compliance over all damage distributions, making also the analysis of the damage model a study in structural optimization. The damage criterion can be included in the optimal design model in a number...... of ways. We present results for finding the optimal topology of the reinforcement of an existing design with the goal of minimizing damage. Also, we treat a problem of finding the topology of a structure were we seek maximal stiffness under service loads with a constraint on the amount of damage which...

  4. A Method for treating Damage Related Criteria in Optimal Topology Design of Continuum Structures

    DEFF Research Database (Denmark)

    Bendsøe, Martin P; Diaz, A.R.

    1998-01-01

    In this paper we present a formulation of the well-known structural topology optimization problem that accounts for the presence of loads capable of causing permanent damage to the structure. Damage is represented in the form of an internal variable model which is standard in continuum damage...... mechanics. Here we employ an interpretation of this model as an optimum remodeling problem for maximal compliance over all damage distributions, making also the analysis of the damage model a study in structural optimization. The damage criterion can be included in the optimal design model in a number...... of ways. We present results for finding the optimal topology of the reinforcement of an existing design with the goal of minimizing damage. Also, we treat the problem of finding the topology of a structure where we seek maximal stiffness under service loads with a constraint on the amount of damage which...

  5. Enhancement of NMDA receptor-mediated excitatory postsynaptic currents by gp120-treated macrophages: implications for HIV-1-associated neuropathology.

    Science.gov (United States)

    Yang, Jianming; Hu, Dehui; Xia, Jianxun; Liu, Jianuo; Zhang, Gang; Gendelman, Howard E; Boukli, Nawal M; Xiong, Huangui

    2013-09-01

    A plethora of prior studies has linked HIV-1-infected and immune activated brain mononuclear phagocytes (MP; blood borne macrophages and microglia) to neuronal dysfunction. These are modulated by N-methyl-D-aspartate receptor (NMDAR) antagonists and supporting their relevance for HIV-1-associated nervous system disease. The role of NMDAR subsets in HIV-1-induced neuronal injury, nonetheless, is poorly understood. To this end, we investigated conditioned media from HIV-1gp120-treated human monocyte-derived-macrophages (MDM) for its abilities to affect NMDAR-mediated excitatory postsynaptic currents (EPSC(NMDAR)) in rat hippocampal slices. Bath application of gp120-treated MDM-conditioned media (MCM) produced an increase of EPSC(NMDAR). In contrast, control (untreated) MCM had limited effects on EPSC(NMDAR). Testing NR2A NMDAR (NR2AR)-mediated EPSC (EPSC(NR2AR)) and NR2B NMDAR (NR2BR)-mediated EPSC (EPSC(NR2BR)) for MCM showed significant increased EPSC(NR2BR) when compared to EPSC(NR2AR) enhancement. When synaptic NR2AR-mediated EPSC was blocked by bath application of MK801 combined with low frequency stimulations, MCM retained its ability to enhance EPSC(NMDAR) evoked by stronger stimulations. This suggested that increase in EPSC(NMDAR) was mediated, in part, through extra-synaptic NR2BR. Further analyses revealed that the soluble factors with low (NR2BR but not NR2AR blockers. Taken together, these results indicate that macrophage secretory products induce neuronal injury through extra-synaptic NR2BRs.

  6. Optimal control of combined therapy in a single strain HIV-1 model

    Directory of Open Access Journals (Sweden)

    Winston Garira

    2005-05-01

    Full Text Available Highly active antiretroviral therapy (HAART is administered to symptomatic human immunodeficiency virus (HIV infected individuals to improve their health. Various administration schemes are used to improve patients' lives and at the same time suppressing development of drug resistance, reduce evolution of new viral strains, minimize serious side effects, improve patient adherence and also reduce the costs of drugs. We deduce an optimal drug administration scheme useful in improving patients' health especially in poor resourced settings. In this paper we use the Pontryagin's Maximum Principle to derive optimal drug dosages based on a mathematical dynamical model. We use methods of optimal control to determine optimal controls analytically, and then use the Runge-Kutta scheme of order four to numerically simulate different therapy effects. We simulate the different effects of a drug regimen composed of a protease inhibitor and a nucleoside reverse transcriptase inhibitor. Our results indicate that for highly toxic drugs, small dosage sizes and allowing drug holidays make a profound impact in both improving the quality of life and reducing economic costs of therapy. The results show that for drugs with less toxicity, continuous therapy is beneficial.

  7. Changes in lipids over twelve months after initiating protease inhibitor therapy among persons treated for HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Hogg Robert S

    2005-02-01

    Full Text Available Abstract Background Protease inhibitors are known to alter the lipid profiles in subjects treated for HIV/AIDS. However, the magnitude of this effect on plasma lipoproteins and lipids has not been adequately quantified. Objective To estimate the changes in plasma lipoproteins and triglycerides occurring within 12 months of initiating PI-based antiretroviral therapy among HIV/AIDS afflicted subjects. Methods We included all antiretroviral naïve HIV-infected persons treated at St-Paul's Hospital, British Columbia, Canada, who initiated therapy with protease inhibitor antiretroviral (ARV drugs between August 1996 and January 2002 and who had at least one plasma lipid measurement. Longitudinal associations between medication use and plasma lipids were estimated using mixed effects models that accounted for repeated measures on the same subjects and were adjusted for age, sex, time dependent CD4+ T-cell count, and time dependent cumulative use of non-nucleoside reverse transcriptase inhibitors and adherence. The cumulative number of prescriptions filled for PIs was considered time dependent. We estimated the changes in the 12 months following any initiation of a PI based regimen. Results A total of 679 eligible subjects were dispensed nucleoside analogues and PI at the initiation of therapy. Over a median 47 months of follow-up (interquartile range (IQR: 29–62, subjects had a median of 3 (IQR: 1–6 blood lipid measurements. Twelve months after treatment initiation of PI use, there was an estimated 20% (95% confidence interval: 17% – 24% increase in total cholesterol and 22% (12% – 33% increase in triglycerides. Conclusions Twelve months after treatment initiation with PIs, statistically significant increases in total cholesterol and triglycerides levels were observed in HIV-infected patients under conditions of standard treatment. Our results contribute to the growing body of evidence implicating PIs in the development of blood lipid

  8. Optimization of Composition and Heat Treating of Die Steels for Extended Lifetime

    Energy Technology Data Exchange (ETDEWEB)

    David Schwam; John F. Wallace; Quanyou Zhou

    2002-01-30

    An ''average'' die casting die costs fifty thousand dollars. A die used in making die cast aluminum engine blocks can cost well over one million dollars. These costs provide a strong incentive for extension of die life. While vacuum quenched Premium Grade H13 dies have become the most widely used in the United States, tool makers and die casters are constantly searching for new steels and heat treating procedures to extend die life. This project was undertaken to investigate the effects of composition and heat treating on die life and optimize these parameters.

  9. Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

    Directory of Open Access Journals (Sweden)

    Roberto Manfredi

    2012-04-01

    Full Text Available A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events, but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs, represents the key point for a debate around the increasing frequency of “polypharmacy” in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a life-threatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS.

  10. Optimizing the Dyeing Process of Alkali-Treated Polyester Fabric with Dolu Natural Dye

    OpenAIRE

    M. F. Shahin; Ahmed, R. M.

    2014-01-01

    An attempt has been made to optimize the process of dyeing polyester (PET) fabric with natural dyes. Polyester has been first treated with NaOH solution in order to study its impact on the dyeability to the natural dye. The required and used colour component was extracted from a natural plant, namely: Rhubarb; Rheum officinale. The chemical structure of the used colouring matter is observed to have all the characteristics of a typical disperse dye. The colour strength of PE...

  11. A Case of an Unusually Aggressive Cutaneous Anaplastic Large T-Cell Lymphoma in an HIV Patient Treated with CHOP

    Directory of Open Access Journals (Sweden)

    Jorge Hurtado-Cordovi

    2011-01-01

    Full Text Available Anaplastic large cell lymphoma (ALCL is the second most common malignancy of T-cell phenotype. This case report describes an unusual rapidly progressing cutaneous anaplastic large T-cell lymphoma in an HIV patient. Our patient is a twenty-year-old African American male with perinatally acquired HIV who presented with a 2×2 centimeter necrotic lesion in the right 1st toe; however, 2-3 weeks later multiple smaller lesions appeared on the anterior aspect of the right foot, ankle, and thigh. Biopsy showed cells strongly positive for CD3 and CD30 and negative for CD56 and the ALK gene product. CT of the chest, abdomen, and pelvis was negative for extracutaneous involvement favoring cutaneous ALCL. Patient was treated with 6 cycles of CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone chemotherapy and went into complete remission. Due to the aggressive course that this malignancy follows in HIV patients we suggest prompt treatment with systemic therapy.

  12. Structural and Preclinical Studies of Computationally Designed Non-Nucleoside Reverse Transcriptase Inhibitors for Treating HIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Kudalkar, Shalley N.; Beloor, Jagadish; Chan, Albert H.; Lee, Won-Gil; Jorgensen, William L.; Kumar, Priti; Anderson, Karen S.

    2017-02-06

    The clinical benefits of HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are hindered by their unsatisfactory pharmacokinetic (PK) properties along with the rapid development of drug-resistant variants. However, the clinical efficacy of these inhibitors can be improved by developing compounds with enhanced pharmacological profiles and heightened antiviral activity. We used computational and structure-guided design to develop two next-generation NNRTI drug candidates, compounds I and II, which are members of a class of catechol diethers. We evaluated the preclinical potential of these compounds in BALB/c mice because of their high solubility (510 µg/ml for compound I and 82.9 µg/ml for compound II), low cytotoxicity, and enhanced antiviral activity against wild-type (WT) HIV-1 RT and resistant variants. Additionally, crystal structures of compounds I and II with WT RT suggested an optimal binding to the NNRTI binding pocket favoring the high anti-viral potency. A single intraperitoneal dose of compounds I and II exhibited a prolonged serum residence time of 48 hours and concentration maximum (Cmax) of 4000- to 15,000-fold higher than their therapeutic/effective concentrations. These Cmax values were 4- to 15-fold lower than their cytotoxic concentrations observed in MT-2 cells. Compound II showed an enhanced area under the curve (0–last) and decreased plasma clearance over compound I and efavirenz, the standard of care NNRTI. Hence, the overall (PK) profile of compound II was excellent compared with that of compound I and efavirenz. Furthermore, both compounds were very well tolerated in BALB/c mice without any detectable acute toxicity. Taken together, these data suggest that compounds I and II possess improved anti-HIV-1 potency, remarkable in vivo safety, and prolonged in vivo circulation time, suggesting strong potential for further development as new NNRTIs for the potential treatment of HIV infection.

  13. Optimal Control of Malaria Transmission using Insecticide Treated Nets and Spraying

    Science.gov (United States)

    Athina, D.; Bakhtiar, T.; Jaharuddin

    2017-03-01

    In this paper, we consider a model of the transmission of malaria which was developed by Silva and Torres equipped with two control variables, namely the use of insecticide treated nets (ITN) to reduce the number of human beings infected and spraying to reduce the number of mosquitoes. Pontryagin maximum principle was applied to derive the differential equation system as optimality conditions which must be satisfied by optimal control variables. The Mangasarian sufficiency theorem shows that Pontryagin maximum principle is necessary as well as sufficient conditions for optimization problem. The 4th-order Runge Kutta method was then performed to solve the differential equations system. The numerical results show that both controls given at once can reduce the number of infected individuals as well as the number of mosquitoes which reduce the impact of malaria transmission.

  14. Treating HIV in rural South Africa “Successes and Challenges"

    NARCIS (Netherlands)

    Barth, R.E.

    2010-01-01

    This thesis presents the first testimony of a unique collaboration between Ndlovu Medical Centre (NMC) in Elandsdoorn, South Africa, and the University Medical Centre in Utrecht (UMCU), The Netherlands. Sub-Saharan Africa continues to be the region most affected by HIV, and South Africa is the count

  15. Long-term outcomes of children treated for HIV-infection

    NARCIS (Netherlands)

    Cohen, S.

    2015-01-01

    Despite the drastic decrease of mortality and morbidity since the introduction of combination antiretroviral therapy (cART) in 1996, children with a chronic HIV-infection remain vulnerable to multiple complications that may negatively impact their physical health, cognitive function and psychologica

  16. Long-term outcomes of children treated for HIV-infection

    NARCIS (Netherlands)

    Cohen, S.

    2015-01-01

    Despite the drastic decrease of mortality and morbidity since the introduction of combination antiretroviral therapy (cART) in 1996, children with a chronic HIV-infection remain vulnerable to multiple complications that may negatively impact their physical health, cognitive function and

  17. Treating HIV in rural South Africa “Successes and Challenges"

    NARCIS (Netherlands)

    Barth, R.E.

    2010-01-01

    This thesis presents the first testimony of a unique collaboration between Ndlovu Medical Centre (NMC) in Elandsdoorn, South Africa, and the University Medical Centre in Utrecht (UMCU), The Netherlands. Sub-Saharan Africa continues to be the region most affected by HIV, and South Africa is the

  18. Rising population cost for treating people living with HIV in the UK, 1997-2013.

    Directory of Open Access Journals (Sweden)

    Sundhiya Mandalia

    Full Text Available BACKGROUND: The number of people living with HIV (PLHIV is increasing in the UK. This study estimated the annual population cost of providing HIV services in the UK, 1997-2006 and projected them 2007-2013. METHODS: Annual cost of HIV treatment for PLHIV by stage of HIV infection and type of ART was calculated (UK pounds, 2006 prices. Population costs were derived by multiplying the number of PLHIV by their annual cost for 1997-2006 and projected 2007-2013. RESULTS: Average annual treatment costs across all stages of HIV infection ranged from £17,034 in 1997 to £18,087 in 2006 for PLHIV on mono-therapy and from £27,649 in 1997 to £32,322 in 2006 for those on quadruple-or-more ART. The number of PLHIV using NHS services rose from 16,075 to 52,083 in 2006 and was projected to increase to 78,370 by 2013. Annual population cost rose from £104 million in 1997 to £483 million in 2006, with a projected annual cost between £721 and £758 million by 2013. When including community care costs, costs increased from £164 million in 1997, to £683 million in 2006 and between £1,019 and £1,065 million in 2013. CONCLUSIONS: Increased number of PLHIV using NHS services resulted in rising UK population costs. Population costs are expected to continue to increase, partly due to PLHIV's longer survival on ART and the relative lack of success of HIV preventing programs. Where possible, the cost of HIV treatment and care needs to be reduced without reducing the quality of services, and prevention programs need to become more effective. While high income countries are struggling to meet these increasing costs, middle- and lower-income countries with larger epidemics are likely to find it even more difficult to meet these increasing demands, given that they have fewer resources.

  19. Renal function in HIV-infected children and adolescents treated with tenofovir disoproxil fumarate and protease inhibitors

    Directory of Open Access Journals (Sweden)

    Pontrelli Giuseppe

    2012-01-01

    Full Text Available Abstract Background Kidney disease is an important complication in HIV infected people, and this may be related to infection or antiretroviral therapy (ART. Our aim is to assess renal function in HIV infected paediatric patients, who may be particularly affected and are likely to take ART for longer than adults, and investigate the long term role of Tenofovir Disoproxil Fumarate (TDF alone or co-administered with Ritonavir-boosted Protease Inhibitors (PI. Methods Serum creatinine, phosphate and potassium levels, with estimated Glomerular Filtration Rate (eGFR, had been prospectively evaluated for 2 years in a cohort of HIV infected children and adolescents (age 9-18 on ART, and data analyzed according to the exposure to TDF or simultaneous TDF and PI. Results Forty-nine patients were studied (57% female, mean age 14. Sixty-three percent were treated with ART containing TDF (Group A, and 37% without TDF (Group B; 47% with concomitant use of TDF and PI (Group C and 53% without this combination (Group D. The groups didn't differ for age, gender or ethnicity. The median creatinine increased in the entire cohort and in all the groups analyzed; eGFR decreased from 143.6 mL/min/1.73 m2 at baseline to 128.9 after 2 years (p = 0.006 in the entire cohort. Three patients presented a mild eGFR reduction, all were on TDF+PI. Phosphatemia decreased significantly in the entire cohort (p = 0.0003 and in TDF+PI group (p = 0.0128 after 2 years. Five patients (10% developed hypophosphatemia (Division of Acquired Immune Deficiency AE grade 1 or 2, and four of them were on TDF+PI. Conclusions Renal function decrease and hypophosphatemia occur over time in HIV infected children and adolescents on ART. The association with co-administration of TDF and PI appears weak, and further studies are warranted.

  20. Immunosenescence of the CD8(+) T cell compartment is associated with HIV-infection, but only weakly reflects age-related processes of adipose tissue, metabolism, and muscle in antiretroviral therapy-treated HIV-infected patients and controls

    DEFF Research Database (Denmark)

    Tavenier, Juliette; Langkilde, Anne; Haupt, Thomas Huneck

    2015-01-01

    -related processes of inflammation, metabolism, adipose tissue, and muscle. T cell immunosenescence and exhaustion were assessed by flow cytometry analysis of CD8 (+) cells from 43 ART-treated HIV-infected patients (HIV(+)) and ten Controls using markers of differentiation: CD27/CD28; maturation: CD27/CD45RA...... differentiated and mature CD8 (+) T cell phenotypes. PD-1 and KLRG1 expression did not differ between HIV(+) and Controls, but depended on differentiation and maturation stages of the cells. CD8 (+) T cell maturation was associated with age. KLRG1 expression was associated with age, metabolic syndrome, visceral...

  1. Relationship between innate immunity, soluble markers and metabolic-clinical parameters in HIV+ patients ART treated with HIV-RNA<50 cp/mL

    Directory of Open Access Journals (Sweden)

    Chiara Dentone

    2014-11-01

    Full Text Available Introduction: The persistence of immune activation and inflammation in HIV patients with HIV-RNA (VL undetectable causes many co-morbidities [1–3]. The aim of this study is to correlate monocytes (m and NK cell activation levels, soluble markers and oxidative stress with clinical, biochemical and metabolic data in HIV-1 infected patients with VL≤50 copies (cp/mL on antiretroviral therapy. Materials and Methods: Multicentre, cross-sectional study in patients with VL≤50 cp/mL and on antiretroviral therapy by at least six months. We studied: activation/homing markers (CD38, HLA-DR, CCR-2, PDL-1 on inflammatory, intermediate, proinflammatory m; activatory receptors NKp30, NKp46 and HLA-DR on NK cells; soluble inflammatory (sCD14, adiponectina, MCP-1 and stress oxidative markers (dRoms, antiRoms. Univariate analyses are performed with non-parametric and Pearson tests. The significant correlations were adjusted for possible known confounding factors (smoking, Cytomegalovirus IgG serology, Raltegravir, Protease Inhibitor [PI] therapy and HCV-RNA with multivariate analysis. Results: In the 68 patients the positive correlation between age and antiRoms was significant also after adjustment for PI use (p=0.05. The% CD8+T was associated with% proinflammatory m (p=0.043 and with their expression of CCR2 mean fluorescence intensity (MFI (p=0.012. The% NKp46+ was positively correlated with CD4+T count (p=0.001. The fibrinogen was positively associated with dRoms (p=0.052 and the positive correlation between triglycerides and antiRoms has been confirmed (p<0.001; the impact of antiRoms on HDL/triglycerides ratio (p=0.006 was observed after adjustment for PI use. The BMI was associated with smoking (p=0.011. Only the maraviroc-treated patients showed minimal arterial pressure, fibrinogen and antiRoms lower (p=0.001, 0.004 e 0.006 and sCD14 values higher (p=0.029. Conclusions: Patients with long history of HIV infection and stable immunological and

  2. Acupuncture and the relaxation response for treating gastrointestinal symptoms in HIV patients on highly active antiretroviral therapy.

    Science.gov (United States)

    Chang, Bei-Hung; Sommers, Elizabeth

    2011-09-01

    To examine the effect of acupuncture and the relaxation response (RR) for treating gastrointestinal (GI) symptoms in HIV patients who are using highly active antiretroviral therapy (HAART). The authors conducted a 4-arm 2×2 double-blind randomised controlled trial in an acupuncture clinic in the USA. Sham acupuncture and health education were used as the control conditions of real acupuncture and RR elicitation, respectively. Enrolled patients were randomised to real acupuncture+RR (AR), sham acupuncture+RR (SR), real acupuncture+health education (AE) or sham acupuncture+health education (SE) study arm. Participants listened to CDs with RR-eliciting instructions or health education while receiving acupuncture intervention. Interventions were provided twice weekly for 4 weeks and once weekly for another 4 weeks. Participants used daily diaries to record GI symptom severity ratings (0-10). The authors estimated the intervention effect as the changes in symptom rating per intervention session increase using a mixed-effects regression model. A total of 130 people with HIV/AIDS who were on HAART and had persistent GI symptoms were enrolled and 115 started the study intervention. The AR group had greater intervention effects for loose stools symptoms than the other three groups (β=-0.149, -0.151 and -0.144, p value=0.013, 0.013 and 0.018 comparing AR to AE, SR and SE, respectively). The AR group also had significant intervention effects on reducing nausea symptoms when the intervention was given twice per week (β=-0.218, p=0.001). Our trial provided preliminary data demonstrating the potential synergistic effects of acupuncture and RR for treating GI symptoms in HIV patients on HAART.

  3. Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada

    DEFF Research Database (Denmark)

    Obel, Niels

    2016-01-01

    OBJECTIVES: To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure. DESIGN: Collaborative analysis of data from eight European and three Canadian cohorts. METHODS: Adults (N>20 000) who started triple ART between 199....... There was no difference in mortality between subtypes A, B and C after viral failure. CONCLUSION: Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors....

  4. Drug resistance mutations and genetic diversity in adults treated for HIV type 1 infection in Mauritania.

    Science.gov (United States)

    Fall-Malick, F-Zahra; Tchiakpé, Edmond; Ould Soufiane, Sid'Ahmed; Diop-Ndiaye, Halimatou; Mouhamedoune Baye, Abderrahmane; Ould Horma Babana, Abdallah; Touré Kane, Coumba; Lo, Baidy; Mboup, Souleymane

    2014-03-01

    The aim of this cross-sectional study was to evaluate the drug resistance mutationprofile observed in patients receiving antiretroviral therapy with virological failure and to document the HIV-1 genetic diversity in Mauritania. Eighty-six subjects were included and 65 samples were amplified successfully and sequenced. HIV-1 genotyping was performed using the Agence Nationale de Recherche sur le SIDA AC11 resistance procedure. The median treatment duration was 32 months (range: 6-88) and the median viral load, 5 log10 copies/ml (range: 3.13-7). Fifty-nine patients (90.8%) were on first line regimens including 32.0% (19/59) on triomune fixed-dose and six on second-line therapy with NonNucleoside Reverse Transcriptase plus a protease inhibitor. Forty-seven patients (72.3%) had at least one drug resistance mutation including 73.0% (43/59) on first-line therapy. For the second-line, one out of six patients presented resistance mutations and only one presented PI DRM. Overall, the most common DRMs detected were M184V/I (n = 32; 49.2%), K103N (n = 28; 43%), and Y181C (n = 13; 20%). Thymidine Analog Mutations (TAMs) were found in 26.0% (n = 17) of strains and the most common was T215Y (n = 11, 16.9%). Phylogenetic analysis revealed 17 HIV-1 variants with the predominance of CRF02_AG (n = 42; 64.6%). A high rate of DRM was found in this study and shows the potential need for a structured virological surveillance including viral load quantification and genotyping. Further studies may also be needed in regards to the great variability of HIV-1 strains in Mauritania. © 2013 Wiley Periodicals, Inc.

  5. Examining geographic and socio-economic differences in outpatient and inpatient consumer expenditures for treating HIV/AIDS in Nigeria

    Directory of Open Access Journals (Sweden)

    Obinna E Onwujekwe

    2016-02-01

    Full Text Available Introduction: The expenditures on treatment of HIV/AIDS to households were examined to quantify the magnitude of the economic burden of HIV/AIDS to different population groups in Nigeria. The information will also provide a basis for increased action towards a reduction of the economic burden on many households when accessing antiretroviral therapy (ART. Methods: A household survey was administered in three states, Adamawa, Akwa Ibom and Anambra, from the South-East, North-East and South-South zones of Nigeria, respectively. A pretested interviewer-administered questionnaire was used to collect data from a minimum sample of 1200 people living with HIV/AIDS (PLHIV. Data were collected on the medical and non-medical expenditures that patients incurred to treat HIV/AIDS for their last treatment episode within three months of the interview date. The expenditures were for outpatient visits (OPV and inpatient stays (IPS. The incidence of catastrophic health expenditure (CHE on ART treatment services was computed for OPV and IPS. Data were disaggregated by socio-economic status (SES and geographic location of the households. Results: The average OPV expenditures incurred by patients per OPV for HIV/AIDS treatment was US$6.1 with variations across SES and urban-rural residence. More than 95% of the surveyed households spent money on transportation to a treatment facility and over 70% spent money on food for OPV. For medical expenditures, the urbanites paid more than rural dwellers. Many patients incurred CHE during outpatient and inpatient visits. Compared to urban dwellers, rural dwellers incurred more CHE for outpatient (p=0.02 and inpatient visits (p=0.002. Conclusions: Treatment expenditures were quite high, inequitable and catastrophic in some instances, hence further jeopardizing the welfare of the households and the PLHIV. Strategically locating fully functional treatment centres to make them more accessible to PLHIV will largely reduce

  6. Examining geographic and socio-economic differences in outpatient and inpatient consumer expenditures for treating HIV/AIDS in Nigeria

    Science.gov (United States)

    Onwujekwe, Obinna E; Ibe, Ogochukwu; Torpey, Kwasi; Dada, Stephanie; Uzochukwu, Benjamin; Sanwo, Olusola

    2016-01-01

    Introduction The expenditures on treatment of HIV/AIDS to households were examined to quantify the magnitude of the economic burden of HIV/AIDS to different population groups in Nigeria. The information will also provide a basis for increased action towards a reduction of the economic burden on many households when accessing antiretroviral therapy (ART). Methods A household survey was administered in three states, Adamawa, Akwa Ibom and Anambra, from the South-East, North-East and South-South zones of Nigeria, respectively. A pretested interviewer-administered questionnaire was used to collect data from a minimum sample of 1200 people living with HIV/AIDS (PLHIV). Data were collected on the medical and non-medical expenditures that patients incurred to treat HIV/AIDS for their last treatment episode within three months of the interview date. The expenditures were for outpatient visits (OPV) and inpatient stays (IPS). The incidence of catastrophic health expenditure (CHE) on ART treatment services was computed for OPV and IPS. Data were disaggregated by socio-economic status (SES) and geographic location of the households. Results The average OPV expenditures incurred by patients per OPV for HIV/AIDS treatment was US$6.1 with variations across SES and urban-rural residence. More than 95% of the surveyed households spent money on transportation to a treatment facility and over 70% spent money on food for OPV. For medical expenditures, the urbanites paid more than rural dwellers. Many patients incurred CHE during outpatient and inpatient visits. Compared to urban dwellers, rural dwellers incurred more CHE for outpatient (p=0.02) and inpatient visits (p=0.002). Conclusions Treatment expenditures were quite high, inequitable and catastrophic in some instances, hence further jeopardizing the welfare of the households and the PLHIV. Strategically locating fully functional treatment centres to make them more accessible to PLHIV will largely reduce expenditures for travel

  7. No. 185-HIV Screening in Pregnancy.

    Science.gov (United States)

    Keenan-Lindsay, Lisa; Yudin, Mark H

    2017-07-01

    The purpose of this guideline is to provide recommendations to obstetric health care providers and to minimize practice variations for HIV screening, while taking provincial and territorial recommendations into account. The risk of transmission of HIV from mother to fetus is significant if the mother is not treated. The primary outcome of screening for and treating HIV in pregnancy is a marked decrease in the rate of vertical transmission of HIV from mother to fetus. Secondary outcomes include confirmation of HIV infection in the woman, which allows optimization of her health and long-term management. The Cochrane Library and Medline were searched for English-language articles published related to HIV screening and pregnancy. Additional articles were identified through the references of these articles. All study types were reviewed. Copyright © 2017. Published by Elsevier Inc.

  8. Daclatasvir plasma level and resistance selection in HIV patients with hepatitis C virus cirrhosis treated with daclatasvir, sofosbuvir, and ribavirin

    Directory of Open Access Journals (Sweden)

    Saverio G. Parisi

    2016-08-01

    Conclusions: Sub-optimal DCV drug levels allow the selection of resistance-associated variants and fail to contribute to antiviral activity. No definite reason for the low DCV level was found. Quantifying the drug is suggested in difficult-to-treat patients.

  9. HIV testing experiences and their implications for patient engagement with HIV care and treatment on the eve of 'test and treat'

    DEFF Research Database (Denmark)

    Wringe, Alison; Moshabela, Mosa; Nyamukapa, Constance

    2017-01-01

    Objective: In view of expanding ‘test and treat’ initiatives, we sought to elicit how the experience of HIV testing influenced subsequent engagement in HIV care among people diagnosed with HIV. Methods: As part of a multisite qualitative study, we conducted in-depth interviews in Uganda, South Af...

  10. Parameter Optimization for Enhancement of Ethanol Yield by Atmospheric Pressure DBD-Treated Saccharomyces cerevisiae

    Science.gov (United States)

    Dong, Xiaoyu; Yuan, Yulian; Tang, Qian; Dou, Shaohua; Di, Lanbo; Zhang, Xiuling

    2014-01-01

    In this study, Saccharomyces cerevisiae (S. cerevisiae) was exposed to dielectric barrier discharge plasma (DBD) to improve its ethanol production capacity during fermentation. Response surface methodology (RSM) was used to optimize the discharge-associated parameters of DBD for the purpose of maximizing the ethanol yield achieved by DBD-treated S. cerevisiae. According to single factor experiments, a mathematical model was established using Box-Behnken central composite experiment design, with plasma exposure time, power supply voltage, and exposed-sample volume as impact factors and ethanol yield as the response. This was followed by response surface analysis. Optimal experimental parameters for plasma discharge-induced enhancement in ethanol yield were plasma exposure time of 1 min, power voltage of 26 V, and an exposed sample volume of 9 mL. Under these conditions, the resulting yield of ethanol was 0.48 g/g, representing an increase of 33% over control.

  11. Optimization of WEDM process parameters using deep cryo-treated Inconel 718 as work material

    Directory of Open Access Journals (Sweden)

    Bijaya Bijeta Nayak

    2016-03-01

    Full Text Available The present work proposes an experimental investigation and optimization of various process parameters during taper cutting of deep cryo-treated Inconel 718 in wire electrical discharge machining process. Taguchi's design of experiment is used to gather information regarding the process with less number of experimental runs considering six input parameters such as part thickness, taper angle, pulse duration, discharge current, wire speed and wire tension. Since traditional Taguchi method fails to optimize multiple performance characteristics, maximum deviation theory is applied to convert multiple performance characteristics into an equivalent single performance characteristic. Due to the complexity and non-linearity involved in this process, good functional relationship with reasonable accuracy between performance characteristics and process parameters is difficult to obtain. To address this issue, the present study proposes artificial neural network (ANN model to determine the relationship between input parameters and performance characteristics. Finally, the process model is optimized to obtain a best parametric combination by a new meta-heuristic approach known as bat algorithm. The results of the proposed algorithm show that the proposed method is an effective tool for simultaneous optimization of performance characteristics during taper cutting in WEDM process.

  12. Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals

    Science.gov (United States)

    Winand, Raf; Theys, Kristof; Eusébio, Mónica; Aerts, Jan; Camacho, Ricardo J.; Gomes, Perpetua; Suchard, Marc A.; Vandamme, Anne-Mieke; Abecasis, Ana B.

    2015-01-01

    Objectives: Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs. Design: This is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients. Methods: The prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility. Results: Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers – above (PRO: D30N, N88D/S, L90 M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads. Conclusion: The significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with

  13. Increasing obesity in treated female HIV patients from Sub-Saharan Africa: Potential causes and possible targets for intervention

    Directory of Open Access Journals (Sweden)

    Claire eMcCormick

    2014-11-01

    Full Text Available Objectives To investigate changing nutritional demographics of treated HIV-1-infected patients and explore causes of obesity, particularly in women of African origin.Methods We prospectively reviewed nutritional demographics of clinic attenders at an urban European HIV clinic during four one-month periods at 3-yearly intervals (2001, 2004, 2007, and 2010 and in two consecutive whole-year reviews (2010-11 and 2011-12. Risk-factors for obesity were assessed by multiple linear regression. A sub-study of 50 HIV-positive African female patients investigated body-size/shape perception using numerical, verbal and pictorial cues. Results We found a dramatic rise in the prevalence of obesity (BMI >30 kg/m2, from 8.5% (2001 to 28% (2011-12 for all clinic attenders, of whom 86% were on antiretroviral treatment. Women of African origin were most affected, 49% being obese, with a further 32% overweight (BMI 25-30 kg/m2, in 2012. Clinical factors strongly associated with obesity included female gender, black African ethnicity, non-smoking, age and CD4 count (all P<0.001; greater duration of cART did not predict obesity. Individual weight-time trends mostly showed slow long-term progressive weight gain. Investigating body weight perception, we found that weight and adiposity were underestimated by obese subjects, who showed a greater disparity between perceived and actual adiposity (P<0.001. Obese subjects targeted more obese target ideal body shapes (P<0.01, but were less satisfied with their body shape overall (P=0.02. Conclusions Seropositive African women on antiretroviral treatment are at heightened risk of obesity. Although multifactorial, bodyweight perception represents a potential target for intervention.

  14. Human Resources for Treating HIV/AIDS: Are the Preventive Effects of Antiretroviral Treatment a Game Changer?

    Science.gov (United States)

    2016-01-01

    Shortages of human resources for treating HIV/AIDS (HRHA) are a fundamental barrier to reaching universal antiretroviral treatment (ART) coverage in developing countries. Previous studies suggest that recruiting HRHA to attain universal ART coverage poses an insurmountable challenge as ART significantly increases survival among HIV-infected individuals. While new evidence about ART’s prevention benefits suggests fewer infections may mitigate the challenge, new policies such as treatment-as-prevention (TasP) will exacerbate it. We develop a mathematical model to analytically study the net effects of these countervailing factors. Using South Africa as a case study, we find that contrary to previous results, universal ART coverage is achievable even with current HRHA numbers. However, larger health gains are possible through a surge-capacity policy that aggressively recruits HRHA to reach universal ART coverage quickly. Without such a policy, TasP roll-out can increase health losses by crowding out sicker patients from treatment, unless a surge capacity exclusively for TasP is also created. PMID:27716813

  15. Human Resources for Treating HIV/AIDS: Are the Preventive Effects of Antiretroviral Treatment a Game Changer?

    Science.gov (United States)

    Bärnighausen, Till; Bloom, David E; Humair, Salal

    2016-01-01

    Shortages of human resources for treating HIV/AIDS (HRHA) are a fundamental barrier to reaching universal antiretroviral treatment (ART) coverage in developing countries. Previous studies suggest that recruiting HRHA to attain universal ART coverage poses an insurmountable challenge as ART significantly increases survival among HIV-infected individuals. While new evidence about ART's prevention benefits suggests fewer infections may mitigate the challenge, new policies such as treatment-as-prevention (TasP) will exacerbate it. We develop a mathematical model to analytically study the net effects of these countervailing factors. Using South Africa as a case study, we find that contrary to previous results, universal ART coverage is achievable even with current HRHA numbers. However, larger health gains are possible through a surge-capacity policy that aggressively recruits HRHA to reach universal ART coverage quickly. Without such a policy, TasP roll-out can increase health losses by crowding out sicker patients from treatment, unless a surge capacity exclusively for TasP is also created.

  16. [Immune reconstitution syndrome due to BCG in HIV-treated children].

    Science.gov (United States)

    Miranda-Choque, Edwin; Candela-Herrera, Jorge; R Segura, Eddy; Farfán-Ramos, Sonia; Barriga, Aldo

    2012-01-01

    The objective of this study is to describe the clinical profile of the immune reconstitution syndrome due to Mycobacterium bovis Bacillus Calmette-Guérin (IRS-BCG) in children with HIV infection who receive highly active antiretroviral treatment (HAART) at Instituto Nacional de Salud del Niño de Lima (National Children's Health Institute of Lima), Peru. A case study was conducted, including 8 children with IRS-BCG, defined as the presence of regional lymphadenopathy or inflammation on the BCG vaccination site with at least one less logarithm in the viral load or immune improvement. All patients had AIDS (C3). The starting median age in HAART was 7.2 months and the event occurred 3 to 11 weeks after the treatment was started. 7 cases showed axillary adenitis. When compared with the Non IRS-BCG group, a significant association between the age at which HAART was started at one year, severe immunodepression, and increased viral load was found. It is concluded that IRS-BCG was related to a rapid clinical progression of the mother-to-child transmitted HIV/AIDS infection, severe immunosuppression and high viral load when the HAART began.

  17. Access to HIV care in the context of universal test and treat: challenges within the ANRS 12249 TasP cluster-randomized trial in rural South Africa

    Directory of Open Access Journals (Sweden)

    Mélanie Plazy

    2016-06-01

    test and treat coverage will require innovative interventions to support linkage to HIV care.

  18. STRike - characteristics of HIV-1-infected patients treated with a single-tablet regimen in daily clinical practice

    Directory of Open Access Journals (Sweden)

    S Esser

    2012-11-01

    Full Text Available The life-long antiretroviral treatment of HIV-1 infection requires effective and well tolerated medications complemented by high rates of adherence in order to achieve viral suppression, immunologic reconstitution and to prevent the development of resistance. Single-tablet regimens (STRs, combining a full antiretroviral regimen in one tablet taken once daily, have been designed to achieve high adherence and better long-term outcomes. “STRike” is the first cohort study, describing the use of various STRs in routine clinical practice in Germany. In this observational cohort study 800 participants will be included in 4 treatment arms, treated with the STRs of TDF/FTC/EFV (a retrospective and prospective arm, TDF/FTC/RPV or TDF/FTC/COBI/EVG after regulatory approval. Patients are followed for at least two years, and reasons for choice of medications and treatment satisfaction will be collected, in addition to safety, demographic, effectiveness data. To date 344 patients on TDF/FTC/EFV and 123 patients on TDF/FTC/RPV are being followed. In general, the spectrum of patients in the study reflects the German HIV-1 infected population with regards to gender (88%/89% male, age (median 40/38 years of age and mode of infection (71%/63% MSM. However, patients starting TDF/FTC/RPV are less progressed in their disease according to their CDC stage compared with patients on TDF/FTC/EFV (74.5% stage “A” vs. 53.2%. Patients starting TDF/FTC/RPV show less comorbidities (54% vs. 82% with a spectrum different from patients on TDF/FTC/EFV. Pre-existing neuropsychiatric comorbidities are relatively more common (10% more among patients starting TDF/FTC/RPV than TDF/FTC/EFV. The decision to use an STR is mostly driven by patient preference to start with a more convenient ART regimen (56% or to simplify their current ART regimen (75%. STRs aim to make treatment of HIV more convenient, more efficacious and more durable and by that allowing for earlier initiation of

  19. Ten-year incidence and risk factors of bone fractures in a cohort of treated HIV1-infected adults

    Science.gov (United States)

    Collin, Fidéline; Duval, Xavier; Lemoing, Vincent; Piroth, Lionel; Al Kaied, Firas; Massip, Patrice; Villes, Virginie; Chêne, Geneviève; Raffi, François

    2009-01-01

    In the ANRS CO8 APROCO-COPILOTE cohort of patients treated with combination antiretroviral therapy since 1997–1999, the incidence density of bone fractures was 3.3 for 1,000 patient-years (95% CI: 2.0–4.6). Rate was 2.9-fold (95% CI: 1.3–6.5) higher among patients with excessive alcohol consumption and 3.6-fold (95% CI: 1.6–8.1) higher in those with Hepatitis C virus (HCV) co-infection. Specific monitoring of HCV/HIV-coinfected patients and active promotion of alcohol cessation should be recommended for the prevention of bone fractures. PMID:19300202

  20. Vibration analysis and optimal design of multi-layer plates partially treated with the MR fluid

    Science.gov (United States)

    Eshaghi, Mehdi; Sedaghati, Ramin; Rakheja, Subhash

    2017-01-01

    The vibration characteristics of a sandwich plate partially treated with the Magneto-Rheological (MR) fluid are investigated numerically and experimentally considering different boundary conditions and intensities of the magnetic flux. A cantilevered sandwich plate consisting of an aluminum host layer with nine equal cavities for the MR fluid treatments and a constraining layer was fabricated for experimental characterizations and validations of the finite-element (FE) model. The dynamic responses of the untreated plate and the partially treated plate, where only one of the nine cavities in the core layer was filled with the MR fluid (MRF 132DG), were measured under harmonic excitation applied at the fixed support. The finite element model of the sandwich plate, developed using the classical plate theory (CPT) and first-order shear deformation theory (FSDT) is verified using the experimental data. The FE model considers the effect of slippage between the top and bottom layers of the structure. The validated FE model is subsequently used to investigate the effects of partial MR fluid treatments, magnetic flux intensity and boundary conditions on the dynamic response characteristics of the structure. The effect of shear deformation on the vibration properties of the MR sandwich plate is further highlighted. Finally, three optimization problems are formulated to identify optimal locations for the MR fluid treatments so as to maximize the variations in the natural frequencies and damping ratios in response to magnetic field. The solution of the optimization problem, attained using the genetic algorithm (GA) suggested that the MR fluid applied to locations with noticeable shear strain can maximize the stiffness variations and damping of the structure, significantly.

  1. (Sub-)Optimality of Treating Interference as Noise in the Cellular Uplink With Weak Interference

    KAUST Repository

    Gherekhloo, Soheil

    2015-11-09

    Despite the simplicity of the scheme of treating interference as noise (TIN), it was shown to be sum-capacity optimal in the Gaussian interference channel (IC) with very-weak (noisy) interference. In this paper, the two-user IC is altered by introducing an additional transmitter that wants to communicate with one of the receivers of the IC. The resulting network thus consists of a point-to-point channel interfering with a multiple access channel (MAC) and is denoted by PIMAC. The sum-capacity of the PIMAC is studied with main focus on the optimality of TIN. It turns out that TIN in its naive variant, where all transmitters are active and both receivers use TIN for decoding, is not the best choice for the PIMAC. In fact, a scheme that combines both time division multiple access and TIN (TDMA-TIN) strictly outperforms the naive-TIN scheme. Furthermore, it is shown that in some regimes, TDMA-TIN achieves the sum-capacity for the deterministic PIMAC and the sum-capacity within a constant gap for the Gaussian PIMAC. In addition, it is shown that, even for very-weak interference, there are some regimes where a combination of interference alignment with power control and TIN at the receiver side outperforms TDMA-TIN. As a consequence, on the one hand, TIN in a cellular uplink is approximately optimal in certain regimes. On the other hand, those regimes cannot be simply described by the strength of interference.

  2. Optimal sludge retention time for a bench scale MBR treating municipal sewage.

    Science.gov (United States)

    Pollice, A; Laera, G; Saturno, D; Giordano, C; Sandulli, R

    2008-01-01

    Membrane bioreactors allow for higher sludge concentrations and improved degradation efficiencies with respect to conventional activated sludge. However, in the current practice these systems are often operated under sub-optimal conditions, since so far no precise indications have yet been issued on the optimal operating conditions of MBR for municipal wastewater treatment. This paper reports some results of four years of operation of a bench scale membrane bioreactor where steady state conditions were investigated under different sludge retention times. The whole experimental campaign was oriented towards the investigation of optimal process conditions in terms of COD removal and nitrification, biomass activity and growth, and sludge characteristics. The membrane bioreactor treated real municipal sewage, and four different sludge ages were tested (20, 40, 60, and 80 days) and compared with previous data on complete sludge retention. The results showed that the the biology of the system, as assessed by the oxygen uptake rate, is less affected than the sludge physical parameters. In particular, although the growth yield was observed to dramatically drop for SRT higher than 80 days, the biological activity was maintained under all the tested conditions. These considerations suggest that high SRT are convenient in terms of limited excess sludge production without losses of the treatment capacity. Physical characteristics such as the viscosity and the filterability appear to be negatively affected by prolonged sludge retention times, but their values remain within the ranges normally reported for conventional activated sludge.

  3. Ready to Use Therapeutic Foods (RUTF improves undernutrition among ART-treated, HIV-positive children in Dar es Salaam, Tanzania

    Directory of Open Access Journals (Sweden)

    Sunguya Bruno F

    2012-08-01

    Full Text Available Abstract Background HIV/AIDS is associated with an increased burden of undernutrition among children even under antiretroviral therapy (ART. To treat undernutrition, WHO endorsed the use of Ready to Use Therapeutic Foods (RUTF that can reduce case fatality and undernutrition among ART-naïve HIV-positive children. However, its effects are not studied among ART-treated, HIV-positive children. Therefore, we examined the association between RUTF use with underweight, wasting, and stunting statuses among ART-treated HIV-positive children in Dar es Salaam, Tanzania. Methods This cross-sectional study was conducted from September-October 2010. The target population was 219 ART-treated, HIV-positive children and the same number of their caregivers. We used questionnaires to measure socio-economic factors, food security, RUTF-use, and ART-duration. Our outcome variables were underweight, wasting, and stunting statuses. Results Of 219 ART-treated, HIV-positive children, 140 (63.9% had received RUTF intervention prior to the interview. The percentages of underweight and wasting among non-RUTF-receivers were 12.4% and 16.5%; whereas those of RUTF-receivers were 3.0% (P = 0.006 and 2.8% (P = 0.001, respectively. RUTF-receivers were less likely to have underweight (Adjusted Odd Ratio (AOR =0.19, CI: 0.04, 0.78, and wasting (AOR = 0.24, CI: 0.07, 0.81, compared to non RUTF-receivers. Among RUTF receivers, children treated for at least four months (n = 84 were less likely to have underweight (P = 0.049, wasting (P = 0.049 and stunting (P  Conclusions Among HIV-positive children under ART, the provision of RUTF for at least four months was associated with low proportions of undernutrition status. RUTF has a potential to improve undernutrition among HIV-positive children under ART in the clinical settings in Dar es Salaam, Tanzania.

  4. Integrative Analysis of Immunological Data to Explore Chronic Immune T-Cell Activation in Successfully Treated HIV Patients

    Science.gov (United States)

    Picat, Marie-Quitterie; Pellegrin, Isabelle; Bitard, Juliette; Wittkop, Linda; Proust-Lima, Cécile; Liquet, Benoît; Moreau, Jean-François; Bonnet, Fabrice; Blanco, Patrick; Thiébaut, Rodolphe

    2017-01-01

    Objectives To unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes. Design Cross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France. Methods Patients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years. CIA was defined by the percentage of HLA-DR+/CD38+ among CD8+T-cells. Integrative analyses were performed using structural equation modelling (SEM). Results The main analysis was performed in 57 HLA-A*0201 positive patients, due to availability of percentages of actin-, vimentin-, lamin-specific CD8+T-cells (HLA-A2-restricted tests) to further characterize autoimmune response. Cytomegalovirus-induced response was assessed by Quantiferon and pp-65 ELISPOT. SEM revealed a direct effect of cytomegalovirus-induced response on CIA (standardized estimate βstd = 0.56, p-value = 0.0004). The effect of autoimmune-induced response on CIA was indirect through alpha-interferon pathway, assessed by expression levels of 5 alpha-interferon-stimulated genes ADAR, ISG15, IFIT1, Mx1 and OAS1 (effect of autoimmune response on alpha-interferon: βstd = 0.36, p-value = 0.0401; effect of alpha-interferon on CIA: βstd = 0.39, p-value = 0.0044). There was no direct effect of autoimmune-induced response on CIA (p-value = 0.3169). Microbial translocation as measured by 16SrDNA and sCD14 in plasma was not associated with CIA. Results were consistent in 142 patients in whom cytomegalovirus and auto-immunity responses were measured by Quantiferon and anti-nuclear antibodies, respectively. All analyses performed in HLA-A*0201 positive patients and in the overall population revealed a significant effect

  5. Puerperal brain cryptococcoma in an HIV-negative woman successfully treated with fluconazole: a case report

    Directory of Open Access Journals (Sweden)

    José Edward Hagan

    2014-04-01

    Full Text Available Cryptococcus spp. cerebral abscesses are uncommon in immunocompetent subjects. The recommended induction treatment is the administration of amphotericin B plus flucytosine combined with resection for lesions ≥3cm. In this paper, we describe an HIV-negative woman diagnosed with a large cryptococcoma in the immediate postpartum period. The lesion was not resected, and due to amphotericin B intolerance, she received an extended course of fluconazole monotherapy. There was no disease recurrence during the 4 years of follow-up. The abrupt onset of her symptoms following delivery suggests that she developed a postpartum immune reconstitution syndrome. This case also demonstrates that in specific situations fluconazole monotherapy can be attempted in immunocompetent patients with cryptococcoma.

  6. 'I am treated well if I adhere to my HIV medication'

    DEFF Research Database (Denmark)

    Ondenge, Kenneth; Renju, Jenny; Bonnington, Oliver

    2017-01-01

    Objectives: The nature of patient–provider interactions and communication is widely documented to significantly impact on patient experiences, treatment adherence and health outcomes. Yet little is known about the broader contextual factors and dynamics that shape patient–provider interactions...... collected using topic guides that explored patient testing and antiretroviral therapy treatment journeys. Thematic analysis was conducted, aided by NVivo V.8.0 software. Results: Our analysis revealed an array of inter-related contextual factors and power dynamics shaping patient–provider interactions....... These included (1) participants’ perceptions of roles and identities of ‘self’ and ‘other’; (2) conformity or resistance to the ‘rules of HIV service engagement’ and a ‘patient-persona’; (3) the influence of significant others’ views on service provision; and (4) resources in health services. We observed...

  7. Status and Prospect in Preventing and Treating HIV/AIDS with Traditional Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    WU Gang

    2006-01-01

    @@ AIDS, as a viral infectious disease, is extremely rapid in transmission, severe in progress, serious in prognosis so that no other disease can be compared with it in the past. Accordingly,the need of prevention and treatment of AIDS has become more and more urgent.In the National Meeting on Exchange of Experience of Demonstration Area for Comprehensive Prevention and Treatment of AIDS recently held in Henan Province, Wang Long-de,the director of office of the Working Committee of AIDS Prevention and Treatment of the State Department and the Vice-minister of Health, said that until August 2005, there has been 132 545 cases of HIV carrier. Of the 30 158 cases infected with AIDS in China, 7 643 cases have already died.

  8. 提高对HIV-1急性感染和HIV-2诊断能力的检测策略%Optimization of Laboratory HIV Testing Algorithm for Acute HIV Infection and HIV-2 Diagnosis

    Institute of Scientific and Technical Information of China (English)

    李敬云

    2016-01-01

    针对多年使用的艾滋病病毒(HIV)检测策略存在的问题,以及目前的检测技术研发和应用状况,美国疾病控制和预防中心在2014年6月提出了新的HIV检测策略,联合使用HIV抗原和抗体检测试剂、能够区分HIV-1和HIV-2抗体的诊断试剂以及HIV-1核酸定性诊断试剂,提高对HIV-1急性感染和HIV-2的检出效能,同时减少需要随访的不确定结果,缩短等待时间.文章对这个检测策略进行了全面介绍,并提出制定适合我国的HIV检测策略的建议.

  9. EFFICACY AND SAFETY OF A MONOCLONAL PURIFIED FACTOR-VIII CONCENTRATE - 5-YEAR FOLLOW-UP IN PREVIOUSLY TREATED HIV-NEGATIVE HEMOPHILIACS

    NARCIS (Netherlands)

    SMID, WM; VANDERMEER, J; HALIE, MR

    1995-01-01

    The efficacy and safety of a monoclonal purified factor VIII concentrate (Hemofil M) were assessed in a historically controlled study in 22 HIV-negative patients with haemophilia A, previously treated with various concentrates. Data from 5 years of follow-up were compared with those from the precedi

  10. Efficacy and safety of a monoclonal purified factor-VIII concentrate - 5-year follow-up in previously treated HIV-negative hemophiliacs

    NARCIS (Netherlands)

    Smid, W. M.; van der Meer, J.; Halie, M. R.

    1995-01-01

    The efficacy and safety of a monoclonal purified factor VIII concentrate (Hemofil M) were assessed in a historically controlled study in 22 HIV-negative patients with haemophilia A, previously treated with various concentrates. Data from 5 years of follow-up were compared with those from the

  11. Site-specific differences in T cell frequencies and phenotypes in the blood and gut of HIV-uninfected and ART-treated HIV+ adults.

    Science.gov (United States)

    Yukl, Steven A; Shergill, Amandeep K; Girling, Valerie; Li, Qingsheng; Killian, Maudi; Epling, Lorrie; Li, Peilin; Kaiser, Philipp; Haase, Ashley; Havlir, Diane V; McQuaid, Kenneth; Sinclair, Elizabeth; Wong, Joseph K

    2015-01-01

    Gastrointestinal T lymphocytes are critical for mucosal immunity and HIV pathogenesis, yet little is known about normal T cell numbers and phenotypes in different regions of the gut, or the degree to which ART can restore levels to those of HIV-uninfected individuals. To investigate these questions, we measured T cell frequencies and markers of memory, activation, anergy, and homing in the blood, ileum, and rectum of HIV- and ART-suppressed HIV+ adults. In HIV- individuals, T cell frequencies and phenotypes differed significantly between sites. Compared to HIV- adults, HIV+ adults had lower absolute CD4+T cell counts in the ileal lamina propria and lower relative CD4+T cell counts in the blood and ileum. In the gut, HIV+ adults had a higher proportion of CD38+ CD4+T cells, a lower proportion of terminally-differentiated effector cells, and, in the rectum, a higher proportion of CTLA-4+ CD4+T cells. In HIV+ individuals, relative CD4+T cell numbers in the ileum correlated with the proportion of CTLA-4+ CD4+T cells, whereas in the rectum, they tended to correlate with the proportion of circulating CD4+T cells expressing α4β7 or CCR6. Mechanisms of T cell reconstitution may differ throughout the gut, with homing contributing more in the rectum while ileal reconstitution is associated with mucosal CD4+T cell anergy.

  12. Site-specific differences in T cell frequencies and phenotypes in the blood and gut of HIV-uninfected and ART-treated HIV+ adults.

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    Steven A Yukl

    Full Text Available Gastrointestinal T lymphocytes are critical for mucosal immunity and HIV pathogenesis, yet little is known about normal T cell numbers and phenotypes in different regions of the gut, or the degree to which ART can restore levels to those of HIV-uninfected individuals. To investigate these questions, we measured T cell frequencies and markers of memory, activation, anergy, and homing in the blood, ileum, and rectum of HIV- and ART-suppressed HIV+ adults. In HIV- individuals, T cell frequencies and phenotypes differed significantly between sites. Compared to HIV- adults, HIV+ adults had lower absolute CD4+T cell counts in the ileal lamina propria and lower relative CD4+T cell counts in the blood and ileum. In the gut, HIV+ adults had a higher proportion of CD38+ CD4+T cells, a lower proportion of terminally-differentiated effector cells, and, in the rectum, a higher proportion of CTLA-4+ CD4+T cells. In HIV+ individuals, relative CD4+T cell numbers in the ileum correlated with the proportion of CTLA-4+ CD4+T cells, whereas in the rectum, they tended to correlate with the proportion of circulating CD4+T cells expressing α4β7 or CCR6. Mechanisms of T cell reconstitution may differ throughout the gut, with homing contributing more in the rectum while ileal reconstitution is associated with mucosal CD4+T cell anergy.

  13. Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial.

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    Christina S Polyak

    2016-01-01

    Full Text Available Cotrimoxazole (CTX prophylaxis is recommended by the World Health Organization (WHO for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART. The threshold for CTX discontinuation following ART is undefined in resource-limited settings.Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥ 18 mo with CD4 count > 350 cells/mm3 in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea and mortality. Incidence rate ratios (IRRs were estimated using Poisson regression. Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72% were women, and 442 (88% reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52-3.38; p < 0.001, driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52-241.02; p = 0.001. Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82-2.27, and IRR = 1.43, 95% CI 0.54-3.75, respectively. Study limitations include a lack of placebo and a lower incidence of morbidity events than expected.CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence. These data support the 2014 WHO CTX

  14. Risk factors for intestinal parasitosis among antiretroviral-treated HIV/AIDS patients in Ethiopia.

    Science.gov (United States)

    Mahmud, Mahmud Abdulkader; Bezabih, Afework Mulugeta; Gebru, Rezene Berhe

    2014-10-01

    Summary A cross-sectional survey was conducted to determine the risk factors associated with intestinal parasitosis in HIV/AIDS patients receiving antiretroviral therapy (ART). Socio-demographic information was collected and faecal samples were analysed from 384 randomly selected patients on ART. Data on CD4+ T-cell counts and World Health Organization clinical staging were obtained from the medical records at the hospital. The overall prevalence of intestinal parasitosis was 56% (95% confidence interval [CI]: 51% to 61%). No opportunistic intestinal parasites or Schistosoma haematobium eggs were detected. Unavailability of latrine and lack of hand washing with soap were associated with Entamoeba histolytica/dispar (adjusted odds ratio [AOR], 2.75; 95% CI: 1.77 to 4.27 and AOR, 2.67; 95% CI: 1.60 to 4.44, respectively) and Giardia lamblia (AOR, 2.08; 95% CI: 1.08 to 3.99 and AOR, 2.46; 95% CI: 1.06 to 5.75, respectively) infections. Intestinal parasitosis was significantly associated with low CD4 cell count (p = 0.002). In contrast, intestinal parasitic infections were not associated (p > 0.05) with the World Health Organization disease staging. In summary, poor personal hygiene and sanitation practice contributed to the high prevalence of intestinal parasitosis. Routine diagnosis for intestinal parasitic infections should be performed in patients attending ART clinics in this setting.

  15. Multicentric Castleman's disease and Kaposi's sarcoma in a cyclosporin treated, HIV-1 negative patient: case report

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    van Oers MHJ

    2003-12-01

    Full Text Available Abstract Background Multicentric Castleman's disease (MCD is a rare disease, but is more frequent in AIDS patients. MCD has only been reported twice before in patients receiving immunosuppressive therapy after renal transplantation, and never in patients receiving immunosuppressive therapy without transplantation. About half of the cases of MCD are human herpesvirus 8 (HHV8 – related, in contrast to Kaposi's sarcoma, a more common complication arising after immunosuppression, where the virus is found in virtually all cases. Case presentation We report a HIV-1 negative, non-transplant patient who developed HHV8-associated multicentric Castleman's disease and Kaposi's sarcoma after 17 years of immunosuppressive treatment with cyclosporin A for a minimal change nephropathy. Chemotherapy with liposomal doxorubicin resolved both symptoms of multicentric Castleman's disease and Kaposi's sarcoma in this patient. A concomitant decline in the HHV8 viral load in serum/plasma, as determined by a quantitative real-time PCR assay, was observed. Conclusions Multicentric Castleman's disease can be a complication of cyclosporin A treatment. Both multicentric Castleman's disease and Kaposi's sarcoma in this patient were responsive to liposomal doxorubicin, the treatment of choice for Kaposi's sarcoma at the moment, again suggesting a common mechanism linking both disorders, at least for HHV8-positive multicentric Castleman's disease and Kaposi's sarcoma. HHV8 viral load measurements can be used to monitor effectiveness of therapy.

  16. Paclitaxel and Carboplatin in Treating Patients With Metastatic or Recurrent Solid Tumors and HIV Infection

    Science.gov (United States)

    2017-08-23

    HIV Infection; Recurrent Anal Cancer; Recurrent Breast Cancer; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Anal Cancer; Stage IV Breast Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Unspecified Adult Solid Tumor, Protocol Specific

  17. Process optimization of biogas energy production from cow dung with alkali pre-treated coffee pulp.

    Science.gov (United States)

    Selvankumar, T; Sudhakar, C; Govindaraju, M; Selvam, K; Aroulmoji, V; Sivakumar, N; Govarthanan, M

    2017-08-01

    Biogas production from cow dung with co-substrate agricultural waste is one of the most demanding technologies for generating energy in a sustainable approach considering eco-friendly. In the present study, coffee pulp (CP) was pre-treated with 1% NaOH and combined with various proportions of cow dung (CD) to explore its biogas producing potentiality. The optimization of the process was studied using Response surface methodology. Statistics based on 3-D plots were generated to evaluate the changes in the response surface and to understand the relationship between the biogas yield and other parameters. The highest methane production (144 mL/kg) was achieved after 90 h of incubation with 1:3 of CP and CD at 40 °C. Gas chromatography analyzes the chemical compositions of the generated biogas and its post combustion emissions. The chemical composition of the substrates before digestion and after fermentation (biogas spent sludge) were measured in terms of fiber content and the values were noted as, total solids (0.53%), ash content (9.2%), volatile fatty acid (100 mg/L), organic carbon (46%) and a total carbohydrate (179 mg/g). The results of the optimization of biogas production presented in this work found to have significance with the process parameters. The outcome of the study has supported the fact of conventional combustion technology that has to be upgraded to prevent these hazardous emissions into the atmosphere.

  18. Nitrogen removal optimization in a sequencing batch reactor treating sanitary landfill leachate.

    Science.gov (United States)

    Spagni, Alessandro; Lavagnolo, M Cristina; Scarpa, Carlotta; Vendrame, Paola; Rizzo, Andrea; Luccarini, Luca

    2007-05-01

    Biological nitrogen removal via nitrite may represent a promising process for the optimization of nitrogen removal, in particular in the presence of a low biodegradable COD/TKN ratio. In the present study a lab-scale sequencing batch reactor (SBR) was monitored for approximately 2 years to evaluate the use of dissolved oxygen (DO), pH and oxidation-reduction potential (ORP) as monitoring parameters in order to optimize nitrogen removal via nitrite from leachate generated in old sanitary landfills. The SBR manifested a nitrification efficiency exceeding 99% whereas, due to the low biodegradability of the organic matter presents in the leachates, COD removal reached approximately 40% and the addition of external COD was required to accomplish denitrification process. Moreover, the results demonstrate that DO, pH and ORP are reliable parameters for use in the monitoring of nitritation and denitritation processes in SBRs treating landfill leachates. Through manual modification of the length of the SBR phases to achieve nitrogen removal via nitrite, the nitritation and denitritation processes were rendered unstable leading to the saving of 20% in addition of external COD, almost half the theoretically achievable value. Furthermore, the low dissolved oxygen concentration applied during the oxic phases in an attempt to increase the nitritation process would appear to cause the settling characteristics of the activated sludge to deteriorate.

  19. Optimizing Single Agent Panitumumab Therapy in Pre-Treated Advanced Colorectal Cancer

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    Giampietro Gasparini

    2014-09-01

    Full Text Available PURPOSE: To improve the selection of advanced colorectal cancer patients to panitumumab by optimizing the assessment of RAS (KRAS-NRAS mutations. EXPERIMENTAL DESIGN: Using a centralized pyrosequencing RAS assay, we analyzed the tumors of 94 patients, wild-type for KRAS mutations (codons 12 to 13 by Sanger sequencing (SS, treated with panitumumab. RESULTS: By SS analysis, 94 (62% of 152 patients were wild-type and their objective response rate to panitumumab was 17%. We first optimized the KRAS test, by performing an accurate tissue-dissection step followed by pyrosequencing, a more sensitive method, and found further mutations in 12 (12.8% cases. Secondly, tumors were subjected to RAS extension analysis (KRAS, exons 3 to 4; NRAS exons 2 to 4 by pyrosequencing that allowed to identify several rare mutations: KRAS codon 61, 5.3%; codon 146, 5.3%; NRAS, 9.5%. Overall, RAS mutation rate was 32.9%. All patients with additional RAS mutations had progressive or stable disease, except 3 patients with mutations at codon 61 of KRAS or NRAS who experienced partial (2 cases or complete response. By excluding from the analysis 11 cases with mutations at codons 61, no patient was responsive to treatment (P = .021. RAS wild-type versus RAS mutated cases had a significantly better time to progression (P = .044, that resulted improved (p = .004 by excluding codon 61 mutations. CONCLUSION: This study shows that by optimizing the RAS test it is possible to significantly improve the identification of patients who do not gain benefit of panitumumab. Prospective studies are warranted to determine the clinical significance of rare mutations.

  20. Optimizing the Dyeing Process of Alkali-Treated Polyester Fabric with Dolu Natural Dye

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    M.F. Shahin

    2014-06-01

    Full Text Available An attempt has been made to optimize the process of dyeing polyester (PET fabric with natural dyes. Polyester has been first treated with NaOH solution in order to study its impact on the dyeability to the natural dye. The required and used colour component was extracted from a natural plant, namely: Rhubarb; Rheum officinale. The chemical structure of the used colouring matter is observed to have all the characteristics of a typical disperse dye. The colour strength of PET fabric was noticed to increase as a result of alkali treatment which may be attributed to the alteration in the hydrophobicity of polyester fibre. The most effective parameters that may affect the dye uptake of the natural dye on alkali-treated PET fabric and the final dyeing properties including dye bath pH, dyeing temperature and time were studied in details. The behaviour of the selected and used natural dye was found to be similar to that of disperse dyes. Addition of salicylic acid to the dye bath accelerated the rate of dyeing and subsequently higher colour strength was attained. Non- ionic dispersing agent was also used to ensure better dyeing uniformity and higher dispersion stability of dye liquor.

  1. Physiochemical Changes and Optimization of Phosphate-Treated Shrimp (Litopenaeus vannamei ) Using Response Surface Methodology.

    Science.gov (United States)

    Omar, Saiah Djebbour; Yang, Je-Eun; Oh, Sang-Cheol; Kim, Dae-Wook; Lee, Yang-Bong

    2016-03-01

    The objective of this study was to determine the factors responsible for the changed physiochemical properties of unpeeled shrimp treated in cold phosphate solution (2~4°C) with the intervention of 4 factors: phosphate concentration, dipping time, rotation speed, and volume of brine solution. Response surface analysis was used to characterize the effect of the phosphate treatment on shrimps by running 33 treatments for optimizing the experiment. For each treatment, phosphate amount, moisture content, and weight gain were measured. The results showed that phosphate concentration is the most important factor than other factors for facilitating phosphate penetration in the meat of the shrimp and for getting the best result. The optimum condition of phosphate-treated shrimp in this study was 110 to 120 min dipping time, 500 to 550 mL brine solution for 100 g shrimp sample, and 190 to 210 rpm agitation speed. The studied conditions can be applied in fisheries and other food industries for good phosphate treatments.

  2. The use of ozone-treated blood in the therapy of HIV infection and immune disease: a pilot study of safety and efficacy.

    Science.gov (United States)

    Garber, G E; Cameron, D W; Hawley-Foss, N; Greenway, D; Shannon, M E

    1991-08-01

    The use of ozone therapy is reported to be effective in a variety of viral illnesses, including HIV disease. We performed a phase I study of ozone blood treatments in 10 patients in whom no significant toxicity was observed. Three patients with moderate immunodeficiency showed improvement in surrogate markers of HIV-associated immune disease. A phase II controlled and randomized double-blinded study was initiated comparing reinjection of ozone-treated blood, and reinjection of unprocessed blood for 8 weeks, followed by a 4-week observation period. Ozone had no significant effect on hematologic, biochemical or clinical toxicity when compared with placebo. CD4 cell count, interleukin-2, gamma-interferon, beta 2-microglobulin, neopterin and p24 antigen were also unaffected by both treatment arms. In conclusion, ozone therapy does not enhance parameters of immune activation nor does it diminish measureable p24 antigen in HIV-infected individuals.

  3. Excellent clinical outcomes and retention in care for adults with HIV-associated Kaposi sarcoma treated with systemic chemotherapy and integrated antiretroviral therapy in rural Malawi

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    Michael E Herce

    2015-05-01

    Full Text Available Introduction: HIV-associated Kaposi sarcoma (HIV-KS is the most common cancer in Malawi. In 2008, the non-governmental organization, Partners In Health, and the Ministry of Health established the Neno Kaposi Sarcoma Clinic (NKSC to treat HIV-KS in rural Neno district. We aimed to evaluate 12-month clinical outcomes and retention in care for HIV-KS patients in the NKSC, and to describe our implementation model, which featured protocol-guided chemotherapy, integrated antiretroviral therapy (ART and psychosocial support delivered by community health workers. Methods: We conducted a retrospective cohort study using routine clinical data from 114 adult HIV-KS patients who received ART and ≥1 chemotherapy cycle in the NKSC between March 2008 and February 2012. Results: At enrolment 97% of patients (n/N=103/106 had advanced HIV-KS (stage T1. Most patients were male (n/N=85/114, 75% with median age 36 years (interquartile range, IQR: 29–42. Patients started ART a median of 77 days prior to chemotherapy (IQR: 36–252, with 97% (n/N=105/108 receiving nevirapine/lamivudine/stavudine. Following standardized protocols, we treated 20 patients (18% with first-line paclitaxel and 94 patients (82% with bleomycin plus vincristine (BV. Of the 94 BV patients, 24 (26% failed to respond to BV requiring change to second-line paclitaxel. A Division of AIDS grade 3/4 adverse event occurred in 29% of patients (n/N=30/102. Neutropenia was the most common grade 3/4 event (n/N=17/102, 17%. Twelve months after chemotherapy initiation, 83% of patients (95% CI: 74–89% were alive, including 88 (77% retained in care. Overall survival (OS at 12 months did not differ by initial chemotherapy regimen (p=0.6. Among patients with T1 disease, low body mass index (BMI (adjusted hazard ratio, aHR=4.10, 95% CI: 1.06–15.89 and 1 g/dL decrease in baseline haemoglobin (aHR=1.52, 95% CI: 1.03–2.25 were associated with increased death or loss to follow-up at 12 months. Conclusions

  4. Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART

    Science.gov (United States)

    O'Sullivan, Cathal E.; Peng, RongSheng; Cole, Kelly Stefano; Montelaro, Ronald C.; Sturgeon, Timothy; Jenson, Hal B.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

    2002-01-01

    Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months. Copyright 2002 Wiley-Liss, Inc.

  5. Vγ9Vδ2 T-Cell Polyfunctionality Is Differently Modulated in HAART-Treated HIV Patients according to CD4 T-Cell Count.

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    Rita Casetti

    Full Text Available Alteration of γδ T-cell distribution and function in peripheral blood is among the earliest defects during HIV-infection. We asked whether the polyfunctional response could also be affected, and how this impairment could be associated to CD4 T-cell count. To this aim, we performed a cross-sectional study on HIV-infected individuals. In order to evaluate the polyfunctional-Vγ9Vδ2 T-cell response after phosphoantigen-stimulation, we assessed the cytokine/chemokine production and cytotoxicity by flow-cytometry in HAART-treated-HIV+ persons and healthy-donors. During HIV-infection Vγ9Vδ2-polyfunctional response quality is affected, since several Vγ9Vδ2 T-cell subsets resulted significantly lower in HIV+ patients in respect to healthy donors. Interestingly, we found a weak positive correlation between Vγ9Vδ2 T-cell-response and CD4 T-cell counts. By dividing the HIV+ patients according to CD4 T-cell count, we found that Low-CD4 patients expressed a lower number of two Vγ9Vδ2 T-cell subsets expressing MIP-1β in different combinations with other molecules (CD107a/IFNγ in respect to High-CD4 individuals. Our results show that the Vγ9Vδ2 T-cell-response quality in Low-CD4 patients is specifically affected, suggesting a direct link between innate Vγ9Vδ2 T-cells and CD4 T-cell count. These findings suggest that Vγ9Vδ2 T-cell quality may be indirectly influenced by HAART therapy and could be included in a new therapeutical strategy which would perform an important role in fighting HIV infection.

  6. Vγ9Vδ2 T-Cell Polyfunctionality Is Differently Modulated in HAART-Treated HIV Patients according to CD4 T-Cell Count.

    Science.gov (United States)

    Casetti, Rita; De Simone, Gabriele; Sacchi, Alessandra; Rinaldi, Alessandra; Viola, Domenico; Agrati, Chiara; Bordoni, Veronica; Cimini, Eleonora; Tumino, Nicola; Besi, Francesca; Martini, Federico

    2015-01-01

    Alteration of γδ T-cell distribution and function in peripheral blood is among the earliest defects during HIV-infection. We asked whether the polyfunctional response could also be affected, and how this impairment could be associated to CD4 T-cell count. To this aim, we performed a cross-sectional study on HIV-infected individuals. In order to evaluate the polyfunctional-Vγ9Vδ2 T-cell response after phosphoantigen-stimulation, we assessed the cytokine/chemokine production and cytotoxicity by flow-cytometry in HAART-treated-HIV+ persons and healthy-donors. During HIV-infection Vγ9Vδ2-polyfunctional response quality is affected, since several Vγ9Vδ2 T-cell subsets resulted significantly lower in HIV+ patients in respect to healthy donors. Interestingly, we found a weak positive correlation between Vγ9Vδ2 T-cell-response and CD4 T-cell counts. By dividing the HIV+ patients according to CD4 T-cell count, we found that Low-CD4 patients expressed a lower number of two Vγ9Vδ2 T-cell subsets expressing MIP-1β in different combinations with other molecules (CD107a/IFNγ) in respect to High-CD4 individuals. Our results show that the Vγ9Vδ2 T-cell-response quality in Low-CD4 patients is specifically affected, suggesting a direct link between innate Vγ9Vδ2 T-cells and CD4 T-cell count. These findings suggest that Vγ9Vδ2 T-cell quality may be indirectly influenced by HAART therapy and could be included in a new therapeutical strategy which would perform an important role in fighting HIV infection.

  7. Optimized Infectivity of the Cell-Free Single-Cycle Human Immunodeficiency Viruses Type 1 (HIV-1 and Its Restriction by Host Cells.

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    Jin H Kim

    Full Text Available The infectivity of retroviruses such as HIV-1 in plasma or cultured media is less than 0.1% in general, the mechanisms of which are not yet fully understood. One possible explanation among others is the potential presence of large numbers of defective virions in a virus pool, which limits the apparent infectivity of HIV virions. To test this hypothesis, we have varied the culture conditions used to generate single-cycle HIV-1 virions. Among these culture variables, virion harvest time, media change after transfection, and envelope plasmid input can all improve HIV-1 infectivity by reducing the number of defective virions. A harvest time of 18-24 hours post transfection as opposed to 48 hours, and a media change six hours post transfection both improve viral infectivity. An optimal quantity of envelope plasmid input during transfection was also found. Collectively, these conditions increased the infectivity of HIV-1 virions by sevenfold compared to normally reported values in TZM-bl indicator cell lines. These conditions also increased the infectivity of HIV-1 in CD4(+ T cells, suggesting that these conditions work by increasing the intrinsic infectivity of a virus pool. Nevertheless, these improvements on virion infectivity were marginal compared to the impact of host cells on HIV infection, which can decrease the apparent infectivity by 19-fold even for the most optimized viruses. These results suggest that the infectivity of HIV-1 virions can be optimized by reducing the number of defective virions; however, viral-cell interactions may pose a major barrier for HIV-1 infectivity.

  8. Accurate episomal HIV 2-LTR circles quantification using optimized DNA isolation and droplet digital PCR

    OpenAIRE

    Eva Malatinkova; Maja Kiselinova; Pawel Bonczkowski; Wim Trypsteen; Peter Messiaen; Jolien Vermeire; Bruno Verhasselt; Karen Vervisch; Linos Vandekerckhove; Ward De Spiegelaere

    2014-01-01

    Introduction: In HIV-infected patients on combination antiretroviral therapy (cART), the detection of episomal HIV 2-LTR circles is a potential marker for ongoing viral replication. Quantification of 2-LTR circles is based on quantitative PCR or more recently on digital PCR assessment, but is hampered due to its low abundance. Sample pre-PCR processing is a critical step for 2-LTR circles quantification, which has not yet been sufficiently evaluated in patient derived samples. Materials and M...

  9. Quality of life of people living with HIV/AIDS treated by the specialized service in Vitória-ES, Brazil.

    Science.gov (United States)

    Soares, Gabriella Barreto; Garbin, Cléa Adas Saliba; Rovida, Tânia Adas Saliba; Garbin, Artênio José Ísper

    2015-04-01

    The aim of this study is to establish the factors that influence the quality of life of people living with HIV/AIDS being treated at a specialized public service. The participants answered the questionnaire on sociodemographic conditions, issues related to HIV and daily habits. The quality of life was analyzed using the HIV/AIDS-targeted quality of life (HAT-QoL) instrument with 42 items divided into 9 fields: General Activity, Sexual Activity, Confidentiality Concerns, Health Concerns, Financial Concerns, HIV Awareness, Satisfaction with Life, Issues related to Medication and Trust in the Physician. Bivariate and multiple linear regressions were performed. Of the participants, 53.1% were women and had a mean age of 42 years. In analyzing the quality of life, the HAT-QoL domain with the lowest average was Financial Concerns (39.4), followed by Confidentiality Concerns (43.2), Sexual Activity (55.2) and Health Concerns (62. 88). There was an association between the variables: not being gainfully employed (p black (p = 0.045) and alcohol consumption (p = 0.041) with the worst quality of life scores. Inadequate socioeconomic and health conditions had a negative impact on the quality of life of people with HIV/AIDS.

  10. Quality of life of people living with HIV/AIDS treated by the specialized service in Vitória-ES, Brazil

    Directory of Open Access Journals (Sweden)

    Gabriella Barreto Soares

    2015-04-01

    Full Text Available The aim of this study is to establish the factors that influence the quality of life of people living with HIV/AIDS being treated at a specialized public service. The participants answered the questionnaire on sociodemographic conditions, issues related to HIV and daily habits. The quality of life was analyzed using the HIV/AIDS-targeted quality of life (HAT-QoL instrument with 42 items divided into 9 fields: General Activity, Sexual Activity, Confidentiality Concerns, Health Concerns, Financial Concerns, HIV Awareness, Satisfaction with Life, Issues related to Medication and Trust in the Physician. Bivariate and multiple linear regressions were performed. Of the participants, 53.1% were women and had a mean age of 42 years. In analyzing the quality of life, the HAT-QoL domain with the lowest average was Financial Concerns (39.4, followed by Confidentiality Concerns (43.2, Sexual Activity (55.2 and Health Concerns (62. 88. There was an association between the variables: not being gainfully employed (p < 0.001, being mulatto or black (p = 0.045 and alcohol consumption (p = 0.041 with the worst quality of life scores. Inadequate socioeconomic and health conditions had a negative impact on the quality of life of people with HIV/AIDS.

  11. Optimizing electrocoagulation and electro-Fenton process for treating car wash wastewater

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    Seyyedali Mirshahghassemi

    2017-02-01

    Full Text Available Background: Car wash wastewater contains several contaminants such as organic matter, oil, grease, detergents and phosphates, all of which are harmful for the environment. In this study, the application of electrocoagulation (EC to treat car wash wastewater has been studied, and the operating parameters optimized. The electro-Fenton (EF for further contaminant removal was also investigated. Methods: In EC process, the effect of pH, current density, and the reaction time of the removal efficiency of chemical oxygen demand (COD, phosphate, and turbidity were investigated using the response surface methodology (RSM. The electrochemical cell consisted of four iron electrodes that were connected to a power supply using a monopolar arrangement. In the EF process, the effect of pH, reaction time, and hydrogen peroxide concentration on COD removal efficiency were probed. Results: The optimum pH, current density, and the reaction time for the EC process were 7.3, 4.2 mA cm-2 and 20.3 minutes, respectively. Under these conditions, the COD, phosphate, and turbidity removal percentages were 80.8%, 94.9% and 85.5%, respectively, and the specific energy consumption was 1.5 kWh m-3. For the EF process, the optimum pH, reaction time, current and hydrogen peroxide dosage were 3, 10 minutes, 2 A and 500 mg L-1, respectively. The EF showed higher COD removal efficiency (85.6% with a lower specific energy consumption (0.5 kWh m-3 and reaction time compared to the EC. Conclusion: This study shows that both EC and EF can effectively treat car wash wastewater with high removal efficiency within a short reaction time.

  12. Lost opportunities to identify and treat HIV-positive patients: results from a baseline assessment of provider-initiated HIV testing and counselling (PITC) in Malawi.

    Science.gov (United States)

    Ahmed, Saeed; Schwarz, Monica; Flick, Robert J; Rees, Chris A; Harawa, Mwelura; Simon, Katie; Robison, Jeff A; Kazembe, Peter N; Kim, Maria H

    2016-04-01

    To assess implementation of provider-initiated testing and counselling (PITC) for HIV in Malawi. A review of PITC practices within 118 departments in 12 Ministry of Health (MoH) facilities across Malawi was conducted. Information on PITC practices was collected via a health facility survey. Data describing patient visits and HIV tests were abstracted from routinely collected programme data. Reported PITC practices were highly variable. Most providers practiced symptom-based PITC. Antenatal clinics and maternity wards reported widespread use of routine opt-out PITC. In 2014, there was approximately 1 HIV test for every 15 clinic visits. HIV status was ascertained in 94.3% (5293/5615) of patients at tuberculosis clinics, 92.6% (30,675/33,142) of patients at antenatal clinics and 49.4% (6871/13,914) of patients at sexually transmitted infection clinics. Reported challenges to delivering PITC included test kit shortages (71/71 providers), insufficient physical space (58/71) and inadequate number of HIV counsellors (32/71) while providers from inpatient units cited the inability to test on weekends. Various models of PITC currently exist at MoH facilities in Malawi. Only antenatal and maternity clinics demonstrated high rates of routine opt-out PITC. The low ratio of facility visits to HIV tests suggests missed opportunities for HIV testing. However, the high proportion of patients at TB and antenatal clinics with known HIV status suggests that routine PITC is feasible. These results underscore the need to develop clear, standardised PITC policy and protocols, and to address obstacles of limited health commodities, infrastructure and human resources. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  13. HIV-1 drug resistance mutations among antiretroviral-naive HIV-1-infected patients in Asia: results from the TREAT Asia Studies to Evaluate Resistance-Monitoring Study.

    Science.gov (United States)

    Sungkanuparph, Somnuek; Oyomopito, Rebecca; Sirivichayakul, Sunee; Sirisanthana, Thira; Li, Patrick C K; Kantipong, Pacharee; Lee, Christopher K C; Kamarulzaman, Adeeba; Messerschmidt, Liesl; Law, Matthew G; Phanuphak, Praphan

    2011-04-15

    Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia.

  14. [Optimization of the immunoelectrophoresis technic (western blot) for the confirmation of human immunodeficiency virus infection (HIV) in Panama].

    Science.gov (United States)

    Pascale, J M; de Austin, E; de Moreno, N O; Ledezma, C; de Márquez, E; Blanco, R; Quiroz, E; Calzada, J; Vincensini, A R; de Martin, M C

    1995-01-01

    The purpose of this study is to report the results of the authors' investigation to apply the western blot technique (WB UP-LCS) in the diagnosis of human immunodeficiency virus type 1 (HIV-1) infection. To do this, the authors separated the proteins of the HIV-1 virus by electrophoresis, based on their molecular weight, in poliacilamide gel with SDS (SDS-PAGE) during 3 hours at 200 volts. Then they electrotransferred these proteins to nitrocellulose paper during four hours at 200 milliamperes, with the aid of external cooling. The nitrocellulose strips were evaluated considering the incubation time (1 and 16 hours), two conjugates (human anti IgG with Peroxidase and human anti IgG Biotin plus Streptatividine with Peroxidase) and two dilutions of the patients' sera (1/50 and 1/100). Based on their results the Authors conclude that, in the first place, the optimal conditions for the test include a dilution of 1/100 of the patients serum, incubation of the serum for 16 hours and the use of the conjugate of anti human IgG with Biotin and Streptavidine with Peroxidase; secondary, that the immunologic reactivity against proteins p24 and gp 160/120 is the most important diagnostic criterion for the confirmation of infection with HIV-1 and that they obtained a diagnostic correlation of 100% at a cost which was 5 to 7 times less than that of the commercial system.

  15. HIV-1包膜单基因Nest-PCR体系优化及包膜基因准种扩增%Optimization of HIV-1 envelope gene PCR amplification system and amplification of envelope gene quasispecies

    Institute of Scientific and Technical Information of China (English)

    全红; 刘松; 张昊天; 任彩云; 庄敏; 凌虹; 李妍

    2012-01-01

    目的 确定HIV-1包膜(envelope,env)单基因扩增(single genome amplification,SGA)的最优反应体系,获得env单基因扩增产物.方法 采用SGA及Nest-PCR扩增HIV-1 env全长基因,并对Nest-PCR反应体系中各成分量进行优化;在此基础上,适当稀释HIV-1感染者cDNA模板进行Nest-PCR,以获得PCR扩增产物阳性率不超过30%的模板稀释度.结果 SGA Nest-PCR扩增HIV-1 env全长基因,引物浓度为0.3 μmol/L,dNTP浓度为0.25 μmol/L时可获得特异性高的env全长基因;凝胶回收纯化及稀释第一轮PCR产物可有效提高特异性条带的产量.采用优化反应体系成功从一名HIV-1感染者体内扩增出18株env单基因序列.结论 优化了HIV-1 env基因SGA Nest-PCR的反应体系,并从HIV-1感染者获得了病毒包膜基因准种,为后续进行准种分析奠定了基础.%Objective To optimize the PCR conditions for single genome amplification (SGA) of HIV-1 envelope (env) gene. Methods The efficiency of the SGA-PCR was assessed based on the amplification results of env gene using the non-diluted cDNA template, the optimal dilution of cDNA template that may result in no more than 30% positive amplification was predicted. Results The elements of SGA and Nested-PCR such as the amounts of primers were 0. 3 μmol/L, dNTP were 0. 25 μmol/L, purification of products of the first-round PCR reactions and diluting cDNA templates increased the amount of interest products effectively. One HIV-1 infected individual after the env gene SGA, 18 interest products confirmed by sequencing env sequence. Conclusion Optimization of the HIV-1 env gene the SGA Nest-PCR reaction system, and the viral envelope gene quasispecies from HIV-1 infection, laid the foundation for subsequent analysis of the quasispecies.

  16. Vitamin D3 supplementation increases fibroblast growth factor-23 in HIV-infected youth treated with tenofovir disoproxil fumarate

    Science.gov (United States)

    Havens, Peter L; Hazra, Rohan; Stephensen, Charles B; Kiser, Jennifer J; Flynn, Patricia M; Wilson, Craig M; Rutledge, Brandy; Bethel, James; Pan, Cynthia G; Woodhouse, Leslie R; Van Loan, Marta D; Liu, Nancy; Lujan-Zilbermann, Jorge; Baker, Alyne; Kapogiannis, Bill G; Gordon, Catherine M; Mulligan, Kathleen

    2014-01-01

    Background Tenofovir (TDF) is associated with phosphaturia and elevated 1,25 dihydroxy vitamin D (1,25-OH(2)D). Fibroblast growth factor 23 (FGF23) causes phosphaturia and increases in response to elevated 1,25-OH(2)D. Vitamin D binding protein (VDBP) binds to 1,25-OH(2)D, decreasing its biologic activity, and is elevated in persons with higher plasma tenofovir concentrations. We compared FGF23 and VDBP before and after vitamin D3 (VITD) supplementation in youth treated with combination antiretroviral therapy (cART) containing or not containing TDF. Methods A randomized controlled trial in HIV+ youth ages 18–25 years enrolled participants based on cART treatment with TDF (TDF, N=118) or without TDF (no-TDF, N=85) and randomized within those groups to VITD (50,000 IU every four weeks) or placebo (PL). We measured FGF23 and VDBP and calculated free 1,25-OH(2)D at baseline and week 12, and compared changes by TDF treatment and VITD randomized group. Results At baseline, serum FGF23 concentration showed a quadratic relationship with 1,25-OH(2)D most pronounced in the TDF group. At week 12, total and free 1,25-OH(2)D increased in the VITD but not PL groups, independent of TDF use. FGF23 increased in the TDF group receiving VITD, but there was no FGF23 change in the no-TDF group receiving VITD or the PL groups. The adjusted mean change in FGF23 from baseline to week 12 was +7.7 pg/mL in the TDF/VITD group, compared to −1.7 (no-TDF/VITD, p=0.010); −1.3 (TDF/PL, p=0.006); and +1.1 (no-TDF/PL, p=0.035). Conclusions These results suggest that TDF-containing cART may alter the FGF23 response to vitamin D supplementation in HIV-infected youth. PMID:24535626

  17. Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients

    DEFF Research Database (Denmark)

    Vandenhende, Marie-Anne; Ingle, Suzanne; May, Margaret

    2015-01-01

    BACKGROUND: The goal of antiretroviral therapy (ART) is to reduce HIV-related morbidity and mortality by suppressing HIV replication. The prognostic value of persistent low-level viremia (LLV), particularly for clinical outcomes, is unknown. OBJECTIVE: Assess the association of different levels o...

  18. What to Start: Selecting a First HIV Regimen

    Science.gov (United States)

    HIV Treatment What to Start: Choosing an HIV Regimen (Last updated 2/24/2016; last reviewed 2/24/ ... of HIV medicines used to treat HIV infection. HIV treatment (also called antiretroviral therapy or ART) begins with ...

  19. In vivo mitochondrial function in HIV-infected persons treated with contemporary anti-retroviral therapy: a magnetic resonance spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Brendan A I Payne

    Full Text Available Modern anti-retroviral therapy is highly effective at suppressing viral replication and restoring immune function in HIV-infected persons. However, such individuals show reduced physiological performance and increased frailty compared with age-matched uninfected persons. Contemporary anti-retroviral therapy is thought to be largely free from neuromuscular complications, whereas several anti-retroviral drugs previously in common usage have been associated with mitochondrial toxicity. It has recently been established that patients with prior exposure to such drugs exhibit irreversible cellular and molecular mitochondrial defects. However the functional significance of such damage remains unknown. Here we use phosphorus magnetic resonance spectroscopy ((31P-MRS to measure in vivo muscle mitochondrial oxidative function, in patients treated with contemporary anti-retroviral therapy, and compare with biopsy findings (cytochrome c oxidase (COX histochemistry. We show that dynamic oxidative function (post-exertional ATP (adenosine triphosphate resynthesis was largely maintained in the face of mild to moderate COX defects (affecting up to ∼10% of fibers: τ½ ADP (half-life of adenosine diphosphate clearance, HIV-infected 22.1±9.9 s, HIV-uninfected 18.8±4.4 s, p = 0.09. In contrast, HIV-infected patients had a significant derangement of resting state ATP metabolism compared with controls: ADP/ATP ratio, HIV-infected 1.24±0.08×10(-3, HIV-uninfected 1.16±0.05×10(-3, p = 0.001. These observations are broadly reassuring in that they suggest that in vivo mitochondrial function in patients on contemporary anti-retroviral therapy is largely maintained at the whole organ level, despite histochemical (COX defects within individual cells. Basal energy requirements may nevertheless be increased.

  20. Genetic Variability of Hepatitis C Virus (HCV 5' Untranslated Region in HIV/HCV Coinfected Patients Treated with Pegylated Interferon and Ribavirin.

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    Iwona Bukowska-Ośko

    Full Text Available Association between hepatitis C virus (HCV quasispecies and treatment outcome among patients with chronic hepatitis C has been the subject of many studies. However, these studies focused mainly on viral variable regions (E1 and E2 and usually did not include human immunodeficiency virus (HIV-positive patients. The aim of the present study was to analyze heterogeneity of the 5' untranslated region (5'UTR in HCV/HIV coinfected patients treated with interferon and ribavirin. The HCV 5'UTR was amplified from serum and peripheral blood mononuclear cells (PBMC samples in 37 HCV/HIV coinfected patients treated for chronic hepatitis C. Samples were collected right before treatment, and at 2, 4, 6, 8, 12, 20, 24, 36, 44, 48, 60, and 72 weeks. Heterogeneity of the 5'UTR was analyzed by single strand conformational polymorphism (SSCP, cloning and sequencing. Sustained virological response (SVR was achieved in 46% of analyzed HCV/HIV co-infected patients. Stable SSCP band pattern was observed in 22 patients (62.9% and SVR rate among these patients was 23%. Decline in the number of bands and/or shift in band positions were found in 6 patients (17.1%, 5 (83% of whom achieved SVR (p=0.009. A novel viral genotype was identified in all but one of these patients. In 5 of these 6 patients a new genotype was dominant. 5'UTR heterogeneity may correlate with interferon and ribavirin treatment outcome. In the analyzed group of HCV/HIV coinfected patients, viral quasispecies stability during treatment favored viral persistence, whereas decrease in the number of variants and/or emergence of new variants was associated with SVR. Among injection drug users (IDU patients, a new genotype may become dominant during treatment, probably due to the presence of mixed infections with various strains, which have different susceptibility to treatment.

  1. 96 Week follow-up of HIV-infected patients in rescue with raltegravir plus optimized backbone regimens: a multicentre Italian experience.

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    Amedeo Capetti

    Full Text Available BACKGROUND: Long term efficacy of raltegravir (RAL-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings. METHODS: Antiretroviral treatment-experienced patients initiating a RAL-containing salvage regimen were enrolled. Routine clinical and laboratory follow-up was performed at baseline, week 4, 12, and every 12 weeks thereafter. Data were censored at week 96. RESULTS: Out of 320 patients enrolled, 292 (91.25% subjects maintained their initial regimen for 96 weeks; 28 discontinued prematurely for various reasons: death (11, viral failure (8, adverse events (5, loss to follow-up (3, consent withdrawal (1. Eight among these 28 subjects maintained RAL but changed the accompanying drugs. The mean CD4+ T-cell increase at week 96 was 227/mm(3; 273 out of 300 patients (91%, who were still receiving RAL at week 96, achieved viral suppression (HIV-1 RNA 4 (n = 40, CD4+ T-cell gain was similar across strata: +270, +214, +216, and +240 cells/mm(3, respectively, as was the proportion of subjects with undetectable viral load. Laboratory abnormalities (elevation of liver enzymes, total cholesterol and triglycerides were rare, ranging from 0.9 to 3.1%. The mean 96-week total cholesterol increase was 23.6 mg/dL. CONCLUSIONS: In a routine clinical setting, a RAL-based regimen allowed most patients in salvage therapy to achieve optimal viral suppression for at least 96 weeks, with relevant immunologic gain and very few adverse events.

  2. 96 Week Follow-Up of HIV-Infected Patients in Rescue with Raltegravir Plus Optimized Backbone Regimens: A Multicentre Italian Experience

    Science.gov (United States)

    Capetti, Amedeo; Landonio, Simona; Meraviglia, Paola; Di Biagio, Antonio; Lo Caputo, Sergio; Sterrantino, Gaetana; Ammassari, Adriana; Menzaghi, Barbara; Franzetti, Marco; De Socio, Giuseppe Vittorio; Pellicanò, Giovanni; Mazzotta, Elena; Soria, Alessandro; Meschiari, Marianna; Trezzi, Michele; Sasset, Lolita; Celesia, Benedetto Maurizio; Zucchi, Patrizia; Melzi, Sara; Ricci, Elena; Rizzardini, Giuliano

    2012-01-01

    Background Long term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings. Methods Antiretroviral treatment-experienced patients initiating a RAL-containing salvage regimen were enrolled. Routine clinical and laboratory follow-up was performed at baseline, week 4, 12, and every 12 weeks thereafter. Data were censored at week 96. Results Out of 320 patients enrolled, 292 (91.25%) subjects maintained their initial regimen for 96 weeks; 28 discontinued prematurely for various reasons: death (11), viral failure (8), adverse events (5), loss to follow-up (3), consent withdrawal (1). Eight among these 28 subjects maintained RAL but changed the accompanying drugs. The mean CD4+ T-cell increase at week 96 was 227/mm3; 273 out of 300 patients (91%), who were still receiving RAL at week 96, achieved viral suppression (HIV-1 RNA 4 (n = 40), CD4+ T-cell gain was similar across strata: +270, +214, +216, and +240 cells/mm3, respectively, as was the proportion of subjects with undetectable viral load. Laboratory abnormalities (elevation of liver enzymes, total cholesterol and triglycerides) were rare, ranging from 0.9 to 3.1%. The mean 96-week total cholesterol increase was 23.6 mg/dL. Conclusions In a routine clinical setting, a RAL-based regimen allowed most patients in salvage therapy to achieve optimal viral suppression for at least 96 weeks, with relevant immunologic gain and very few adverse events. PMID:22808029

  3. Distinguishing HIV-1 drug resistance, accessory, and viral fitness mutations using conditional selection pressure analysis of treated versus untreated patient samples

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    Lee Christopher

    2006-05-01

    Full Text Available Abstract Background HIV can evolve drug resistance rapidly in response to new drug treatments, often through a combination of multiple mutations 123. It would be useful to develop automated analyses of HIV sequence polymorphism that are able to predict drug resistance mutations, and to distinguish different types of functional roles among such mutations, for example, those that directly cause drug resistance, versus those that play an accessory role. Detecting functional interactions between mutations is essential for this classification. We have adapted a well-known measure of evolutionary selection pressure (Ka/Ks and developed a conditional Ka/Ks approach to detect important interactions. Results We have applied this analysis to four independent HIV protease sequencing datasets: 50,000 clinical samples sequenced by Specialty Laboratories, Inc.; 1800 samples from patients treated with protease inhibitors; 2600 samples from untreated patients; 400 samples from untreated African patients. We have identified 428 mutation interactions in Specialty dataset with statistical significance and we were able to distinguish primary vs. accessory mutations for many well-studied examples. Amino acid interactions identified by conditional Ka/Ks matched 80 of 92 pair wise interactions found by a completely independent study of HIV protease (p-value for this match is significant: 10-70. Furthermore, Ka/Ks selection pressure results were highly reproducible among these independent datasets, both qualitatively and quantitatively, suggesting that they are detecting real drug-resistance and viral fitness mutations in the wild HIV-1 population. Conclusion Conditional Ka/Ks analysis can detect mutation interactions and distinguish primary vs. accessory mutations in HIV-1. Ka/Ks analysis of treated vs. untreated patient data can distinguish drug-resistance vs. viral fitness mutations. Verification of these results would require longitudinal studies. The result

  4. Optimism and education buffer the effects of syndemic conditions on HIV status among African American men who have sex with men.

    Science.gov (United States)

    O'Leary, Ann; Jemmott, John B; Stevens, Robin; Rutledge, Scott Edward; Icard, Larry D

    2014-11-01

    The present study sought to replicate effects of the number of syndemic psychosocial health conditions on sexual risk behavior and HIV infection among a sample of high-risk African American men who have sex with men (MSM) and to identify resilience factors that may buffer these effects. We used baseline data from an HIV risk-reduction trial to examine whether a higher number of syndemic conditions was associated with higher rates of self-reported sexual risk behavior and HIV infection. Using logistic regression models, we tested for interactions between number of syndemic conditions and several potential resilience factors to identify buffering effects. Replicating previous studies, we found significant associations between numbers of syndemic conditions and higher rates of sexual risk behavior and HIV infection. Surprisingly, we also replicated a previous finding (Stall et al., Am J Public Health, 93(6):939-942, 2003) that the effects of syndemic burden on HIV status fell off at the highest levels of syndemic conditions. Among a variety of potential resilience factors, two-optimism and education-buffered the syndemic effect on HIV prevalence. This is, to our knowledge, the first paper to identify resilience factors buffering against syndemic effects among MSM. It also constitutes a significant contribution to the literature regarding prevention among black MSM. These results point to the need to identify HIV-positive black MSM and provide effective treatment for them and to develop interventions addressing both syndemic and resilience factors.

  5. Accurate episomal HIV 2-LTR circles quantification using optimized DNA isolation and droplet digital PCR

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    Eva Malatinkova

    2014-11-01

    Full Text Available Introduction: In HIV-infected patients on combination antiretroviral therapy (cART, the detection of episomal HIV 2-LTR circles is a potential marker for ongoing viral replication. Quantification of 2-LTR circles is based on quantitative PCR or more recently on digital PCR assessment, but is hampered due to its low abundance. Sample pre-PCR processing is a critical step for 2-LTR circles quantification, which has not yet been sufficiently evaluated in patient derived samples. Materials and Methods: We compared two sample processing procedures to more accurately quantify 2-LTR circles using droplet digital PCR (ddPCR. Episomal HIV 2-LTR circles were either isolated by genomic DNA isolation or by a modified plasmid DNA isolation, to separate the small episomal circular DNA from chromosomal DNA. This was performed in a dilution series of HIV-infected cells and HIV-1 infected patient derived samples (n=59. Samples for the plasmid DNA isolation method were spiked with an internal control plasmid. Results: Genomic DNA isolation enables robust 2-LTR circles quantification. However, in the lower ranges of detection, PCR inhibition caused by high genomic DNA load substantially limits the amount of sample input and this impacts sensitivity and accuracy. Moreover, total genomic DNA isolation resulted in a lower recovery of 2-LTR templates per isolate, further reducing its sensitivity. The modified plasmid DNA isolation with a spiked reference for normalization was more accurate in these low ranges compared to genomic DNA isolation. A linear correlation of both methods was observed in the dilution series (R2=0.974 and in the patient derived samples with 2-LTR numbers above 10 copies per million peripheral blood mononuclear cells (PBMCs, (R2=0.671. Furthermore, Bland–Altman analysis revealed an average agreement between the methods within the 27 samples in which 2-LTR circles were detectable with both methods (bias: 0.3875±1.2657 log10. Conclusions: 2-LTR

  6. Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.

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    Hubert Barennes

    Full Text Available INTRODUCTION: In resource limited settings, patients entering an antiretroviral therapy (ART program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. METHODS: This retrospective study, conducted in 2010-2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia assessed virological failure (VF rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF (>1,000 copies/ml underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. RESULTS: On a total of 209 patients, 164 (78.4% were naive and 45 (21.5% were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30-194 and 279 cells/mm3 (IQR: 103-455 (p<0.001, respectively. Twenty seven patients (12.9% exhibited VF (95% CI: 8.6-18.2%, including 10 naive (10/164, 6.0% and 17 pre-treated (17/45, 37.8% patients (p<0.001. Among these viremic patients, twenty-two (81.4% were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3% harbored ≥1 drug resistance mutations (DRMs whereas 3 (all belonging to pre-treated patients harbored wild-types viruses. The most frequent DRMs were M184V (86.3%, K103N (45.5% and thymidine analog mutations (TAMs (40.9%. Two (13.3% pre-treated patients harbored viruses that showed a multi-nucleos(tide resistance including Q151M, K65R, E33A/D, E44A/D mutations. CONCLUSION: In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre-treated

  7. Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996-2006: collaborative analysis of 13 HIV cohort studies

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2010-01-01

    We examined specific causes of mortality in human immunodeficiency virus type 1 (HIV-1)-infected patients who initiated antiretroviral therapy (ART) in Europe and North America from 1996 through 2006, and we quantified associations of prognostic factors with cause-specific mortality....

  8. Specific protein profile in cerebrospinal fluid from HIV-1-positive cART-treated patients affected by neurological disorders.

    Science.gov (United States)

    Zanin, Valentina; Delbue, Serena; Marcuzzi, Annalisa; Tavazzi, Eleonora; Del Savio, Rossella; Crovella, Sergio; Marchioni, Enrico; Ferrante, Pasquale; Comar, Manola

    2012-10-01

    Cytokines/chemokines are involved in the immune response of infections, including HIV-1. We defined the profile of 48 cytokines/chemokines in cerebrospinal fluid from 18 cART patients with chronic HIV-1 infection by Luminex technology. Nine patients were affected with leukoencephalopathies: five with John Cunningham virus (JCV) + progressive multifocal leukoencephalopathy (PML) and four with JCV-not determined leukoencephalopathy (NDLE). In addition, nine HIV-1-positive patients with no neurological signs (NND) and five HIV-1-negative patients affected with acute disseminated encephalomyelitis (ADEM) were enrolled. Ten cytokines (IL-15, IL-3, IL-16, IL-18, CTACK, GRO1, SCF, MCP-1, MIF, SDF) were highly expressed in HIV-1-positive patients while IL-1Ra and IL-17 were present at a lower level. In addition, the levels of IL-17, IL-9, FGF-basic, MIP-1β, and MCP-1 were significantly higher (p < 0.05) in patients with neurological diseases (PML, NDLE, ADEM) with respect to NND. Focusing the attention to the cytokine profile in JCV + PML patients with respect to JCV-NDLE patients, only TNF-β was significantly downregulated (p < 0.05) in JCV + PML patients. This pilot study emphasized the role of immunoregulation in HIV-1-related neurological disorders during cART treatment.

  9. An RNAi in silico approach to find an optimal shRNA cocktail against HIV-1.

    Science.gov (United States)

    Méndez-Ortega, María C; Restrepo, Silvia; Rodríguez-R, Luis M; Pérez, Iván; Mendoza, Juan C; Martínez, Andrés P; Sierra, Roberto; Rey-Benito, Gloria J

    2010-12-20

    HIV-1 can be inhibited by RNA interference in vitro through the expression of short hairpin RNAs (shRNAs) that target conserved genome sequences. In silico shRNA design for HIV has lacked a detailed study of virus variability constituting a possible breaking point in a clinical setting. We designed shRNAs against HIV-1 considering the variability observed in naïve and drug-resistant isolates available at public databases. A Bioperl-based algorithm was developed to automatically scan multiple sequence alignments of HIV, while evaluating the possibility of identifying dominant and subdominant viral variants that could be used as efficient silencing molecules. Student t-test and Bonferroni Dunn correction test were used to assess statistical significance of our findings. Our in silico approach identified the most common viral variants within highly conserved genome regions, with a calculated free energy of ≥ -6.6 kcal/mol. This is crucial for strand loading to RISC complex and for a predicted silencing efficiency score, which could be used in combination for achieving over 90% silencing. Resistant and naïve isolate variability revealed that the most frequent shRNA per region targets a maximum of 85% of viral sequences. Adding more divergent sequences maintained this percentage. Specific sequence features that have been found to be related with higher silencing efficiency were hardly accomplished in conserved regions, even when lower entropy values correlated with better scores. We identified a conserved region among most HIV-1 genomes, which meets as many sequence features for efficient silencing. HIV-1 variability is an obstacle to achieving absolute silencing using shRNAs designed against a consensus sequence, mainly because there are many functional viral variants. Our shRNA cocktail could be truly effective at silencing dominant and subdominant naïve viral variants. Additionally, resistant isolates might be targeted under specific antiretroviral selective

  10. An RNAi in silico approach to find an optimal shRNA cocktail against HIV-1

    Directory of Open Access Journals (Sweden)

    Mendoza Juan C

    2010-12-01

    Full Text Available Abstract Background HIV-1 can be inhibited by RNA interference in vitro through the expression of short hairpin RNAs (shRNAs that target conserved genome sequences. In silico shRNA design for HIV has lacked a detailed study of virus variability constituting a possible breaking point in a clinical setting. We designed shRNAs against HIV-1 considering the variability observed in naïve and drug-resistant isolates available at public databases. Methods A Bioperl-based algorithm was developed to automatically scan multiple sequence alignments of HIV, while evaluating the possibility of identifying dominant and subdominant viral variants that could be used as efficient silencing molecules. Student t-test and Bonferroni Dunn correction test were used to assess statistical significance of our findings. Results Our in silico approach identified the most common viral variants within highly conserved genome regions, with a calculated free energy of ≥ -6.6 kcal/mol. This is crucial for strand loading to RISC complex and for a predicted silencing efficiency score, which could be used in combination for achieving over 90% silencing. Resistant and naïve isolate variability revealed that the most frequent shRNA per region targets a maximum of 85% of viral sequences. Adding more divergent sequences maintained this percentage. Specific sequence features that have been found to be related with higher silencing efficiency were hardly accomplished in conserved regions, even when lower entropy values correlated with better scores. We identified a conserved region among most HIV-1 genomes, which meets as many sequence features for efficient silencing. Conclusions HIV-1 variability is an obstacle to achieving absolute silencing using shRNAs designed against a consensus sequence, mainly because there are many functional viral variants. Our shRNA cocktail could be truly effective at silencing dominant and subdominant naïve viral variants. Additionally, resistant

  11. Predicting intention to treat HIV-infected patients among Tanzanian and Sudanese medical and dental students using the theory of planned behaviour - a cross sectional study

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    Nasir Elwalid F

    2009-11-01

    Full Text Available Abstract Background The HIV epidemic poses significant challenges to the low income countries in sub Saharan Africa (SSA, affecting the attrition rate among health care workers, their level of motivation, and absenteeism from work. Little is known about how to deal with deterioration of human resources in the health care systems. This study aimed to predict the intention to provide surgical treatment to HIV infected patients among medical- and dental students in Tanzania and Sudan using an extended version of the Theory of Planned Behaviour (TPB. Methods Four hundred and seventy five medical- and dental students at the University of Dar es Salaam (mean age, 25 yr and 642 dental students attending 6 public and private dental faculties in Khartoum (mean age 21.7 yr completed self-administered TPB questionnaires in 2005 and 2007, respectively. Results Both Tanzanian and Sudanese students demonstrated strong intentions to provide care for people with HIV and AIDS. Stepwise linear regression revealed that the TPB accounted for 51% (43% in Tanzania and Sudan of the variance in intention across study sites. After having controlled for country and past behaviour, the TPB in terms of attitudes, subjective norms and perceived behavioural control accounted for 34% and moral norms for an additional 2,3% of the explainable variance in intention. Across both study sites, attitudes were the strongest predictor of intention followed in descending order by subjective norms, moral norms and perceived behavioural control. Conclusion The TPB is applicable to students' care delivery intentions in the context of HIV and AIDS across the two SSA countries investigated. It is suggested that attitudes, subjective norms, moral norms and perceived behavioural control are key factors in students' willingness to treat AIDS and HIV infected patients and should be targets of interventions aimed at improving the quality of health care delivery in this context.

  12. High retention and appropriate use of insecticide-treated nets distributed to HIV-affected households in Rakai, Uganda: results from interviews and home visits

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    Ludigo James

    2009-04-01

    Full Text Available Abstract Background Distribution of insecticide-treated nets (ITNs has recently been incorporated into comprehensive care strategies for HIV-positive people in malaria-endemic areas. WHO now recommends free or low-cost distribution of ITNs to all persons in malaria-endemic areas, regardless of age, pregnancy and HIV status. Knowledge about and appropriate use of ITNs among HIV-positive ITN recipients and their household members has not been well characterized. Methods 142 randomly selected adults were interviewed in July–August 2006 to assess knowledge, retention, and appropriate use of ITNs they had received through a PEPFAR-funded comprehensive HIV care programme in rural Uganda. Results Among all participants, 102 (72%, CI: 65%–79% reported they had no ITNs except those provided by the programme. Of 131 participants who stated they were given ≥ 1 ITN, 128 (98%, CI: 96%–100% stated they still possessed at least one programme-provided ITN. Reported programme-ITN (pITN use by participants was high: 119 participants (91%, CI: 86%–96% reported having slept under pITN the night prior to the survey and 115 (88%, CI: 82%–94% reported sleeping under pITN seven days per week. Being away from home and heat were the most common reasons given for not sleeping under an ITN. A sub-study of thirteen random home visits demonstrated concordance between participants' survey reports and actual use of ITNs in homes. Conclusion There was excellent self-reported retention and appropriate use of ITNs distributed as a part of a community-based outpatient HIV care programme. Participants perceived ITNs as useful and were unlikely to have received ITNs from other sources.

  13. Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability

    Science.gov (United States)

    Kong, Leopold; He, Linling; de Val, Natalia; Vora, Nemil; Morris, Charles D.; Azadnia, Parisa; Sok, Devin; Zhou, Bin; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Zhu, Jiang

    2016-06-01

    The trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and neutralization. Despite advances in trimer design, the roots of Env trimer metastability remain elusive. Here we investigate the contribution of two Env regions to metastability. First, we computationally redesign a largely disordered bend in heptad region 1 (HR1) of SOSIP trimers that connects the long, central HR1 helix to the fusion peptide, substantially improving the yield of soluble, well-folded trimers. Structural and antigenic analyses of two distinct HR1 redesigns confirm that redesigned Env closely mimics the native, prefusion trimer with a more stable gp41. Next, we replace the cleavage site between gp120 and gp41 with various linkers in the context of an HR1 redesign. Electron microscopy reveals a potential fusion intermediate state for uncleaved trimers containing short but not long linkers. Together, these results outline a general approach for stabilization of Env trimers from diverse HIV-1 strains.

  14. Performance of a Redesigned HIV Selectest Enzyme-Linked Immunosorbent Assay Optimized To Minimize Vaccine-Induced Seropositivity in HIV Vaccine Trial Participants

    Science.gov (United States)

    Penezina, Oksana; Krueger, Neil X.; Rodriguez-Chavez, Isaac R.; Busch, Michael P.; Hural, John; Kim, Jerome H.; O'Connell, Robert J.; Hunter, Eric; Aboud, Said; Higgins, Keith; Kovalenko, Victor; Clapham, David; Crane, David

    2014-01-01

    Vaccine-induced seropositivity (VISP) or seroreactivity (VISR), defined as the reaction of antibodies elicited by HIV vaccines with antigens used in HIV diagnostic immunoassays, can result in reactive assay results for vaccinated but uninfected individuals, with subsequent misclassification of their infection status. The eventual licensure of a vaccine will magnify this issue and calls for the development of mitigating solutions in advance. An immunoassay that discriminates between antibodies elicited by vaccine antigens and those elicited by infection has been developed to address this laboratory testing need. The HIV Selectest is based on consensus and clade-specific HIV peptides that are omitted in many HIV vaccine constructs. The assay was redesigned to enhance performance across worldwide clades and to simplify routine use via a standard kit format. The redesigned assay was evaluated with sera from vaccine trial participants, HIV-infected and uninfected individuals, and healthy controls. The HIV Selectest exhibited specificities of 99.5% with sera from uninfected recipients of 6 different HIV vaccines and 100% with sera from normal donors, while detecting HIV-1 infections, including intercurrent infections, with 95 to 100% sensitivity depending on the clade, with the highest sensitivities for clades A and C. HIV Selectest sensitivity decreased in very early seroconversion specimens, which possibly explains the slightly lower sensitivity observed for asymptomatic blood donors than for clinical HIV cases. Thus, the HIV Selectest provides a new laboratory tool for use in vaccine settings to distinguish the immune response to HIV vaccine antigens from that due to true infection. PMID:24403525

  15. Optimization of struvite precipitation in synthetic biologically treated swine wastewater--determination of the optimal process parameters.

    Science.gov (United States)

    Capdevielle, Aurélie; Sýkorová, Eva; Biscans, Béatrice; Béline, Fabrice; Daumer, Marie-Line

    2013-01-15

    A sustainable way to recover phosphorus (P) in swine wastewater involves a preliminary step of P dissolution followed by the separation of particulate organic matter. The next two steps are firstly the precipitation of struvite crystals done by adding a crystallization reagent (magnesia) and secondly the filtration of the crystals. A design of experiments with five process parameters was set up to optimize the size of the struvite crystals in a synthetic swine wastewater. More than 90% of P was recovered as large crystals of struvite in optimal conditions which were: low Mg:Ca ratio (2.25:1), the leading parameter, high N:P ratio (3:1), moderate stirring rate (between 45 and 90 rpm) and low temperature (below 20 °C).These results were obtained despite the presence of a large amount of calcium and using a cheap reactant (MgO). The composition of the precipitates was identified by Raman analysis and solid dissolution. Results showed that amorphous calcium phosphate (ACP) co-precipitated with struvite and that carbonates were incorporated with solid fractions.

  16. Nutrition outcomes of HIV-infected malnourished adults treated with ready-to-use therapeutic food in sub-Saharan Africa: a longitudinal study

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    Ahoua Laurence

    2011-01-01

    Full Text Available Abstract Background Among people living with HIV/AIDS, nutritional support is increasingly recognized as a critical part of the essential package of care, especially for patients in sub-Saharan Africa. The objectives of the study were to evaluate the outcomes of HIV-positive malnourished adults treated with ready-to-use therapeutic food and to identify factors associated with nutrition programme failure. Methods We present results from a retrospective cohort analysis of patients aged 15 years or older with a body mass index of less than 17 kg/m2 enrolled in three HIV/AIDS care programmes in Africa between March 2006 and August 2008. Factors associated with nutrition programme failure (patients discharged uncured after six or more months of nutritional care, defaulting from nutritional care, remaining in nutritional care for six or more months, or dead were investigated using multiple logistic regression. Results Overall, 1340 of 8685 (15.4% HIV-positive adults were enrolled in the nutrition programme. At admission, median body mass index was 15.8 kg/m2 (IQR 14.9-16.4 and 12% received combination antiretroviral therapy (ART. After a median of four months of follow up (IQR 2.2-6.1, 524 of 1106 (47.4% patients were considered cured. An overall total of 531 of 1106 (48.0% patients failed nutrition therapy, 132 (11.9% of whom died and 250 (22.6% defaulted from care. Men (OR = 1.5, 95% CI 1.2-2.0, patients with severe malnutrition at nutrition programme enrolment (OR = 2.2, 95% CI 1.7-2.8, and those never started on ART (OR = 4.5, 95% CI 2.7-7.7 for those eligible; OR = 1.6, 95% CI 1.0-2.5 for those ineligible for ART at enrolment were at increased risk of nutrition programme failure. Diagnosed tuberculosis at nutrition programme admission or during follow up, and presence of diarrhoeal disease or extensive candidiasis at admission, were unrelated to nutrition programme failure. Conclusions Concomitant administration of ART and ready

  17. The immunologic effects of mesalamine in treated HIV-infected individuals with incomplete CD4+ T cell recovery: a randomized crossover trial.

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    Ma Somsouk

    Full Text Available The anti-inflammatory agent, mesalamine (5-aminosalicylic acid has been shown to decrease mucosal inflammation in ulcerative colitis. The effect of mesalamine in HIV-infected individuals, who exhibit abnormal mucosal immune activation and microbial translocation (MT, has not been established in a placebo-controlled trial. We randomized 33 HIV-infected subjects with CD4 counts <350 cells/mm3 and plasma HIV RNA levels <40 copies/ml on antiretroviral therapy (ART to add mesalamine vs. placebo to their existing regimen for 12 weeks followed by a 12 week crossover to the other arm. Compared to placebo-treated subjects, mesalamine-treated subjects did not experience any significant change in the percent CD38+HLA-DR+ peripheral blood CD4+ and CD8+ T cells at week 12 (P = 0.38 and P = 0.63, respectively, or in the CD4+ T cell count at week 12 (P = 0.83. The percent CD38+HLA-DR+ CD4+ and CD8+ T cells also did not change significantly in rectal tissue (P = 0.86, P = 0.84, respectively. During the period of mesalamine administration, plasma sCD14, IL-6, D-dimer, and kynurenine to tryptophan ratio were not changed significantly at week 12 and were similarly unchanged at week 24. This study suggests that, at least under the conditions studied, the persistent immune activation associated with HIV infection is not impacted by the anti-inflammatory effects of mesalamine.ClinicalTrials.gov NCT01090102.

  18. Taguchi optimization of machining parameters in drilling of AISI D2 steel using cryo-treated carbide drills

    Indian Academy of Sciences (India)

    GULSAH AKINCIOGLU; FARUK MENDI; ADEM CICEK; SITKI AKINCIOGLU

    2017-02-01

    This study focused on using the Taguchi technique to optimize the process parameters in drilling of AISI D2 steel with carbide drills to minimize the surface roughness (Ra) and thrust forces (Ff). The drilling experiments were conducted on a CNC vertical machining centre according to the L18 experimental design. Uncoated drills were classified into three groups: untreated (U), cryo-treated (CT) and cryo-treated and tempered (CTT). The experimental results showed that the CTT drills exhibited the best performance in terms of Ra and Ff due to the improved wear resistance of carbide drills after the cryogenic treatment and tempering. As a result of analysis of variance (ANOVA), it was found that the most influential parameter on both Ra and Ff was the feed rate, with percentage contributions of 66.97% and 80.07%, respectively. The results showed that the Taguchitechnique is a powerful method to optimize the process parameters in drilling of tool steel.

  19. Optimal costs of HIV pre-exposure prophylaxis for men who have sex with men.

    Science.gov (United States)

    McKenney, Jennie; Chen, Anders; Hoover, Karen W; Kelly, Jane; Dowdy, David; Sharifi, Parastu; Sullivan, Patrick S; Rosenberg, Eli S

    2017-01-01

    Men who have sex with men (MSM) are disproportionately affected by HIV due to their increased risk of infection. Oral pre-exposure prophylaxis (PrEP) is a highly effictive HIV-prevention strategy for MSM. Despite evidence of its effectiveness, PrEP uptake in the United States has been slow, in part due to its cost. As jurisdictions and health organizations begin to think about PrEP scale-up, the high cost to society needs to be understood. We modified a previously-described decision-analysis model to estimate the cost per quality-adjusted life-year (QALY) gained, over a 1-year duration of PrEP intervention and lifetime time horizon. Using updated parameter estimates, we calculated: 1) the cost per QALY gained, stratified over 4 strata of PrEP cost (a function of both drug cost and provider costs); and 2) PrEP drug cost per year required to fall at or under 4 cost per QALY gained thresholds. When PrEP drug costs were reduced by 60% (with no sexual disinhibition) to 80% (assuming 25% sexual disinhibition), PrEP was cost-effective (at <$100,000 per QALY averted) in all scenarios of base-case or better adherence, as long as the background HIV prevalence was greater than 10%. For PrEP to be cost saving at base-case adherence/efficacy levels and at a background prevalence of 20%, drug cost would need to be reduced to $8,021 per year with no disinhibition, and to $2,548 with disinhibition. Results from our analysis suggest that PrEP drug costs need to be reduced in order to be cost-effective across a range of background HIV prevalence. Moreover, our results provide guidance on the pricing of generic emtricitabine/tenofovir disoproxil fumarate, in order to provide those at high risk for HIV an affordable prevention option without financial burden on individuals or jurisdictions scaling-up coverage.

  20. Characteristics of foot fractures in HIV-infected patients previously treated with tenofovir versus non-tenofovir-containing highly active antiretroviral therapy

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    Horizon AA

    2011-06-01

    Full Text Available Arash A Horizon1, Robert J Joseph2, Qiming Liao3, Steven T Ross3, Gary E Pakes31Center for Rheumatology, 2Surgical Podiatry, Los Angeles, CA, USA; 3GlaxoSmithKline, Research Triangle Park, NC, USASummary: In a retrospective case series study, medical records were evaluated for all male patients infected with human immunodeficiency virus (HIV diagnosed over a one-year period with foot fractures (n = 30 confirmed by magnetic resonance imaging at a Los Angeles outpatient private practice rheumatology clinic. Proportionally more patients had received tenofovir prefracture (17 [57%] than those who had not (13 [43%]. At fracture diagnosis, these two groups were similar in median age (49 versus 48 years, HIV-1 RNA (both 1.7 log10 copies/mL, CD4 count (300 versus 364/mm3, time between HIV diagnosis and foot fracture (both 17 years, family history of degenerative bone disease (24% versus 23%, prevalence of malabsorption syndrome, renal failure, calcium deficiency, or vitamin D deficiency, and concurrent use of bisphosphonates, calcitonin, and diuretics. However, more tenofovir-treated patients had osteoporosis (35% versus 8%, stress-type fractures (53% versus 31%, concurrent fractures (12% versus 0%, wasting syndrome (29% versus 15%, truncal obesity (18% versus 8%, smoked cigarettes (more than one pack/day for more than one year; 35% versus 8%, dual energy X-ray absorptiometry (DEXA T scores <–2.4 (denoting osteoporosis at the femur (24% versus 9% and spine (47% versus 36%, and had received protease inhibitors (71% versus 46%, non-nucleoside reverse transcriptase inhibitors (24% versus 0%, prednisone (24% versus 0%, testosterone (47% versus 23%, and teriparatide (29% versus 8%. Median time from tenofovir initiation until fracture was 2.57 (range 1.17–5.69 years. In conclusion, more foot fractures were observed in tenofovir-treated patients than in non-tenofovir-treated patients with HIV infection. Comorbidities and/or coadministered drugs may have

  1. A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients.

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    Dominique L Braun

    Full Text Available The efficacy of first-generation protease inhibitor based triple-therapy against hepatitis C virus (HCV infection is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and non-response to previous peginterferon-ribavirin. These patients have a low chance of achieving a sustained virologic response (SVR using first generation triple-therapy, with a success rate of only 20%. We investigated the efficacy and safety of lead-in therapy with intravenous silibinin followed by triple-therapy in this difficult-to-treat patient group.Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented previous treatment failure on peginterferon-ribavirin. The intervention was a lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days, followed by triple-therapy (peginterferon-ribavirin and telaprevir for 12 weeks, and peginterferon-ribavirin alone for 36 weeks. Outcome measurements were HCV-RNA after silibinin lead-in and during triple-therapy, SVR data at week 12, and safety and tolerability of silibinin.We examined sixteen HIV/HCV-coinfected patients with previous peginterferon-ribavirin failure, of whom 14 had a fibrosis grade METAVIR ≥F3. All were on successful antiretroviral therapy. Median (IQR HCV-RNA decline after silibinin therapy was 2.65 (2.1-2.8 log10 copies/mL. Fifteen of sixteen patients (94% had undetectable HCV RNA at weeks 4 and 12, eleven patients (69% showed end-of-treatment response (i.e., undetectable HCV-RNA at week 48, and ten patients (63% reached SVR at week 12 (SVR 12. Six of the sixteen patients (37% did not reach SVR 12: One patient had rapid virologic response (RVR (i.e., undetectable HCV-RNA at week 4 but stopped treatment at week 8 due to major depression. Five patients had RVR, but experienced viral breakthroughs at week 21, 22, 25, or 32, or a relapse at week 52. The HIV RNA remained below the limit of detection in all patients during the complete treatment period. No

  2. Long-term kinetics of T cell production in HIV-infected subjects treated with highly active antiretroviral therapy

    Science.gov (United States)

    Fleury, S.; Rizzardi, G. P.; Chapuis, A.; Tambussi, G.; Knabenhans, C.; Simeoni, E.; Meuwly, J.-Y.; Corpataux, J.-M.; Lazzarin, A.; Miedema, F.; Pantaleo, G.

    2000-01-01

    The long-term kinetics of T cell production following highly active antiretroviral therapy (HAART) were investigated in blood and lymph node in a group of HIV-infected subjects at early stage of established infection and prospectively studied for 72 wk. Before HAART, CD4 and CD8 T cell turnover was increased. However, the total number of proliferating CD4+ T lymphocytes, i.e., CD4+Ki67+ T lymphocytes, was not significantly different in HIV-infected (n = 73) and HIV-negative (n = 15) subjects, whereas proliferating CD8+Ki67+ T lymphocytes were significantly higher in HIV-infected subjects. After HAART, the total body number of proliferating CD4+Ki67+ T lymphocytes increased over time and was associated with an increase of both naive and memory CD4+ T cells. The maximal increase (2-fold) was observed at week 36, whereas at week 72 the number of proliferating CD4+ T cells dropped to baseline levels, i.e., before HAART. The kinetics of the fraction of proliferating CD4 and CD8 T cells were significantly correlated with the changes in the total body number of these T cell subsets. These results demonstrate a direct relationship between ex vivo measures of T cell production and quantitative changes in total body T lymphocyte populations. This study provides advances in the delineation of the kinetics of T cell production in HIV infection in the presence and/or in the absence of HAART. PMID:10805798

  3. Use of an HIV-risk screening tool to identify optimal candidates for PrEP scale-up among men who have sex with men in Toronto, Canada: disconnect between objective and subjective HIV risk.

    Science.gov (United States)

    Wilton, James; Kain, Taylor; Fowler, Shawn; Hart, Trevor A; Grennan, Troy; Maxwell, John; Tan, Darrell Hs

    2016-01-01

    Identifying appropriate pre-exposure prophylaxis (PrEP) candidates is a challenge in planning for the safe and effective roll-out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM), to identify "optimal" candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada. Between November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify "optimal" candidates for scaling up PrEP roll-out, defined as being at high objective HIV risk (scoring ≥10 on the HIRI-MSM), perceiving oneself at moderate-to-high HIV risk and being willing to use PrEP. Cascades were constructed to identify barriers to broader PrEP uptake. The association between HIRI-MSM score and both willingness to use PrEP and perceived HIV risk were explored in separate multivariable logistic regression analyses. Of 420 respondents, 64.4% were objectively at high risk, 52.5% were willing to use PrEP and 27.2% perceived themselves at moderate-to-high HIV risk. Only 16.4% were "optimal" candidates. Higher HIRI-MSM scores were positively associated with both willingness to use PrEP (aOR=1.7 per 10 score increase, 95%CI=1.3-2.2) and moderate-to-high perceived HIV risk (aOR=1.7 per 10 score increase, 95%CI=1.2-2.3). The proportion of men who were "optimal" candidates increased to 42.9% when the objective HIV risk cut-off was changed to top quartile of HIRI-MSM scores (≥26). In our full cascade, a very low proportion (5.3%) of MSM surveyed could potentially benefit from PrEP under current conditions. The greatest barrier in the cascade was low perception of HIV risk among high-risk men, but considerable numbers were also lost in downstream cascade steps. Of men at high objective HIV risk, 68.3% did not perceive themselves to be at moderate-to-high HIV risk, 23.6% were unaware of PrEP, 40.1% were not

  4. Consensus statement: Management of drug-induced liver injury in HIV-positive patients treated for TB

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    E Jong

    2013-09-01

    Full Text Available Drug-induced liver injury (DILI in HIV/tuberculosis (TB co-infected patients is a common problem in the South African setting, and re-introduction of anti-TB drugs can be challenging for the healthcare worker. Although international guidelines on the re-introduction of TB treatment are available, the definition of DILI is not uniform, management of antiretroviral therapy (ART in HIV co-infection is not mentioned, and the guidance on management is not uniform and lacks a practical approach. In this consensus statement, we summarise important aspects of DILI and provide practical guidance for healthcare workers for different patient groups and healthcare settings on the re-introduction of anti-TB drugs and ART in HIV/TB co-infected individuals presenting with DILI.

  5. Engineering broadly neutralizing antibodies for HIV prevention and therapy.

    Science.gov (United States)

    Hua, Casey K; Ackerman, Margaret E

    2016-08-01

    A combination of advances spanning from isolation to delivery of potent HIV-specific antibodies has begun to revolutionize understandings of antibody-mediated antiviral activity. As a result, the set of broadly neutralizing and highly protective antibodies has grown in number, diversity, potency, and breadth of viral recognition and neutralization. These antibodies are now being further enhanced by rational engineering of their anti-HIV activities and coupled to cutting edge gene delivery and strategies to optimize their pharmacokinetics and biodistribution. As a result, the prospects for clinical use of HIV-specific antibodies to treat, clear, and prevent HIV infection are gaining momentum. Here we discuss the diverse methods whereby antibodies are being optimized for neutralization potency and breadth, biodistribution, pharmacokinetics, and effector function with the aim of revolutionizing HIV treatment and prevention options.

  6. Optimism alongside new challenges: using a rehabilitation framework to explore experiences of a qualitative longitudinal cohort of people living with HIV on antiretroviral treatment in Lusaka, Zambia.

    Science.gov (United States)

    Nixon, Stephanie A; Bond, Virginia; Solomon, Patricia; Cameron, Cathy; Mwamba, Chanda; Hanass-Hancock, Jill; Maimbolwa, Margaret C; Menon, J Anitha; Simwaba, Phillimon; Sinyinza, Robert; Siwale, Margaret; Tattle, Stephen; Yates, Tammy

    2017-08-21

    Previous research has demonstrated increased comorbidities related to the chronic effects of HIV. Rehabilitation science offers a useful approach for studying chronic illness. This longitudinal qualitative study used a rehabilitation science approach to explore the experiences over time of women and men living with HIV and on antiretroviral therapy (ART) in the high HIV-prevalence setting of Lusaka, Zambia. Thirty-five participants participated in a total of 99 in-depth interviews from 2012 to 2015. The central pattern that emerged across the participants' narratives was the paradoxical experience of profound optimism alongside significant new challenges. Participants' stories of hopefulness in the face of ongoing struggles played out in three interconnected themes: (1) impacts on my body and life; (2) interventions I am grateful to have and new interventions I need; and (3) stigma reduced and created by ART. Results reflected the ups and downs of life with HIV as a chronic illness. Participants, whilst committed to and healthier on ART, typically experienced multiple physical, psychological and sensory impairments that varied in type, severity and trajectory. Participants valued improved relationships enabled by ART, but yearned for support for living long-term with HIV. Frequently participants reflected that their needs were overlooked related to managing side-effects, exercise, family planning and healthy sexuality. ART strengthened acceptance by self and others through improved health and productivity and through becoming a source of support for others. However, being on ART also led to stigma, driven by persistent associations with sickness, death, lack of productivity and uncertainty. This study points to shortcomings in the current focus of HIV care in Zambia and the region, which centres on initiating and adhering to ART. Findings call for evolution of the HIV care continuum to embrace a more holistic and long-term approach to living with HIV as a chronic

  7. Abacavir does not influence the rate of virological response in HIV-HCV-coinfected patients treated with pegylated interferon and weight-adjusted ribavirin.

    Science.gov (United States)

    Laufer, Natalia; Laguno, Montserrat; Perez, Iñaki; Cifuentes, Carmen; Murillas, Javier; Vidal, Francesc; Bonet, Lucia; Veloso, Sergio; Gatell, José María; Mallolas, Josep

    2008-01-01

    The combination of pegylated interferon (PEG-IFN) plus ribavirin (RBV) is the standard of care for hepatitis C virus (HCV) treatment in HIV-coinfected individuals. In 2007, abacavir (ABC)-based antiretroviral therapy was, for the first time, reported to be associated with early virological failure during HCV treatment. The aim of our study was to evaluate the effect of ABC on the response rate to HCV therapy. A retrospective analysis of HIV-HCV-coinfected patients treated with PEG-IFN and weight-adjusted RBV in four hospitals in Spain was performed. An analysis of baseline descriptive variables was conducted. Logistic regression models were used to test possible associations between non-response and pretreatment characteristics, including antiretroviral drugs. A total of 244 HIV-HCV-coinfected patients treated with PEG-IFN and RBV were included. Overall, 85% of patients were on highly active antiretroviral therapy; of these patients, 24% received ABC-based regimens. The most frequent genotypes were 1 and 3. RBV dosing was 213.2 mg/kg/day in 97% of the patients. In the global intent-to-treat analyses, 46.3% of patients reached a sustained virological response (SVR; 46.2% in ABC group versus 46.7% in non-ABC group, P=1). The only two factors in the multivariate analysis that were statistically associated with an increased risk of failure to achieve SVR were HCV genotypes 1 or 4 and older age. The use of ABC was not associated with failure to achieve SVR at any of the other time points evaluated. Our data suggest that the use of ABC-based regimens in the context of HCV therapy does not negatively affect the outcome of this treatment.

  8. Prevalence of antiretroviral drug resistance among treatment-naive and treated HIV-infected patients in Venezuela

    Directory of Open Access Journals (Sweden)

    Héctor Rafael Rangel

    2009-05-01

    Full Text Available An in-house, low-cost method was developed to determine the genotypic resistance of immunodeficiency virus type 1 (HIV-1 isolates. All 179 Venezuelan isolates analysed belonged to subtype B. Primary drug resistance mutations were found in 11% of 63 treatment-naïve patients. The prevalence of resistance in isolates from 116 HIV-positive patients under antiretroviral treatment was 47% to protease inhibitors, 65% to nucleoside inhibitors and 38% to non-nucleoside inhibitors, respectively. Around 50% of patients in the study harboured viruses with highly reduced susceptibility to the three classical types of drugs after only five years from their initial diagnoses.

  9. Free terminal time optimal control problem for the treatment of HIV infection

    Directory of Open Access Journals (Sweden)

    Amine Hamdache

    2016-01-01

    to provide the explicit formulations of the optimal controls. The corresponding optimality system with the additional transversality condition for the terminal time is derived and solved numerically using an adapted iterative method with a Runge-Kutta fourth order scheme and a gradient method routine.

  10. The case for addressing primary resistance mutations to non-nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Khady Kébé

    2014-01-01

    Full Text Available The prevalence of human immunodeficiency virus (HIV drug resistance mutations (DRMs was estimated in 25 untreated infants who were living with HIV-1, younger than 13 months and living in Senegal. Antiretroviral DRMs were detected in 8 of 25 (32% children. Non-nucleoside reverse transcriptase inhibitor (NNRTI DRMs were present in all (100% children whose viruses harboured DRMs: K103N in 43%; Y181C, K101E and V106M each in 29%; and Y188L in 14%. The D67N thymidine-analogue mutation was observed in only two children whose mothers had received chemoprophylaxis of mother-to-child transmission (MTCT. The proportion of children whose viruses harboured DRMs was then 6.5-fold higher in children whose mother–child couples had received nevirapine (NVP-based chemoprophylaxis than in other couples without prophylaxis [7 of 13 (53.8% vs. 1 of 12 (8.3%]. These findings point to the absolute need to address primary resistance mutations in case of virological failure in young children treated by antiretroviral drugs, and to make more effective treatment regimens available to NVP-exposed infants living with HIV-1 in Senegal.

  11. Treating an HIV/AIDS Patient's PTSD and Medication Nonadherence with Cognitive-Behavioral Therapy: A Principle-Based Approach

    Science.gov (United States)

    Chernoff, Robert A.

    2007-01-01

    HIV/AIDS patients with medication adherence problems are vulnerable to developing drug resistance, immune system degradation, and opportunistic infections. Poor adherence to antiretroviral medication regimens can be aggravated by psychiatric problems, including depression and posttraumatic stress disorder. This article presents the case study of a…

  12. Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With Stage II-IV HIV-Associated Hodgkin Lymphoma

    Science.gov (United States)

    2017-08-14

    AIDS-Related Hodgkin Lymphoma; Classical Hodgkin Lymphoma; HIV Infection; Stage II Hodgkin Lymphoma; Stage IIA Hodgkin Lymphoma; Stage IIB Hodgkin Lymphoma; Stage III Hodgkin Lymphoma; Stage IIIA Hodgkin Lymphoma; Stage IIIB Hodgkin Lymphoma; Stage IV Hodgkin Lymphoma; Stage IVA Hodgkin Lymphoma; Stage IVB Hodgkin Lymphoma

  13. [Optimization of emollient formulation for treating atopic dermatitis by skin physiological index testing].

    Science.gov (United States)

    Huang, Song-Gen; Yang, Xi-Xiao; Mo, Li-Qian; Zhou, Xian-Yi

    2017-07-20

    To optimize the formulation of an emollient for treatment of atopic dermatitis prepared using ceramide, sodium hyaluronate, paeonol, and camellia-seed oil. The emollients with different ratios of the 4 components were designed according to the L9(34)orthogonal table with 4 factors and 3 levels. The efficacy of the prepared emollients was tested in 4-6 week-old BALB/c mouse models of atopic dermatitis to determine the optimal formulation of the emollient by evaluating skin water content, transepidermal water loss (TEWL), pharmacodynamics and skin irritation. Range analysis of the orthogonal table and analysis of variance showed that ceramide and camellia seed oil contents had the greatest impact on the skin water content and TEWL, respectively, and the optimal composition of the emollient contained the 4 components at the ratios of D1E1F1G1. Pharmacodynamic experiments showed that at high, medium and low doses, the emollient with the optimal formulation significantly improved the skin water content, pH and TEWL in the mice (Peffects in the positive control group (P>0.05) and a skin irritation test score of 0. The emollient we prepared can significantly improve skin water content, pH and TEWL in the mouse model of atopic dermatitis without skin irritations.

  14. Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

    Science.gov (United States)

    Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D; Kamya, Moses R; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet

    2015-03-01

    T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa. © 2014 John Wiley & Sons Ltd.

  15. Nitric acid treated multi-walled carbon nanotubes optimized by Taguchi method

    Science.gov (United States)

    Shamsuddin, Shahidah Arina; Derman, Mohd Nazree; Hashim, Uda; Kashif, Muhammad; Adam, Tijjani; Halim, Nur Hamidah Abdul; Tahir, Muhammad Faheem Mohd

    2016-07-01

    Electron transfer rate (ETR) of CNTs can be enhanced by increasing the amounts of COOH groups to their wall and opened tips. With the aim to achieve the highest production amount of COOH, Taguchi robust design has been used for the first time to optimize the surface modification of MWCNTs by nitric acid oxidation. Three main oxidation parameters which are concentration of acid, treatment temperature and treatment time have been selected as the control factors that will be optimized. The amounts of COOH produced are measured by using FTIR spectroscopy through the absorbance intensity. From the analysis, we found that acid concentration and treatment time had the most important influence on the production of COOH. Meanwhile, the treatment temperature will only give intermediate effect. The optimum amount of COOH can be achieved with the treatment by 8.0 M concentration of nitric acid at 120 °C for 2 hour.

  16. Increased ex vivo cell death of central memory CD4 T cells in treated HIV infected individuals with unsatisfactory immune recovery.

    Science.gov (United States)

    Massanella, Marta; Gómez-Mora, Elisabet; Carrillo, Jorge; Curriu, Marta; Ouchi, Dan; Puig, Jordi; Negredo, Eugènia; Cabrera, Cecilia; Clotet, Bonaventura; Blanco, Julià

    2015-07-17

    High levels of ex vivo CD4 T-cell death and the accumulation of highly differentiated and/or immunosenescent T cells have been associated with poor CD4 T-cell recovery in treated HIV-infected individuals. However, the relationship between cell death and T-cell differentiation is still unclear. We have analyzed cell death, immunosenescence and differentiation parameters in HAART-treated subjects (VL 400 cells/μL (immunoconcordant, n = 33). We included 11 healthy individuals as reference. As expected, suboptimal CD4 T-cell recovery was associated with low frequencies of naïve cells, high frequencies of transitional and effector memory cells and a subsequent low ratio of central/transitional memory cells in the CD4 compartment. These alterations correlated with spontaneous CD4 T-cell death. A deeper analysis of cell death in CD4 T-cell subsets showed increased cell death in memory cells of immunodiscordant individuals, mainly affecting central memory cells. Immunosenescence was also higher in immunodiscordant individuals albeit unrelated to cell death. The CD8 compartment was similar in both HIV-infected groups, except for an underrepresentation of naïve cells in immunodiscordant individuals. Immunodiscordant individuals show alterations in memory CD4 T-cell differentiation associated with a short ex vivo lifespan of central memory cells and an in vivo low central/transitional memory cell ratio. These alterations may contribute to poor CD4 T-cell repopulation.

  17. Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates.

    Science.gov (United States)

    Van Wesenbeeck, L; Rondelez, E; Feyaerts, M; Verheyen, A; Van der Borght, K; Smits, V; Cleybergh, C; De Wolf, H; Van Baelen, K; Stuyver, L J

    2011-01-01

    The integrase inhibitor raltegravir (RAL) is currently used for the treatment of both treatment-naïve and treatment-experienced HIV-1-infected patients. Elvitegravir (EVG) is in late phases of clinical development. Since significant cross-resistance between RAL and EVG is observed, there is a need for second-generation integrase inhibitors (INIs) with a higher genetic barrier and limited cross-resistance to RAL/EVG. A panel of HIV-1 integrase recombinants, derived from plasma samples from raltegravir-treated patients (baseline and follow-up samples), were used to study the cross-resistance profile of two second-generation integrase inhibitors, MK-2048 and compound G. Samples with Q148H/R mutations had elevated fold change values with all compounds tested. Although samples with the Y143R/C mutation had reduced susceptibility to RAL, they remained susceptible to MK-2048 and compound G. Samples with the N155H mutation had no reduced susceptibility to compound G. In conclusion, our results allowed ranking of the INIs on the basis of the antiviral activities using recombinant virus stocks from RAL-treated patient viruses. The order according to decreasing susceptibility is compound G, MK-2048, and EVG.

  18. Expanded GDoF-optimality Regime of Treating Interference as Noise in the $M\\times 2$ X-Channel

    KAUST Repository

    Gherekhloo, Soheil

    2016-11-14

    Treating interference as noise (TIN) as the most appropriate approach in dealing with interference and the conditions on its optimality has attracted the interest of researchers recently. However, our knowledge on necessary and sufficient conditions of TIN is restricted to a few setups with limited number of users. In this paper, we study the optimality of TIN in terms of the generalized degrees of freedom (GDoF) for a fundamental network, namely, the M× 2 X-channel. To this end, the achievable GDoF of TIN with power allocations at the transmitters is studied. It turns out that the transmit power allocation maximizing the achievable GDOF is given by on-off signaling as long as the receivers use TIN. This leads to two variants of TIN, namely, P2P-TIN and 2-IC-TIN. While in the first variant the M× 2 X-channel is reduced to a point-to-point (P2P) channel, in the second variant, the setup is reduced to a two-user interference channel in which the receivers use TIN. The optimality of these two variants is studied separately. To this end, novel genie-aided upper bounds on the capacity of the X-channel are established. The conditions on the optimality of P2P-TIN can be summarized as follows. P2P-TIN is GDoF-optimal if there exists a dominant multiple access channel or a dominant broadcast channel embedded in the X channel. Furthermore, the necessary and sufficient conditions on the GDoF-optimality of 2-IC-TIN are presented. Interestingly, it turns out that operating the M× 2 X-channel in the 2-IC-TIN mode might be still GDOF optimal, although the conditions given by Geng et al. are violated. However, 2-IC-TIN is sub-optimal if there exists a single interferer which causes sufficiently strong interference at both receivers. The comparison of the results with the state of the art shows that the GDOF optimality of TIN is expanded significantldy.

  19. Structural community factors and sub-optimal engagement in HIV care among low-income women in the Deep South of the USA.

    Science.gov (United States)

    Walcott, Melonie; Kempf, Mirjam-Colette; Merlin, Jessica S; Turan, Janet M

    2016-01-01

    This study describes the ways in which poverty and other structural factors create a risk environment for sub-optimal engagement in HIV care among low-income women living with HIV in the Southern USA, contributing to existing health disparities. We conducted a qualitative study in 2012, involving in-depth interviews with 14 stakeholders (service providers and representatives of community-based organisations) and 7 focus-group discussions with 46 women living with HIV (89% African American). A thematic approach in the context of the social ecological model guided data analysis. Data were coded and analysed using NVivo qualitative software. The findings suggested that structural community factors, such as poverty, poor employment opportunities, limited access to healthcare resources, stigma, transportation challenges and access to illicit substances, may work independently and in synergy to impact women's health seeking behaviour and decision-making, thereby influencing their ability to engage in HIV care. Interventions designed to improve engagement in HIV care should address structural factors to bolster low-income women's ability to engage in care.

  20. HIV signaling through CD4 and CCR5 activates Rho family GTPases that are required for optimal infection of primary CD4+ T cells.

    Science.gov (United States)

    Lucera, Mark B; Fleissner, Zach; Tabler, Caroline O; Schlatzer, Daniela M; Troyer, Zach; Tilton, John C

    2017-01-24

    HIV-1 hijacks host cell machinery to ensure successful replication, including cytoskeletal components for intracellular trafficking, nucleoproteins for pre-integration complex import, and the ESCRT pathway for assembly and budding. It is widely appreciated that cellular post-translational modifications (PTMs) regulate protein activity within cells; however, little is known about how PTMs influence HIV replication. Previously, we reported that blocking deacetylation of tubulin using histone deacetylase inhibitors promoted the kinetics and efficiency of early post-entry viral events. To uncover additional PTMs that modulate entry and early post-entry stages in HIV infection, we employed a flow cytometric approach to assess a panel of small molecule inhibitors on viral fusion and LTR promoter-driven gene expression. While viral fusion was not significantly affected, early post-entry viral events were modulated by drugs targeting multiple processes including histone deacetylation, methylation, and bromodomain inhibition. Most notably, we observed that inhibitors of the Rho GTPase family of cytoskeletal regulators-including RhoA, Cdc42, and Rho-associated kinase signaling pathways-significantly reduced viral infection. Using phosphoproteomics and a biochemical GTPase activation assay, we found that virion-induced signaling via CD4 and CCR5 activated Rho family GTPases including Rac1 and Cdc42 and led to widespread modification of GTPase signaling-associated factors. Together, these data demonstrate that HIV signaling activates members of the Rho GTPase family of cytoskeletal regulators that are required for optimal HIV infection of primary CD4+ T cells.

  1. Optimizing outcome in SLE: treating-to-target and definition of treatment goals.

    Science.gov (United States)

    Doria, Andrea; Gatto, Mariele; Zen, Margherita; Iaccarino, Luca; Punzi, Leonardo

    2014-07-01

    Patients affected with systemic lupus erythematosus (SLE) display poor-long term prognosis and increased mortality in respect of general population. This may be due to continuous organ damage accrual which is fostered both by persistent disease activity (mainly in the short term) and prolonged corticosteroid exposure (mainly in the long term). The effort of defining novel therapeutic goals to which patients should be treated in order to have their prognosis improved is named treat-to-target. Remission in SLE was shown to be associated with better outcome and prolonged survival; in clinical practice, patients may experience either complete or clinical remission, which are defined as complete clinical/serological healing or no clinical signs of lupus with active serology, respectively. The main treat-to-target in SLE is complete remission, however since longitudinal observations suggest that clinical remission or low disease activity even with minimal corticosteroid intake do improve patients prognosis and survival as well, they may be assumed as acceptable alternative targets. Suitable therapeutic strategies have to be defined in order for these goals to be achieved including early diagnosis, effective treatment and proper corticosteroid tapering which in turn require development of more reliable serum biomarkers for early disease detection and less toxic targeted therapies with a steroid-sparing potential.

  2. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada.

    Directory of Open Access Journals (Sweden)

    Hasina Samji

    Full Text Available Combination antiretroviral therapy (ART has significantly increased survival among HIV-positive adults in the United States (U.S. and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000-2007 in the U.S. and Canada.Participants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD, aged ≥20 years and on ART. Mortality rates were calculated using participants' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables.The crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 [standard error (SE 0.5] to 51.4 [SE 0.5] years from 2000-2002 to 2006-2007. Men and women had comparable life expectancies in all periods except the last (2006-2007. Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts <350 cells/mm(3.A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain.

  3. Empathy and avoidance in treating patients living with HIV/AIDS (PLWHA) among service providers in China

    OpenAIRE

    Lin, Chunqing; Li, Li; WAN, Dai; Wu, Zunyou; Yan, Zhihua

    2012-01-01

    This study aims to investigate health care providers’ empathy levels and its association with avoidance in providing service to patients living with HIV/AIDS (PLWHA) in China. A total of 1760 health service providers were randomly sampled from 40 county hospitals in two provinces of China. Using a self-administered questionnaire, participants’ demographic characteristics, work history, empathy level, and avoidance attitudes toward PLWHA were collected in a cross-sectional survey. Empathy was ...

  4. A HHV-8 positive, HIV negative multicentric Castleman disease treated with R-CEOP chemotherapy and valganciclovir combination.

    Science.gov (United States)

    Kantarci, Fatma Eda Nuhoglu; Eren, Rafet; Gündoğan, Cihan; Huq, Gülben Erdem; Doğu, Mehmet Hilmi; Suyanı, Elif

    2016-07-01

    Multicentric Castleman disease (MCD) is a lymphoproliferative disorder characterized by systemic symptoms like recurrent lymphadenopathy, fever and hepatosplenomegaly. Human herpes virus 8 (HHV-8) can be associated with MCD whether the patient is infected with human immunodeficiency virus (HIV) or not. A 59-year-old male patient presented with fatigue, drowsiness and enlarged lymph nodes. Thoracic and abdominal computed tomography showed enlarged mediastinal, axillary, paracardiac, paraaortic, celiac, mesenteric, obturator and inguinal lymph nodes concomitant with enlarged liver and spleen. Cervical lymph node biopsy revealed HHV-8 positive plasma cell MCD. The patient's tests were negative for HIV. R-CEOP (rituximab, cyclophosphamide, etoposide, vincristin, prednisolone) and valganciclovir treatments were started simultaneously. After sixth cycle of R-CEOP, the patient achieved unconfirmed complete remission. Rituximab combined with CEOP protocol and antiviral therapy against HHV-8 might be an effective therapeutic approach without a considerable side effect for HHV-8-positive HIV-negative MCD patients. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  5. [How I treat...Recommendations for controlling and optimizing a pharmacological therapy].

    Science.gov (United States)

    Scheen, A J

    2014-11-01

    Any pharmacological treatment should ideally be effective and safe. The supervision of an ongoing therapy should control that individualized goals are reached while tolerance and safety are present. In case of not reaching the predefined objectives, the causes of failure should first be screened (for instance, exclusion of poor patient compliance), and the treatment should be then optimized: dose adjustment, add-on of another drug (if possible synergistic combination) and/or shift to a more effective pharmacological therapy. In some cases, therapeutic monitoring may be useful or even mandatory in order to better adjust drug dosing and thus guarantee both efficacy and safety.

  6. Optimal use of proton pump inhibitors for treating acid peptic diseases in primary care.

    Science.gov (United States)

    Tack, J; Louis, E; Persy, V; Urbain, D

    2013-12-01

    Heartburn, reflux and epigastric pain are frequently encountered symptoms in primary care medicine. Acid peptic diseases such as peptic ulcer and gastrointestinal reflux disease have a high prevalence, can have important impact on patient quality of life and represent a considerable health care cost. Proton pump inhibitors (PPIs) are the most potent pharmacological inhibitors of gastric acid secretion currently available and are the mainstay medical therapy for acid peptic diseases. This review summarizes current evidence on treatment of acid-peptic diseases with proton pump inhibitors and provides primary care clinicians with best practice guidelines for optimal use of these drugs.

  7. Sub-optimal vitamin B-12 levels among ART-naive HIV-positive individuals in an urban cohort in Uganda.

    Directory of Open Access Journals (Sweden)

    Aggrey S Semeere

    Full Text Available Malnutrition is common among HIV-infected individuals and is often accompanied by low serum levels of micronutrients. Vitamin B-12 deficiency has been associated with various factors including faster HIV disease progression and CD4 depletion in resource-rich settings. To describe prevalence and factors associated with sub-optimal vitamin B-12 levels among HIV-infected antiretroviral therapy (ART naïve adults in a resource-poor setting, we performed a cross-sectional study with a retrospective chart review among individuals attending either the Mulago-Mbarara teaching hospitals' Joint AIDS Program (MJAP or the Infectious Diseases Institute (IDI clinics, in Kampala, Uganda. Logistic regression was used to determine factors associated with sub-optimal vitamin B-12. The mean vitamin B-12 level was 384 pg/ml, normal range (200-900. Sub-optimal vitamin B-12 levels (<300 pg/ml were found in 75/204 (36.8%. Twenty-one of 204 (10.3% had vitamin B-12 deficiency (<200 pg/ml while 54/204 (26.5% had marginal depletion (200-300 pg/ml. Irritable mood was observed more among individuals with sub-optimal vitamin B-12 levels (OR 2.5, 95% CI; 1.1-5.6, P=0.03. Increasing MCV was associated with decreasing serum B-12 category; 86.9 fl (± 5.1 vs. 83 fl (± 8.4 vs. 82 fl (± 8.4 for B-12 deficiency, marginal and normal B-12 categories respectively (test for trend, P=0.017. Compared to normal B-12, individuals with vitamin B-12 deficiency had a longer known duration of HIV infection: 42.2 months (± 27.1 vs. 29.4 months (± 23.8; P=0.02. Participants eligible for ART (CD4<350 cells/µl with sub-optimal B-12 had a higher mean rate of CD4 decline compared to counterparts with normal B-12; 118 (± 145 vs. 22 (± 115 cells/µl/year, P=0.01 respectively. The prevalence of a sub-optimal vitamin B-12 was high in this HIV-infected, ART-naïve adult clinic population in urban Uganda. We recommend prospective studies to further clarify the causal relationships of sub-optimal

  8. Statistical optimization and fabrication of a press coated pulsatile dosage form to treat nocturnal acid breakthrough.

    Science.gov (United States)

    Agarwal, Vaibhav; Bansal, Mayank

    2013-08-01

    Present work focuses on the use of mimosa seed gum to develop a drug delivery system making combined use of floating and pulsatile principles, for the chrono-prevention of nocturnal acid breakthrough. The desired aim was achieved by fabricating a floating delivery system bearing time - lagged coating of Mimosa pudica seed polymer for the programmed release of Famotidine. Response Surface Methodology was the statistical tool that was employed for experiment designing, mathematical model generation and optimization study. A 3(2) full factorial design was used in designing the experiment.% weight ratio of mimosa gum to hydroxy propyl methyl cellulose in the coating combination and the coating weight were the independent variables, whereas the lag time and the cumulative % drug release in 360 minutes were the observed responses. Results revealed that both the coating composition and the coating weight significantly affected the release of drug from the dosage form. The optimized formulation prepared according to the computer generated software, Design-Expert(®) deciphered response which were in close proximity with the experimental responses, thus confirming the robustness as well as accuracy of the predicted model for the utilization of natural polymer like mimosa seed gum for the chronotherapeutic treatment of nocturnal acid breakthrough.

  9. Proposal to optimize ecotoxicological evaluation of wastewater treated by conventional biological and ozonation processes.

    Science.gov (United States)

    Wigh, Adriana; Devaux, Alain; Brosselin, Vanessa; Gonzalez-Ospina, Adriana; Domenjoud, Bruno; Aït-Aïssa, Selim; Creusot, Nicolas; Gosset, Antoine; Bazin, Christine; Bony, Sylvie

    2016-02-01

    A mixture of urban and hospital effluents (50% v/v) was evaluated for ecotoxicity with an advanced bioassay battery. Mixed effluents were tested before any treatment, after biological treatment alone, and after biological treatment followed by a tertiary ozonation (15 mg O3/L). Laying a high value on the continuance of organisms' fitness, essential to preserve a healthy receiving ecosystem, the main objective of this study was to combine normalized bioassays with newly developed in vivo and in vitro tests in order to assess alteration of embryo development, growth and reproduction, as well as genotoxic effects in aquatic organisms exposed to complex wastewater effluents. Comparison of the bioassays sensitivity was considered. Contrary to the lack of toxicity observed with normalized ecotoxicity tests, endpoints measured on zebrafish embryos such as developmental abnormalities and genotoxicity demonstrated a residual toxicity in wastewater both after a biological treatment followed or not by a tertiary O3 treatment. However, the ozonation step allowed to alleviate the residual endocrine disrupting potential measure in the biologically treated effluent. This study shows that normalized bioassays are not sensitive enough for the ecotoxicological evaluation of wastewaters and that there is a great need for the development of suitable sensitive bioassays in order to characterize properly the possible residual toxicity of treated effluents.

  10. Performance evaluation of chemical coagulation process to treat bagasse wastewater: modeling and optimization

    Directory of Open Access Journals (Sweden)

    Thirugnanasambandham K.

    2016-03-01

    Full Text Available In this present study, chemical coagulation process (CC treatment process was investigated under different conditions such as pH, ferric chloride dose, agitation time and settling time to treat bagasse wastewater using response surface methodology (RSM. The outcomes were evaluated using Pareto analysis of variance (ANOVA and second order polynomial models were created with the aim of being able to predict the responses. Ideal conditions were observed to be as per the following: agitation time of 25 min, pH of 7, ferric chloride dose of 6 g/L and settling time of 60 min. Under these conditions, turbidity removal of 62%, COD removal of 67%, TDS removal 53% and sludge production of 32 mL/L were obtained with operating cost of 3.50 Rupee/L. The mechanism of CC was analyzed using XRD spectrum and founds to be adsorption.

  11. USING TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS TO TREAT DEPRESSION IN HIV-INFECTED PERSONS: THE OUTCOMES OF A FEASIBILITY STUDY

    Directory of Open Access Journals (Sweden)

    Helena eKnotkova

    2012-06-01

    Full Text Available Transcranial direct current stimulation (tDCS is a novel non-invasive neuromodulatory method that influences neuronal firing rates and activity on dopaminergic and serotoninergic circuits. TDCS has been shown to relieve Major Depressive Disorder (MDD in the general population, suggesting its potential for other vulnerable -populations with high MDD prevalence. Aims: This study evaluated l feasibility, safety, acceptability and clinical outcomes of a two-week tDCS antidepressant treatment in HIV-MDD co-diagnosed patients, and the feasibility of collecting serum and saliva for analysis of immunity-biomarkers.. Methods: Ten enrolled patients underwent baseline evaluation and started the tDCS treatment (Mon-Fri for two weeks delivered with Phoressor II 850 PM for 20 min at 2 mA at each visit, using 2 electrodes (36cm2 placed over F3 position of EEG 10-20 system and the contralateral supraorbital region. Outcome-measures were collected at baseline, after the last tDCS and two weeks later. A quantitative microarray (Ray Bio Tech Inc for TH1/TH2 cytokines was used for saliva and blood analysis. Results: Analyzable outcome-data were obtained from 8 subjects. Depression scores significantly decreased (p<.0005 after the treatment. No serious adverse events occurred. Several transient minor AEs and occasional changes of blood pressure and heart rate were noted. Mini-mental status scores remained unchanged or increased after the treatment. All subjects were highly satisfied with the protocol and treatment results and described the desire to find new treatments for HIV-MDD as motivating participation. Conclusions: F indings support feasibility and clinical potential of tDCS for HIV-MDD patients, and justify larger-sample, sham-controlled trials.

  12. Integrating Household Water Treatment, Hand Washing, and Insecticide-Treated Bed Nets into Pediatric HIV Care in Mombasa, Kenya: Impact on Diarrhea and Malaria Risk.

    Science.gov (United States)

    Sugar, Naomi R; Schilling, Katharine A; Kim, Sunkyung; Ahmed, Aabid; Muyanga, Dennis Ngui; Sivapalasingam, Sumathi; Quick, Robert

    2017-08-04

    In developing countries, HIV-infected children are at higher risk for morbidity and mortality from opportunistic infections than HIV-uninfected children. To address this problem, the Healthy Living Initiative (HLI) in Mombasa, Kenya distributed basic care packages (BCPs) containing improved water storage vessels, water treatment solution, soap, and insecticide-treated bednets (ITNs) to prevent diarrhea and malaria in children, and had community health workers (CHWs) make bimonthly home visits to encourage adherence with HLI interventions and antiretroviral medicine use. To evaluate HLI, we enrolled 500 HIV-infected children from Bomu Hospital. In the implementation phase, from February-August 2011, we conducted surveys of caregivers, then provided free BCPs. In the evaluation phase, from September 2011-August 2012, CHWs recorded observations of BCP use during home visits. We abstracted hospital data to compare diarrhea and malaria episodes, and pharmacy data on antiretrovirals (ARVs) dispensed, between the 12-month pre-implementation baseline phase (February 2010-January 2011) and the evaluation phase. The retention rate of children in HLI was 78.4%. In a multivariable logistic regression model adjusting for demographic characteristics, number of CHW home visits, distance to clinic, orphan status, and number of ARVs dispensed, children in HLI had 71 % lower risk of diarrhea (relative risk [RR] 0.29, pdiarrhea and malaria during the evaluation phase than the baseline phase.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  13. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study

    Science.gov (United States)

    Ekouevi, Didier K.; Balestre, Eric; Coffie, Patrick A.; Minta, Daouda; Messou, Eugene; Sawadogo, Adrien; Minga, Albert; Sow, Papa Salif; Bissagnene, Emmanuel; Eholie, Serge P.; Gottlieb, Geoffrey S.; Dabis, François; Zannou, Djimon Marcel; Ahouada, Carin; Akakpo, Jocelyn; Ahomadegbé, Christelle; Bashi, Jules; Gougounon-Houéto, Alice; Azon-Kouanou, Angèle; Houngbé, Fabien; Koumakpaï, Sikiratou; Alihonou, Florence; d’Almeida, Marcelline; Hodonou, Irvine; Hounhoui, Ghislaine; Sagbo, Gracien; Tossa-Bagnan, Leïla; Adjide, Herman; Drabo, Joseph; Bognounou, René; Dienderé, Arnaud; Traore, Eliezer; Zoungrana, Lassane; Zerbo, Béatrice; Sawadogo, Adrien Bruno; Zoungrana, Jacques; Héma, Arsène; Soré, Ibrahim; Bado, Guillaume; Tapsoba, Achille; Yé, Diarra; Kouéta, Fla; Ouedraogo, Sylvie; Ouédraogo, Rasmata; Hiembo, William; Gansonré, Mady; Messou, Eugène; Gnokoro, Joachim Charles; Koné, Mamadou; Kouakou, Guillaume Martial; Bosse, Clarisse Amani; Brou, Kouakou; Assi, Achi Isidore; Chenal, Henri; Hawerlander, Denise; Soppi, Franck; Minga, Albert; Abo, Yao; Bomisso, Germain; Eholié, Serge Paul; Amego, Mensah Deborah Noelly; Andavi, Viviane; Diallo, Zelica; Ello, Frédéric; Tanon, Aristophane Koffi; Koule, Serge Olivier; Anzan, Koffi Charles; Guehi, Calixte; Aka, Edmond Addi; Issouf, Koffi Ladji; Kouakou, Jean-Claude; N’Gbeche, Marie-Sylvie; Touré, Pety; Avit-Edi, Divine; Kouakou, Kouadio; Moh, Magloire; Yao, Valérie Andoblé; Folquet, Madeleine Amorissani; Dainguy, Marie-Evelyne; Kouakou, Cyrille; Méa-Assande, Véronique Tanoh; Oka-Berete, Gladys; Zobo, Nathalie; Acquah, Patrick; Kokora, Marie-Berthe; Eboua, Tanoh François; Timité-Konan, Marguerite; Ahoussou, Lucrèce Diecket; Assouan, Julie Kebé; Sami, Mabéa Flora; Kouadio, Clémence; Renner, Lorna; Goka, Bamenla; Welbeck, Jennifer; Sackey, Adziri; Owiafe, Seth Ntiri; Wejse, Christian; Silva, Zacarias José Da; Paulo, Joao; Rodrigues, Amabelia; da Silva, David; Medina, Candida; Oliviera-Souto, Ines; Østergaard, Lars; Laursen, Alex; Sodemann, Morten; Aaby, Peter; Fomsgaard, Anders; Erikstrup, Christian; Eugen-Olsen, Jesper; Maïga, Moussa Y; Diakité, Fatoumata Fofana; Kalle, Abdoulaye; Katile, Drissa; Traore, Hamar Alassane; Minta, Daouda; Cissé, Tidiani; Dembelé, Mamadou; Doumbia, Mohammed; Fomba, Mahamadou; Kaya, Assétou Soukho; Traoré, Abdoulaye M; Traoré, Hamady; Toure, Amadou Abathina; Dicko, Fatoumata; Sylla, Mariam; Berthé, Alima; Traoré, Hadizatou Coulibaly; Koïta, Anta; Koné, Niaboula; N'Diaye, Clémentine; Coulibaly, Safiatou Touré; Traoré, Mamadou; Traoré, Naïchata; Charurat, Man; Ajayi, Samuel; Dapiap, Stephen; Otu; Igbinoba, Festus; Benson, Okwara; Adebamowo, Clément; James, Jesse; Obaseki; Osakede, Philip; Olasode, John; Sow, Papa Salif; Diop, Bernard; Manga, Noël Magloire; Tine, Judicael Malick; Signate Sy, Haby; Ba, Abou; Diagne, Aida; Dior, Hélène; Faye, Malick; Gueye, Ramatoulaye Diagne; Mbaye, Aminata Diack; Patassi, Akessiwe; Kotosso, Awèrou; Kariyare, Benjamin Goilibe; Gbadamassi, Gafarou; Komi, Agbo; Mensah-Zukong, Kankoé Edem; Pakpame, Pinuwe; Lawson-Evi, Annette Koko; Atakouma, Yawo; Takassi, Elom; Djeha, Améyo; Ephoévi-gah, Ayoko; Djibril, Sherifa El-Hadj; Dabis, François; Bissagnene, Emmanuel; Arrivé, Elise; Coffie, Patrick; Ekouevi, Didier; Jaquet, Antoine; Leroy, Valériane; Lewden, Charlotte; Sasco, Annie; Azani, Jean-Claude; Allou, Gérard; Balestre, Eric; Bohossou, Franck; Karcher, Sophie; Gonsan, Jules Mahan; Carrou, Jérôme Le; Lenaud, Séverin; Nchot, Célestin; Malateste, Karen; Yao, Amon Roseamonde; Siloué, Bertine; Clouet, Gwenaelle; Djetouan, Hugues; Doring, Alexandra; Kouakou, Adrienne; Rabourdin, Elodie; Rivenc, Jean; Anglaret, Xavier; Ba, Boubacar; Essanin, Jean Bosco; Ciaranello, Andrea; Datté, Sébastien; Desmonde, Sophie; Diby, Jean-Serge Elvis; Gottlieb, Geoffrey S.; Horo, Apollinaire Gninlgninrin; Kangah, Serge N'zoré; Malvy, Denis; Meless, David; Mounkaila-Harouna, Aida; Ndondoki, Camille; Shiboski, Caroline; Thiébaut, Rodolphe; PAC-CI; Abidjan

    2013-01-01

    Background HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). Methods We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d’Ivoire, Mali, and Senegal, in the West Africa region. Results Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3–51.7) and 42.4 years, IQR (37.0–47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm3, IQR (83–247) among HIV-2 infected patients and 146 cells/mm3, IQR (55–249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm3 after 24 months on ART for HIV-2 patients and 169 cells/mm3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7–4.3). Conclusions This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population. PMID:23824279

  14. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

    Directory of Open Access Journals (Sweden)

    Didier K Ekouevi

    Full Text Available HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA.We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region.Data was merged for 1,754 patients (56% female, including 1,021 HIV-2 infected patients (551 on ART and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART. At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7 and 42.4 years, IQR (37.0-47.3 for dually seropositive patients (p = 0.048. Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C. The median CD4 count at the ART initiation is 166 cells/mm(3, IQR (83-247 among HIV-2 infected patients and 146 cells/mm(3, IQR (55-249 among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3 after 24 months on ART for HIV-2 patients and 169 cells/mm(3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3.This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

  15. Response Surface Optimization of Process Parameters and Fuzzy Analysis of Sensory Data of High Pressure-Temperature Treated Pineapple Puree.

    Science.gov (United States)

    Chakraborty, Snehasis; Rao, Pavuluri Srinivasa; Mishra, Hari Niwas

    2015-08-01

    The high-pressure processing conditions were optimized for pineapple puree within the domain of 400-600 MPa, 40-60 °C, and 10-20 min using the response surface methodology (RSM). The target was to maximize the inactivation of polyphenoloxidase (PPO) along with a minimal loss in beneficial bromelain (BRM) activity, ascorbic acid (AA) content, antioxidant capacity, and color in the sample. The optimum condition was 600 MPa, 50 °C, and 13 min, having the highest desirability of 0.604, which resulted in 44% PPO and 47% BRM activities. However, 93% antioxidant activity and 85% AA were retained in optimized sample with a total color change (∆E*) value less than 2.5. A 10-fold reduction in PPO activity was obtained at 600 MPa/70 °C/20 min; however, the thermal degradation of nutrients was severe at this condition. Fuzzy mathematical approach confirmed that sensory acceptance of the optimized sample was close to the fresh sample; whereas, the thermally pasteurized sample (treated at 0.1 MPa, 95 °C for 12 min) had the least sensory score as compared to others.

  16. Optimizing drugs to reach treatment targets for children and adolescents living with HIV

    Directory of Open Access Journals (Sweden)

    Martina Penazzato

    2015-12-01

    Full Text Available Introduction: As the global community makes progress towards the 90-90-90 targets by 2020, a key challenge is ensuring that antiretroviral drugs for children and adolescents are suitable to the context of resource-limited settings. Drug optimization aims to support the expanded use of more simplified, less toxic drug regimens with high barriers to drug resistance that require minimal clinical monitoring while maintaining therapeutic efficacy. This manuscript summarizes the progress made and outlines further critical steps required to ensure that the right drugs are available to start children and adolescents on treatment and to keep them virologically suppressed. Discussion: Building upon previous work in drug optimization, several important steps were taken in 2014 to ensure alignment between WHO dosing recommendations and the requirements of regulatory bodies, to accelerate drug development, to reduce intellectual property barriers to generic production of combined formulations and rationalize drug selection in countries. The priority for the future is to improve access to antiretroviral therapy (ART at the two ends of the paediatric age spectrum – infants and adolescents – where the treatment gap is greatest, and optimize drug sequencing with better use of available medicines for second- and third-line ART. Future efforts in this area will require continuous collaboration and coordination, and the promotion of innovative approaches to accelerate access to new drugs and formulations. Conclusions: While significant progress has been made, additional efforts are needed to ensure that treatment targets are reached by 2020.

  17. Review of life expectancy in people with HIV in settings with optimal ART access: what we know and what we don't

    Directory of Open Access Journals (Sweden)

    Sabin C

    2012-11-01

    Full Text Available Life expectancy (LE is an important indicator of health used widely by government and healthcare agencies to monitor trends over time and to determine resource allocation, as well as by insurance companies and pension providers. LE of the HIV-positive population has increased dramatically since the introduction of combination antiretroviral therapy (cART; indeed, it is now believed that LE may be similar to that of the general population in some subgroups. There are, however, specific subgroups in which LE remains substantially impaired. The impact of HIV and of cART on mortality may be expressed in several ways. LE itself provides an estimate of the average additional number of years that an individual would be expected to live beyond a particular age. However, the detrimental impact of HIV may also be described in terms of the number of years of life lost or the gains in LE if HIV were to be eliminated as a cause of morbidity in the population. My presentation will start with a description of the different methods that researchers have used to describe the mortality outcomes of those with HIV, and the impact of cART on these. I will then consider how LE in the HIV-positive population has changed over time and will describe the impact of demographic factors (e.g. gender, age, ethnic group on LE. To investigate the circumstances under which LE may return to normal levels, I will also consider the potential impact of timely diagnosis and linkage into care, continued engagement with care, optimal initiation of cART and maintenance of viral suppression on LE. Finally, I will discuss some of the limitations of the approaches used to estimate LE, with particular emphasis on the confounding effects of lifestyle and behavioural factors when making any comparison with LE in the general population.

  18. MicroRNA-210, microRNA-331 and microRNA-7 are differentially regulated in treated HIV-1-infected individuals, and are associated with markers of systemic inflammation

    DEFF Research Database (Denmark)

    Ballegaard, Vibe; Ralfkiaer, Ulrik; Pedersen, Karin K

    2017-01-01

    OBJECTIVE: Inflammation may contribute to increased risk of cardiovascular disease (CVD) in HIV-1 infection. MicroRNAs (miRNAs) are involved in the regulation of inflammation. In treated HIV-1-infected individuals, we aimed to identify differentially expressed miRNAs with known roles...... in inflammation and CVD risk, and to investigate associations between these and systemic inflammation. METHODS: In a screening cohort including 14 HIV-1-infected individuals and nine uninfected controls microarray profiling was performed using peripheral blood mononuclear cells (PBMC). Differentially regulated miRNAs...... previously related to inflammation and CVD were validated using real-time quantitative PCR (qRT-PCR) in 26 HIV-1-infected individuals and 20 uninfected controls. Validated miRNAs were measured in PBMC, CD4 and CD8 T-cells. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), high-sensitivity CRP...

  19. Should patients with polycystic ovarian syndrome be treated with metformin? A note of cautious optimism.

    Science.gov (United States)

    Homburg, Roy

    2002-04-01

    Hyperinsulinaemia has proved to be a key link in the enigmatic generation of the symptoms of polycystic ovarian syndrome (PCOS), i.e. anovulatory infertility and the skin stigmata induced by hyperandrogenism. Regression of these symptoms may be achieved by reducing the hyperinsulinaemia. As obesity exaggerates the expression of the symptoms induced by hyperinsulinaemia, a low calorie diet and lifestyle change resulting in loss of weight for obese women with PCOS is capable of reversing these symptoms. Insulin-sensitizing agents, predominantly metformin, have been examined for their ability, in all patients with PCOS, to achieve similar beneficial changes to those induced by loss of weight in the obese. While the scientific value of many of these studies is questionable and solid evidence of efficiency and safety is not complete, the honourable intent of lowering high insulin levels in this way prompts the bottom line of this debate to strike a note of cautious optimism that insulin-sensitizing agents will be of some clinical usefulness both in the short-term aiding of infertility treatment and, possibly, in the prevention of the long-term sequelae for this troublesome and very prevalent condition.

  20. Design of the HPTN 065 (TLC-Plus) study: A study to evaluate the feasibility of an enhanced test, link-to-care, plus treat approach for HIV prevention in the United States.

    Science.gov (United States)

    Gamble, Theresa; Branson, Bernard; Donnell, Deborah; Hall, H Irene; King, Georgette; Cutler, Blayne; Hader, Shannon; Burns, David; Leider, Jason; Wood, Angela Fulwood; G Volpp, Kevin; Buchacz, Kate; El-Sadr, Wafaa M

    2017-08-01

    Background/Aims HIV continues to be a major public health threat in the United States, and mathematical modeling has demonstrated that the universal effective use of antiretroviral therapy among all HIV-positive individuals (i.e. the "test and treat" approach) has the potential to control HIV. However, to accomplish this, all the steps that define the HIV care continuum must be achieved at high levels, including HIV testing and diagnosis, linkage to and retention in clinical care, antiretroviral medication initiation, and adherence to achieve and maintain viral suppression. The HPTN 065 (Test, Link-to-Care Plus Treat [TLC-Plus]) study was designed to determine the feasibility of the "test and treat" approach in the United States. Methods HPTN 065 was conducted in two intervention communities, Bronx, NY, and Washington, DC, along with four non-intervention communities, Chicago, IL; Houston, TX; Miami, FL; and Philadelphia, PA. The study consisted of five components: (1) exploring the feasibility of expanded HIV testing via social mobilization and the universal offer of testing in hospital settings, (2) evaluating the effectiveness of financial incentives to increase linkage to care, (3) evaluating the effectiveness of financial incentives to increase viral suppression, (4) evaluating the effectiveness of a computer-delivered intervention to decrease risk behavior in HIV-positive patients in healthcare settings, and (5) administering provider and patient surveys to assess knowledge and attitudes regarding the use of antiretroviral therapy for prevention and the use of financial incentives to improve health outcomes. The study used observational cohorts, cluster and individual randomization, and made novel use of the existing national HIV surveillance data infrastructure. All components were developed with input from a community advisory board, and pragmatic methods were used to implement and assess the outcomes for each study component. Results A total of 76 sites in

  1. Optimal diagnostic measures and thresholds for hypogonadism in men with HIV/AIDS: comparison between 2 transdermal testosterone replacement therapy gels.

    Science.gov (United States)

    Blick, Gary

    2013-03-01

    To determine the incidence of hypogonadism in men with human immunodeficiency virus (HIV)/acquired immunodeficiency virus (AIDS), the most useful serum testosterone measurement and threshold for diagnosing hypogonadism, and the comparative efficacy of 2 testosterone replacement therapy (TRT) 1% gels (AndroGel® [Abbott Laboratories] and Testim® [Auxilium Pharmaceuticals, Inc.]). This was a 2-stage observational study. In stage 1, patient records from 2 medical practices specializing in HIV/AIDS were reviewed. Eligible patients were aged ≥ 18 years; had HIV-seropositive status confirmed by enzyme-linked immunosorbent assay and western blot test or HIV-1 viremia confirmed by HIV-1 RNA polymerase chain reaction; and had prior baseline testosterone assessments for hypogonadism (ie, presence of signs/symptoms of hypogonadism as well as total testosterone [TT] and free testosterone [FT] level measurements). Stage 2 included the evaluation of patients from stage 1 who were treated with 5 to 10 g/day of TRT. The stage 2 inclusion criteria were a diagnosis of low testosterone (defined as TT level testosterone level therapy due to adverse events. The most useful serum testosterone measurement and threshold for diagnosing hypogonadism in men with HIV/AIDS was FT level < 100 pg/mL, which identified 64% of men as hypogonadal with the presence of ≥ 1 hypogonadal symptom. This is above currently accepted thresholds. Criteria using TT level < 300 ng/dL and FT level < 50 pg/mL only diagnosed 24% and 19% of patients, respectively, as having hypogonadism. Testim® was more effective than AndroGel® in increasing TT and FT levels and improving hypogonadal symptoms.

  2. Dynamics of immune reconstitution and activation markers in HIV+ treatment-naive patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine.

    Directory of Open Access Journals (Sweden)

    Nicholas T Funderburg

    Full Text Available BACKGROUND: The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART are incompletely defined and their underlying mechanisms poorly understood. METHODS: Thirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy. RESULTS: Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels and inflammation (IL-6 and TNFr1. These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy. CONCLUSIONS: ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT00660972.

  3. Enhanced production of functional extracellular single chain variable fragment against HIV-1 matrix protein from Escherichia coli by sequential simplex optimization.

    Science.gov (United States)

    Intachai, Kannaporn; Singboottra, Panthong; Leksawasdi, Noppol; Kasinrerk, Watchara; Tayapiwatana, Chatchai; Butr-Indr, Bordin

    2015-01-01

    The optimal culture condition for extracellular recombinant single chain variable fragment anti HIV-1 p17 protein (scFv anti-p17) production in Escherichia coli HB2151 was investigated by the sequential simplex optimization (SS) method. Five variable parameters were submitted in the fermentation process. The most favorable condition obtained from 19 independent experiments was as followed: 58 µM of IPTG induction to 1.7 OD600 nm at 25.5°C for 16 h with 202 rpm agitation rate. The amount of secreted scFv anti-p17 at the optimal condition was 38% higher than under the control condition. The binding activity of soluble extracellular scFv anti-p17 protein increased 95.5% and 73.2% in comparison with the control condition and non-optimized condition respectively. The soluble scFv anti-p17 from crude HB2151 lysated was subsequently purified by immobilized metal ion affinity chromatography (IMAC) with His-tag. The purified scFv anti-p17 was intact and retained its antigen-binding affinity against HIV-1 p17. We demonstrated that the sequential simplex optimization method was a key for exertion of high yield with fewer experimental requirements for acquiring of large scale secretory protein production.

  4. Empathy and avoidance in treating patients living with HIV/AIDS (PLWHA) among service providers in China.

    Science.gov (United States)

    Lin, Chunqing; Li, Li; Wan, Dai; Wu, Zunyou; Yan, Zhihua

    2012-01-01

    This study aims to investigate health care providers' empathy levels and its association with avoidance in providing service to patients living with HIV/AIDS (PLWHA) in China. A total of 1760 health service providers were randomly sampled from 40 county hospitals in two provinces of China. Using a self-administered questionnaire, participants' demographic characteristics, work history, empathy level, and avoidance attitudes toward PLWHA were collected in a cross-sectional survey. Empathy was higher among participants aged 31-40 years, those who had an associated medical degree, and those who had served in the medical profession for less than 20 years. Nurses, younger providers, and providers with lower education tended to avoid contact with PLWHA. Multiple linear regression model showed that a higher level of empathic attitude toward patients was significantly negatively associated with avoidance attitude toward PLWHA. Service providers' empathy level plays an important role in providing quality care to HIV-infected patients. Future stigma reduction interventions should cultivate empathy as a platform for understanding, effective communication, and trusting provider-patient relationships. PLWHA could potentially benefit from attitudinal change in medical settings.

  5. Fatal Relapse of Myelodysplastic Syndrome in a Patient with HIV/Hepatitis C Coinfection Treated with Simeprevir/Sofosbuvir.

    Science.gov (United States)

    Diejomaoh, Efemena Michael; Gathe, Joseph Clayton; Mayberry, Carl Craig; Clemmons, John Benjamin; Miguel, Bernie; Glombicki, Alan; Daquioag, Benjamin

    2017-01-01

    Registrational studies and observational cohorts clearly suggest sustained virologic response (SVR) rates in HIV-/hepatitis C-coinfected patients are similar to monoinfected patients when utilizing interferon-free regimens, and this can be accomplished with agents that are well tolerated with minimal adverse events. These randomized trials that led to the approval of several of our new direct-acting antiviral agents, however, specifically excluded patients who had significant comorbidities and none to our knowledge accepted patients with a history of cancer. Therefore, the effect of treatment of active hepatitis C in such patients and the effect on preexisting neoplasia are relatively unknown. We prospectively followed a 62-year-old male coinfected with HIV/hepatitis C who had a history of anal squamous cell carcinoma, prostate carcinoma, renal cell carcinoma all clinically cured and a myelodysplastic syndrome that was in remission. The patient achieved an SVR of hepatitis C with simeprevir/sofosbuvir without ribavirin and died shortly thereafter of a fatal relapse of his previously clinically controlled myelodysplastic syndrome.

  6. High attrition among HIV-infected patients with advanced disease treated in an intermediary referral center in Maputo, Mozambique

    Directory of Open Access Journals (Sweden)

    Lucas Molfino

    2014-04-01

    Full Text Available Background: In Mozambique, antiretroviral therapy (ART scale-up has been successfully implemented. However, attrition in care remains a major programmatic challenge. In 2009, an intermediary-level HIV referral center was created in Maputo to ensure access to specialized care for HIV-infected patients with complications (advanced clinical-immunological stage, Kaposi sarcoma, or suspected ART failure. Objective: To determine the attrition from care and to identify risk factors that lead to high attrition among patients referred to an intermediary-level HIV referral center. Design: This was a retrospective cohort study from 2009 to 2011. Results: A total of 1,657 patients were enrolled, 847 (51% were men, the mean age was 36 years (standard deviation: 11, the mean CD4 count was 27 cells/µl (interquartile range: 11–44, and one-third were severely malnourished. The main reasons for referral were advanced clinical stages (WHO stages 3 and 4, and CD4 count <50 cells/µl in 70% of the cases, and 19% had Kaposi sarcoma. The overall attrition rate was 28.7 per 100 person-years (PYs – the mortality rate was 5.0 (95% confidence interval [CI]: 4.2–5.9 per 100 PYs, and the loss-to-follow-up rate was 23.7 (95% CI: 21.9–25.6 per 100 PYs. There were 793 attritions – 137 deaths and 656 lost to follow-up (LTFU; 77% of all attrition happened within the first year. The factors independently associated with attrition were male sex (adjusted hazard ratio [aHR]: 1.15, 95% CI: 1.0–1.3, low body mass index (aHR: 1.51, 95% CI: 1.2–1.8, WHO clinical stage 3 or 4 (aHR: 1.30, 95% CI: 1.0–1.6; and aHR: 1.91, 95% CI: 1.4–2.5, later year of enrollment (aHR 1.61, 95% CI 1.3–1.9, and ‘being already on ART’ at enrollment (aHR 13.71, 95% CI 11.4–16.4. Conclusions: Attrition rates among HIV-infected patients enrolled in an intermediary referral center were high, mainly related to advanced stage of clinical disease. Measures are required to address this

  7. Optimization of parameters for enhanced oil recovery from enzyme treated wild apricot kernels.

    Science.gov (United States)

    Rajaram, Mahatre R; Kumbhar, Baburao K; Singh, Anupama; Lohani, Umesh Chandra; Shahi, Navin C

    2012-08-01

    Present investigation was undertaken with the overall objective of optimizing the enzymatic parameters i.e. moisture content during hydrolysis, enzyme concentration, enzyme ratio and incubation period on wild apricot kernel processing for better oil extractability and increased oil recovery. Response surface methodology was adopted in the experimental design. A central composite rotatable design of four variables at five levels was chosen. The parameters and their range for the experiments were moisture content during hydrolysis (20-32%, w.b.), enzyme concentration (12-16% v/w of sample), combination of pectolytic and cellulolytic enzyme i.e. enzyme ratio (30:70-70:30) and incubation period (12-16 h). Aspergillus foetidus and Trichoderma viride was used for production of crude enzyme i.e. pectolytic and cellulolytic enzyme respectively. A complete second order model for increased oil recovery as the function of enzymatic parameters fitted the data well. The best fit model for oil recovery was also developed. The effect of various parameters on increased oil recovery was determined at linear, quadric and interaction level. The increased oil recovery ranged from 0.14 to 2.53%. The corresponding conditions for maximum oil recovery were 23% (w.b.), 15 v/w of the sample, 60:40 (pectolytic:cellulolytic), 13 h. Results of the study indicated that incubation period during enzymatic hydrolysis is the most important factor affecting oil yield followed by enzyme ratio, moisture content and enzyme concentration in the decreasing order. Enzyme ratio, incubation period and moisture content had insignificant effect on oil recovery. Second order model for increased oil recovery as a function of enzymatic hydrolysis parameters predicted the data adequately.

  8. Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV-infected adults in Dakar, Senegal.

    Science.gov (United States)

    Byabene, A K; Fortes-Déguénonvo, L; Niang, K; Manga, M N; Bulabula, A N H; Nachega, J B; Seydi, M

    2017-06-01

    To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV-infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal. Cross-sectional study from 1 September 2013 to 30 January 2014. (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF. Of 98 HIV-infected patients on ART, 68% were female. The median (IQR) age was 42 (20-50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4-93.9%), Sp (20.0%, 95% CI: 11.1-31.7), PPV (22.4, 95% CI: 13.1-34.2%) and NPV (76.5%, 95% CI: 50.1-93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score <10 ([aOR] = 13.0, 95% CI: 1.1-147.9; P = 0.04) and being a boosted PI-based ART regimen ([aOR] = 27.0, 95% CI: 2.4-309.4; P = 0.008). Optimal ART adherence is achievable in a high proportion of HIV-infected adults in this study population. CASE Index Score was independently associated with virological outcomes, supporting usefulness of this low-cost ART adherence monitoring tool in this setting. © 2017 John Wiley & Sons Ltd.

  9. Hepatitis B and C co-infection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Neuhaus, Jacqueline; Peters, Lars

    2012-01-01

    Chronic kidney disease (CKD) is an important cause of morbidity and mortality in HIV-positive individuals. Hepatitis C (HCV) co-infection has been associated with increased risk of CKD, but prior studies lack information on potential mechanisms. We evaluated the association between HCV or hepatitis...... B (HBV) co-infection and progressive CKD among 3,441 antiretroviral-treated clinical trial participants. Progressive CKD was defined as the composite of end-stage renal disease, renal death, or significant glomerular filtration rate (eGFR) decline (25% decline to eGFR 800,000 IU/ml had increased...... odds (OR 3.07; 95% CI 1.60-5.90). Interleukin-6, hyaluronic acid, and the FIB-4 hepatic fibrosis index were higher among participants who developed progressive CKD, but were no longer associated with progressive CKD after adjustment. Future studies should validate the relationship between HCV viremia...

  10. Reverse transcriptase and protease inhibitor resistant mutations in art treatment naïve and treated HIV-1 infected children in India A Short Review

    Directory of Open Access Journals (Sweden)

    Dinesh Bure,

    2016-08-01

    Full Text Available Introduction of first line and second line antiretroviral therapy has dramatically improved the quality of life and survival of the HIV-1 infected individuals. Extension of this therapy in children has similar effect. However the emergence of drug selected resistance has hampered the response to the therapy. A database of prevalence of drug resistance mutations in the Indian children both ART naïve and treated will help in deciding the appropriate regimen for the individual patient as well as formulating the policies regarding the composition of drugs included in the fixed dose combinations and its periodic review by analysis of the information that is made available from time to time. This will enable us to utilize our limited resources in most prudent way.

  11. Generation of HIV-1 Gag VLPs by transient transfection of HEK 293 suspension cell cultures using an optimized animal-derived component free medium.

    Science.gov (United States)

    Cervera, Laura; Gutiérrez-Granados, Sonia; Martínez, Marta; Blanco, Julià; Gòdia, Francesc; Segura, María Mercedes

    2013-07-20

    Virus-like particles (VLPs) offer great promise as candidates for new vaccine strategies. Large-scale approaches for the manufacturing of HIV-1 Gag VLPs have mainly focused on the use of the baculovirus expression system. In this work, the development and optimization of an HIV-1 Gag VLP production protocol by transient gene expression in mammalian cell suspension cultures is reported. To facilitate process optimization, a Gag-GFP fusion construct enabling the generation of fluorescent VLPs was used. The great majority of Gag-GFP present in cell culture supernatants was shown to be correctly assembled into virus-like particles of the expected size and morphology consistent with immature HIV-1 particles. Medium optimization was performed using design of experiments (DoE). Culture medium supplementation with non-animal derived components including recombinant proteins and lipids of synthetic or non-animal-derived origin resulted in improved HEK 293 cell growth and VLP production. The maximum cell density attained using the optimized Freestyle culture medium was 5.4×10(6)cells/mL in batch mode, almost double of that observed using the unsupplemented medium (2.9×10(6)cells/mL). Best production performance was attained when cells were transfected at mid-log phase (2-3×10(6)cells/mL) with medium exchange at the time of transfection using standard amounts of plasmid DNA and polyethylenimine. By using an optimized production protocol, VLP titers were increased 2.4-fold obtaining 2.8μg of Gag-GFP/mL or 2.7×10(9)VLPs/mL according to ELISA and nanoparticle tracking quantification analyses, respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. High prevalence and impact on the quality of life of facial lipoatrophy and other abnormalities in fat tissue distribution in HIV-infected patients treated with antiretroviral therapy.

    Science.gov (United States)

    Leclercq, Pascale; Goujard, Cecile; Duracinsky, Martin; Allaert, François; L'henaff, Marianne; Hellet, Maeva; Meunier, Jean Pierre; Carret, Sophie; Thevenon, Jacques; Ngo Van, Philippe; Pialoux, Gilles

    2013-05-01

    Few data report the prevalence in actual clinical settings of lipodystrophy (LD), and in particular of facial lipoatrophy (LA), in HIV-infected patients treated with long-term antiretroviral therapy (ART). A French, multicenter, cross-sectional, observational study was conducted in HIV-infected patients on continuous ART for more than 12 months. The main objective was to assess the prevalence of facial LA in this population. Additional objectives were to make the same assessments for nonfacial LA and lipohypertrophy. The presence of LD signs, type, and severity was assessed by clinicians and compared with patient self-evaluations through two questionnaires. A total of 2,131 assessable patients had a median age of 46 years and a median time on ART of 10 years. Physicians diagnosed facial LA in 54% of patients and these subjects had received ART for a longer duration than those without LA. Thymidine analog usage was associated with an increased likelihood of facial LA, but 28% of patients recently treatment-initiated (1-5 years) were also affected. At other sites, LA and lipohypertrophy were diagnosed in 59% and 57% of cases, respectively. The concordance between physician and patient assessments was good for facial and buttocks LA. In this study, facial LA affects more than half of the subjects and is frequent even among the most recently treated patients. The prevalence of facial LA significantly increases with the duration of ART, with male gender, hepatitis C virus (HCV) coinfection, and non-African origin being independent risk factors. Lipohypertrophy is frequent and appears early after ART initiation.

  13. Interleukin 1-Beta (IL-1β) Production by Innate Cells Following TLR Stimulation Correlates With TB Recurrence in ART-Treated HIV-Infected Patients.

    Science.gov (United States)

    Thobakgale, Christina; Naidoo, Kewreshini; McKinnon, Lyle R; Werner, Lise; Samsunder, Natasha; Karim, Salim Abdool; Ndungʼu, Thumbi; Altfeld, Marcus; Naidoo, Kogieleum

    2017-02-01

    Tuberculosis (TB) remains a major cause of global morbidity and mortality, especially in the context of HIV coinfection because immunity is not completely restored following antiretroviral therapy (ART). The identification of immune correlates of risk for TB disease could help in the design of host-directed therapies and clinical management. This study aimed to identify innate immune correlates of TB recurrence in HIV+ ART-treated individuals with a history of previous successful TB treatment. Twelve participants with a recurrent episode of TB (cases) were matched for age, sex, time on ART, pre-ART CD4 count with 12 participants who did not develop recurrent TB in 60 months of follow-up (controls). Cryopreserved peripheral blood mononuclear cells from time-points before TB recurrence were stimulated with ligands for Toll-like receptors (TLR) including TLR-2, TLR-4, and TLR-7/8. Multicolor flow cytometry and intracellular cytokine staining were used to detect IL-1β, TNF-α, IL-12, and IP10 responses from monocytes and myeloid dendritic cells (mDCs). Elevated production of IL-1β from monocytes following TLR-2, TLR-4, and TLR-7/8 stimulation was associated with reduced odds of TB recurrence. In contrast, production of IL-1β from both monocytes and mDCs following Bacillus Calmette-Guérin (BCG) stimulation was associated with increased odds of TB recurrence (risk of recurrence increased by 30% in monocytes and 42% in mDCs, respectively). Production of IL-1β by innate immune cells following TLR and BCG stimulations correlated with differential TB recurrence outcomes in ART-treated patients and highlights differences in host response to TB.

  14. Incidence and predictors of adverse drug events in an African cohort of HIV-infected adults treated with efavirenz

    Science.gov (United States)

    Abah, Isaac Okoh; Akanbi, Maxwell; Abah, Mercy Enuwa; Finangwai, Amos Istifanus; Dady, Christy W; Falang, Kakjing Dadul; Ebonyi, Augustine Odoh; Okopi, Joseph Anejo; Agbaji, Oche Ochai; Sagay, Altiene Solomon; Okonkwo, Prosper; Idoko, John A; Kanki, Phyllis J

    2015-01-01

    Introduction Adverse drug reactions associated with efavirenz (EFV) therapy are poorly described beyond the first year of treatment. We aimed to describe the incidence and predictors of EFV-related adverse drug reactions (ADRs) in a cohort of adult Nigerian HIV-infected patients on antiretroviral therapy (ART). Methods This retrospective cohort study utilized clinical data of HIV-1 infected adults (aged ≥15 years), commenced on efavirenz containing-regimen between January 2004 and December 2011. The time-dependent occurrence of clinical adverse events as defined by the World Health Organization was analyzed by Cox regression analysis. Results A total of 2920 patients with baseline median (IQR) age of 39 (33-46) years, largely made up of men (78%) were included in the study. During 8834 person-years of follow up, 358 adverse drug events were reported; the incidence rate was 40.3 ADRs per 1000 person-years of treatment. Lipodystrophy and neuropsychiatric disorders were the most common ADRs with incidences of 63 and 30 per 1000 patients respectively. About one-third of the neuropsychiatric adverse events were within 12 months of commencement of ART. The risk of neuropsychiatric ADRs was independently predicted for women [adjusted hazard ratio (aHR) 9.05; 95% CI: 5.18-15.82], those aged <40 years (aHR 2.59; 95% CI: 1.50-4.45), advanced HIV disease (WHO stage 3 or 4) [aHR 2.26; 95% CI: 1.37-3.72], and zidovudine [aHR 2.21; 95% CI: 1.27-3.83] or stavudine [aHR 4.22; 95% CI: 1.99-8.92] containing regimen compared to tenofovir. Conclusion Neuropsychiatric adverse drug events associated with efavirenz-based ART had both early and late onset in our clinical cohort of patients on chronic EFV therapy. Continuous neuropsychiatric assessment for improved detection and management of neuropsychiatric ADRs is recommended in resource-limited settings where the use of efavirenz-based regimens has been scaled up. PMID:26405676

  15. Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine plus atazanavir, with or without ritonavir, for 144 weeks

    Directory of Open Access Journals (Sweden)

    Squires KE

    2017-03-01

    Full Text Available Kathleen E Squires,1 Benjamin Young,2,3 Lizette Santiago,4 Robin H Dretler,5 Sharon L Walmsley,6 Henry H Zhao,7 Gary E Pakes,8 Lisa L Ross,8 Mark S Shaefer8 On behalf of the ARIES Study Team 1Thomas Jefferson University, Philadelphia, PA, 2Apex Family Medicine and Research, Denver, CO, 3International Association of Physicians in AIDS Care, Washington DC, USA; 4HOPE Clinic and Wellness Center, San Juan, Puerto Rico; 5ID Specialists of Atlanta, Decatur, GA, USA; 6University Health Network, Toronto, ON, Canada; 7GlaxoSmithKline, 8ViiV Healthcare, Research Triangle Park, NC, USA Purpose: The 144-week results of the open-label, multicenter Atazanavir/Ritonavir Induction with Epzicom Study (ARIES were stratified by gender to compare treatment responses.Methods: A total of 369 HIV-infected, antiretroviral-naïve subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r whose HIV-1 RNA was <50 copies/mL by week 30 were randomized 1:1 at week 36 to maintain or discontinue ritonavir for 108 subsequent weeks. Between- and within-treatment gender-related efficacy and safety differences were analyzed.Results: Subjects were 85% male; 64% white; and had a mean age of 39 years, baseline median HIV-1 RNA of 114,815 copies/mL, and median CD4+ cell count of 198 cells/mm3. Gender (ATV [n=189]: 29 females/160 males; ATV/r [n=180]: 25 females/155 males and most other demographics were similar between groups; more females than males were black (65% vs 25% and fewer females had baseline HIV-1 RNA ≥100,000 copies/mL (41% vs 58%. At week 144, no significant differences between genders were observed in proportion maintaining HIV-1 RNA <50 copies/mL (ATV, 79% vs 77%; ATV/r, 60% vs 75% or <400 copies/mL (ATV, 83% vs 84%; ATV/r, 68% vs 82% (intent-to-treat-exposed: time to loss of virologic response analysis; median CD4+ change from baseline (ATV, +365 vs +300 cells/mm3; ATV/r, +344 vs +301 cells/mm3; proportion with treatment-related grade 2–4

  16. US youths in the early stages of HIV disease have low intakes of some micronutrients important for optimal immune function.

    Science.gov (United States)

    Kruzich, Laurie A; Marquis, Grace S; Carriquiry, Alicia L; Wilson, Craig M; Stephensen, Charles B

    2004-07-01

    We examined the association between micronutrient intakes and human immunodeficiency virus (HIV) infection in youths who were at increased nutritional risk because of the demands of growth and disease as well as poor dietary habits. This was a cross-sectional study to collect dietary intake data using the Block Food Frequency Questionnaire (98.2). Anthropometric, biochemical, clinical, and sociodemographic data were available.Subjects/Setting Participants included 264 HIV-infected and 127 HIV-uninfected adolescents and young adults from the Reaching for Excellence in Adolescent Care and Health network, a multisite observational study on HIV progression. Statistical analyses CD4(+) T cells were stratified for HIV-infected youths: >/=500, 200 to 499, and /=500 cells/microL. After controlling for other factors, HIV-infected participants with CD4(+) T cells >/=500 had decreased iron intake (P<.05) and tended to be associated with lower intakes of vitamins C and E (P<.10) compared with those with more advanced disease and HIV-uninfected youths. Among those youths with CD4(+) T cells between 200 and 499 cells/microL, a high anxiety score was associated with a sixfold increase in vitamin A intake as compared with those with a low score.Applications/conclusions Given the increased micronutrient requirements, nutrition counseling with HIV-infected youths should focus on early increase of intake of foods rich in micronutrients to improve growth, slow disease progression, and increase survival.

  17. An 84-month observational study of the changes in CD4 T-lymphocyte cell count of 110 HIV/AIDS patients treated with traditional Chinese medicine.

    Science.gov (United States)

    Wang, Jian; Liang, Biyan; Zhang, Xiaoping; Xu, Liran; Deng, Xin; Li, Xiuhui; Fang, Lu; Tan, Xinghua; Mao, Yuxiang; Zhang, Guoliang; Wang, Yuguang

    2014-09-01

    This study aimed to evaluate the therapeutic effect of traditional Chinese medicine (TCM) by observing the changes in CD4 T-lymphocyte cell count of 110 cases with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treated continuously with TCM for 84 months. Information of 110 HIV/AIDS patients from 19 provinces and cities treated with TCM from 2004 to 2013 was collected. Changes in the indexes of CD4 counts ( ≤ 200, 201-350, 351-500 and > 500 cells/mm(3)) at five time points (0, 12, 36, 60 and 84 months) and different treatments [TCM and TCM plus antiretroviral therapy (ART)] were compared. Repeated measures test indicated no interaction between group and time (P > 0.05). Degrees of increasing and decreasing CD4 count of the two groups at four different frames were statistically significant compared with the baseline. The CD4 count between the two groups was not statistically significant. For CD4 count of ≤ 200 cells/mm(3), the mean CD4 count changes were 21 and 28 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 201-350 cells/mm(3), the mean CD4 count changes were 6 and 25 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 351-500 cells/mm(3), the mean CD4 count changes were -13 and -7 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. For CD4 count of > 500 cells/mm(3), the mean CD4 count changes were -34 and -17 cells/mm(3) per year for the TCM group and TCM plus ART group, respectively. Long-term use of TCM could maintain or slow the pace of declining CD4 counts in patients with HIV/AIDS, and may achieve lasting effectiveness.

  18. What is an Investigational HIV Drug?

    Science.gov (United States)

    ... Children and Adolescents HIV and Women HIV and Gay and Bisexual Men HIV and Older Adults HIV ... vaccines to treat or prevent HIV. In most cases, an investigational drug ... Medical research studies—also called clinical trials—are done to evaluate ...

  19. Improvement of endothelial function after switching previously treated HIV-infected patients to an NRTI-sparing bitherapy with maraviroc

    Directory of Open Access Journals (Sweden)

    Enrique Bernal

    2014-11-01

    Full Text Available Introduction: Nucleoside reverse transcriptase inhibitor (NRTI is associated with endothelial dysfunction and proinflammatory effects. Maraviroc (MVC is an antagonist of CCR5 receptor. CCR5 is the receptor of RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted, a mediator of chronic inflammation and endothelial function. Our aim was to evaluate the maintenance of viral suppression and improvement of endothelial function in virologically suppressed HIV-infected patients switched to an NRTI-sparing combined antiretroviral therapy (cART with MVC. Materials and Methods: This observational, non-interventional, multicenter study was performed at the Infectious Diseases Service of Santa Lucia, Morales Meseguer, Virgen de la Arrixaca and Reina Sofía University Hospital (Murcia, Spain. The selection criteria were to be asymptomatic on a regimen with undetectable viral load (<50 HIV-RNA copies/mL for at least six months, no previous treatment with R5 antagonists, no evidence of previous protease inhibitor (PI failure and available R5 tropism test. Twenty-one HIV-infected patients were selected after the treatment regimen was changed to Maraviroc 150 mg/once daily plus ritonavir-boosted PI therapy. Endothelial function was prospectively evaluated through flow-mediated dilatation (FMD of the brachial artery at baseline and at weeks 24. Results: We included 21 patients on treatment with PI in combination with 2 NRTI. The mean cART exposition was 133±68.9 months. Fourteen (66.6% were males, aged 49±9 years, 15 (71.4% smokers, 4 (19.04% family history of coronary heart disease, 1 (5.76% type 2 diabetes and 3 (14.28% hypertensive, mean total cholesterol was 185.5±35 mg/dL, c-LDL 100.2±37 mg/dL, tryglicerides 170.42±92.03 mg/dL, cHDL 52.6±15.5 mg/dL, CD4 779,5±383.28 cells/mL, nadir CD4 187,96±96 cells/mL. After 24 weeks of follow-up of a switch to an NRTI-sparing regimen, 95.2% of HIV-patients on viral suppressive cART maintained

  20. Relapse of visceral leishmaniasis in an HIV-infected patient successfully treated with a combination of miltefosine and amphotericin B.

    Science.gov (United States)

    McQuarrie, Shauna; Kasper, Ken; Moffatt, Dana C; Marko, Daniel; Keynan, Yoav

    2015-01-01

    The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm(3), despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated.

  1. Relapse of Visceral Leishmaniasis in an HIV-Infected Patient Successfully Treated with a Combination of Miltefosine and Amphotericin B

    Directory of Open Access Journals (Sweden)

    Shauna McQuarrie

    2015-01-01

    Full Text Available The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm3, despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated.

  2. Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis

    Science.gov (United States)

    2016-01-01

    Objectives: To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure. Design: Collaborative analysis of data from eight European and three Canadian cohorts. Methods: Adults (N>20 000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4+ cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression. Results: The most prevalent subtypes were B (15 419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104 649 person-years of observation, 1172/20 784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4+ cell count below, or more than, 100 cells/μl, respectively. There was no difference in mortality between subtypes A, B and C after viral failure. Conclusion: Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors. PMID:26562844

  3. Macronutrient supplementation and food prices in HIV treatment.

    Science.gov (United States)

    Sztam, Kevin A; Fawzi, Wafaie W; Duggan, Christopher

    2010-01-01

    Infection caused by HIV and malnutrition have a complex interaction and often coexist geographically. Malnutrition has synergistic immune effects and HIV affects nutritional status. HIV care and treatment programs are compelled to confront this dual burden to optimize HIV outcomes. In this article, we review the published literature concerning intervention studies in adults and children and the effect of food prices on HIV treatment programs. While the evidence base is relatively incomplete for specific macronutrient interventions in the context of HIV treatment, it is clear that a new standard of care is needed, guided by experience, rationale, and existing data, in which malnourished patients may easily access nutritional therapies within HIV treatment. From this clinical foundation, we may both treat patients and evaluate novel therapies. Some HIV care and treatment programs provide food-based supplements; however, rising food costs and economic instability may jeopardize the success of these programs. HIV treatment programs may struggle to meet the needs of patients with potential increased rates of malnutrition and food insecurity in the setting of high food prices.

  4. HIV-Positive-to-HIV-Positive Liver Transplantation

    OpenAIRE

    Calmy, Alexandra; van Delden, Christian; Giostra, Emiliano; Junet, C; Rubbia Brandt, L; Yerly, S; Chave, J-P; Samer, Caroline Flora; Elkrief, Laure; Vionnet, J; Berney, Thierry

    2016-01-01

    Most countries exclude human immunodeficiency virus (HIV)-positive patients from organ donation because of concerns regarding donor-derived HIV transmission. The Swiss Federal Act on Transplantation has allowed organ transplantation between HIV-positive donors and recipients since 2007. We report the successful liver transplantation from an HIV-positive donor to an HIV-positive recipient. Both donor and recipient had been treated for many years with antiretroviral therapy and harbored multidr...

  5. Broad antibody mediated cross-neutralization and preclinical immunogenicity of new codon-optimized HIV-1 clade CRF02_AG and G primary isolates.

    Directory of Open Access Journals (Sweden)

    Simon M Agwale

    Full Text Available Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary "street strain" isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G. Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G and consensus tat (CRF02_AG and G antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G.

  6. The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial

    NARCIS (Netherlands)

    Hunt, P.W.; Shulman, N.S.; Hayes, T.L.; Dahl, V.; Somsouk, M.; Funderburg, N.T.; McLaughlin, B.; Landay, A.L.; Adeyemi, O.; Gilman, L.E.; Clagett, B.; Rodriguez, B.; Martin, J.N.; Schacker, T.W.; Shacklett, B.L.; Palmer, S.; Lederman, M.M.; Deeks, S.G.

    2013-01-01

    The CCR5 inhibitor maraviroc has been hypothesized to decrease T-cell activation in HIV-infected individuals, but its independent immunologic effects have not been established in a placebo-controlled trial. We randomized 45 HIV-infected subjects with CD4 counts <350 cells per mm(3) and plasma HIV

  7. Effect of hyperbilirubinaemia on neurocognitive, renal, bone and cardiovascular markers in HIV infection treated with boosted protease inhibitors

    Directory of Open Access Journals (Sweden)

    Tristan J Barber

    2014-11-01

    Full Text Available Introduction: Use of some protease inhibitors (PI is associated with unconjugated hyperbilirubinaemia (HBR, due to inhibition of UGT1A1. As observed in Gilbert's syndrome, HBR may have antioxidant and anti-inflammatory effects. Inflammation may be relevant to neurocognitive (NC impairment, cardiovascular, renal and bone co-morbidities in HIV infection. This study aimed to analyse correlations between antiretroviral associated HBR and NC impairment as well as renal, bone and cardiovascular parameters. Material and Methods: This cross-sectional study included 101 HIV-1-infected individuals stable (>6 months on antiretroviral regimens including tenofovir/emtricitabine or abacavir/lamivudine plus a ritonavir-boosted PI. Patients with >grade 2 HBR were compared to patients with normal bilirubin on NC data collected using CogState. An overall composite score was calculated for each subject. Two-tail P-values were calculated using the Mann-Whitney U test. We measured the following parameters in all participants: Bone – Calcaneal Stiffness Index (CSI, blood bone markers, calculated FRAX score; CV – vascular endothelial function markers (iCAM, vCAM, lipid fractions and sub fractions (Total, HDL and LDL cholesterol, triglycerides, ApoB, Carotid Intimal Thickness (CIT, Pulse Wave Velocity (PWV, glucose and insulin for calculation of HOMA-IR, IL-6, d-dimer, uric acid, and hsCRP; Renal – urea and electrolytes (U&E, urinary protein/creatinine ratio (uPCR, urinary retinal binding protein (RBP/creatinine ratio. Results: Forty-three participants had normal bilirubin (NBR levels and 35 had high bilirubin (HBR; >2.5 times upper limit; the remaining 23 patients had intermediate bilirubin levels or violated the protocol. The mean age of participants was 48 years; 93% were male and 84% Caucasian. Mostly no significant differences were seen in any of the markers when comparing the NBR and HBR groups. Two component tests of the CogState were seen to be different

  8. HIV/AIDS and Infections

    Science.gov (United States)

    Having HIV/AIDS weakens your body's immune system. It destroys the white blood cells that fight infection. This puts ... such as crypto (cryptosporidiosis) and toxo (toxoplasmosis) Having HIV/AIDS can make infections harder to treat. People ...

  9. Optimizing HIV pre-exposure prophylaxis implementation among men who have sex with men in a large urban centre: a dynamic modelling study

    Directory of Open Access Journals (Sweden)

    Derek R MacFadden

    2016-09-01

    Full Text Available Introduction: Once-daily tenofovir/emtricitabine-based pre-exposure prophylaxis (PrEP can reduce HIV acquisition in men who have sex with men (MSM, by 44% in the iPrEx trial, and reaching up to 99% with high adherence. We examined the potential population-level impact and cost-effectiveness of different PrEP implementation strategies. Methods: We developed a dynamic, stochastic compartmental model of HIV transmission among the estimated 57,400 MSM in Toronto, Canada. Parameterization was performed using local epidemiologic data. Strategies examined included (1 uniform PrEP delivery versus targeting the highest risk decile of MSM (with varying coverage proportions; (2 increasing PrEP efficacy as a surrogate of adherence (44% to 99%; and (3 varying HIV test frequency (once monthly to once yearly. Outcomes included HIV infections averted and the incremental cost ($CAD per incremental quality-adjusted-life-year (QALY gained over 20 years. Results: Use of PrEP among all HIV-uninfected MSM at 25, 50, 75 and 100% coverage prevented 1970, 3427, 4317, and 4581 infections, respectively, with cost/QALY increasing from $500,000 to $800,000 CAD. Targeted PrEP for the highest risk MSM at 25, 50, 75 and 100% coverage prevented 1166, 2154, 2816, and 3012 infections, respectively, with cost/QALY ranging from $35,000 to $70,000 CAD. Maximizing PrEP efficacy, in a scenario of 25% coverage of high-risk MSM with PrEP, prevented 1540 infections with a cost/QALY of $15,000 CAD. HIV testing alone (Q3 months averted 898 of infections with a cost savings of $4,000 CAD per QALY. Conclusions: The optimal implementation strategy for PrEP over the next 20 years at this urban centre is to target high-risk MSM and to maximize efficacy by supporting PrEP adherence. A large health benefit of PrEP implementation could come from engaging undiagnosed HIV-infected individuals into care.

  10. Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2015-05-06

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  11. State estimation and optimal long period clinical treatment of HIV seropositive patients

    Directory of Open Access Journals (Sweden)

    Juliana M. Grégio

    2009-03-01

    Full Text Available Optimal control theory provides a very interesting quantitative method that can be used to assist the decision making process in several areas of application, such as engineering, biology, economics and sociology. The main idea is to determine the values of the manipulated variables, such as drug doses, so that some cost function is minimized, subject to physical constraints. In this work, the cost function reflects the number of CD4+T cells, viral particles and the drug doses. It is worth noticing that high drug doses are related to more intense side-effects, apart from the impact on the actual cost of the treatment. In a previous paper by the authors, the LQR - Linear Quadratic Regulator approach was proposed for the computation of long period maintenance doses for the drugs, which turns out to be of state feedback form. However, it is not practical to determine all the components of the state vector, due to the fact that infected and uninfected CD4+T cells are not microscopically distinguishable. In order to overcome this difficulty, this work proposes the use of Extended Kalman Filter to estimate the state, even though, because of the nonlinear nature of the involved state equations, the separation principle may not be valid. Extensive simulations were then carried out to investigate numerically if the control strategy consisting of the feedback of estimated states yielded satisfactory clinical results.A teoria de controle ótimo apresenta um método quantitativo muito interessante que pode ajudar no processo de tomada de decisão em algumas áreas de aplicação, tais como engenharia, biologia, economia e sociologia. A principal idéia é determinar os valores das variáveis controladas, tais como doses de medicamentos, onde alguma função-custo é minimizada, sujeito às restrições físicas. Neste trabalho, a função-custo reflete o número de células CD4+T, partículas virais e doses de medicamentos. É fato que altas dosagens de

  12. Optimizing management of treatment-naïve and treatment-experienced HIV+ patients: the role of maraviroc

    Directory of Open Access Journals (Sweden)

    Eva Poveda

    2010-03-01

    Full Text Available Eva Poveda, Vincent SorianoDepartment of Infectious Diseases, Hospital Carlos III, Madrid, SpainAbstract: Maraviroc is the first CCR5 antagonist approved for the treatment of HIV-1 infection. It specifically inhibits the replication of R5 viruses by blocking viral entry. HIV-1 tropism can be estimated accurately and predict viral response to maraviroc. Genotypic tools are increasingly replacing phenotypic assays in most places. The favorable pharmacokinetic properties and the good safety profile of maraviroc may support an earlier use of the drug in HIV-1 infection, as well as favor its consideration as part of switch strategies in patients under suppressive antiretroviral regimens containing less-well-tolerated drugs. Moreover, a particular immune benefit of maraviroc might encourage its use as part of intensification strategies in HIV-infected patients with impaired CD4 gains despite prolonged suppression of HIV replication with antiretroviral therapy. However, the long-term consequences of using maraviroc must be carefully checked, given its particular mechanism of action, blocking a physiologic cell receptor.Keywords: maraviroc, tropism, HIV, antiretroviral therapy, treatment strategies

  13. MO-F-CAMPUS-T-02: Optimizing Orientations of Hundreds of Intensity-Modulated Beams to Treat Multiple Brain Targets

    Energy Technology Data Exchange (ETDEWEB)

    Ma, L; Dong, P; Larson, D [University of California San Francisco, San Francisco, CA (United States); Keeling, V; Hossain, S; Ahmad, S [University of Oklahoma Health Science Center, Oklahoma City, OK (United States); Sahgal, A [University of Toronto, Toronto, ON (Canada)

    2015-06-15

    Purpose: To investigate a new modulated beam orientation optimization (MBOO) approach maximizing treatment planning quality for the state-of-the-art flattening filter free (FFF) beam that has enabled rapid treatments of multiple brain targets. Methods: MBOO selects and optimizes a large number of intensity-modulated beams (400 or more) from all accessible beam angles surrounding a patient’s skull. The optimization algorithm was implemented on a standalone system that interfaced with the 3D Dicom images and structure sets. A standard published data set that consisted of 1 to 12 metastatic brain tumor combinations was selected for MBOO planning. The planning results from various coplanar and non-coplanar configurations via MBOO were then compared with the results obtained from a clinical volume modulated arc therapy (VMAT) delivery system (Truebeam RapidArc, Varian Oncology). Results: When planning a few number of targets (n<4), MBOO produced results equivalent to non-coplanar multi-arc VMAT planning in terms of target volume coverage and normal tissue sparing. For example, the 12-Gy and 4-Gy normal brain volumes for the 3-target plans differed by less than 1 mL ( 3.0 mLvs 3.8 mL; and 35.2 mL vs 36.3 mL, respectively) for MBOO versus VMAT. However, when planning a larger number of targets (n≥4), MBOO significantly reduced the dose to the normal brain as compared to VMAT, though the target volume coverage was equivalent. For example, the 12-Gy and 4-Gy normal brain volumes for the 12-target plans were 10.8 mL vs. 18.0 mL and 217.9 mL vs. 390.0 mL, respectively for the non-coplanar MBOO versus the non-coplanar VMAT treatment plans, yielding a reduction in volume of more than 60% for the case. Conclusion: MBOO is a unique approach for maximizing normal tissue sparing when treating a large number (n≥4) of brain tumors with FFF linear accelerators. Dr Ma and Dr Sahgal are currently on the board of international society of stereotactic radiosurgery. Dr Sahgal has

  14. Estimated Glomerular Filtration Rate Trajectories in HIV-Infected Subjects Treated With Different Ritonavir-Boosted Protease Inhibitors and Tenofovir Disoproxil Fumarate or Abacavir.

    Science.gov (United States)

    Gianotti, Nicola; Galli, Laura; Poli, Andrea; Salpietro, Stefania; Nozza, Silvia; Carbone, Alessia; Merli, Marco; Ripa, Marco; Lazzarin, Adriano; Castagna, Antonella

    2016-05-01

    The aim of the study was to evaluate in human immunodeficiency virus (HIV)-infected patients estimated glomerular filtration rate (eGFR) trajectories during treatment with different protease inhibitors (PIs) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus tenofovir (TDF) or abacavir (ABC) and lamivudine or emtricitabine (xTC).Retrospective study of patients followed at a single clinical center; all patients who started TDF or ABC for the first time with a NNRTI or lopinavir/r (LPV/r) or atazanavir/r (ATV/r) or darunavir/r (DRV/r), for whom at least 1 eGFR value before the start and during the studied treatment was known, were included in this analysis. eGFR was calculated by means of the CKD-EPI formula. Univariate and multivariate mixed linear model (MLM) was applied to estimate eGFR slope with the considered antiretroviral treatment.In the 1658 patients treated with TDF/xTC (aged 43 [37-48] years, with an eGFR of 105 [96; 113] mL/min/1.73 m, 80% males, 92% Caucasians, 10% coinfected with HCV, 4% with diabetes, 11% with hypertension, 38% naive for antiretroviral therapy (ART), 37% with HIV-RNA <50 copies/mL) the median follow-up was 2.5 (1.2-4.6) years. Their adjusted eGFR slopes (95% CI) were -1.26 (-1.58; -0.95), -0.43 (-1.20; +0.33), -0.86 (-1.28; -0.44), and -0.20 (-0.42; +0.02) mL/min/1.73 m per year in patients treated with ATV/r, DRV/r, LPV/r, and NNRTI, respectively. Patients receiving ATV/r or LPV/r had a greater adjusted decline in eGFR compared with those receiving NNRTIs (difference -1.06 [-1.44; -0.69] mL/min/1.73 m per year, P <0.001; and -0.66 [-1.13; -0.20] mL/min/1.73 m per year, P = 0.005, respectively); adjusted eGFR slopes were similar in patients receiving DRV/r and in those receiving NNRTIs. Patients receiving ATV/r had a greater adjusted eGFR decline than those treated with DRV/r (difference -0.83 [-1.65; -0.02] mL/min/1.73 m per year; P = 0.04), but not than those receiving LPV/r; no significant difference was

  15. Start-up, performance and optimization of a compost biofilter treating gas-phase mixture of benzene and toluene.

    Science.gov (United States)

    Rene, Eldon R; Kar, Saurajyoti; Krishnan, Jagannathan; Pakshirajan, K; López, M Estefanía; Murthy, D V S; Swaminathan, T

    2015-08-01

    The performance of a compost biofilter inoculated with mixed microbial consortium was optimized for treating a gas-phase mixture of benzene and toluene. The biofilter was acclimated to these VOCs for a period of ∼18d. The effects of concentration and flow rate on the removal efficiency (RE) and elimination capacity (EC) were investigated by varying the inlet concentration of benzene (0.12-0.95g/m(3)), toluene (0.14-1.48g/m(3)) and gas-flow rate (0.024-0.072m(3)/h). At comparable loading rates, benzene removal in the mixture was reduced in the range of 6.6-41% in comparison with the individual benzene degradation. Toluene removal in mixture was even more affected as observed from the reductions in REs, ranging from 18.4% to 76%. The results were statistically interpreted by performing an analysis of variance (ANOVA) to elucidate the main and interaction effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Effect of Optimal Medical Therapy Before Procedures on Outcomes in Coronary Patients Treated With Drug-Eluting Stents.

    Science.gov (United States)

    Iijima, Raisuke; Nakamura, Masato; Matsuyama, Yutaka; Muramatsu, Toshiya; Yokoi, Hiroyoshi; Hara, Hidehiko; Okada, Hisayuki; Ochiai, Masahiko; Suwa, Satoru; Hozawa, Hidenari; Kawai, Kazuya; Awata, Masaki; Mukawa, Hiroaki; Fujita, Hiroshi; Nanto, Shinsuke

    2016-09-15

    It has not been established whether the achievement of optimal medical therapy (OMT) before implantation of a drug-eluting stent has a clinical benefit for patients with stable coronary artery disease (CAD). This study included 3,004 patients with CAD treated with drug-eluting stent from 123 Japanese participating centers. The achievement of OMT was defined as control of blood pressure OMT group), whereas the remaining 2,456 patients failed to achieve one or more criteria (the non-OMT group). At 24 months, the incidence of target vessel failure was 7.0% in the achieved OMT group versus 10.0% in the non-OMT group (hazard ratio 0.68, 95% CI 0.48 to 0.96, p = 0.03). The incidence of non-Q-wave myocardial infarction was also lower in the achieved OMT group than in the non-OMT group (0.5% vs 1.5%, p = 0.08). Multivariate logistic regression analysis identified that hemoglobin A1c OMT before percutaneous coronary intervention significantly reduced subsequent cardiac events. Achievement of OMT is still insufficient in modern clinical practice.

  17. Early diagnosis and retention in care of HIV-infected patients through rapid salivary testing: a test-and-treat fast track pilot study.

    Science.gov (United States)

    Parisi, Maria Rita; Soldini, Laura; Negri, Silvia; Vidoni, Gian Marino; Gianotti, Nicola; Nozza, Silvia; Schlusnus, Karin; Dorigatti, Fernanda; Lazzarin, Adriano

    2016-01-01

    Aim of this study was to evaluate the efficacy and the retention-in-care of individuals diagnosed during six years of salivary HIV testing (EASY-test project). Among those linked-to-care at the Infectious Diseases Department of San Raffaele Hospital (Milan, Italy), the proportion of patients engaged, retained in care and virologically suppressed after the antiretroviral treatment was 96%, 100% and 95.2%, respectively. Results from our study suggest that salivary HIV testing may help bring to light cases of HIV infection otherwise undiagnosed, and thus favour a more rapid and wider reduction of the HIV infection burden at the population level.

  18. Raltegravir concentrations in the genital tract of HIV-1-infected women treated with a raltegravir-containing regimen (DIVA 01 study).

    Science.gov (United States)

    Clavel, Cyril; Peytavin, Gilles; Tubiana, Roland; Soulié, Cathia; Crenn-Hebert, Catherine; Heard, Isabelle; Bissuel, François; Ichou, Houria; Ferreira, Claudia; Katlama, Christine; Marcelin, Anne-Geneviève; Mandelbrot, Laurent

    2011-06-01

    We studied the penetration of raltegravir and HIV shedding in the genital tract among 14 HIV-1-infected women receiving a raltegravir-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median raltegravir concentrations were 235 ng/ml in BP and 93 ng/ml in CVF, with a CVF/BP ratio of approximately 2.3. This good penetration of raltegravir may contribute to the control of viral replication in the female genital tract.

  19. Hepatitis B and C co-infection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults.

    Directory of Open Access Journals (Sweden)

    Amanda Mocroft

    Full Text Available Chronic kidney disease (CKD is an important cause of morbidity and mortality in HIV-positive individuals. Hepatitis C (HCV co-infection has been associated with increased risk of CKD, but prior studies lack information on potential mechanisms. We evaluated the association between HCV or hepatitis B (HBV co-infection and progressive CKD among 3,441 antiretroviral-treated clinical trial participants. Progressive CKD was defined as the composite of end-stage renal disease, renal death, or significant glomerular filtration rate (eGFR decline (25% decline to eGFR 800,000 IU/ml had increased odds (OR 3.07; 95% CI 1.60-5.90. Interleukin-6, hyaluronic acid, and the FIB-4 hepatic fibrosis index were higher among participants who developed progressive CKD, but were no longer associated with progressive CKD after adjustment. Future studies should validate the relationship between HCV viremia and CKD.ClinicalTrials.gov NCT00027352; NCT00004978.

  20. Levels of soluble endothelial protein C receptor are associated with CD4+ changes in Maraviroc-treated HIV-infected patients.

    Directory of Open Access Journals (Sweden)

    Silvia Nozza

    Full Text Available BACKGROUND: Inflammation is a key feature of HIV infection and is correlated with long-term negative cardiovascular outcomes. Therapy-induced increases in CD4(+ cell counts can control inflammation, as shown by decreases of coagulation and inflammation markers during efficacious therapy. Maraviroc, a CCR5-antagonist, has resulted in larger increases in CD4(+ counts both in naïve and experienced subjects compared to traditional antiretroviral therapy. OBJECTIVES AND METHODS: To examine if a member of the protein C anticoagulant and anti-inflammatory pathway, and marker of coagulation and inflammation, the soluble endothelial protein C receptor, is modified by infection and therapy-related variables in patients treated with Maraviroc. Endothelial protein C receptor, together with other established markers of inflammation and coagulation (CRP, IL-6, D-dimer and soluble thrombomodulin was studied in 43 patients on traditional antiretroviral therapy and in 45 on Maraviroc during 48 weeks of follow-up. RESULTS: Soluble endothelial protein C receptor was the only marker that could discriminate at least partially between patients with a good response to Maraviroc and patients who did not respond with an adequate increase in CD4(+ cell counts (more than 500 cells/µL by week 48. CONCLUSIONS: Elevated levels of soluble endothelial protein C receptor, a sensitive marker of endothelial damage, indicated a low level of inflammation and coagulation activation in Maraviroc treated patients not picked up by other widely used markers. Persistent elevated levels of this marker at 48 weeks from beginning of treatment with Maraviroc were related to a poor increase in CD4(+ cells.

  1. HIV-1 Vif Protein Mediates the Degradation of APOBEC3G in Fission Yeast When Over-expressed Using Codon Optimization

    Institute of Scientific and Technical Information of China (English)

    Lin LI; Jing-yun LI; Hong-shuai SUI; Richard Y. Zhao; Yong-jian LIU; Zuo-yi BAO; Si-yang LIU; Dao-min ZHUANG

    2008-01-01

    Interaction between the HIV-1 Vif protein and the cellular host APOBEC3G protein is a promising target for inhibition of HIV-1 replication. Considering that human cells are a very complicated environment for the study of protein interactions, the goal of this study was to check whether fission yeast could be used as a model cell for studying the Vif-APOBEC3G interaction. Vif and APOBEC3G were expressed in fusion with GFP protein in the S. pombe SP223 strain. Subcellular localizations of Vif and APOBEC3G were observed with fluorescent microscopy. Codon optimization was used to over express the Vif protein in S. pombe cells. The degradation of APOBEC3G mediated by Vif was tested through expressing Vif and GFP-APOBEC3G proteins in the same cell. Western Blot analysis was used to measure the corresponding protein levels under different experimental conditions. The results showed that the Vif protein was predominantly localized in the nucleus of S.pombe cells, APOBEC3G was localized in the cytoplasm and concentrated at punctate bodies that were often in close proximity to the nucleus but were not necessarily restricted from other regions in the cytoplasm. Vif protein expression levels were increased significantly by using codon optimization and APOBEC3G was degraded when Vif was over-expressed in the same S. pombe cells. These results indicate that fission yeast is a good model for studying the interaction between the Vif and APOBEC3G proteins.

  2. Optimism

    Science.gov (United States)

    Carver, Charles S.; Scheier, Michael F.; Segerstrom, Suzanne C.

    2010-01-01

    Optimism is an individual difference variable that reflects the extent to which people hold generalized favorable expectancies for their future. Higher levels of optimism have been related prospectively to better subjective well-being in times of adversity or difficulty (i.e., controlling for previous well-being). Consistent with such findings, optimism has been linked to higher levels of engagement coping and lower levels of avoidance, or disengagement, coping. There is evidence that optimism is associated with taking proactive steps to protect one's health, whereas pessimism is associated with health-damaging behaviors. Consistent with such findings, optimism is also related to indicators of better physical health. The energetic, task-focused approach that optimists take to goals also relates to benefits in the socioeconomic world. Some evidence suggests that optimism relates to more persistence in educational efforts and to higher later income. Optimists also appear to fare better than pessimists in relationships. Although there are instances in which optimism fails to convey an advantage, and instances in which it may convey a disadvantage, those instances are relatively rare. In sum, the behavioral patterns of optimists appear to provide models of living for others to learn from. PMID:20170998

  3. Finding the optimal dose of vitamin K1 to treat vitamin K deficiency and to avoid anaphylactoid reactions.

    Science.gov (United States)

    Mi, Yan-Ni; Ping, Na-Na; Li, Bo; Xiao, Xue; Zhu, Yan-Bing; Cao, Lei; Ren, Jian-Kang; Cao, Yong-Xiao

    2017-10-01

    Vitamin K1 injection induces severe dose-related anaphylactoid reactions and overdose for the treatment of vitamin K deficiency. We aimed to find an optimal and small dose of vitamin K1 injection to treat vitamin K deficiency and avoid anaphylactoid reactions in animal. Rats were administered a vitamin K-deficient diet and gentamicin to establish vitamin K deficiency model. Behaviour tests were performed in beagle dogs to observe anaphylactoid reactions. The results showed an increased protein induced by vitamin K absence or antagonist II (PIVKA-II) levels, a prolonging of prothrombin time (PT) and activated partial thromboplastin time (APTT) and a decrease in vitamin K-dependent coagulation factor (F) II, VII, IX and X activities in the model group. In vitamin K1 0.01 mg/kg group, the liver vitamin K1 levels increased fivefold and the liver vitamin K2 levels increased to the normal amount. Coagulation markers PT, APTT, FVII and FIX activities returned to normal. Both in the 0.1 and 1.0 mg/kg vitamin K1 groups, coagulation functions completely returned to normal. Moreover, the amount of liver vitamin K1 was 40 (0.1 mg/kg) or 100 (1.0 mg/kg) times as in normal. Vitamin K2 was about 4 (0.1 mg/kg) or 5 (1.0 mg/kg) times as the normal amount. There was no obvious anaphylactoid symptom in dogs with the dose of 0.03 mg/kg, which is equivalent to the dose of 0.01 mg/kg in rats. These results demonstrated that a small dose of vitamin K1 is effective to improve vitamin K deficiency and to prevent anaphylactoid reactions, simultaneously. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  4. Plasma Mitochondrial DNA Levels as a Biomarker of Lipodystrophy Among HIV-infected Patients Treated with Highly Active Antiretroviral Therapy (HAART).

    Science.gov (United States)

    Dai, Z; Cai, W; Hu, F; Lan, Y; Li, L; Chung, C; Caughey, B; Zhang, K; Tang, X

    2015-01-01

    Lipodystrophy is a common complication in HIV-infected patients taking highly active antiretroviral therapy. Its early diagnosis is crucial for timely modification of antiretroviral therapy. We hypothesize that mitochondrial DNA in plasma may be a potential marker of LD in HIV-infected individuals. In this study, we compared plasma mitochondrial DNA levels in HIV-infected individuals and non-HIV-infected individuals to investigate its potential diagnostic value. Total plasma DNA was extracted from 67 HIV-infected patients at baseline and 12, 24 and 30 months after initiating antiretroviral therapy. Real-time quantitative PCR was used to determine the mitochondrial DNA levels in plasma. Lipodystrophy was defined by the physician-assessed presence of lipoatrophy or lipohypertrophy in one or more body regions. The mitochondrial DNA levels in plasma were significantly higher at baseline in HIV-infected individuals than in non-HIV-infected individuals (pmitochondrial DNA levels in lipodystrophy patients were significantly higher compared to those without lipodystrophy at month 24 (pmitochondrial DNA level (with cut-off value mitochondrial DNA levels may help to guide therapy selection with regards to HIV lipodystrophy risk.

  5. Influence of Hepatitis C Virus Sustained Virological Response on Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected Patients

    NARCIS (Netherlands)

    Jenabian, Mohammad-Ali; Mehraj, Vikram; Costiniuk, Cecilia T.; Vyboh, Kishanda; Kema, Ido; Rollet, Kathleen; Ramirez, Robert Paulino; Klein, Marina B.; Routy, Jean-Pierre

    2016-01-01

    Background: We previously reported an association between tryptophan (Trp) catabolism and immune dysfunction in HIV monoinfection. Coinfection with HIV is associated with more rapid evolution of hepatitis C virus (HCV)-associated liver disease despite antiretroviral therapy (ART), possibly due to im

  6. Adherence in HIV-positive patients treated with single-tablet regimens and multi-pill regimens: findings from the COMPACT study

    Directory of Open Access Journals (Sweden)

    A Antinori

    2012-11-01

    Full Text Available The use of Combination AntiRetroviral Therapy (cART has decreased the morbidity and mortality of patients infected with HIV. However, adherence to cART remains crucial to prevent virological failure and disease progression. The aim of this study was to assess adherence to treatment among patients treated with Single Tablet Regimen (STR or with multi-pill regimens based on Protease Inhibitors (PI, Non-Nucleoside Reverse-Transcriptase Inhibitors (NNRTI, or raltegravir (RAL. An observational retrospective cohort analysis based on administrative and clinical databases was conducted at the National Institute for Infectious Diseases (Rome, Italy. HIV-positive patients treated with a cART between Jan 1st, 2008–Dec 31st, 2010 were included. Patients were followed-up for one year since the first prescription during the inclusion period or up to death or switch of at least one drug of the regimen. Adherence and selective non-adherence (days without backbone or 3rd drug were calculated using pharmacy refill compliance [1]. cART regimens were classified based on number of daily pills (STR vs multi-pill regimen and on type of third drug. Viral Load (VL and CD4 cell counts at the end of the follow-up were evaluated. A total of 1,604 patients were analyzed, 70.0% male, age 45.0±8.7, 14.3% newly treated. Patients on STR were 159 (9.9%, PI 878 (54.7%, NNRTI 523 (32.6%, RAL 44 (2.7%. Presence of at least one AIDS-defining conditions (according to Centers for Disease Control classification was 30% in the STR group, 34% PI, 26% NNRTI, 34% RAL (p=n.s.. Adherence was 80.4±14.7% for STR, 71.8±21.8% PI, 77.1±20.3% NNRTI, 74.0±22.4% RAL. Selective non-adherence was 5.5% (18 days PI, 2.8% (8 days NNRTI, 12.5% (43 days RAL (Figure 1. At the end of the follow-up, VL/CD4 values were available among 709 patients (44%; CD4 count >500 cell/mm3 was observed among 61% of patients on STR, 44% PI, 48% NNRTI, 42% RAL and VL < 50 copies/ml was observed among 96% of patients

  7. Optimization

    CERN Document Server

    Pearce, Charles

    2009-01-01

    Focuses on mathematical structure, and on real-world applications. This book includes developments in several optimization-related topics such as decision theory, linear programming, turnpike theory, duality theory, convex analysis, and queuing theory.

  8. Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome following HAART Initiation in an HIV-infected Patient Being Treated for Severe Pneumonia: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Dong Won Park

    2016-05-01

    Full Text Available Pnuemocystis jirovecii pneumonia (PJP is one of leading causes of acute respiratory failure in patients infected with human immunodeficiency virus (HIV, and the mortality rate remains high in mechanically ventilated HIV patients with PJP. There are several reported cases who received extracorporeal membrane oxygenation (ECMO treatment for respiratory failure associated with severe PJP in HIV-infected patients. We report a patient who was newly diagnosed with HIV and PJP whose condition worsened after highly active antiretroviral therapy (HAART initiation and progressed to acute respiratory distress syndrome requiring veno-venous ECMO. The patient recovered from PJP and is undergoing treatment with HAART. ECMO support can be an effective life-saving salvage therapy for acute respiratory failure refractory to mechanical ventilation following HAART in HIV-infected patients with severe PJP.

  9. HIV Transmission

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... on HIV Syndicated Content Website Feedback HIV/AIDS HIV Transmission Language: English (US) Español (Spanish) Recommend ...

  10. HIV type-1 group O infection in Gabon: low prevalence rate but circulation of genetically diverse and drug-resistant HIV type-1 group O strains.

    Science.gov (United States)

    Liégeois, Florian; Boué, Vanina; Butel, Christelle; Mouinga-Ondémé, Augustin; Sica, Jeanne; Zamba, Chantal; Peeters, Martine; Delaporte, Eric; Rouet, François

    2013-07-01

    The goals of this study conducted in Gabon were to determine the prevalence rate of HIV-1 group O (HIV-1/O) infections and to characterize the genetic diversity of HIV-1/O strains as well as implications on antiretroviral (ARV) drug resistance. During 2010-2011, 1,176 samples from HIV-positive subjects were tested at the CIRMF (Centre International de Recherches Médicales de Franceville) retrovirology laboratory using an in-house serotyping assay. Plasma HIV-1/O RNA viral loads (VL) were determined using the Abbott RealTime HIV-1 assay. After full genome sequencing, drug resistance patterns were analyzed using two different algorithms (Agence Nationale de Recherches sur le SIDA et les hépatites virales and Stanford). Overall, four subjects (0.34%) were diagnosed as HIV-1/O infected. One subject, untreated by ARVs, died 2 months after HIV-1/O diagnosis. One was lost to follow-up. Two additional patients, treated with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, showed CD4 counts Gabon, an accurate diagnosis and a reliable virological follow-up are required in Central Africa to optimize ARV treatments of HIV-1/O-infected patients.

  11. HIV integrase inhibitors: from diketoacids to heterocyclic templates: a history of HIV integrase medicinal chemistry at Merck West Point and Merck Rome (IRBM).

    Science.gov (United States)

    Egbertson, Melissa S

    2007-01-01

    Replication of the human immunodeficiency virus (HIV) is dependent upon the enzyme HIV integrase (IN), one of three essential enzymes encoded in the viral genome. HIV-1 IN catalyzes the insertion of the proviral DNA into the host genome (strand transfer). HIV-1 IN therefore presents an attractive chemotherapeutic target for the treatment of HIV infection and AIDS that could provide patients and physicians with an additional option for treatment. Assays were developed to identify inhibitors of IN strand transfer. Diketoacid lead compounds were explored and developed into a variety of heterocyclic templates that are potent inhibitors of integrase strand transfer with suitable medicinal chemical properties for treating HIV infection and AIDS. The 1,6-naphthyridine L-870810 (Antiviral activity in cells IC(95) NHS = 102 nM, n=237), was shown to be efficacious in reducing viral RNA by 1.7 log units after doses of 400mg BID to HIV infected patients. Optimization of physical properties led to L-900564, an inhibitor of HIV IN that has excellent cell potency in the presence of protein (Antiviral activity in cells IC(95) NHS = 16 nM, n=15), excellent activity against mutants raised to HIV integrase inhibitors, and a very good pharmacokinetic profile.

  12. HIV/AIDS

    Science.gov (United States)

    ... People who are infected with HIV sometimes try dietary supplements that claim to boost the immune system or counteract side effects of anti-HIV drugs. Supplements that may be helpful Acetyl-L-carnitine. Researchers have used acetyl-L-carnitine to treat ...

  13. Prevalência da infecção pelo HIV em pacientes com tuberculose na atenção básica em Fortaleza, Ceará Prevalence of HIV infection in tuberculosis patients treated at primary health care clinics in the city of Fortaleza, Brazil

    Directory of Open Access Journals (Sweden)

    Helder Oliveira e Silva

    2012-06-01

    Full Text Available O objetivo deste trabalho foi determinar a prevalência da infecção pelo HIV em indivíduos com > 15 anos de idade e diagnóstico confirmado de tuberculose, acompanhados em Centros de Saúde da Família de Fortaleza (CE. Uma amostra aleatória de 110 pacientes com diagnóstico de tuberculose de 26 Centros de Saúde da Família foi incluída no estudo, realizado entre os meses de janeiro e maio de 2009. Todos os participantes responderam a um questionário com dados sociodemográficos e clínicos e realizaram sorologia para o HIV. Nesta amostra, a prevalência de coinfecção tuberculose/HIV foi de 3,6% (IC95%: 0,2-7,0.The objective of this study was to determine the prevalence of HIV infection among individuals > 15 years of age with a confirmed diagnosis of tuberculosis and treated at family health care clinics in the city of Fortaleza, Brazil. We evaluated a random sample of 110 patients with tuberculosis, treated at a total of 26 family health care clinics between January and May of 2009. All of the participants completed a questionnaire regarding sociodemographic and clinical data, and all underwent HIV testing. In this sample, the prevalence of tuberculosis/HIV co-infection was 3.6% (95% CI: 0.2-7.0.

  14. First-Line Antiretroviral Treatment Outcomes and Durability in HIV-Infected Children Treated Through the Universal Coverage Health Program in Thailand.

    Science.gov (United States)

    Teeraananchai, Sirinya; Bunupuradah, Torsak; Puthanakit, Thanyawee; Kerr, Stephen J; Ruxrungtham, Kiat; Chaivooth, Suchada; Bhakeecheep, Sorakij; Law, Matthew G; Chokephaibulkit, Kulkanya

    2017-06-01

    We assessed the treatment outcomes on first-line antiretroviral therapy (ART), and factors associated with switching regimen in HIV-infected children treated through the universal coverage health program (UC) in Thailand. Children aged <15 years at ART initiation who had been receiving ART for at least 6 months between 2008 and 2014 through UC were included in the analysis. The Kaplan-Meier method was used to estimate immunological recovery (IMR), immunological failure, and virological failure (VF). Cox models were used to assess predictors of IMR and VF. Competing risk models were used to assess factors associated with switching to a second-line regimen, with death considered as a competing risk. A total of 4120 children initiated ART at a median (interquartile range) age of 9.3 (5.8-12.0) years. The median duration of ART was 3.7 years with 17,950 person-years of follow-up. Two thousand eight hundred five children achieved IMR, and the probability of IMR increased to 76% by 3 years after ART initiation. Among 1054 children switched to second-line regimens, 84% had VF and 19% had immunological failure. The cumulative rate of switching regimen increased from 4% to 20% from 1 to 3 years after treatment. Children aged ≥12 years at ART initiation, starting with nonnucleoside reverse-transcriptase inhibitors, and baseline CD4% <10% had an increased risk of switching to second-line regimens. Children receiving ART through UC had good treatment outcomes, although a fifth required switching regimen by 3 years. Earlier treatment initiation and avoiding nonnucleoside reverse-transcriptase inhibitor first-line regimens in high-risk children may prevent treatment failure.

  15. Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database

    Directory of Open Access Journals (Sweden)

    Lim Poh-Lian

    2012-01-01

    Full Text Available Abstract Background Pneumocystis jiroveci pneumonia (PCP prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD receiving PCP prophylaxis, and its effect on PCP and mortality. Methods TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models. Results There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years and 169 died from all causes (1.36/100 person-years. After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p 3, lowering mortality rates from 33.5 to 6.3 per 100 person-years. Conclusions Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits.

  16. Renal and urologic disorders in antiretroviral-treated patients with HIV infection or AIDS: spectrum of cross-sectional imaging findings.

    Science.gov (United States)

    Tonolini, Massimo; Villa, Federica; Villa, Chiara; Ippolito, Sonia; Bianco, Roberto

    2013-01-01

    In the aging human immunodeficiency virus (HIV)-infected population with improved immune function under antiretroviral treatment, many different opportunistic disorders may be encountered, along with rare presentations or complicated forms of common diseases. Renal and urologic abnormalities observed in the setting of HIV infection or acquired immunodeficiency syndrome are reviewed with their imaging appearances, including renal dysfunction, urolithiasis, urinary tract infections and related complications, genitourinary tuberculosis, vascular lesions, urogenital tumors, and bladder abnormalities, with emphasis on characterization. In HIV-positive patients, early cross-sectional imaging is warranted to detect uncommon disorders and complications, with the aim to preserve renal function. © 2013 Mosby, Inc. All rights reserved.

  17. Intimate Partner Violence Against HIV-Positive Women is Associated with Sub-Optimal Infant Feeding Practices in Lusaka, Zambia.

    Science.gov (United States)

    Hampanda, Karen

    2016-12-01

    Objectives The aim of this study is to determine how intimate partner violence against HIV-positive women affects safe infant feeding practices in Lusaka, Zambia. Methods A cross-sectional face-to-face survey was conducted with 320 married postpartum women at a large public health center in Lusaka, Zambia, in 2014. Variables were measured using previously validated instruments from the Demographic and Health Survey. Data were analyzed using simple and multivariate logistic regression in Stata 12. Results Thirty-seven percent of women report early mixed infant feeding prior to six months. Women who experienced intimate partner violence have 2.8 higher adjusted odds of early mixed infant feeding (p feeding (p feeding (p feeding (p feeding, putting infants at greater risk for both mother-to-child transmission of HIV and other infant morbidities. Intimate partner violence should thus be given increased attention within the context of infant feeding and HIV in sub-Saharan Africa.

  18. HIV and Hepatitis B

    Science.gov (United States)

    ... AIDS-Related Opportunistic Infections and Coinfections HIV and Hepatitis B (Last updated 8/31/2016; last reviewed ... should be treated for both diseases. What is hepatitis B? Hepatitis B is a liver disease caused ...

  19. HIV-1 Drug Resistance Mutations Among Antiretroviral-Naïve HIV-1–Infected Patients in Asia: Results From the TREAT Asia Studies to Evaluate Resistance-Monitoring Study

    Science.gov (United States)

    Oyomopito, Rebecca; Sirivichayakul, Sunee; Sirisanthana, Thira; Kantipong, Pacharee; Lee, Christopher K. C.; Kamarulzaman, Adeeba; Messerschmidt, Liesl; Law, Matthew G.; Phanuphak, Praphan

    2011-01-01

    (See editorial commentary by Jordan on pages 1058–1060.) Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia. PMID:21460324

  20. Predicting intention to treat HIV-infected patients among Tanzanian and Sudanese medical and dental students using the theory of planned behaviour--a cross sectional study

    National Research Council Canada - National Science Library

    Astrøm, Anne N; Nasir, Elwalid F

    2009-01-01

    .... This study aimed to predict the intention to provide surgical treatment to HIV infected patients among medical- and dental students in Tanzania and Sudan using an extended version of the Theory of Planned Behaviour (TPB...

  1. Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study

    Directory of Open Access Journals (Sweden)

    Danielle P. Porter

    2015-12-01

    Full Text Available At Week 96 of the Single-Tablet Regimen (STaR study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF developed resistance mutations compared to those treated with efavirenz (EFV/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33, as well as baseline samples from control subjects with virologic response (n = 118. Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20% were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.

  2. Streamlining HIV Testing for HIV Preexposure Prophylaxis

    OpenAIRE

    Guanira, Juan V.; Leigler, Teri; Kallas, Esper; Schechter, Mauro; Sharma, Usha; Glidden, David; Grant, Robert M.

    2014-01-01

    HIV-testing algorithms for preexposure prophylaxis (PrEP) should be optimized to minimize the risk of drug resistance, the time off PrEP required to evaluate false-positive screening results, and costs and to expedite the start of therapy for those confirmed to be infected. HIV rapid tests (RTs) for anti-HIV antibodies provide results in less than 1 h and can be conducted by nonlicensed staff at the point of care. In many regions, Western blot (WB) testing is required to confirm reactive RT r...

  3. Accurate prediction of HIV-1 drug response from the reverse transcriptase and protease amino acid sequences using sparse models created by convex optimization.

    Science.gov (United States)

    Rabinowitz, Matthew; Myers, Lance; Banjevic, Milena; Chan, Albert; Sweetkind-Singer, Joshua; Haberer, Jessica; McCann, Kelly; Wolkowicz, Roland

    2006-03-01

    Genotype-phenotype modeling problems are often overcomplete, or ill-posed, since the number of potential predictors-genes, proteins, mutations and their interactions-is large relative to the number of measured outcomes. Such datasets can still be used to train sparse parameter models that generalize accurately, by exerting a principle similar to Occam's Razor: When many possible theories can explain the observations, the most simple is most likely to be correct. We apply this philosophy to modeling the drug response of Type-1 Human Immunodeficiency Virus (HIV-1). Owing to the decreasing expense of genetic sequencing relative to in vitro phenotype testing, a statistical model that reliably predicts viral drug response from genetic data is an important tool in the selection of antiretroviral therapy (ART). The optimization techniques described will have application to many genotype-phenotype modeling problems for the purpose of enhancing clinical decisions. We describe two regression techniques for predicting viral phenotype in response to ART from genetic sequence data. Both techniques employ convex optimization for the continuous subset selection of a sparse set of model parameters. The first technique, the least absolute shrinkage and selection operator, uses the l(1) norm loss function to create a sparse linear model; the second, the support vector machine with radial basis kernel functions, uses the epsilon-insensitive loss function to create a sparse non-linear model. The techniques are applied to predict the response of the HIV-1 virus to 10 reverse transcriptase inhibitor and 7 protease inhibitor drugs. The genetic data are derived from the HIV coding sequences for the reverse transcriptase and protease enzymes. When tested by cross-validation with actual laboratory measurements, these models predict drug response phenotype more accurately than models previously discussed in the literature, and other canonical techniques described here. Key features of the

  4. Streamlining HIV Testing for HIV Preexposure Prophylaxis

    Science.gov (United States)

    Leigler, Teri; Kallas, Esper; Schechter, Mauro; Sharma, Usha; Glidden, David; Grant, Robert M.

    2014-01-01

    HIV-testing algorithms for preexposure prophylaxis (PrEP) should be optimized to minimize the risk of drug resistance, the time off PrEP required to evaluate false-positive screening results, and costs and to expedite the start of therapy for those confirmed to be infected. HIV rapid tests (RTs) for anti-HIV antibodies provide results in less than 1 h and can be conducted by nonlicensed staff at the point of care. In many regions, Western blot (WB) testing is required to confirm reactive RT results. WB testing, however, causes delays in diagnosis and adds expense. The iPrEx study evaluated the safety and efficacy of daily oral emtricitabine-tenofovir disoproxil fumarate among HIV-seronegative men and transgender women who have sex with men: HIV infection was assessed with two RTs plus WB confirmation, followed by HIV-1 plasma viral load testing. During the iPrEx study, there were 51,260 HIV status evaluations among 2,499 volunteers using RTs: 142 (0.28%) had concordant positive results (100% were eventually confirmed) and 19 (0.04%) had discordant results among 14 participants; 11 were eventually determined to be HIV infected. A streamlined approach using only one RT to screen and a second RT to confirm (without WB) would have had nearly the same accuracy. Discrepant RT results are best evaluated with nucleic acid testing, which would also increase sensitivity. PMID:25378570

  5. Analysis of HIV-1 protease gene reveals frequent multiple infections followed by recombination among drug treated individuals living in Sao Paulo and Santos, Brazil.

    Directory of Open Access Journals (Sweden)

    Edsel Renata De Morais Nunes

    Full Text Available The present study investigated the prevalence of HIV-1 multiple infections in a population composed by 47 patients under HAART failure and enrolled at the National DST/AIDS, Program, Ministry of Health, Brazil.Detection of multiple infections was done using a previously published RFLP assay for the HIV-1 protease gene, which is able of distinguishing between infections caused by a single or multiple HIV-1 subtypes. Samples with multiple infections were cloned, and sequence data submitted to phylogenetic analysis. We were able to identify 17 HIV-1 multiple infections out of 47 samples. Multiple infections were mostly composed by a mixture of recombinant viruses (94%, with only one case in which protease gene pure subtypes B and F were recovered. This is the first study that reports the prevalence of multiple infections and intersubtype recombinants in a population undergoing HAART in Brazil. Based on the data there was a steep increase of multiple infections after the introduction of the combined antiretroviral therapy in Brazil. Cases of multiple infections may be associated with HIV-1 genetic diversity through recombination allowing for the generation of viruses showing a combination of resistance mutations.

  6. Transmissão vertical do HIV em população atendida no serviço de referência Vertical transmission of HIV in the population treated at a reference center

    Directory of Open Access Journals (Sweden)

    Sueli Teresinha Cruz Rodrigues

    2013-01-01

    Full Text Available OBJETIVO: Identificar a taxa de transmissão vertical do HIV e avaliar os fatores envolvidos em partes materna e fetal. MÉTODOS: Estudo transversal realizado no Serviço de Atendimento Especializado. Foram investigados 102 prontuários de mulheres com HIV que deram à luz a recém-nascidos vivos. RESULTADOS: A prevalência de 6,6% de transmissão vertical. Entre as crianças infectadas: 40,0% de mães sem pré-natal e 75% sem a profilaxia com anti-retrovirais durante o pré-natal, 50,0% sem profilaxia com AZT com oral e amamentado. Entre as crianças não infectadas: 91,5% iniciaram a profilaxia com AZT oral ao nascimento e 84,1% das mães receberam ARV. CONCLUSÃO: A ocorrência de transmissão vertical do HIV no serviço de referência correspondeu a 6,6%, o que indica uma alta prevalência.OBJECTIVE: To identify the rate of vertical transmission of HIV and assess the factors involved in maternal and fetal share. METHODS: Cross-sectional study conducted in the Specialized Care Service. We investigated 102 clinical records of HIV positive women who had given birth to live newborns. The primary variable was the occurrence of vertical transmission of HIV and the secondary variables were the factors associated with vertical transmission of HIV. RESULTS: Prevalence of 6.6% of vertical transmission. Among the infected children: 40.0% of mothers with out prenatal care and 75% without prophylaxis with antiretroviral drugs during the prenatal, 50.0% without AZT prophylaxis with oral and breast-fed. Among the uninfected children: 91.5% were started on prophylaxis with oral AZT at birth and 84.1% of mothers received ARV delivery. CONCLUSION: The occurrence of vertical transmission of HIV in the reference service corresponded to 6.6%, indicating a high prevalence.

  7. Relationship of vitamin D, HIV, HIV treatment, and lipid levels in the Women's Interagency HIV Study of HIV-infected and uninfected women in the United States.

    Science.gov (United States)

    Schwartz, Janice B; Moore, Kelly L; Yin, Michael; Sharma, Anjali; Merenstein, Dan; Islam, Talat; Golub, Elizabeth T; Tien, Phyllis C; Adeyemi, Oluwatoyin M

    2014-01-01

    Relationships between vitamin D, lipids, HIV infection, and HIV treatment (±antiretroviral therapy [ART]) were investigated with Women's Interagency HIV Study data (n = 1758 middle-aged women) using multivariable regression. Sixty-three percent of women had vitamin D deficiency. Median 25-hydroxyvitamin D (25-OH vitamin D) was highest in HIV-infected + ART-treated women (17 ng/mL; P HIV treatment. Similarly, vitamin D levels were positively related to triglycerides only in ART-treated HIV-infected women and unrelated to cholesterol.

  8. Dawn of antioxidants and immune modulators to stop HIV-progression and boost the immune system in HIV/AIDS patients: An updated comprehensive and critical review.

    Science.gov (United States)

    Singh, Gurinder; Pai, Roopa S

    2015-06-01

    In the last two decades, human immunodeficiency virus (HIV), the retrovirus responsible for the acquired immunodeficiency syndrome (AIDS), is one of the leading causes of morbidity and mortality, worldwide. Providing the optimum management of HIV/AIDS is a major challenge in the 21st century. Since, HIV-infected persons have an extended lifespan due to the development of effective antiretroviral therapies, malnutrition is becoming central factors of long-term survivors. The nutrition status of AIDS patients has a significant influence on the maintenance and optimal effectiveness of the immune system. Micronutrient therapy in combination with allopathic treatments can extend and improve the quality and quantity of life in individuals infected with HIV/AIDS. HIV infection is thought to lead to augmented oxidative stress which may in turn lead to faster development of HIV disease. Hence, antioxidants might have a significant role in the treatment of HIV/AIDS. An additional approach to treating HIV infection is fortifying the immune response of infected people. Immune modulators help to activate and boost the normal immune function. The present review first describes the boon of antioxidants (especially Vitamin A) and immune modulators (cytolin, resveratrol, murabutide, setarud, tucaresol, AVR118, Immunitin (HE2000), reticulose, and interleukin-7) in the treatment of HIV/AIDS. Then, providing a comparatively succinct outline on updated patents study on antioxidants and immune modulators to treat HIV/AIDS will be discussed. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate.

    Directory of Open Access Journals (Sweden)

    Jurjen van der Schans

    Full Text Available Attention-Deficit/Hyperactivity Disorder (ADHD is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at school often leads to reduced compliance, sub-optimal treatment, and therefore economic loss. Replacement of IR-MPH with a single-dose extended release (ER-MPH formulation may improve drug response and economic efficiency.To evaluate the cost-effectiveness from a societal perspective of a switch from IR-MPH to ER-MPH in patients who are sub-optimally treated.A daily Markov-cycle model covering a time-span of 10 years was developed including four different health states: (1 optimal response, (2 sub-optimal response, (3 discontinued treatment, and (4 natural remission. ER-MPH options included methylphenidate osmotic release oral system (MPH-OROS and Equasym XL/Medikinet CR. Both direct costs and indirect costs were included in the analysis, and effects were expressed as quality-adjusted life years (QALYs. Univariate, multivariate as well as probabilistic sensitivity analysis were conducted and the main outcomes were incremental cost-effectiveness ratios.Switching sub-optimally treated patients from IR-MPH to MPH-OROS or Equasym XL/Medikinet CR led to per-patient cost-savings of €4200 and €5400, respectively, over a 10-year treatment span. Sensitivity analysis with plausible variations of input parameters resulted in cost-savings in the vast majority of estimations.This study lends economic support to switching patients with ADHD with suboptimal response to short-acting IR-MPH to long-acting ER-MPH regimens.

  10. Stability of hepatitis C virus (HCV) RNA levels among interferon-naïve HIV/HCV-coinfected individuals treated with combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Grint, D; Peters, Lars; Reekie, J;

    2013-01-01

    Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals.......Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals....

  11. HIV treatment for prevention

    Directory of Open Access Journals (Sweden)

    Ambrosioni Juan

    2011-05-01

    Full Text Available Abstract "No virus, no transmission." Studies have repeatedly shown that viral load (the quantity of virus present in blood and sexual secretions is the strongest predictor of HIV transmission during unprotected sex or transmission from infected mother to child. Effective treatment lowers viral load to undetectable levels. If one could identify and treat all HIV-infected people immediately after infection, the HIV/AIDS epidemic would eventually disappear. Such a radical solution is currently unrealistic. In reality, not all people get tested, especially when they fear stigma and discrimination. Thus, not all HIV-infected individuals are known. Of those HIV-positive individuals for whom the diagnosis is known, not all of them have access to therapy, agree to be treated, or are taking therapy effectively. Some on effective treatment will stop, and in others, the development of resistance will lead to treatment failure. Furthermore, resources are limited: should we provide drugs to asymptomatic HIV-infected individuals without indication for treatment according to guidelines in order to prevent HIV transmission at the risk of diverting funding from sick patients in urgent need? In fact, the preventive potential of anti-HIV drugs is unknown. Modellers have tried to fill the gap, but models differ depending on assumptions that are strongly debated. Further, indications for antiretroviral treatments expand; in places like Vancouver and San Francisco, the majority of HIV-positive individuals are now under treatment, and the incidence of new HIV infections has recently fallen. However, correlation does not necessarily imply causation. Finally, studies in couples where one partner is HIV-infected also appear to show that treatment reduces the risk of transmission. More definite studies, where a number of communities are randomized to either receive the "test-and-treat" approach or continue as before, are now in evaluation by funding agencies. Repeated

  12. HIV-infected patients with a large thymus maintain higher CD4 counts in a 5-year follow-up study of patients treated with highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Kolte, L; Ryder, L P; Albrecht-Beste, E;

    2009-01-01

    CD4 recovery in HIV-infected patients treated with highly active antiretroviral therapy (HAART) is in part believed to be dependent on the degree of preserved thymic function. We investigated whether the thymus has a prolonged effect on CD4 recovery. Total and naïve CD4 counts as well as thymic...... with larger thymic size at follow-up. However, no difference in the increase in thymic output was seen between thymic groups. In conclusion, the importance of the thymus to the rate of cellular restoration seems primarily to lie within the first two years of HAART. However, patients with larger thymic size...

  13. Optimizing HIV prevention for women: a review of evidence from microbicide studies and considerations for gender-sensitive microbicide introduction

    Directory of Open Access Journals (Sweden)

    Elizabeth G Doggett

    2015-12-01

    Full Text Available Introduction: Microbicides were conceptualized as a product that could give women increased agency over HIV prevention. However, gender-related norms and inequalities that place women and girls at risk of acquiring HIV are also likely to affect their ability to use microbicides. Understanding how gendered norms and inequalities may pose obstacles to women's microbicide use is important to inform product design, microbicide trial implementation and eventually microbicide and other antiretroviral-based prevention programmes. We reviewed published vaginal microbicide studies to identify gender-related factors that are likely to affect microbicide acceptability, access and adherence. We make recommendations on product design, trial implementation, positioning, marketing and delivery of microbicides in a way that takes into account the gender-related norms and inequalities identified in the review. Methods: We conducted PubMed searches for microbicide studies published in journals between 2000 and 2013. Search terms included trial names (e.g. “MDP301”, microbicide product names (e.g. “BufferGel”, researchers’ names (e.g. “van der Straten” and other relevant terms (e.g. “microbicide”. We included microbicide clinical trials; surrogate studies in which a vaginal gel, ring or diaphragm was used without an active ingredient; and hypothetical studies in which no product was used. Social and behavioural studies implemented in conjunction with clinical trials and surrogate studies were also included. Although we recognize the importance of rectal microbicides to women, we did not include studies of rectal microbicides, as most of them focused on men who have sex with men. Using a standardized review template, three reviewers read the articles and looked for gender-related findings in key domains (e.g. product acceptability, sexual pleasure, partner communication, microbicide access and adherence. Results and discussion: The gendered norms

  14. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial

    Science.gov (United States)

    Objective: To determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), serum parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C telopeptide (CTX) in HIV-infected youth receiving and not receiving tenofovir-containing cART (TDF). Design: Ra...

  15. The course of preexistent immune abnormalities in HIV-negative hemophiliacs treated for 2 years with a monoclonal purified factor-VIII concentrate

    NARCIS (Netherlands)

    Smid, W. M.; van der Meer, J.; Smit, J. W.; Halie, M. R.

    1993-01-01

    The administration of factor VIII concentrates has been associated with immune abnormalities in patients with severe haemophilia A, even in the absence of HIV infection. The effects of a monoclonal purified factor VIII concentrate, Hemofil M (Baxter), on preexistent immune abnormalities were

  16. Prognostic significance of the interval between the initiation of antiretroviral therapy and the initiation of anti-tuberculosis treatment in HIV/tuberculosis-coinfected patients: results from the TREAT Asia HIV Observational Database.

    Science.gov (United States)

    Han, S H; Zhou, J; Lee, M P; Zhao, H; Chen, Y-M A; Kumarasamy, N; Pujari, S; Lee, C; Omar, S F S; Ditangco, R; Phanuphak, N; Kiertiburanakul, S; Chaiwarith, R; Merati, T P; Yunihastuti, E; Tanuma, J; Saphonn, V; Sohn, A H; Choi, J Y

    2014-02-01

    We evaluated the effect of the time interval between the initiation of antiretroviral therapy (ART) and the initiation of tuberculosis (TB) treatment on clinical outcomes in HIV/TB-coinfected patients in an Asian regional cohort. Adult HIV/TB-coinfected patients in an observational HIV-infected cohort database who had a known date of ART initiation and a history of TB treatment were eligible for study inclusion. The time interval between the initiation of ART and the initiation of TB treatment was categorized as follows: TB diagnosed while on ART, ART initiated ≤ 90 days after initiation of TB treatment ('early ART'), ART initiated > 90 days after initiation of TB treatment ('delayed ART'), and ART not started. Outcomes were assessed using survival analyses. A total of 768 HIV/TB-coinfected patients were included in this study. The median CD4 T-cell count at TB diagnosis was 100 [interquartile range (IQR) 40-208] cells/μL. Treatment outcomes were not significantly different between the groups with early ART and delayed ART initiation. Kaplan-Meier analysis indicated that mortality was highest for those diagnosed with TB while on ART (3.77 deaths per 100 person-years), and the prognoses of other groups were not different (in deaths per 100 person-years: 2.12 for early ART, 1.46 for delayed ART, and 2.94 for ART not started). In a multivariate model, the interval between ART initiation and TB therapy initiation did not significantly impact all-cause mortality. A negative impact of delayed ART in patients coinfected with TB was not observed in this observational cohort of moderately to severely immunosuppressed patients. The broader impact of earlier ART initiation in actual clinical practice should be monitored more closely. © 2013 British HIV Association.

  17. Nutritional assessment and lipid profile in HIV-infected children and adolescents treated with highly active antiretroviral therapy Avaliação nutricional e do perfil lipídico em crianças e adolescentes infectadas pelo HIV tratadas com terapia antirretroviral de alta potência

    Directory of Open Access Journals (Sweden)

    Marina Hjertquist Tremeschin

    2011-06-01

    Full Text Available INTRODUCTION: HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART regimens that include a protease inhibitor (PI can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336, and 136 (63 - 271 versus control group: 54.5 (20 - 162; p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273 versus 67.5 (33 - 117; p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58 and 36 (23 - 43; control 49.5 (34 - 69; p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.INTRODUÇÃO: Crianças e adolescentes infectadas pelo HIV e tratadas com terapia antirretroviral de alta potência (TAAP, que inclui inibidor de protease (IP podem apresentar significante melhora clínica no estado nutricional e na qualidade de vida. O objetivo é relatar as alterações nutricionais e metabólicas em pacientes pediátricos expostos a TAAP e controles saud

  18. Atendimento odontológico de portadores de HIV/AIDS: fatores associados à disposição de cirurgiões-dentistas do Sistema Único de Saúde de Belo Horizonte, Minas Gerais, Brasil Factors associated with dentists' willingness to treat HIV/AIDS patients in the National Health System in Belo Horizonte, Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Maria Inês Barreiros Senna

    2005-02-01

    Full Text Available Um estudo seccional foi conduzido entre cirurgiões-dentistas do Sistema Único de Saúde de Belo Horizonte, Minas Gerais, Brasil, com o objetivo de identificar fatores associados à disposição para o atendimento odontológico de portadores do HIV/AIDS. Questionários foram distribuídos aos participantes em seu local de trabalho. Um total de 140/345 (41,0% dentistas selecionados participaram do estudo. A prevalência de disposição para o atendimento foi de 55,0%. Resultados ajustados pela regressão logística múltipla mostraram que a disposição para o atendimento foi significativamente associada a ter percepção correta sobre o risco ocupacional (OR = 4,8; IC95%: 1,32-18,04, conhecer protocolo pós-exposição ocupacional (OR = 4,5; IC95%: 1,61-13,07, ter atitudes positivas frente à epidemia (OR = 3,2; IC95%: 1,37-7,45, ter experiência profissional com paciente portador de HIV/AIDS (OR = 3,0; IC95%: 1,30-7,19 e ser contra o exame diagnóstico compulsório anti-HIV de pacientes (OR = 2,3; IC95%: 0,96-5,40. Dentistas que tiveram acidente perfurocortante apresentaram menor disposição para o atendimento (OR = 0,4; IC95%: 0,15-0,85. Estes resultados mostram que o medo do contágio é a principal fonte de ansiedade para os trabalhadores da saúde com relação ao atendimento de pacientes com HIV/AIDS.A cross-sectional study was conducted among dentists in the Unified National Health System (SUS in Belo Horizonte, Minas Gerais, Brazil, to identify factors associated with their willingness to treat HIV/AIDS patients. Questionnaires were distributed at the participant's workplace. Some 140 out of 345 selected dentists (41.0% participated. Prevalence of willingness to treat was 55.0%. Results adjusted by multiple logistic regression showed that willingness to treat was significantly associated with a realistic perception of occupational risk (OR = 4.8; 95%CI: 1.32-18.04, knowledge of the exposure protocol (OR = 4.5; 95%CI: 1

  19. Bone Marrow Gene Therapy for HIV/AIDS.

    Science.gov (United States)

    Herrera-Carrillo, Elena; Berkhout, Ben

    2015-07-17

    Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described.

  20. Challenges in delivering HIV-care in Indonesia: experience from a referral hospital.

    Science.gov (United States)

    Wisaksana, Rudi; Alisjahbana, Bachti; van Crevel, Reinout; Kesumah, Nirmala; Sudjana, Primal; Sumantri, Rachmat

    2009-07-01

    HIV in Indonesia is strongly associated with injecting drug use (IDU), and surrounding stigma and lack of knowledge reduce accessibility of services. Uptake of HIV-testing is low and many patients present with advanced AIDS. A comprehensive evaluation was made of HIV-services provided between 2006 and 2008 in a referral hospital in West-Java, the province with the highest burden of HIV in Indonesia. A total of 826 HIV-positive patients, mostly infected through IDU (73.9%), presented between 2006 - 2008. Targeted screening and provider-initiated testing and counseling (PITC) led to earlier HIV-diagnosis. Operational research helped optimize diagnosis and treatment of important disease complications. Systematic monitoring of treatment response, and collaboration with other providers, methadone maintenance program and prison help improve treatment outcome. Over the last three years, the number of individuals tested and treated for HIV increased approximately two-fold and six-month mortality decreased from 13.6% to 7.5%. Loss to follow-up was 12.2% at six months. Significant progress has been made in delivering HIV-care in West-Java through operational research, systematic treatment monitoring, and the use of simple indicators to evaluate the quantity and quality of care.

  1. HIV-Associated Tuberculosis

    Directory of Open Access Journals (Sweden)

    Kogieleum Naidoo

    2011-01-01

    Full Text Available The intersecting HIV and Tuberculosis epidemics in countries with a high disease burden of both infections pose many challenges and opportunities. For patients infected with HIV in high TB burden countries, the diagnosis of TB, ARV drug choices in treating HIV-TB coinfected patients, when to initiate ARV treatment in relation to TB treatment, managing immune reconstitution, minimising risk of getting infected with TB and/or managing recurrent TB, minimizing airborne transmission, and infection control are key issues. In addition, given the disproportionate burden of HIV in women in these settings, sexual reproductive health issues and particular high mortality rates associated with TB during pregnancy are important. The scaleup and resource allocation to access antiretroviral treatment in these high HIV and TB settings provide a unique opportunity to strengthen both services and impact positively in meeting Millennium Development Goal 6.

  2. HIV Testing

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... All Collapse All Should I get tested for HIV? CDC recommends that everyone between the ages of ...

  3. The global HIV epidemic: current status and challenges.

    Science.gov (United States)

    Abdool Karim, Quarraisha

    2013-06-01

    Three decades after the first reported cases of AIDS we have within our reach sufficient evidence to substantially alter the HIV epidemic at a country level regardless of mode of transmission of HIV. There are a growing number of countries demonstrating control of the epidemic. Human rights violations and/or legislation relating to sexual orientation, status of minors, injecting drug use and sex work together with stigma and discrimination remain key barriers to knowledge of HIV status and access to appropriate services. The use of anti-retrovirals prophylactically to reduce sexual and vertical transmission and systemically to treat infected infants and adults is central to the optimism in responses to the epidemic. In the current fiscal climate careful thought needs to be given to how to efficiently optimise combinations of what is available to have the biggest impact in the context of limited human and infrastructure resources.

  4. Biogas-pH automation control strategy for optimizing organic loading rate of anaerobic membrane bioreactor treating high COD wastewater.

    Science.gov (United States)

    Yu, Dawei; Liu, Jibao; Sui, Qianwen; Wei, Yuansong

    2016-03-01

    Control of organic loading rate (OLR) is essential for anaerobic digestion treating high COD wastewater, which would cause operation failure by overload or less efficiency by underload. A novel biogas-pH automation control strategy using the combined gas-liquor phase monitoring was developed for an anaerobic membrane bioreactor (AnMBR) treating high COD (27.53 g·L(-1)) starch wastewater. The biogas-pH strategy was proceeded with threshold between biogas production rate >98 Nml·h(-1) preventing overload and pH>7.4 preventing underload, which were determined by methane production kinetics and pH titration of methanogenesis slurry, respectively. The OLR and the effluent COD were doubled as 11.81 kgCOD·kgVSS(-1)·d(-1) and halved as 253.4 mg·L(-1), respectively, comparing with a constant OLR control strategy. Meanwhile COD removal rate, biogas yield and methane concentration were synchronously improved to 99.1%, 312 Nml·gCODin(-1) and 74%, respectively. Using the biogas-pH strategy, AnMBR formed a "pH self-regulation ternary buffer system" which seizes carbon dioxide and hence provides sufficient buffering capacity.

  5. Hepatocellular Carcinoma Metastasis to the Orbit in a Coinfected HIV+ HBV+ Patient Previously Treated with Orthotopic Liver Transplantation: A Case Report

    Directory of Open Access Journals (Sweden)

    S. Guerriero

    2011-01-01

    Full Text Available Hepatocellular carcinoma rarely metastasizes to the orbit. We report a 45-year-old male, HBV+, HIV+, with a past history of a liver transplant for ELSD (end-stage liver disease with hepatocellular carcinoma and recurrent HCC, who presented with proptosis and diplopia of the left eye. CT scans of the head revealed a large, irregular mass in the left orbit causing superior and lateral destruction of the orbital bone. Biopsy specimens of the orbital tumor showed features of metastatic foci of hepatocellular carcinoma. Only 16 other cases of HCC metastasis to the orbit have been described in literature, and this is the first case in a previously transplanted HIV+, HBV+ patient.

  6. One-year mortality of HIV-positive patients treated for rifampicin- and isoniazid-susceptible tuberculosis in Eastern Europe, Western Europe, and Latin America

    DEFF Research Database (Denmark)

    Podlekareva, Daria; Kirk, Ole; Lundgren, Jens Dilling

    2017-01-01

    OBJECTIVES: The high mortality among HIV/tuberculosis (TB) coinfected patients in Eastern Europe is partly explained by the high prevalence of drug-resistant TB. It remains unclear whether outcomes of HIV/TB patients with rifampicin/isoniazid-susceptible TB in Eastern Europe differ from those...... regression modelsRESULTS:: Three hundred and forty-one patients were included (Eastern Europe 127, Western Europe 165, Latin America 49). Proportions of patients with disseminated TB (50, 58, 59%) and initiating rifampicin + isoniazid + pyrazinamide-based treatment (93, 94, 94%) were similar in Eastern.......023). CONCLUSIONS: Despite comparable use of recommended anti-TB treatment, mortality of patients with rifampicin/isoniazid-susceptible TB remained higher in Eastern Europe when compared with Western Europe/Latin America. The high mortality in Eastern Europe was only partially explained by IDU, use of ART and CD4...

  7. Dry Sliding Wear Behaviour of Micro oven Treated Fly Ash Reinforced Epoxy Composite using ExtendedTaguchi Approach Optimization

    Science.gov (United States)

    Pattanaik, A.; Bhyan, S. K.; Mishra, S. C.; Patro, S. S.; Behera, Ajit

    2017-02-01

    Fly ash epoxy composite has been developed in ultrasonic mixing method with the aim of reducing the impact of hazardous waste like fly ash on the environment. Post curing has been done in micro oven to modify the surface so as to have better wear resistance properties. An orthogonal array, L32 has been designed with the influencing parameters like % fly ash, applied normal load, speed, track diameter and time of operation. A multi objective parametric condition, TOPSIS is used to convert it into a single objective optimization technique and ANOVA helps in getting the percentage contribution of each parameter for the wear of the material. In general, this article emphasizes the importance of micro oven treatment on the surface modification of polymeric material which retards the wear.

  8. HIV Prevention

    Science.gov (United States)

    ... on HIV Syndicated Content Website Feedback HIV/AIDS Prevention Language: English (US) Español (Spanish) Recommend on ... All Is abstinence the only 100% effective HIV prevention option? Yes. Abstinence means not having oral, vaginal, ...

  9. Analysis of regulatory T-cells and of their naïve and memory-like subsets in long-term treated aviremic HIV+ patients and untreated viremic patients

    Directory of Open Access Journals (Sweden)

    L Imberti

    2012-11-01

    Full Text Available Purpose of the study: Although HIV infection impacts the proportion and phenotype of regulatory T-cells (Tregs, discrepant results have been reported depending on the surface markers employed to characterize them and on the patient populations. In addition, the effects of a long-term combined antiretroviral therapy (cART on Treg cells have not been thoroughly documented. Our study investigated the frequency and number of Tregs and their phenotype in two different groups of HIV-infected patients: one aviremic undergoing long-term cART and one viremic naïve to cART showing a similar CD4+ cell count. Methods: Thirty-six HIV+ patients with sustained suppression of plasma viremia (<37 copies/mL on effective cART for more than 6 years and 22 HIV+patients naïve to cART and without clinical signs of opportunistic infections or tumors at the time of study (untreated group were included in the study. Healthy donors (HD were used as control. Flow cytometry on fresh whole blood was used to quantify total Tregs (defined as CD25+CD127low/-CD4+ cells and the following Treg subsets: naïve (CD45RA+CCR7+ Tregs, central-memory like Tregs (CD45RA-CCR7+, TregCM, effector-memory like Tregs (CD45RA-CCR7−, TregEM Statistical comparisons of the percentages and number of Tregs and Treg subpopulations were performed by ANOVA or Kruskal-Wallis test. Analysis of covariance was employed in order to adjust for the effect of the age. The Spearman's test was used to assess correlations. Summary of results: In viremic untreated and aviremic long-term cART-treated patients the percentage and number of the total Treg cells were not different from those of HD. However, the analysis of Treg phenotype showed a marked redistribution of the Treg subpopulations: in the untreated viremic patients, both the percentage and number of the TregCM subset decreased compared to HD and cART-treated patients, whereas only the percentage of naïve Tregs increased. In particular, the percentage

  10. Do HIV-1 non-B subtypes differentially impact resistance mutations and clinical disease progression in treated populations? Evidence from a systematic review

    Directory of Open Access Journals (Sweden)

    Madhavi Bhargava

    2014-07-01

    Full Text Available There are 31 million adults living with HIV-1 non-B subtypes globally, and about 10 million are on antiretroviral therapy (ART. Global evidence to guide clinical practice on ART response in HIV-1 non-B subtypes remains limited. We systematically searched 11 databases for the period 1996 to 2013 for evidence. Outcomes documented included time to development of AIDS and/or death, resistance mutations, opportunistic infections, and changes in CD4 cell counts and viral load. A lack of consistent reporting of all clinical end points precluded a meta-analysis. In sum, genetic diversity that precipitated differences in disease progression in ART-naïve populations was minimized in ART-experienced populations, although variability in resistance mutations persisted across non-B subtypes. To improve the quality of patient care in global settings, recording HIV genotypes at baseline and at virologic failure with targeted non-B subtype-based point-of-care resistance assays and timely phasing out of resistance-inducing ART regimens is recommended.

  11. Circulating Biomarkers of Immune Activation Distinguish Viral Suppression from Nonsuppression in HAART-Treated Patients with Advanced HIV-1 Subtype C Infection

    Directory of Open Access Journals (Sweden)

    Glen Malherbe

    2014-01-01

    Full Text Available Few studies have examined immune activation profiles in patients with advanced HIV-1 subtype C infection or assessed their potential to predict responsiveness to HAART. BioPlex, ELISA, and nephelometric procedures were used to measure plasma levels of inflammatory biomarkers in HIV-1 subtype C-infected patients sampled before and after 6 months of successful HAART (n=20; in patients failing HAART (n=30; and in uninfected controls (n=8. Prior to HAART, CXCL9, CXCL10, β2M, sTNF-R1, TGF-β1, IFN-γ, IL-6, TNF, and sCD14 were significantly elevated in HIV-1-infected patients compared to controls (P<0.01. All of these markers, with the exception of sTNF-R1, were also elevated in patients failing HAART (P<0.05. The persistently elevated levels of CXCL9, CXCL10, and β2M in patients failing therapy in the setting of a marked reduction in these markers in patients on successful HAART suggest that they may be useful not only to monitor immune activation during HAART, but also to distinguish between good and poor responders. In the case of sCD14 and TGF-β1, the levels of these biomarkers remained persistently elevated despite HAART-induced virological suppression, a finding that is consistent with ongoing monocyte-macrophage activation, underscoring a potential role for adjuvant anti-inflammatory therapy.

  12. Introduction: Linkage, engagement, and retention in HIV care: essential for optimal individual- and community-level outcomes in the era of highly active antiretroviral therapy.

    Science.gov (United States)

    Mayer, Kenneth Hugh

    2011-01-15

    Engagement in medical care after a diagnosis of human immunodeficiency virus (HIV) infection is essential to initiate lifesaving antiretroviral therapy and facilitate the delivery of important prevention messages for reducing HIV transmission. Failure to engage and be retained in HIV care can be associated with negative outcomes for both the individual and the community. However, many Americans living with HIV infection are, for a variety of reasons, undiagnosed, not in medical care, or not receiving HIV treatment. The articles in this supplement describe the barriers, challenges, and successes in linking HIV-infected patients to expert care in the United States, with a focus on the unique issues faced by specific populations of men who have sex with men, heterosexual men, and women, and the role of the health care system and other structural factors in facilitating or impeding engagement in care.

  13. Optimizing levodopa therapy to treat wearing-off symptoms in Parkinson's disease: focus on levodopa/carbidopa/entacapone.

    Science.gov (United States)

    Reichmann, Heinz; Emre, Murat

    2012-02-01

    Levodopa has been the mainstay of Parkinson's disease (PD) therapy for over 40 years, with its efficacy surpassing that of other antiparkinsonian medications. As such, most PD patients eventually require levodopa-based therapy during the course of the disease. However, despite its proven efficacy, long-term levodopa therapy is associated with motor complications, with wearing-off being the most prevalent. Wearing-off occurs, in part, as a result of the short half-life of levodopa, which leads to fluctuations in plasma levodopa levels. A pharmacokinetic profile characterized by a higher trough value of levodopa can be achieved by combining levodopa/carbidopa with entacapone, which inhibits the peripheral breakdown of levodopa, resulting in higher plasma levodopa levels. Here, we review the limitations of conventional levodopa and the clinical data for levodopa/carbidopa/entacapone in treating patients with wearing-off.

  14. Mortality in HIV-infected patients with tuberculosis treated with streptomycin and a two-week intensified regimen: data from an HIV cohort study using inverse probability of treatment weighting

    Directory of Open Access Journals (Sweden)

    Gerardo Alvarez-Uria

    2016-05-01

    Full Text Available Background. Despite the dramatic scale-up of antiretroviral therapy in low- and middle-income countries, tuberculosis (TB is still the main cause of death among HIV-infected patients in resource-limited settings. Previous studies in patients with TB meningitis suggest that the use of higher doses of common anti-TB drugs could reduce mortality. Methods. Using clinical data from an HIV cohort study in India, we compared the mortality among HIV-infected patients diagnosed with TB according to the regimen received during the first two weeks of treatment: standard anti-tuberculosis therapy (ATT (N = 847, intensified ATT (N = 322, and intensified ATT with streptomycin (N = 446. The intensified ATT comprised double dose of rifampicin and substitution of ethambutol with levofloxacin. Multivariate analysis was performed using Cox proportional hazard models and inverse probability of treatment weighting (IPTW based on propensity scores. Patients with TB meningitis were excluded. Results. The use of intensified ATT alone did not improve survival. However, when streptomycin was added, the use intensified ATT was associated with reduced mortality in Cox models (adjusted hazard ratio 0.72, 95% CI [0.57–0.91] and after IPTW (hazard ratio 0.77, 95% CI [0.67–0.96]. Other factors associated with improved survival were high serum albumin concentration, high CD4 lymphocyte cell-counts, and high glomerular filtration rates. Factors associated with increased mortality were high urea concentrations, being on antiretroviral therapy at the time of ATT initiation and high BUN/creatinine ratio. In an effect modification analysis, the survival benefits of the intensified ATT with streptomycin disappeared in patients with severe hypoalbuminemia. Conclusion. The results of this study are in accordance with a previous study from our cohort involving patients with TB meningitis, and suggest that an intensified 2-week ATT with streptomycin could reduce mortality in HIV

  15. The Decline in HIV-1 Drug Resistance in Heavily Antiretroviral-Experienced Patients Is Associated with Optimized Prescriptions in a Treatment Roll-Out Program in Mexico.

    Science.gov (United States)

    Calva, Juan J; Larrea, Silvana; Tapia-Maltos, Marco A; Ostrosky-Frid, Mauricio; Lara, Carolina; Aguilar-Salinas, Pedro; Rivera, Héctor; Ramírez, Juan P

    2017-07-01

    A decrease in the rate of acquired antiretroviral (ARV) drug resistance (ADR) over time has been documented in high-income settings, but data on the determinants of this phenomenon are lacking. We tested the hypothesis that in heavily ARV-experienced patients in the Mexican ARV therapy (ART) roll-out program, the drop in ADR would be associated with changes in ARV drug usage. Genotypic resistance tests obtained from 974 HIV-infected patients with virological failure and at least 2 previously failed ARV regimens from throughout the country were analyzed for the presence of nucleos(t)ide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitor (PI) resistance-associated mutations (RAMs). Patients were divided into two groups according to their first ART start date: 488 patients initiated ART before mid-2003 (group 1) and 486 after mid-2003 (group 2). The rate of RAMs, median resistance score of several sentinel ARVs, and composition of ART drugs in patient's entire treatment history were compared between both groups. Patients in group 2 were less likely to have >3 thymidine analogue-associated mutations (TAMs) and >3 PI-mRAMs [adjusted odds ratio (aOR) = 0.37; 95% confidence interval (95% CI) = 0.25-0.54; p mRAM has significantly declined over time. This can be explained by treatment optimization in the national ART roll-out program in recent years.

  16. Factors Associated With Optimal Long-Term Cosmetic Results in Patients Treated With Accelerated Partial Breast Irradiation Using Balloon-Based Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Vicini, Frank A., E-mail: fvicini@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Keisch, Martin [Miami Brachytherapy Center, Cancer Healthcare Associates, Miami, FL (United States); Shah, Chirag [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Goyal, Sharad; Khan, Atif J. [Department of Radiation Oncology, Cancer Institute of New Jersey, New Brunswick, NJ (United States); Beitsch, Peter D. [Dallas Breast Center, Dallas, TX (United States); Lyden, Maureen [BioStat International Inc, Tampa, FL (United States); Haffty, Bruce G. [Department of Radiation Oncology, Cancer Institute of New Jersey, New Brunswick, NJ (United States)

    2012-06-01

    Purpose: To evaluate factors associated with optimal cosmetic results at 72 months for early-stage breast cancer patients treated with Mammosite balloon-based accelerated partial breast irradiation (APBI). Methods and Materials: A total of 1,440 patients (1,449 cases) with early-stage breast cancer undergoing breast-conserving therapy were treated with balloon-based brachytherapy to deliver APBI (34 Gy in 3.4-Gy fractions). Cosmetic outcome was evaluated at each follow-up visit and dichotomized as excellent/good (E/G) or fair/poor (F/P). Follow-up was evaluated at 36 and 72 months to establish long-term cosmesis, stability of cosmesis, and factors associated with optimal results. Results: The percentage of evaluable patients with excellent/good (E/G) cosmetic results at 36 months and more than 72 months were 93.3% (n = 708/759) and 90.4% (n = 235/260). Factors associated with optimal cosmetic results at 72 months included: larger skin spacing (p = 0.04) and T1 tumors (p = 0.02). Using multiple regression analysis, the only factors predictive of worse cosmetic outcome at 72 months were smaller skin spacing (odds ratio [OR], 0.89; confidence interval [CI], 0.80-0.99) and tumors greater than 2 cm (OR, 4.96, CI, 1.53-16.07). In all, 227 patients had both a 36-month and a 72-month cosmetic evaluation. The number of patients with E/G cosmetic results decreased only slightly from 93.4% at 3 years to 90.8% (p = 0.13) at 6 years, respectively. Conclusions: APBI delivered with balloon-based brachytherapy produced E/G cosmetic results in 90.4% of cases at 6 years. Larger tumors (T2) and smaller skin spacing were found to be the two most important independent predictors of cosmesis.

  17. Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer

    Science.gov (United States)

    2015-08-28

    Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV Infection; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Central Nervous System Lymphoma; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma

  18. Different electrode configurations to optimize performance of multi-electrode microbial fuel cells for generating power or treating domestic wastewater

    KAUST Repository

    Ahn, Yongtae

    2014-03-01

    Scaling-up of microbial fuel cells (MFCs) for practical applications requires compact, multiple-electrode designs. Two possible configurations are a separator electrode assembly (SEA) or closely spaced electrodes (SPA) that lack a separator. It is shown here that the optimal configuration depends on whether the goal is power production or rate of wastewater treatment. SEA MFCs produced a 16% higher maximum power density (328 ± 11 mW m-2) than SPA MFCs (282 ± 29 mW m-2), and higher coulombic efficiencies (SEAs, 9-31%; SPAs, 2-23%) with domestic wastewater. However, treatment was accomplished in only 12 h with the SPA MFC, compared to 36 h with the SEA configuration. Ohmic resistance was not a main factor in performance as this component contributed only 4-7% of the total internal resistance. Transport simulations indicated that hindered oxygen diffusion into the SEA reactor was the primary reason for the increased treatment time. However, a reduction in the overall rate of substrate diffusion also may contribute to the long treatment time with the SEA reactor. These results suggest that SEA designs can more effectively capture energy from wastewater, but SPA configurations will be superior in terms of treatment efficiency due to a greatly reduced time needed for treatment. © 2013 Elsevier B.V. All rights reserved.

  19. Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design.

    Science.gov (United States)

    de Mattos, Cristiane Bastos; Argenta, Débora Fretes; Melchiades, Gabriela de Lima; Cordeiro, Marlon Norberto Sechini; Tonini, Maiko Luis; Moraes, Milene Hoehr; Weber, Tanara Beatriz; Roman, Silvane Souza; Nunes, Ricardo José; Teixeira, Helder Ferreira; Steindel, Mário; Koester, Letícia Scherer

    2015-01-01

    Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 2(2) full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant - soybean lecithin or sorbitan monooleate and type of co-surfactants - polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential -39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g(-1)) - the main response of interest - confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment.

  20. Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase

    Science.gov (United States)

    2016-01-01

    We report the results of a binding free energy-based virtual screening campaign of a library of 77 α-hydroxytropolone derivatives against the challenging RNase H active site of the reverse transcriptase (RT) enzyme of human immunodeficiency virus-1. Multiple protonation states, rotamer states, and binding modalities of each compound were individually evaluated. The work involved more than 300 individual absolute alchemical binding free energy parallel molecular dynamics calculations and over 1 million CPU hours on national computing clusters and a local campus computational grid. The thermodynamic and structural measures obtained in this work rationalize a series of characteristics of this system useful for guiding future synthetic and biochemical efforts. The free energy model identified key ligand-dependent entropic and conformational reorganization processes difficult to capture using standard docking and scoring approaches. Binding free energy-based optimization of the lead compounds emerging from the virtual screen has yielded four compounds with very favorable binding properties, which will be the subject of further experimental investigations. This work is one of the few reported applications of advanced-binding free energy models to large-scale virtual screening and optimization projects. It further demonstrates that, with suitable algorithms and automation, advanced-binding free energy models can have a useful role in early-stage drug-discovery programs. PMID:27713931

  1. Optimization of micro-aeration intensity in acidogenic reactor of a two-phase anaerobic digester treating food waste.

    Science.gov (United States)

    Xu, Suyun; Selvam, Ammaiyappan; Wong, Jonathan W C

    2014-02-01

    Micro-aeration is known to promote the activities of hydrolytic exo-enzymes and used as a strategy to improve the hydrolysis of particulate substrate. The effect of different micro-aeration rates, 0, 129, 258, and 387 L-air/kg TS/d (denoted as LBR-AN, LBR-6h, LBR-3h and LBR-2h, respectively) on the solubilization of food waste was evaluated at 35°C in four leach bed reactors (LBR) coupled with methanogenic upflow anaerobic sludge blanket (UASB) reactor. Results indicate that the intensity of micro-aeration influenced the hydrolysis and methane yield. Adequate micro-aeration intensity in LBR-3h and LBR-2h significantly enhanced the carbohydrate and protein hydrolysis by 21-27% and 38-64% respectively. Due to the accelerated acidogenesis, more than 3-fold of acetic acid and butyric acid were produced in LBR-3h as compared to the anaerobic treatment LBR-AN resulting in the maximum methane yield of 0.27 L CH4/g VS(added) in the UASB. The performance of LBR-6h with inadequate aeration was similar to that of LBR-AN with a comparable hydrolysis degree. Nevertheless, higher aeration intensity in LBR-2h was also unfavorable for methane yield due to significant biomass generation and CO2 respiration of up to 18.5% and 32.8% of the total soluble hydrolysate, respectively. To conclude, appropriate micro-aeration rate can promote the hydrolysis of solid organic waste and methane yield without undesirable carbon loss and an aeration intensity of 258 L-air/kg TS/d is recommended for acidogenic LBR treating food waste.

  2. Modeling and simulation approach to support dosing and study design requirements for treating HIV-related neuropsychiatric disease with the NK1-R antagonist aprepitant.

    Science.gov (United States)

    Barrett, Jeffrey S; Bajaj, Gaurav; McGuire, Jennifer; Wu, Di; Spitsin, Sergei; Moorthy, Ganesh; Zhao, Xianguo; Tebas, Pablo; Evans, Dwight L; Douglas, Steven D

    2014-01-01

    Psychiatric illness is common in HIV-infected patients and underlines the importance for screening not only for cognitive impairment but also for co-morbid mental disease. The rationale for combining immunomodulatory neurokinin- 1 receptor (NK1-R) antagonists with combined antiretroviral therapy (cART) is based on multimodal pharmacologic mechanisms. The NK1-R antagonist aprepitant's potential utility as a drug for depression is complicated by >99.9% protein binding and both enzyme inhibition and induction of CYP3A4. A population-based PK model developed from a pilot Phase 1B trial in 19 HIV-infected patients (125 or 250 mg/d aprepitant for 2 weeks) was modified to account for enzyme induction and impact of an exposure enhancer on CYP3A4 metabolism. Likelihood of clinical success in depression was assessed based on achievement of target trough plasma concentration and evaluated using Monte Carlo simulation. Scenarios were generated for varying daily dose (375, 625, 750 and 875 mg), pharmacokinetic variability, exposure enhancement (EE), duration (2 and 6 months) and sample size (n=12 and 24/arm). Daily dosing of ≥ 625 mg with EE yielded desirable troughs (based on in vitro infectivity experiments) of > 2.65 ug/mL for the majority of virtual patients simulated. Results are dependent on the degree of exposure enhancement and extent of enzyme induction. Actual threshold exposure requirements for aprepitant in HIV-associated depression are unknown though preclinical evidence supports trough levels > 2.65 ug/mL. If 100% NK1r blockage is necessary for efficacy, doses of 875 mg (625 mg with EE) or higher may be required. The benefit of aprepitant on innate immunity(natural killer cells) and absence of negative effects onex vivo neutrophil chemotaxis alleviates concerns regarding drug dependent inhibition (DDI)-mediated infection risk.

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Since the late 1980s, research has shown that treating drug abuse is an effective way to prevent the spread ... increasingly at risk for HIV infection through risky sexual behaviors. NIDA researchers have studied and continue to study the links between drug abuse and HIV/AIDS. In the early years of ...

  4. HIV infection in the elderly

    Directory of Open Access Journals (Sweden)

    Nancy Nguyen

    2008-09-01

    Full Text Available Nancy Nguyen1, Mark Holodniy21University of the Pacific School of Pharmacy and Health Sciences, Stockton, CA, USA; 2VA Palo Alto Health Care System, Palo Alto, CA, USAAbstract: In the US, an estimated 1 million people are infected with HIV, although one-third of this population are unaware of their diagnosis. While HIV infection is commonly thought to affect younger adults, there are an increasing number of patients over 50 years of age living with the condition. UNAIDS and WHO estimate that of the 40 million people living with HIV/AIDS in the world, approximately 2.8 million are 50 years and older. With the introduction of highly active antiretroviral therapy (HAART in the mid-1990s, survival following HIV diagnosis has risen dramatically and HIV infection has evolved from an acute disease process to being managed as a chronic medical condition. As treated HIV-infected patients live longer and the number of new HIV diagnoses in older patients rise, clinicians need to be aware of these trends and become familiar with the management of HIV infection in the older patient. This article is intended for the general clinician, including geriatricians, and will review epidemiologic data and HIV treatment as well as provide a discussion on medical management issues affecting the older HIV-infected patient.Keywords: HIV, epidemiology, treatment, aging, review

  5. Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design

    Directory of Open Access Journals (Sweden)

    Mattos CB

    2015-09-01

    Full Text Available Cristiane Bastos de Mattos,1 Débora Fretes Argenta,1 Gabriela de Lima Melchiades,1 Marlon Norberto Sechini Cordeiro,2 Maiko Luis Tonini,3 Milene Hoehr Moraes,3 Tanara Beatriz Weber,4 Silvane Souza Roman,4 Ricardo José Nunes,2 Helder Ferreira Teixeira,1 Mário Steindel,3 Letícia Scherer Koester1 1Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 2Departamento de Química, 3Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil; 4Departamento de Ciências Biológicas, Universidade Regional Integrada do Alto Uruguai e das Missões, Erechim, Rio Grande do Sul, Brazil Abstract: Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL. In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 22 full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant – soybean lecithin or sorbitan monooleate and type of co-surfactants – polysorbate 20 or polysorbate 80 on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size

  6. Optimization of micro-aeration intensity in acidogenic reactor of a two-phase anaerobic digester treating food waste

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Suyun [Department of Environmental and Low-Carbon Science, School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai (China); Sino-Forest Applied Research Centre for Pearl River Delta Environment, Department of Biology, Hong Kong Baptist University, Hong Kong Special Administrative Region (Hong Kong); Selvam, Ammaiyappan [Sino-Forest Applied Research Centre for Pearl River Delta Environment, Department of Biology, Hong Kong Baptist University, Hong Kong Special Administrative Region (Hong Kong); Wong, Jonathan W.C., E-mail: jwcwong@hkbu.edu.hk [Sino-Forest Applied Research Centre for Pearl River Delta Environment, Department of Biology, Hong Kong Baptist University, Hong Kong Special Administrative Region (Hong Kong)

    2014-02-15

    Highlights: • Effect of micro-aeration on acidogenesis and hydrolysis of food waste was investigated. • Micro-aeration at 258 L-air/kg TS/d increased the VFAs production 3-fold. • High aeration leads to loss of substrate through microbial biomass and respiration. • Optimum aeration increased methane recovery while high aeration intensity reduced methane yield. - Abstract: Micro-aeration is known to promote the activities of hydrolytic exo-enzymes and used as a strategy to improve the hydrolysis of particulate substrate. The effect of different micro-aeration rates, 0, 129, 258, and 387 L-air/kg TS/d (denoted as LBR-AN, LBR-6h, LBR-3h and LBR-2h, respectively) on the solubilization of food waste was evaluated at 35 °C in four leach bed reactors (LBR) coupled with methanogenic upflow anaerobic sludge blanket (UASB) reactor. Results indicate that the intensity of micro-aeration influenced the hydrolysis and methane yield. Adequate micro-aeration intensity in LBR-3h and LBR-2h significantly enhanced the carbohydrate and protein hydrolysis by 21–27% and 38–64% respectively. Due to the accelerated acidogenesis, more than 3-fold of acetic acid and butyric acid were produced in LBR-3h as compared to the anaerobic treatment LBR-AN resulting in the maximum methane yield of 0.27 L CH{sub 4}/g VS{sub added} in the UASB. The performance of LBR-6h with inadequate aeration was similar to that of LBR-AN with a comparable hydrolysis degree. Nevertheless, higher aeration intensity in LBR-2h was also unfavorable for methane yield due to significant biomass generation and CO{sub 2} respiration of up to 18.5% and 32.8% of the total soluble hydrolysate, respectively. To conclude, appropriate micro-aeration rate can promote the hydrolysis of solid organic waste and methane yield without undesirable carbon loss and an aeration intensity of 258 L-air/kg TS/d is recommended for acidogenic LBR treating food waste.

  7. HIV-Associated Neuroretinal Disorder in Patients With Well-Suppressed HIV-Infection : A Comparative Cohort Study

    NARCIS (Netherlands)

    Demirkaya, Nazli; Wit, Ferdinand W N M; van Den Berg, Thomas J T P; Kooij, Katherine W; Prins, Maria; Schlingemann, Reinier O; Abramoff, Michael D; Reiss, Peter; Verbraak, Frank D

    2016-01-01

    PURPOSE: Loss of neuroretinal structure and function, ascribed to a 'HIV-associated Neuroretinal Disorder' (HIV-NRD), in the absence of ocular opportunistic infections, has been reported in HIV-infected individuals treated with combination antiretroviral therapy (cART). Whether HIV-infected individu

  8. [Clinical research on post-stroke hemiplegia treated with the optimized rehabilitation program of integrated Chinese and western medicine].

    Science.gov (United States)

    Zhang, Xiao-Li; Qi, Rui; Yan, Jun-Tao

    2013-12-01

    To explore the optimized rehabilitation program in the treatment of post-stroke hemiplegia at the recovery stage. Based on the randomized controlled principle, 60 patients were randomized into an rehabilita tion + massage group (group A) and an rehabilitation + acupuncture group (group B), 30 cases in each one. Bobath sport therapy and functional training were adopted in the two groups. In the group A, the massage therapy was added. The rolling method and palm-rubbing method were used on the affected side, the pressing, kneading and plucking methods were applied to Jianliao (LI 15), Jianzhen (SI 9), Quchi (LI 11), Huantiao (GB 30), Weizhong (BL 40), Chengshan (BL 57), Zusanli (ST 36) and the other acu points; and the nipping method was adopted at the twelve Jing-well points. In the group B, acupuncture was applied to Baihui (BL 20), Jianliao (LI 15), Quchi (LI 11), Shousanli (LI 10), Huantiao (GB 30), Yanglingquan (GB 34), Jiexi (ST 41) and the other acupoints. The treatment was given once a day, 5 treatments a week in the two groups. The efficacy was evaluated in 3 weeks. Fugl-Meyer scale, Barthel index (BI) score, modified Rankin scale and stroke-specific quality of life (SS-QOL) were used to assess the limb motor function, the activity of daily life (ADL), independent activity of life and the quality of life of the patients in the two groups before and after treatment. Based on the total cost and benefit, the health economics evaluation was conducted in the patients of the two groups. The treatments all improved the limb motor function (group A: 26.00 (22) vs 37.00 (33); group B: 30.50 (21) vs 39.50 (36)), the independent activity of life, ADL (group A: 43.50 +/- 22.25 vs 57.50 +/- 22.25; group B: 52.83 +/- 16.59 vs 66.67 +/- 12.82) and the quality of life (group A: 122.23 +/- 30.00 vs 145.50 +/- 28.14; group B: 132.43 +/- 23.87 vs 151.47 +/- 22.37) in the patients of the two groups. The differences in all the indices were significant statistically before and

  9. Statistical optimization of process parameters for the simultaneous adsorption of Cr(VI) and phenol onto Fe-treated tea waste biomass

    Science.gov (United States)

    Gupta, Ankur; Balomajumder, Chandrajit

    2017-06-01

    In this study, simultaneous removal of Cr(VI) and phenol from binary solution was carried out using Fe-treated tea waste biomass. The effect of process parameters such as adsorbent dose, pH, initial concentration of Cr(VI) (mg/L), and initial concentration of phenol (mg/L) was optimized. The analysis of variance of the quadratic model demonstrates that the experimental results are in good agreement with the predicted values. Based on experimental design at an initial concentration of 55 mg/L of Cr(VI), 27.50 mg/L of phenol, pH 2.0, 15 g/L adsorbent dose, 99.99% removal of Cr(VI), and phenol was achieved.

  10. Use of rosuvastatin to treat protease inhibitor-associated hypercholesterolaemia in a HIV-infected patient at high risk of cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Leonardo Calza

    2010-09-01

    Full Text Available Rosuvastatin represents one of the latest inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase introduced in clinical practice for the treatment of hypercholesterolaemia. In comparative trials, across dose ranges this statin reduced low-density lipoprotein (LDL cholesterol and total cholesterol significantly more than atorvastatin, simvastatin, and pravastatin, and triglycerides significantly more than simvastatin and pravastatin. In healthy subjects with normal LDL cholesterol and elevated C-reactive protein, rosuvastatin treatment produced a significant decrease in the incidence of cardiovascular events.Its chemical and pharmacokinetic properties suggest a very limited penetration in extrahepatic tissues with a lower risk of muscle toxicity and metabolically mediated drug-drug interactions, suggesting a low risk of pharmacokinetic interactions with antiretroviral drugs in patients with HIV infection. We describe a case of protease inhibitor-associated hypercholesterolaemia in a male HIV-infected patient with high cardiovascular risk. Treatment with rosuvastatin leaded to a significant reduction in total and LDL cholesterol levels, with a good tolerability profile after 15 months of follow-up.

  11. An efficient procedure for the expression and purification of HIV-1 protease from inclusion bodies.

    Science.gov (United States)

    Nguyen, Hong-Loan Thi; Nguyen, Thuy Thi; Vu, Quy Thi; Le, Hang Thi; Pham, Yen; Trinh, Phuong Le; Bui, Thuan Phuong; Phan, Tuan-Nghia

    2015-12-01

    Several studies have focused on HIV-1 protease for developing drugs for treating AIDS. Recombinant HIV-1 protease is used to screen new drugs from synthetic compounds or natural substances. However, large-scale expression and purification of this enzyme is difficult mainly because of its low expression and solubility. In this study, we constructed 9 recombinant plasmids containing a sequence encoding HIV-1 protease along with different fusion tags and examined the expression of the enzyme from these plasmids. Of the 9 plasmids, pET32a(+) plasmid containing the HIV-1 protease-encoding sequence along with sequences encoding an autocleavage site GTVSFNF at the N-terminus and TEV plus 6× His tag at the C-terminus showed the highest expression of the enzyme and was selected for further analysis. The recombinant protein was isolated from inclusion bodies by using 2 tandem Q- and Ni-Sepharose columns. SDS-PAGE of the obtained HIV-1 protease produced a single band of approximately 13 kDa. The enzyme was recovered efficiently (4 mg protein/L of cell culture) and had high specific activity of 1190 nmol min(-1) mg(-1) at an optimal pH of 4.7 and optimal temperature of 37 °C. This procedure for expressing and purifying HIV-1 protease is now being scaled up to produce the enzyme on a large scale for its application.

  12. Benchmarking HIV health care

    DEFF Research Database (Denmark)

    Podlekareva, Daria; Reekie, Joanne; Mocroft, Amanda

    2012-01-01

    ABSTRACT: BACKGROUND: State-of-the-art care involving the utilisation of multiple health care interventions is the basis for an optimal long-term clinical prognosis for HIV-patients. We evaluated health care for HIV-patients based on four key indicators. METHODS: Four indicators of health care were...... assessed: Compliance with current guidelines on initiation of 1) combination antiretroviral therapy (cART), 2) chemoprophylaxis, 3) frequency of laboratory monitoring, and 4) virological response to cART (proportion of patients with HIV-RNA 90% of time on cART). RESULTS: 7097 Euro...... to North, patients from other regions had significantly lower odds of virological response; the difference was most pronounced for East and Argentina (adjusted OR 0.16[95%CI 0.11-0.23, p HIV health care utilization...

  13. Donovanosis treated with thiamphenicol

    Directory of Open Access Journals (Sweden)

    Walter Belda Junior

    Full Text Available Ten patients with donovanosis were treated with thiamphenicol for two weeks. In eight of them, included two HIV infected patients, lesions healed. The safety profile of thiamphenicol makes it a useful and cost-effective agent in the management of donovanosis. Randomized controlled trials should be conducted with these treatment options.

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... has shown that treating drug abuse is an effective way to prevent the spread of HIV. Drug ... that use text messaging as a means of communication. The "Text Message" PSA features two young girls ...

  15. Atazanavir/ritonavir monotherapy as maintenance strategy in HIV-1 treated subjects with viral suppression: 96-week analysis results of the MODAT study

    Directory of Open Access Journals (Sweden)

    Vincenzo Spagnuolo

    2014-11-01

    Full Text Available Introduction: The 48-week interim analysis of the MODAT study showed that confirmed virologic failure (CVF was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r-based triple therapy. The DSMB recommended stopping study enrollment but continuing follow-up of enrolled patients. We present the 96-week efficacy analysis. Material and Methods: Multicentre, randomized, open-label, non-inferiority trial (non-inferiority margin −10%. Treatment failure (TF was defined as CVF (two consecutive HIV-RNA >50 cp/mL or discontinuation for any cause. In the monotherapy arm, patients with CVF re-introduced their previous NRTIs and remained in the study if HIV-RNA <50 copies/mL within 12 weeks of re-intensification. Results: 101 patients evaluated (Figure 1: 85% males, 21% HCV-positive, median (IQR age of 42 (36–48 years, baseline CD4+ 576 (447–743 cells/µL. In the 96-week analysis (ITT; TF=failure, efficacy was 64% (32/50 in the monotherapy arm and 63% (32/51 in the triple-therapy arm (difference +1.3%, 95% CI −17.5–20.1. Fourteen patients in monotherapy and two in triple-therapy arm had CVF; median HIV-RNA was 136 (72–376 copies/mL. In monotherapy arm, no PI or NRTI associated resistance mutations were observed at CVF. All patients who re-intensified re-suppressed. In monotherapy arm, TF was more frequent in HCV-co-infected patients (64% vs 28%; p=0.041. In the secondary analysis (ITT; re-intensification=success, 82% (41/50 in monotherapy arm and 63% (32/51 in triple-therapy arm were on study at week 96 (difference +19.3%, 95% CI 2.2–36.3. SAEs occurred in four (8% patients in the monotherapy arm (one left basal pneumonia, one acute coronary stenosis, one traumatic lesion, one nephrolithiasis and two (4% in the triple therapy arm (one sepsis, one renal failure. Drug-related adverse events (AEs leading to discontinuation were three (6% in the monotherapy arm (two AEs occurred in patients after successful re

  16. Evaluation of mHealth strategies to optimize adherence and efficacy of Option B+ prevention of mother-to-child HIV transmission: Rationale, design and methods of a 3-armed randomized controlled trial.

    Science.gov (United States)

    Drake, Alison L; Unger, Jennifer A; Ronen, Keshet; Matemo, Daniel; Perrier, Trevor; DeRenzi, Brian; Richardson, Barbra A; Kinuthia, John; John-Stewart, Grace

    2017-06-01

    Lifelong antiretroviral therapy (ART) (Option B+) is recommended for all HIV-infected pregnant/postpartum women, but high adherence is required to maximize HIV prevention potential and maintain maternal health. Mobile health (mHealth) interventions may provide treatment adherence support for women during, and beyond, the pregnancy and postpartum periods. We are conducting an unblinded, triple-arm randomized clinical trial (Mobile WACh X) of one-way short message service (SMS) vs. two-way SMS vs. control (no SMS) to improve maternal ART adherence and retention in care by 2years postpartum. We will enroll 825 women from Nairobi and Western Kenya. Women in the intervention arms receive weekly, semi-automated motivational and educational SMS and visit reminders via an interactive, human-computer hybrid communication system. Participants in the two-way SMS arm are also asked to respond to a question related to the message. SMS are based in behavioral theory, are tailored to participant characteristics through SMS tracks, and are timed along the pregnancy/postpartum continuum. After enrollment, follow-up visits are scheduled at 6weeks; 6, 12, 18, and 24months postpartum. The primary outcomes, virological failure (HIV viral load ≥1000copies/mL), maternal retention in care, and infant HIV infection or death, will be compared in an intent to treat analysis. We will also measure ART adherence and drug resistance. Personalized and tailored SMS to support HIV-infected women during and after pregnancy may be an effective strategy to motivate women to adhere to ART and remain in care and improve maternal and infant outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Vitamin D3 Decreases Parathyroid Hormone in HIV-Infected Youth Being Treated With Tenofovir: A Randomized, Placebo-Controlled Trial

    Science.gov (United States)

    Stephensen, Charles B.; Hazra, Rohan; Flynn, Patricia M.; Wilson, Craig M.; Rutledge, Brandy; Bethel, James; Pan, Cynthia G.; Woodhouse, Leslie R.; Van Loan, Marta D.; Liu, Nancy; Lujan-Zilbermann, Jorge; Baker, Alyne; Kapogiannis, Bill G.; Mulligan, Kathleen

    2012-01-01

    Background. The study goal was to determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C-telopeptide (CTX) in youth infected with human immunodeficiency virus (HIV) receiving and not receiving combination antiretroviral therapy (cART) containing tenofovir disoproxil fumarate (TDF). Methods. This randomized, double-blind, placebo-controlled multicenter trial enrolled HIV-infected youth 18–25 years based on stable treatment with cART containing TDF (n = 118) or no TDF (noTDF; n = 85), and randomized within those groups to vitamin D3, 50 000 IU (n = 102) or placebo (n = 101), administered at 0, 4, and 8 weeks. Outcomes included change in TRP, PTH, BAP, and CTX from baseline to week 12 by TDF/noTDF; and VITD/placebo. Results. At baseline, VITD and placebo groups were similar except those on TDF had lower TRP and higher PTH and CTX. At week 12, 95% in the VITD group had sufficient serum 25-hydroxy vitamin D (25-OHD; ≥20 ng/mL), increased from 48% at baseline, without change in placebo (P < .001). PTH decreased in the TDF group receiving VITD (P = .031) but not in the noTDF group receiving VITD, or either placebo group. The decrease in PTH with VITD in those on TDF occurred with insufficient and sufficient baseline 25-OHD (mean PTH change, −7.9 and −6.2 pg/mL; P = .031 and .053, respectively). Conclusions. In youth on TDF, vitamin D3 supplementation decreased PTH, regardless of baseline 25-OHD concentration. Clinical Trials Registration. NCT00490412. PMID:22267714

  18. Addressing psychosocial problems among persons living with HIV

    African Journals Online (AJOL)

    Inventory, 43.7% had a diagnosable mental disorder.4 Of these, ... counsellors, as well as on-going supervision and support to patient advocates is necessary to ensure optimal ..... HIV care and HIV prevention: Legal, policy and programmatic.

  19. Comparison of immunologic restoration and virologic response in plasma, tonsillar tissue, and cerebrospinal fluid in HIV-1-infected patients treated with double versus triple antiretroviral therapy in very early stages: The Spanish EARTH-2 Study. Early Anti-Retroviral Therapy Study.

    Science.gov (United States)

    García, F; Alonso, M M; Romeu, J; Knobel, H; Arrizabalaga, J; Ferrer, E; Dalmau, D; Ruiz, I; Vidal, F; Frances, A; Segura, F; Gomez-Sirvent, J L; Cruceta, A; Clotet, B; Pumarola, T; Gallart, T; O'Brien, W A; Miró, J M; Gatell, J M

    2000-09-01

    The objective of antiretroviral therapy is to obtain an almost complete and durable suppression of viral replication in all compartments to facilitate recovery of the immune system. We assessed the virologic effect in plasma, tonsillar tissue, and cerebrospinal fluid (CSF) in 94 HIV-1-infected patients with CD4 counts >500 x 106 cells per liter and viral load >5000 copies/ml randomly assigned to triple antiretroviral therapy (two nucleoside reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor) versus double therapy (two NRTIs). We also analyzed the immunologic recovery in this cohort of patients. Lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to HIV-1 specific antigens, and other immunophenotypic markers were analyzed. The proportion of patients who achieved a decrease in HIV RNA levels to <200 copies/ml was significantly greater in the triple therapy group than in the two drug groups (p =.0002 for each pair-wise difference). At week 52, tonsillar tissue HIV RNA from 5 patients treated with triple therapy was lower than the limit of detection, whereas the mean +/- standard error in patients with double therapy (n = 5) was 5.03 +/- 0.34 copies/mg/tissue. In all 10 patients, CSF viral load (VL) was <20 HIV-1 RNA copies/ml at week 52. CSF cell counts and protein levels tended to decrease after 52 weeks of antiretroviral therapy. After 1 year of therapy, 13 of 21 patients (62%) in the double-therapy groups (zidovudine plus lamivudine [n = 9] and stavudine plus lamivudine [n = 12]) had evidence of M184V mutation. None of the 10 samples of patients receiving triple therapy could be amplified because of low HIV RNA levels. The mean increase in CD4 cells at week 52 was greater in the stavudine and lamivudine and indinavir group than in the double-treatment arms (186 versus 67 and 102, respectively; p =.03). In patients treated with triple therapy, the increase in naive T cells (CD4 and CD8

  20. Macronutrient Supplementation and Food Prices in HIV Treatment12

    OpenAIRE

    Sztam, Kevin A.; Fawzi, Wafaie W.; Duggan, Christopher

    2010-01-01

    Infection caused by HIV and malnutrition have a complex interaction and often coexist geographically. Malnutrition has synergistic immune effects and HIV affects nutritional status. HIV care and treatment programs are compelled to confront this dual burden to optimize HIV outcomes. In this article, we review the published literature concerning intervention studies in adults and children and the effect of food prices on HIV treatment programs. While the evidence base is relatively incomplete f...

  1. Women and HIV

    Science.gov (United States)

    ... Consumer Information by Audience For Women Women and HIV Share Tweet Linkedin Pin it More sharing options ... HIV? What should pregnant women know about HIV? HIV Quick Facts What is HIV? HIV is the ...

  2. Use of an HIV-risk screening tool to identify optimal candidates for PrEP scale-up among men who have sex with men in Toronto, Canada: disconnect between objective and subjective HIV risk

    Directory of Open Access Journals (Sweden)

    James Wilton

    2016-06-01

    Full Text Available Introduction: Identifying appropriate pre-exposure prophylaxis (PrEP candidates is a challenge in planning for the safe and effective roll-out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM, to identify “optimal” candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada. Methods: Between November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify “optimal” candidates for scaling up PrEP roll-out, defined as being at high objective HIV risk (scoring ≥10 on the HIRI-MSM, perceiving oneself at moderate-to-high HIV risk and being willing to use PrEP. Cascades were constructed to identify barriers to broader PrEP uptake. The association between HIRI-MSM score and both willingness to use PrEP and perceived HIV risk were explored in separate multivariable logistic regression analyses. Results: Of 420 respondents, 64.4% were objectively at high risk, 52.5% were willing to use PrEP and 27.2% perceived themselves at moderate-to-high HIV risk. Only 16.4% were “optimal” candidates. Higher HIRI-MSM scores were positively associated with both willingness to use PrEP (aOR=1.7 per 10 score increase, 95%CI=1.3–2.2 and moderate-to-high perceived HIV risk (aOR=1.7 per 10 score increase, 95%CI=1.2–2.3. The proportion of men who were “optimal” candidates increased to 42.9% when the objective HIV risk cut-off was changed to top quartile of HIRI-MSM scores (≥26. In our full cascade, a very low proportion (5.3% of MSM surveyed could potentially benefit from PrEP under current conditions. The greatest barrier in the cascade was low perception of HIV risk among high-risk men, but considerable numbers were also lost in downstream cascade steps. Of men at high objective HIV risk, 68.3% did not perceive themselves to be at moderate

  3. Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

    Science.gov (United States)

    Peluso, Michael J; Spudich, Serena

    2014-09-01

    The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

  4. Optimization of thermophysical properties of Pacific white shrimp (Litopenaeus vannamei) previously treated with freezing-point regulators using response surface methodology.

    Science.gov (United States)

    Wang, Liang; Liu, Zunying; Zhao, Yuanhui; Dong, Shiyuan; Zeng, Mingyong; Yang, Huicheng

    2015-08-01

    Three freezing-point regulators (glycine, sodium chloride and D-sorbitol) were employed to optimize thermophysical properties of Pacific white shrimp (Litopenaeus vannamei) using response surface methodology (RSM). The independent variables were glycine content (0.250-1.250 %), sodium chloride content (0.500-2.500 %) and D-sorbitol content (0.125-0.625 %) and analysis of variance showed that the effects of glycine, sodium chloride and D-sorbitol on the thermophysical properties were statistically significant (P < 0.05). The coefficient of determination, R (2) values for initial freezing point (T i ), unfreezable water mass fraction (W u ), apparent specific heat (C app ) and Enthalpy (H) were 0.896 ~ 0.999. The combined effects of these independent variables on T i , W u , C app and H were investigated. The results indicated that T i , C app and H varied curvilinearly with increasing of glycine, sodium chloride and D-sorbitol content whereas W u increased nearly linearly. Based on response plots and desirability functions, the optimum combination of process variables for Pacific white shrimp previously treated with freezing-point regulators were 0.876 % for glycine content, 2.298 % for sodium chloride content and 0.589 % for D-sorbitol content, correspondently the optimized thermophysical properties were T i , - 5.086 °C; W u , 17.222 %; C app , 41.038 J/g °C and H, 155.942 J/g, respectively. Briefly, the application of freezing-point regulators depressed T i and obtained the optimum W u , C app and H, which would be obviously beneficial for the exploitation of various thermal processing and food storage.

  5. Economic costs of HIV infection: an employer's perspective.

    Science.gov (United States)

    Liu, G G; Yin, D D; Lyu, R; Chaikledkaew, U; Louie, S

    2002-01-01

    The introduction of highly active antiretroviral therapy has proven highly effective in treating patients with HIV/AIDS. However, the high cost of the advanced antiretroviral therapy has led to increased financial constraints on both patients and payers. From business firms'perspective, especially those with operations in developing countries, it is crucial to determine the long-term economic cost implications of alternative employment and benefit policies for HIV-infected workers or those at high risk for the disease. A simulation model is developed to predict the comprehensive lifetime economic costs of HIV-infected workers to an employer. This model employs age,CD4(+) cell counts,and plasma HIV-1 RNA level as major predictors of the disease progression and patient survival in the determination of various cost functions. Major cost components considered include direct expenses on health insurance premium,life insurance premium, short-term disability benefits, long-term disability benefits, hiring/training expenses, and indirect costs resulting from reduced or lost productivity at work. An individual model and a group model are derived to estimate the costs of an individual and a group of HIV-infected patients, respectively. Over a 10-year period, following the nonadvanced antiretroviral treatment regimen, the group model predicts that the total lifetime cost of an HIV-infected worker can be as high as U.S. 90,000 dollars to his/her employer, of which 60,000 dollars would be various explicit costs and 30,000 dollars lost work productivity. Sensitivity analysis further demonstrated that changes in the initial level of age,CD4(+) cell count, HIV-1 RNA viral load,CD4(+) cell decline rate, and the costs of medical care influence the dynamics of the cost functions. HIV infection can result in sizable economic costs to an employer over the lifetime course of an infected employee if not treated with the advanced antiretroviral therapy. These cost estimates provide a

  6. to prevent hiv infection

    African Journals Online (AJOL)

    2008-10-14

    Oct 14, 2008 ... about other things. ‡ ... deliberately trying to forget the entire experience. .... pleasant nor easy, and almost all of the rape survivors .... make it easier to treat HIV/AIDS in adults, but development of simplified drugs for children ...

  7. Operations research in HIV/AIDS.

    Science.gov (United States)

    Kumar, Anant

    2013-01-01

    Operations research is mainly applied to decision making in industries and corporations using quantitative methods to optimize production. The applications of operations research in social sciences research or health research in HIV, service delivery, and program performance improvement are minimal. Considering the complexity of the HIV/AIDS epidemic, it is imperative to learn from operations research in scaling up HIV treatment, prevention, and intervention in resource-poor settings. In this article the author discusses the methodological issues in operations research within the context of HIV/AIDS research. The author also suggests a framework for using operations research in the field of HIV/AIDS research and program intervention.

  8. Vaccination in HIV-Infected Adults

    Science.gov (United States)

    Wallace, Mark R.

    2014-01-01

    Abstract Vaccines are critical components for protecting HIV-infected adults from an increasing number of preventable diseases. However, missed opportunities for vaccination among HIV-infected persons persist, likely due to concerns regarding the safety and efficacy of vaccines, as well as the changing nature of vaccine guidelines. In addition, the optimal timing of vaccination among HIV-infected adults in regards to HIV stage and receipt of antiretroviral therapy remain important questions. This article provides a review of the current recommendations regarding vaccines among HIV-infected adults and a comprehensive summary of the evidence-based literature of the benefits and risks of vaccines among this vulnerable population. PMID:25029589

  9. Vitamin D3 Decreases Parathyroid Hormone in HIV-Infected Youth Being Treated With Tenofovir: A Randomized, Placebo-Controlled Trial

    OpenAIRE

    Havens, Peter L.; Stephensen, Charles B.; Hazra, Rohan; Flynn, Patricia M.; Wilson, Craig M.; Rutledge, Brandy; Bethel, James; Pan, Cynthia G; Woodhouse, Leslie R.; Van Loan, Marta D; Liu, Nancy; Lujan-Zilbermann, Jorge; Baker, Alyne; Kapogiannis, Bill G.; Mulligan, Kathleen

    2012-01-01

    In this randomized, double-blind, placebo-controlled trial of human immunodeficiency virus–infected youths aged 18–25, vitamin D3, 50000 IU once monthly for 3 months decreased parathyroid hormone in participants treated with tenofovir-containing antiretroviral regimens but not in those participants whose regimens did not contain tenofovir.

  10. Sub-optimal adherence to combination anti-retroviral therapy and its associated factors according to self-report, clinician-recorded and pharmacy-refill assessment methods among HIV-infected adults in Addis Ababa.

    Science.gov (United States)

    Mekuria, Legese A; Prins, Jan M; Yalew, Alemayehu W; Sprangers, Mirjam A G; Nieuwkerk, Pythia T

    2017-04-01

    Adherence to combination antiretroviral therapy (cART) is generally high in most resource-limited settings. However, sub-optimal adherence occurs in a sizable proportion of patients, and is independently predictive of detectable viremia. We investigated sub-optimal adherence according to self-report, clinician-recorded, and pharmacy-refill assessment methods, and their associated factors among HIV-infected adults receiving cART in Addis Ababa, Ethiopia. Eight-hundred seventy patients who initiated cART between May 2009 and April 2012 were randomly selected, and 664 patients who were alive, had remained in clinical care and were receiving cART for at least six-months were included. Sub-optimal adherence was defined as patients' response of less than "all-of the time" to the self-report adherence question, or any clinician-recorded poor adherence during the six most recent clinic visits, or a pharmacy-refill of sub-optimal adherence. The average adherence level to cART, expressed as MPR, was nearly 97%. However, sub-optimal adherence occurred in 12%, 4%, and 27% of patients according to self-report, clinician-recorded, and pharmacy-refill measures, respectively. More satisfaction with social support was significantly associated with less sub-optimal adherence according to self-report and clinician-record. Younger age, lower educational level, and lower CD4 cell count at cART initiation were significantly associated with sub-optimal refill-based adherence. Findings from our large multi-center study suggest that sub-optimal adherence was present in up to a quarter of the patients, despite a high degree of average adherence to cART. Interventions aimed at preventing sub-optimal adherence should focus on improving social support, on younger patients, on patients with lower educational level, and on those who started cART at a lower CD4 cell count.

  11. HIV and Orthopaedics: Musculoskeletal Manifestations and Outcomes.

    Science.gov (United States)

    Pretell-Mazzini, Juan; Subhawong, Ty; Hernandez, Victor H; Campo, Rafael

    2016-05-04

    ➤Advances in combined antiretroviral therapy (cART) in recent years have transformed HIV infection into a chronic disease when treatment is available, increasing a patient's life expectancy and the chances that orthopaedic surgeons will encounter such patients in their clinical practice.➤Musculoskeletal manifestations in patients with HIV infection are common and sometimes are the initial presentation of the disease. Knowledge about neoplasms and associated conditions affecting muscle, bones, and joints is essential for successful management.➤Since the advent of cART, total joint arthroplasty has been shown to be a safe procedure; however, perioperative infection is still a small risk in patients with uncontrolled viral loads or CD4 counts of <400 cells/mm(3).➤With regard to trauma surgery, the rates of early and late infection around implants, as well as union rates, are comparable with those in the HIV-negative population; however, there is an increased risk of pulmonary, renal, and infectious or septic complications in the polytrauma setting.➤Factors such as CD4 count, nutritional status, cART therapy, viral load count, and other comorbidities (hemophilia, infection among intravenous drug users, etc.) should be considered when treating these patients in order to optimize their clinical outcomes. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

  12. 3种用药方案治疗HIV/TB患者抗结核药物性肝损伤126例临床疗效分析%Clinical analysis of effects of 3 Therapeutic Schemes in Treating Antituberculosis Drug-induced Hepatotoxicity in 126 HIV/TB Patients

    Institute of Scientific and Technical Information of China (English)

    杜红; 汤卓; 吴念宁; 葛利辉

    2012-01-01

    Objective To probe into the therapeutic efficacy and safety of 3 therapeutic schemes in the treatment of antituberculo-sis drug-induced hepatotoxicity in HIV/TB patients. Methods A total of 126 patients were randomly into three groups, including Group A ( deoxidized glutathione by oral administration ), Group B ( compound glycyrrhizin by oral administration ) and Group C ( deoxidized gluta-thione and compound glycyrrhizin by intravenous injection ). The clinical effects of the three groups were observed and compared. Results The effective rates for the 3 treatment schemes were respectively 92. 9% , 90. 5% and 97. 6% , without significant differences between the groups( P >0. 05 ). The cure rate were respectively 52. 4% , 45. 2% and 71. 4% , with significant differences between the groups( P 0. 05 ). There was no significant difference in the effective rates and the adverse effect rates produced by three therapeutic schemes when they were used to treat the antituberculosis drug-induced hepatotoxicity in HIV/TB patients, while there was a significant difference in the cure rate. Conclusion Group C had the best therapeutic effect.%目的 探讨3种不同治疗方案用于治疗HIV/TB患者抗结核药物性肝损伤的有效性及安全性.方法 将126例患者随机分成3组,A组(还原型谷胱甘肽口服)、B组(复方甘草酸苷口服),C组(还原型谷胱甘肽+复方甘草酸苷静滴),观察比较疗效.结果 3种药物治疗方案有效率分别为92.9% 、90.5% 、97.6%(P>0.05),治愈率分别为52.4%、45.2%、71.4%(P0.05);三种方案治疗HIV/TB患者抗结核药物性肝损伤在有效率和不良反应发生率方面无显著差异,但在治愈率上三组有显著差异.结论 C组临床疗效最好.

  13. Analysis of HIV-1 proviral DNA in peripheral blood cells from long-term HAART-treated AIDS patients in China%经长期HAART治疗的中国HIV-AIDS患者外周血细胞内HIV-1前病毒DNA的检测及其意义

    Institute of Scientific and Technical Information of China (English)

    陈霞; 姚运海; 郑煜煌; Diallo MA; 何艳; 周华英; 谌资; 罗艳; 贺波; 贺梅

    2012-01-01

    Objective The aim of this study was to verify that NK cells were one type of the virus reservoir cells,and to observe whether NK cells,T lymphocytes and monocyte are long-term viral reservoir cells of HIV-1.Methods A group of 15 chronic HIV-l-infected adults,who received 4 ~7 years-HAART treatment[ mean(62.45 ± 13.53) months],participated in this study for crosssectional study.After the ethical approval was obtained,a volume (40 ml) of peripheral whole blood was obtained from each patient.The number of T cell subgroup was detected with flow cytomctry.The NK cells,T lymphocytes,and monocytes were separated from peripheral blood mononuclear cells (PBMC) using microbead sorting method ( CD3 +,CD14 + and CD56 + antibody microbeads).DNA was extracted with human DNA kit.Real-time fluorescent quantitative PCR was used to detect the serum HIV RNA and DNA in the three types of cells.Graphpad prism5 software was used to analyze the collected data.Results Among 15 patients with 4 ~ 7-year-HAART treatment,plasma HIV-1 RNA of all the patients are undetectable; however,HIV-1 DNA was detected in 6 patients'T lymphocyte [ mean(2.03 ± 0.48)logl0copies/106 cells],in 4 patients'Nk cells [mean ( 1.82 ± 0.32 ) logl0copies/106 cells ],and in 2 patients'monocytes [ mean( 1.75 ± 0.19) logl0copies/106 cells ].Conclusions These findings revealed that NK cells were another important HIV cellular reservoir besides T-lymphocytes and monocytes,and T-lymphocytes might be the main long-lasting HIV reservoir.%目的 探索NK细胞是否是HIV-1病毒的储存库细胞之一,并观察在长期HAART治疗后,T淋巴细胞及单核细胞内是否仍有HIV-1前病毒DNA存在.方法 对15例规范接受HAART治疗4~7年的HIV-AIDS患者采集血标本进行横断面研究.使用磁珠分选法从外周血单个核细胞(PBMC)中分离出T淋巴细胞、单核细胞和NK细胞,通过HIV实时荧光定量检测外周血HIV-1 RNA病毒载量和NK细胞、单核细胞、T淋巴细胞内的HIV-1

  14. Establishment and optimization of a method for screening HIV-1 integrase 3′-processing inhibitor%HIV-1整合酶3′端加工抑制剂筛选方法的建立与优化

    Institute of Scientific and Technical Information of China (English)

    陆翠林; 张旋; 詹金彪; 杨柳萌; 郑永唐

    2014-01-01

    Aim To establish and optimize a method for screening HIV-1 integrase 3′-processing inhibitor. Methods Fluorescence resonance energy transfer ( FRET) was used to create an assay for screening in-tegrase 3′-processing inhibitors; wavelength was de-fined by DNaseⅠ; factors affecting IN activity were optimized, including buffer composition, substrate con-centration, enzyme concentration, metal ion concentra-tion. Results Integrase 3′-processing optimizing reac-tion conditions were buffer 1 , 500 nmol · L-1 sub-strate, 1 μmol·L-1 integrase, 20mmol·L-1 magne-sium ion. Positive drug raltegravir and myricetin could effectively inhibit integrase 3′-processing activity using this assay. Two integrase 3′-processing inhibitors were screened by this method. Conclusion The method for screening HIV-1 integrase 3′-processing inhibitor is successfully established and optimized.%目的:建立与优化HIV-1整合酶3′端加工抑制剂筛选方法。方法利用荧光共振能量转移原理建立筛选方法,用DNaseⅠ切割底物 DNA确定底物检测波长,在该检测波长下,对缓冲液成分、底物浓度、酶浓度、金属离子浓度等影响整合酶活性的条件进行优化,并用阳性药物雷特格韦和杨梅黄素进行方法验证。结果检测波长为495 nm/525 nm,使用缓冲液1、底物浓度500 nmol·L-1,整合酶浓度1μmol· L-1,镁离子浓度20 mmol · L-1时整合酶3′端加工活性最强。在此反应条件下雷特格韦和杨梅黄素能有效地抑制整合酶3′端加工活性。用所建立的方法筛选到2个有较强抑制整合酶3′端加工活性的抑制剂。结论该文成功建立并优化了HIV-1整合酶3′端加工抑制剂筛选方法。

  15. Molecular basis of the association of H208Y and thymidine analogue resistance mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated patients.

    Science.gov (United States)

    Betancor, Gilberto; Nevot, María; Mendieta, Jesús; Gómez-Puertas, Paulino; Martínez, Miguel A; Menéndez-Arias, Luis

    2014-06-01

    Thymidine analogue resistance mutations (TAMs) in HIV-1 reverse transcriptase (RT) associate in two clusters: (i) TAM1 (M41L, L210W and T215Y) and TAM2 (D67N, K70R, K219E/Q, and sometimes T215F). The amino acid substitution H208Y shows increased prevalence in patients treated with nucleoside analogues and is frequently associated with TAM1 mutations. We studied the molecular mechanism favoring the selection of H208Y in the presence of zidovudine, tenofovir and other nucleoside RT inhibitors (NRTIs). NRTI susceptibility was not affected by the addition of H208Y in phenotypic assays carried out in MT-4 cells using recombinant HIV-1 containing wild-type (subtype B, BH10), H208Y, M41L/L210W/T215Y or M41L/H208Y/L210W/T215Y RTs. However, enzymatic studies carried out with purified RTs revealed that in the presence of M41L/L210W/T215Y, H208Y increases the RT's ability to unblock and extend primers terminated with zidovudine, tenofovir and in a lesser extent, stavudine. These effects were observed with DNA/DNA complexes (but not with RNA/DNA) and resulted from the higher ATP-dependent excision activity of the M41L/H208Y/L210W/T215Y RT compared with the M41L/L210W/T215Y mutant. The increased rescue efficiency of the M41L/H208Y/L210W/T215Y RT was observed in the presence of ATP but not with GTP or ITP. Molecular dynamics studies predict an alteration of the stacking interactions between Tyr(215) and the adenine ring of ATP due to long-distance effects caused by tighter packaging of Tyr(208) and Trp(212). These studies provide a mechanistic explanation for the association of TAM-1 and H208Y mutations in viral isolates from patients treated with NRTIs. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Microvascular oxygen delivery-to-utilization mismatch at the onset of heavy-intensity exercise in optimally treated patients with CHF.

    Science.gov (United States)

    Sperandio, Priscila Abreu; Borghi-Silva, Audrey; Barroco, Adriano; Nery, Luiz Eduardo; Almeida, Dirceu R; Neder, J Alberto

    2009-11-01

    Impaired muscle blood flow at the onset of heavy-intensity exercise may transiently reduce microvascular O(2) pressure and decrease the rate of O(2) transfer from capillary to mitochondria in chronic heart failure (CHF). However, advances in the pharmacological treatment of CHF (e.g., angiotensin-converting enzyme inhibitors and third-generation beta-blockers) may have improved microvascular O(2) delivery to an extent that intramyocyte metabolic inertia might become the main locus of limitation of O(2) uptake (Vo(2)) kinetics. We assessed the rate of change of pulmonary Vo(2) (Vo(2)(p)), (estimated) fractional O(2) extraction in the vastus lateralis (approximately Delta[deoxy-Hb+Mb] by near-infrared spectroscopy), and cardiac output (Qt) during high-intensity exercise performed to the limit of tolerance (Tlim) in 10 optimally treated sedentary patients (ejection fraction = 29 + or - 8%) and 11 controls. Sluggish Vo(2)(p) and Qt kinetics in patients were significantly related to lower Tlim values (P < 0.05). The dynamics of Delta[deoxy-Hb+Mb], however, were faster in patients than controls [mean response time (MRT) = 15.9 + or - 2.0 s vs. 19.0 + or - 2.9 s; P < 0.05] with a subsequent response "overshoot" being found only in patients (7/10). Moreover, tauVo(2)/MRT-[deoxy-Hb+Mb] ratio was greater in patients (4.69 + or - 1.42 s vs. 2.25 + or - 0.77 s; P < 0.05) and related to Qt kinetics and Tlim (R = 0.89 and -0.78, respectively; P < 0.01). We conclude that despite the advances in the pharmacological treatment of CHF, disturbances in "central" and "peripheral" circulatory adjustments still play a prominent role in limiting Vo(2)(p) kinetics and tolerance to heavy-intensity exercise in nontrained patients.

  17. Optimization of Purification Condition for Inclusion Body of Recombinant HIV-1 Transmembrane Protein Gp41%重组HIV-1跨膜蛋白Gp41包涵体纯化条件的优化

    Institute of Scientific and Technical Information of China (English)

    孙静; 傅晶晶; 霍烛; 陈佩; 胡云章; 刘勇; 郝彦玲

    2009-01-01

    目的 优化重组HIV-1跨膜蛋白Gp41包涵体的纯化条件.方法 将表达Gp41的大肠杆菌菌体高压匀浆破碎、洗涤分离提取包涵体,以不同pH值的低浓度变性剂溶解包涵体,稀释复性并用离子交换层析纯化目的 蛋白,纯化产物经Western blot进行鉴定.结果 以50 mmol/L Tris buffer、2 mol/L,pH 11.5尿素溶解的包涵体蛋白得到很好的溶解,目的 蛋白复性得率大于40%.经纯化后,目的 蛋白的纯度大于90%,且具有良好的反应原性.结论 优化了重组HIV-1跨膜蛋白Gp41包涵体的纯化条件,为HIV-1 Gp41抗原纯化工艺的放大提供了依据.

  18. HIV Treatment: The Basics

    Science.gov (United States)

    HIV Treatment HIV Treatment: The Basics (Last updated 2/24/2017; last reviewed 2/24/2017) Key Points Antiretroviral therapy (ART) ... reduces the risk of HIV transmission . How do HIV medicines work? HIV attacks and destroys the infection- ...

  19. HIV/AIDS Treatment

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin HIV/AIDS Treatment HIV/AIDS HIV/AIDS Vaccine Development ... such as hepatitis, malaria, and tuberculosis. Treatment of HIV Infection In the early 1980s when the HIV/ ...

  20. Early ART initiation among HIV-positive pregnant women in central Mozambique: a stepped wedge randomized controlled trial of an optimized Option B+ approach.

    Science.gov (United States)

    Cowan, James F; Micek, Mark; Cowan, Jessica F Greenberg; Napúa, Manuel; Hoek, Roxanne; Gimbel, Sarah; Gloyd, Stephen; Sherr, Kenneth; Pfeiffer, James T; Chapman, Rachel R

    2015-04-30

    Despite effective prevention strategies and increasing investments in global health, maternal to child transmission (MTCT) of HIV remains a significant problem globally, especially in sub-Saharan Africa. In 2012, there were 94,000 HIV-positive pregnant women in Mozambique. Approximately 15% of these women transmitted HIV to their newborn infants, resulting in nearly 14,000 new pediatric HIV infections that year. To address this issue, in 2013, the Mozambican Ministry of Health implemented the World Health Organization-recommended "Option B+" strategy in which all newly diagnosed HIV-positive pregnant women are counseled to initiate combination anti-retroviral therapy (ART) immediately upon diagnosis regardless of CD4 count and to continue treatment for life. Given the limited experience with Option B+ in sub-Saharan Africa, few rigorous pragmatic trials have studied this new treatment strategy. This study utilizes an initial formative research process involving patient and health care provider interviews and focus groups, workforce assessments, value stream mapping, and commodity utilization assessments to understand the strengths and weaknesses in the current Option B+ care cascade. The formative research is intended to guide identification and prioritization of key workflow modifications and the development of an enhanced adherence and retention package. These two components are bundled into a defined intervention implemented and evaluated across six health facilities utilizing a stepped wedge randomized controlled trial study design. The overall objective of this trial is to develop and test a pilot intervention in central Mozambique to implement the new Option B+ guidelines with high fidelity and increase the proportion of HIV-positive pregnant women in target antenatal clinics (ANC) who start ART prior to delivery and are retained in care. This pragmatic study utilizes research strategies that have the potential to meaningfully improve the Option B+ care

  1. The Impact of Implementing a Test, Treat and Retain HIV Prevention Strategy in Atlanta among Black Men Who Have Sex with Men with a History of Incarceration: A Mathematical Model.

    Directory of Open Access Journals (Sweden)

    Viviane D Lima

    Full Text Available Annually, 10 million adults transition through prisons or jails in the United States (US and the prevalence of HIV among entrants is three times higher than that for the country as a whole. We assessed the potential impact of increasing HIV Testing/Treatment/Retention (HIV-TTR in the community and within the criminal justice system (CJS facilities, coupled with sexual risk behavior change, focusing on black men-who-have-sex-with-men, 15-54 years, in Atlanta, USA.We modeled the effect of a HIV-TTR strategy on the estimated cumulative number of new (acquired infections and mortality, and on the HIV prevalence at the end of ten years. We additionally assessed the effect of increasing condom use in all settings.In the Status Quo scenario, at the end of 10 years, the cumulative number of new infections in the community, jail and prison was, respectively, 9246, 77 and 154 cases; HIV prevalence was 10815, 69 and 152 cases, respectively; and the cumulative number of deaths was 2585, 18 and 34 cases, respectively. By increasing HIV-TTR coverage, the cumulative number of new infections could decrease by 15% in the community, 19% in jail, and 8% in prison; HIV prevalence could decrease by 8%, 9% and 7%, respectively; mortality could decrease by 20%, 39% and 18%, respectively. Based on the model results, we have shown that limited use and access to condoms have contributed to the HIV incidence and prevalence in all settings.Aggressive implementation of a CJS-focused HIV-TTR strategy has the potential to interrupt HIV transmission and reduce mortality, with benefit to the community at large. To maximize the impact of these interventions, retention in treatment, including during the period after jail and prison release, and increased condom use was vital for decreasing the burden of the HIV epidemic in all settings.

  2. Combination HIV prevention: significance, challenges, and opportunities.

    Science.gov (United States)

    Kurth, Ann E; Celum, Connie; Baeten, Jared M; Vermund, Sten H; Wasserheit, Judith N

    2011-03-01

    No single HIV prevention strategy will be sufficient to control the HIV pandemic. However, a growing number of interventions have shown promise in partially protecting against HIV transmission and acquisition, including knowledge of HIV serostatus, behavioral risk reduction, condoms, male circumcision, needle exchange, treatment of curable sexually transmitted infections, and use of systemic and topical antiretroviral medications by both HIV-infected and uninfected persons. Designing the optimal package of interventions that matches the epidemiologic profile of a target population, delivering that package at the population level, and evaluating safety, acceptability, coverage, and effectiveness, all involve methodological challenges. Nonetheless, there is an unprecedented opportunity to develop "prevention packages" that combine various arrays of evidence-based strategies, tailored to the needs of diverse subgroups and targeted to achieve high coverage for a measurable reduction in population-level HIV transmission. HIV prevention strategies that combine partially effective interventions should be scaled up and evaluated.

  3. Beyond viral suppression of HIV

    DEFF Research Database (Denmark)

    Lazarus, Jeffrey V.; Safreed-Harmon, Kelly; Barton, Simon E

    2016-01-01

    BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed......, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target...... for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV...

  4. The kidney in HIV infection: beyond HIV-associated nephropathy.

    Science.gov (United States)

    Wyatt, Christina M

    2012-01-01

    Acute kidney injury (AKI) and chronic kidney disease (CKD) are more common in HIV-infected persons than in the general population. AKI is associated with poor health outcomes, including increased risk of heart failure, cardiovascular events, end-stage renal disease (ESRD), and mortality. The most common causes of AKI in HIV-infected persons are systemic infections and adverse drug effects. The prevalence of CKD is rising in the HIV-infected population and CKD is increasingly likely to be caused by comorbid conditions, such as diabetes and hypertension, that frequently cause CKD in the general population. Guidelines for CKD screening in HIV-infected patients are being revised. It is currently recommended that all patients be screened for creatinine-based estimates of glomerular filtration rate and for urine protein at the time of HIV diagnosis. Annual screening is recommended for high-risk patients. Hemodialysis, peritoneal dialysis, and kidney transplantation are all options for treating ESRD in HIV-infected patients. Hemodialysis and peritoneal dialysis offer similar survival in HIV-infected patients with ESRD. In selected patients with well-controlled HIV infection, kidney transplantation is associated with survival intermediate between that in the overall transplant population and that among transplant recipients older than 65 years. This article summarizes a presentation by Christina M. Wyatt, MD, at the IAS-USA continuing medical education program held in Chicago in May 2012, describing AKI and CKD using case illustrations.

  5. Dynamics of adaptive and innate immunity in patients treated during primary human immunodeficiency virus infection: results from Maraviroc in HIV Acute Infection (MAIN) randomized clinical trial.

    Science.gov (United States)

    Ripa, M; Pogliaghi, M; Chiappetta, S; Galli, L; Pensieroso, S; Cavarelli, M; Scarlatti, G; De Biasi, S; Cossarizza, A; De Battista, D; Malnati, M; Lazzarin, A; Nozza, S; Tambussi, G

    2015-09-01

    We evaluated the dynamics of innate and adaptive immunity in patients treated with combined antiretroviral therapy (cART) during primary human immunodeficiency virus infection (PHI), enrolled in a prospective randomized trial (MAIN, EUDRACT 2008-007004-29). After 48 weeks of cART, we documented a reduction in activated B cells and CD8(+) T cells. Natural killer cell and dendritic cell frequencies were measured and a decrease in CD16(+) CD56(dim) with a reciprocal rise in CD56(high) natural killer cells and an increase in myeloid and plasmacytoid dendritic cells were recorded. In conclusion, 48 weeks of cART during PHI showed significant benefits for both innate and adaptive immunity.

  6. Clinical Evaluation of BioPlex 2200 HIV Ag-Ab, an Automated Screening Method Providing Discrete Detection of HIV-1 p24 Antigen, HIV-1 Antibody, and HIV-2 Antibody

    OpenAIRE

    Salmona, Maud; Delarue, Severine; Delaugerre, Constance; Simon, François; Maylin, Sarah

    2014-01-01

    Early and accurate diagnosis is essential for optimal therapeutic outcomes in patients infected with HIV. Currently, none of the commercially available fourth-generation assays differentiate HIV-1 and HIV-2 antibodies (Ab) or the HIV-1 p24 antigen (Ag). The aim of this study was to evaluate the performance of a novel assay, the BioPlex 2200 HIV Ag-Ab. This assay uses a multiplex flow immunoassay design allowing the simultaneous detection and identification of antibodies to HIV-1 (groups M and...

  7. LTR real-time PCR for HIV-1 DNA quantitation in blood cells for early diagnosis in infants born to seropositive mothers treated in HAART area (ANRS CO 01).

    Science.gov (United States)

    Avettand-Fènoël, Véronique; Chaix, Marie-Laure; Blanche, Stéphane; Burgard, Marianne; Floch, Corinne; Toure, Kadidia; Allemon, Marie-Christine; Warszawski, Josiane; Rouzioux, Christine

    2009-02-01

    HIV-1 diagnosis in babies born to seropositive mothers is one of the challenges of HIV epidemics in children. A simple, rapid protocol was developed for quantifying HIV-1 DNA in whole blood samples and was used in the ANRS French pediatric cohort in conditions of prevention of mother-to-child transmission. A quantitative HIV-1 DNA protocol (LTR real-time PCR) requiring small blood volumes was developed. First, analytical reproducibility was evaluated on 172 samples. Results obtained on blood cell pellets and Ficoll-Hypaque separated mononuclear cells were compared in 48 adult HIV-1 samples. Second, the protocol was applied to HIV-1 diagnosis in infants in parallel with plasma HIV-RNA quantitation. This prospective study was performed in children born between May 2005 and April 2007 included in the ANRS cohort. The assay showed good reproducibility. The 95% detection cut-off value was 6 copies/PCR, that is, 40 copies/10(6) leukocytes. HIV-DNA levels in whole blood were highly correlated with those obtained after Ficoll-Hypaque separation (r = 0.900, P mothers have received HAART. (c) 2008 Wiley-Liss, Inc.

  8. "Every drug goes to treat its own disease…" - a qualitative study of perceptions and experiences of taking anti-retrovirals concomitantly with anti-malarials among those affected by HIV and malaria in Tanzania

    DEFF Research Database (Denmark)

    Mangesho, Peter E; Reynolds, Joanna; Lemnge, Martha;

    2014-01-01

    , and in-depth interviews with health workers responsible for HIV care and members of the clinical trial team. Data were analysed inductively to identify themes and develop theoretical narratives. RESULTS: Results suggest that people living with HIV perceived malaria to be more harmful to them due...

  9. Ongoing HIV replication in cerebrospinal fluid under successful monotherapy

    NARCIS (Netherlands)

    M. Bierhoff (Marieke); C.A. Boucher (Charles); A. Fibriani (Azzania); R.W. ten Kate (Reinier)

    2013-01-01

    textabstractWe report a case of an HIV-infected patient who was successfully treated with ritonavir/lopinavir (r/LPV) monotherapy for several years. He presented with neurological symptoms and high HIV RNA levels in cerebrospinal fluid (CSF). Sequencing of the HIV from the CSF revealed mutations in

  10. HIV diagnosis in a patient presenting with vasculitis.

    Science.gov (United States)

    Sharif, M; Hameed, S; Akin, I; Natarajan, U

    2016-02-01

    A patient with digital ischaemia and gangrene was treated with iloprost and antiplatelets for two weeks. His vasculitic screen was negative except for a positive HIV test. His vasculitis improved three weeks after treatment with antiretroviral medications. Though vasculitis is well known to be associated with HIV infection, very few cases of HIV present as vasculitis.

  11. HIV Prevention

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, talks about steps people can take to protect their health from HIV.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  12. Wash durability and optimal drying regimen of four brands of long-lasting insecticide-treated nets after repeated washing under tropical conditions

    Directory of Open Access Journals (Sweden)

    Atieli Francis K

    2010-08-01

    Full Text Available Abstract Background The current study was undertaken to determine the optimal wash-drying regimen and the effects of different washing procedures on the efficacy, and durability of four brands of newly introduced long-lasting insecticide-treated nets (LLINs under tropical conditions. Methods In the current study, the following four LLINs were tested: Olyset®, PermaNet ®2.0, BASF® and TNT®. Nets were divided into three sets; one set was washed by hand rubbing and air-dried either hanging or spread on the ground in direct sunlight or hanging or spread on the ground under the shade. A second set was washed using the WHO protocol (machine and the third set was washed by beating the nets on rocks. The biological activities of the nets were assessed by a three-minute bioassay cone test and the residual insecticide contents were determined using high performance liquid chromatography (HPLC procedure. Results Nets that were dried hanging under the shade retained more insecticide, 62.5% and recorded higher mortality compared to nets which were dried lying on the ground in direct sunlight 58.8%, nets dried under the shade spread on the ground 56.3%, and 57.8% for nets dried hanging in direct sunlight. It was also observed that nets washed by the standard WHO protocol, retained more insecticide and were more effective in killing mosquitoes compared to nets washed by local methods of hand rubbing and beating on rocks. There were significant differences between drying regimens (p ® and TNT there were no significant differences observed between the four drying regimens (p = 0.7944 and 0.4703 respectively. For BASF and Olyset, the differences were significant (p 0.0001. Conclusion The results of this study suggest that washing and drying regimen influence the insecticidal activity of LLINs. The standard WHOPES washing protocol underestimates the amount of insecticide washed from LLINs compared to the abrasive washing procedures that are used in the field

  13. INCIDENCE OF LYMPHOMAS AND OTHER CANCERS IN HIV-INFECTED AND HIV-UNINFECTED PATIENTS WITH HEMOPHILIA

    NARCIS (Netherlands)

    RABKIN, CS; HILGARTNER, MW; HEDBERG, KW; ALEDORT, LM; HATZAKIS, A; EICHINGER, S; EYSTER, ME; WHITE, GC; KESSLER, CM; LEDERMAN, MM; DEMOERLOOSE, P; BRAY, GL; COHEN, AR; ANDES, WA; MANCOJOHNSON, M; SCHRAMM, W; KRONER, BL; BLATTNER, WA; GOEDERT, JJ

    1992-01-01

    Objective. - To determine the types and rates of cancers occurring in excess in the presence of infection with the human immunodeficiency virus type 1 (HIV-1). Design. - Cohort analytic study of HIV-infected and HIV-uninfected subjects followed for up to 12 years. Setting. - Fifteen hemophilia treat

  14. Optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of HIV capsid assembly inhibitors 1: addressing configurational instability through scaffold modification.

    Science.gov (United States)

    Fader, Lee D; Landry, Serge; Morin, Sébastien; Kawai, Stephen H; Bousquet, Yves; Hucke, Oliver; Goudreau, Nathalie; Lemke, Christopher T; Bonneau, Pierre; Titolo, Steve; Mason, Stephen; Simoneau, Bruno

    2013-06-01

    The optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly that possess a labile stereocenter at C3 is described. Quaternization of the C3 position of compound 1 in order to prevent racemization gave compound 2, which was inactive in our capsid disassembly assay. A likely explanation for this finding was revealed by in silico analysis predicting a dramatic increase in energy of the bioactive conformation upon quaternization of the C3 position. Replacement of the C3 of the diazepine ring with a nitrogen atom to give the 1,5-dihydro-benzo[f][1,3,5]triazepine-2,4-dione analog 4 was well tolerated. Introduction of a rigid spirocyclic system at the C3 position gave configurationally stable 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione analog 5, which was able to access the bioactive conformation without a severe energetic penalty and inhibit capsid assembly. Preliminary structure-activity relationships (SAR) and X-ray crystallographic data show that knowledge from the 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly can be transferred to these new scaffolds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. SU-E-T-452: Impact of Respiratory Motion On Robustly-Optimized Intensity-Modulated Proton Therapy to Treat Lung Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Liu, W; Schild, S; Bues, M [Mayo Clinic Arizona, Phoenix, AZ (United States); Liao, Z; Sahoo, N [MD Anderson Cancer Center, Houston, TX (United States); Park, P [Scottsdale, GA (United States); Li, H [M.D. Anderson Cancer Center, Houston, TX (United States); Li, Y [Varian Medical Systems, Houston, TX (United States); Li, X; Shen, J [Mayo Clinic Arizona, Phoenix, AA (United States); Anand, A [Mayo Clinic Arizona, Phoenix (United States); Dong, L [Scripps Proton Therapy Center, San Diego, CA (United States); Zhu, X; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

    2014-06-01

    Purpose: We compared conventionally optimized intensity-modulated proton therapy (IMPT) treatment plans against the worst-case robustly optimized treatment plans for lung cancer. The comparison of the two IMPT optimization strategies focused on the resulting plans' ability to retain dose objectives under the influence of patient set-up, inherent proton range uncertainty, and dose perturbation caused by respiratory motion. Methods: For each of the 9 lung cancer cases two treatment plans were created accounting for treatment uncertainties in two different ways: the first used the conventional Method: delivery of prescribed dose to the planning target volume (PTV) that is geometrically expanded from the internal target volume (ITV). The second employed the worst-case robust optimization scheme that addressed set-up and range uncertainties through beamlet optimization. The plan optimality and plan robustness were calculated and compared. Furthermore, the effects on dose distributions of the changes in patient anatomy due to respiratory motion was investigated for both strategies by comparing the corresponding plan evaluation metrics at the end-inspiration and end-expiration phase and absolute differences between these phases. The mean plan evaluation metrics of the two groups were compared using two-sided paired t-tests. Results: Without respiratory motion considered, we affirmed that worst-case robust optimization is superior to PTV-based conventional optimization in terms of plan robustness and optimality. With respiratory motion considered, robust optimization still leads to more robust dose distributions to respiratory motion for targets and comparable or even better plan optimality [D95% ITV: 96.6% versus 96.1% (p=0.26), D5% - D95% ITV: 10.0% versus 12.3% (p=0.082), D1% spinal cord: 31.8% versus 36.5% (p =0.035)]. Conclusion: Worst-case robust optimization led to superior solutions for lung IMPT. Despite of the fact that robust optimization did not explicitly

  16. HIV Replication at Low Copy Number and its Correlation with the HIV Reservoir: A Clinical Perspective.

    Science.gov (United States)

    Sarmati, Loredana; D'Ettorre, Gabriella; Parisi, Saverio Giuseppe; Andreoni, Massimo

    2015-01-01

    The efficacy of combination therapy (antiretroviral therapy--ARV) is demonstrated by the high rates of viral suppression achieved in most treated HIV patients. Whereas contemporary treatments may continuously suppress HIV replication, they do not eliminate the latent reservoir, which can reactivate HIV infection if ARV is discontinued. The persistence of HIV proviral DNA and infectious viruses in CD4+ T cells and others cells has long been considered a major obstacle in eradicating the HIV virus in treated patients. Moreover, recent studies have demonstrated the persistence of HIV replication at low copies in most patients on suppressive ARV. The source of this 'residual viraemia' and whether it declines over years of therapy remain unknown. Similarly, little is known regarding the biological relationships between the HIV reservoir and viral replication at low copies. The question of whether this 'residual viraemia' represents active replication or the release of non-productive virus from the reservoir has not been adequately resolved. From a clinical perspective, both the quantification of the HIV reservoir and the detection of low levels of replication in full-responder patients on prolonged ARV may provide important information regarding the effectiveness of treatment and the eradication of HIV. To date, the monitoring of these two parameters has been conducted only for research purposes; the routine use of standardised tests procedure is lacking. This review aims to assess the current data regarding the correlation between HIV replication at low copies and the HIV reservoir and to provide useful information for clinicians.

  17. Comorbidity and ageing in HIV infection

    NARCIS (Netherlands)

    Kooij, K.W.

    2017-01-01

    In the era of modern combination antiretroviral therapy (cART) the HIV-infected population is ageing. Studies have suggested that HIV-infected individuals, even if appropriately treated with cART, may be at increased risk for several age-related conditions. In this thesis a variety of age-related co

  18. Comorbidity and ageing in HIV infection

    NARCIS (Netherlands)

    Kooij, K.W.

    2017-01-01

    In the era of modern combination antiretroviral therapy (cART) the HIV-infected population is ageing. Studies have suggested that HIV-infected individuals, even if appropriately treated with cART, may be at increased risk for several age-related conditions. In this thesis a variety of age-related co

  19. HIV treatment cascade in tuberculosis patients

    Science.gov (United States)

    Lessells, Richard J.; Swaminathan, Soumya; Godfrey-Faussett, Peter

    2015-01-01

    Purpose of review Globally, the number of deaths associated with tuberculosis (TB) and HIV coinfection remains unacceptably high. We review the evidence around the impact of strengthening the HIV treatment cascade in TB patients and explore recent findings about how best to deliver integrated TB/HIV services. Recent findings There is clear evidence that the timely provision of antiretroviral therapy (ART) reduces mortality in TB/HIV coinfected adults. Despite this, globally in 2013, only around a third of known HIV-positive TB cases were treated with ART. Although there is some recent evidence exploring the barriers to achieve high coverage of HIV testing and ART initiation in TB patients, our understanding of which factors are most important and how best to address these within different health systems remains incomplete. There are some examples of good practice in the delivery of integrated TB/HIV services to improve the HIV treatment cascade. However, evidence of the impact of such strategies is of relatively low quality for informing integrated TB/HIV programming more broadly. In most settings, there remain barriers to higher-level organizational and functional integration. Summary There remains a need for commitment to patient-centred integrated TB/HIV care in countries affected by the dual epidemic. There is a need for better quality evidence around how best to deliver integrated services to strengthen the HIV treatment cascade in TB patients, both at primary healthcare level and within community settings. PMID:26352390

  20. 3种用药方案治疗HIV/TB患者抗结核药物性肝损伤成本-效果分析%Cost-effectiveness Analysis of 3 Therapeutic Schemes in Treating Antituberculosis Drug-induced Hepatotoxicity in HIV/TB Patients

    Institute of Scientific and Technical Information of China (English)

    杜红; 汤卓; 葛利辉; 吴念宁; 林群英; 何琦

    2012-01-01

    Objective To probe into the economic-effectiveness of different therapeutic schemes in the treatment of antituberculo-sis dnig-induced hepatotoxicity in HIV/TB patients. Method 168 cases were randomly divided into three groups, including Croup A ( sequential therapy of deoxidized glutathione ), Croup B ( sequential therapy of compound glycyrrhizin ) and Croup C ( sequential therapy of deoxidized glutathione vein and compound glycyrrhizin orally ). Results The costs for the 3 treatment schemes were respectively 1221 yuan, 1076.5 yuan and 960. 7 yuan; their incidences for adverse effects were respectively 50% , 41. 1% and 44. 6%( P > 0. 05 ); the cost-effectiveness ratio were respectively 12. 91 , 12. 83 and 10. 55; the effective rates were respectively 94.6% , 83. 8% and 91. 1% ; There were no significant differences in the effective rates produced respectively by three therapeutic schemes when they were used to treat the antituberculosis drug-induced hepatotoxicity in HIV/TB patients, while there was a significant difference in the liver function( Total bilimbin) between Croup A and Croup B. Conclusion Taking everything into consideration, schemes C is the preferable one.%目的 探讨3种不同治疗方案用于治疗HIV/TB患者抗结核药物性肝损的经济效果.方法 将168例患者随机分成3组,A组还原型谷胱甘肽序贯、B组复方甘草酸苷序贯,C组还原型谷胱甘肽静滴序贯复方甘草酸苷口服,观察疗效和不良反应.结果 3种药物治疗方案成本分别为1221元、1076.5元、960.7元; 发生不良反应率分别为50%、41.1%、44.6%(P>0.05);成本-效果比分别为12.91、12.83、10.55;有效率分别为94.6%、83.8%、91.1% (P<0.05);三种方案治疗HIV/TB患者抗结核药物性肝损在有效率上无显著差异,在A、B两组肝功能上(总胆红素)有显著差异.结论 还原型谷胱甘肽静滴序贯复方甘草酸苷口服方案为较佳方案.

  1. Current status of HIV/AIDS in the ART era.

    Science.gov (United States)

    Yoshimura, Kazuhisa

    2017-01-01

    Human immunodeficiency virus (HIV) spread to humans from chimpanzees (HIV-1 groups M and N), gorillas (HIV-1 groups P and O), and sooty mangabeys (HIV-2). HIV is spread mainly through blood or body fluids. Subjects can become infected with HIV by sexual contact, needle sharing, blood transfusions, or maternal transmissions as a blood-borne virus or via breast-milk. The incubation period of HIV-1 from infection to the development of AIDS ranges from 8 to 11 years. In the past 3 decades, HIV has caused a great burden to global wealth and health. According to the WHO global health survey, 36.7 million people were infected with HIV, causing 1.1 million deaths in 2015. Since the discovery of HIV-1, many anti-retroviral drugs have been developed. Following the discovery and wide-spread use of anti-retroviral therapy (ART) the life expectancy of HIV infected individuals has substantially increased. By 2015, all major guidelines recommended treating all HIV-infected adults regardless of their CD4 count. Despite effective ART with virological suppression, HIV-associated neurocognitive disorders (HAND), cardiovascular diseases (CVD), metabolic syndrome (MS), bone abnormalities and non-HIV-associated malignancies remain a major complication associated with HIV infection. In this review article, I would like to describe recent ART status and problems in the ART-era.

  2. Effect of hepatitis C infection on HIV-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Tomasz Laskus

    Full Text Available BACKGROUND: Hepatitis C virus (HCV coinfection was reported to negatively affect HIV disease and HIV infection has a deleterious effect on HCV-related liver disease. However, despite common occurrence of HCV/HIV coinfection little is known about the mechanisms of interactions between the two viruses. METHODS: We studied CD4+ and CD8+ T cell and CD19+ B cell apoptosis in 104 HIV-positive patients (56 were also HCV-positive and in 22 HCV/HIV-coinfected patients treated for chronic hepatitis C with pegylated interferon and ribavirin. We also analyzed HCV/HIV coinfection in a Daudi B-cell line expressing CD4 and susceptible to both HCV and HIV infection. Apoptosis was measured by AnnexinV staining. RESULTS: HCV/HIV coinfected patients had lower CD4+ and CD8+ T cell apoptosis and higher CD19+ B cell apoptosis than those with HIV monoinfection. Furthermore, anti-HCV treatment of HCV/HIV coinfected patients was followed by an increase of CD4+ and CD8+ T cell apoptosis and a decrease of CD19+ B cell apoptosis. In the Daudi CD4+ cell line, presence of HCV infection facilitated HIV replication, however, decreased the rate of HIV-related cell death. CONCLUSION: In HCV/HIV coinfected patients T-cells were found to be destroyed at a slower rate than in HIV monoinfected patients. These results suggest that HCV is a molecular-level determinant in HIV disease.

  3. Treating Infertility

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Treating Infertility Home For Patients Search FAQs Treating Infertility Page ... Treating Infertility FAQ137, March 2015 PDF Format Treating Infertility Gynecologic Problems What is infertility? What treatment options ...

  4. Recent trends in HIV-1 drug resistance.

    Science.gov (United States)

    Siliciano, Janet D; Siliciano, Robert F

    2013-10-01

    Once considered an inevitable consequence of HIV treatment, drug resistance is declining. This decline supports the hypothesis that antiretroviral therapy can arrest replication and prevent the evolution of resistance. Further support comes from excellent clinical outcomes, the failure of treatment intensification to reduce residual viremia, the lack of viral evolution in patients on optimal therapy, pharmacodynamics studies explaining the extraordinarily high antiviral activity of modern regimens, and recent reports of potential cures. Evidence supporting ongoing replication includes higher rates of certain complications in treated patients and an increase in circular forms of the viral genome after intensification with integrase inhibitors. Recent studies also provide an explanation for the observation that some patients fail protease-inhibitor based regimens without evidence for resistance. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. A constant threat for HIV: Fc-engineering to enhance broadly neutralizing antibody activity for immunotherapy of the acquired immunodeficiency syndrome.

    Science.gov (United States)

    Nimmerjahn, Falk

    2015-08-01

    Passive immunotherapy with polyclonal or hyperimmune serum immunoglobulin G (IgG) preparations provides an efficient means of protecting immunocompromised patients from microbial infections. More recently, the use of passive immunotherapy to prevent or to treat established infections with the human immunodeficiency virus (HIV) has gained much attention, due to promising preclinical data obtained in monkey and humanized mouse in vivo model systems, demonstrating that the transfer of HIV-specific antibodies can not only prevent HIV infection, but also diminish virus load during chronic infection. Furthermore, an array of broadly neutralizing HIV-specific antibodies has become available and the importance of the IgG constant region as a critical modulator of broadly neutralizing activity has been demonstrated. The aim of this review is to summarize the most recent findings with regard to the molecular and cellular mechanisms responsible for antibody-mediated clearance of HIV infection, and to discuss how this may help to improve HIV therapy via optimizing Fcγ-receptor-dependent activities of HIV-specific antibodies.

  6. Applying HIV testing guidelines in clinical practice.

    Science.gov (United States)

    Mahoney, Megan R; Fogler, Jess; Weber, Shannon; Goldschmidt, Ronald H

    2009-12-15

    An estimated one fourth of persons with human immunodeficiency virus (HIV) are not aware they are infected. Early diagnosis of HIV has the potential to ensure optimal outcomes for infected persons and to limit the spread of the virus. Important barriers to testing among physicians include insufficient time, reimbursement issues, and lack of patient acceptance. Current HIV testing guidelines address many of these barriers by making the testing process more streamlined and less stigmatizing. The opt-out consent process has been shown to improve test acceptance. Formal pretest counseling and written consent are no longer recommended by the Centers for Disease Control and Prevention. Nevertheless, pretest discussions provide an opportunity to give information about HIV, address fears of discrimination, and identify ongoing high-risk activities. With increased HIV screening in the primary care setting, more persons with HIV could be identified earlier, receive timely and appropriate care, and get treatment to prevent clinical progression and transmission.

  7. "When they know that you are a sex worker, you will be the last person to be treated": Perceptions and experiences of female sex workers in accessing HIV services in Uganda.

    Science.gov (United States)

    Wanyenze, Rhoda K; Musinguzi, Geofrey; Kiguli, Juliet; Nuwaha, Fred; Mujisha, Geoffrey; Musinguzi, Joshua; Arinaitwe, Jim; Matovu, Joseph K B

    2017-05-05

    HIV prevalence among female sex workers (FSWs) in high burden countries in sub-Saharan Africa varies between 24 and 72%, however their access to HIV services remains limited. This study explored FSWs' perspectives of the barriers and opportunities to HIV service access in Uganda. The cross-sectional qualitative study was conducted between October and December 2013. Twenty-four focus group discussions were conducted with 190 FSWs in 12 districts. Data were analysed using manifest content analysis, using Atlas.ti software, based on the socio-ecological model. FSWs indicated that HIV services were available and these included condoms, HIV testing and treatment, and management of sexually transmitted infections. However, access to HIV services was affected by several individual, societal, structural, and policy related barriers. Individual level factors included limited awareness of some prevention services, fears, and misconceptions while societal stigma was prominent. Structural and policy level barriers included inconvenient hours of operation of the clinics, inflexible facility based distribution of condoms, interuptions in the supply of condoms and other commodities, and limited package of services with virtually no access to lubricants, HIV pre- and post-exposure prophylaxis, and support following client perpetrated violence. Policies such as partner testing and involvement at antenatal care, and using only one facility for antiretroviral drug refills hindered HIV service uptake and retention in care. FSWs had major concerns with the quality of services especially discrimination and rude remarks from providers, denial or delay of services, and potential for breach of confidentiality. However, some FSWs reported positive experiences including interface with friendly providers and participated in formal and informal FSW groups, which supported them to access health services. Despite availability of services, FSWs faced major challenges in access to services

  8. [Stroke in HIV-infected patients].

    Science.gov (United States)

    Lino, Ireneia; Sousa, António; Correia, José

    2007-01-01

    The spectrum of human immunodeficiency virus infection (HIV) is changing. New drug treatments have reduced morbidity and mortality of this disease, therefore it is necessary to start treating the HIV infection as a chronical disease. The association of the stroke with the HIV infection was inicially thought to be a result of other opportunistic infeccions and tumors. However, the vascular disease associated with HIV infection has been a subject of research and debate. New evidence shows that the vascular diseases could be a threat for the pacients doing highly active antirretroviral therapy (HAART). In this paper, we review the association between the HIV infection and stroke. Furthermore, we have done an analysis of the risk for the stroke on pacients with HIV infection considering the changes of the infection spectrum by the introduction of HAART.

  9. Effect of isoprinosine on HIV antigenaemia

    DEFF Research Database (Denmark)

    Teglbjærg, Lars Stubbe; Kroon, S; Sandström, E

    1992-01-01

    OBJECTIVE: The objective of this study was to evaluate the effect of isoprinosine on HIV-antigen expression in HIV-positive patients without AIDS. DESIGN: Serum samples from anti-HIV-positive patients without AIDS participating in a double-blind, placebo-controlled trial of isoprinosine...... in the treatment of HIV infection were analysed for the presence of HIV antigen. SETTING: Data and samples were collected from the 21 medical centres who participated in the Scandinavian multicentre placebo-controlled isoprinosine study. PATIENTS, PARTICIPANTS: Samples were available from 19 of 21 participating...... centres. Of 866 patients who enrolled, baseline serum samples were available for 642 (74%; 308 isoprinosine- and 334 placebo-treated patients). INTERVENTIONS: Treatment was 1 g isoprinosine administered orally three times a day or matching placebo for 24 weeks. MAIN OUTCOME MEASURES: Comparison of HIV...

  10. HIV/AIDS

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most ...

  11. HIV Medication Adherence

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Medication Adherence Last Reviewed: March 2, 2017 Key ...

  12. HIV and Pulmonary Hypertension

    Science.gov (United States)

    ... 03-13T18:29:11+00:00 PH and HIV Print PH and HIV Brochure (PDF) Order Copies ... to know about pulmonary hypertension in connection with HIV? Although pulmonary hypertension and HIV are two separate ...

  13. HIV and Rheumatic Disease

    Science.gov (United States)

    ... A Patient / Caregiver Diseases & Conditions HIV & Rheumatic Diseases HIV and Rheumatic Disease Fast Facts Rheumatic diseases related ... knows he or she has HIV. What are HIV-associated rheumatic diseases? Some diseases of the joints ...

  14. HIV and AIDS

    Science.gov (United States)

    ... Emergency Room? What Happens in the Operating Room? HIV and AIDS KidsHealth > For Kids > HIV and AIDS ... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ...

  15. HIV and Rheumatic Disease

    Science.gov (United States)

    ... A Patient / Caregiver Diseases & Conditions HIV & Rheumatic Diseases HIV and Rheumatic Disease Fast Facts Rheumatic diseases related ... knows he or she has HIV. What are HIV-associated rheumatic diseases? Some diseases of the joints ...

  16. HIV Medication Adherence

    Science.gov (United States)

    HIV Treatment HIV Medication Adherence (Last updated 3/2/2017; last reviewed 3/2/2017) Key Points Medication adherence means sticking ... exactly as prescribed. Why is adherence to an HIV regimen important? Adherence to an HIV regimen gives ...

  17. HIV and Pregnancy

    Science.gov (United States)

    ... Events Advocacy For Patients About ACOG HIV and Pregnancy Home For Patients Search FAQs HIV and Pregnancy ... Pregnancy FAQ113, December 2012 PDF Format HIV and Pregnancy Pregnancy What is human immunodeficiency virus (HIV)? How ...

  18. 4. CRIMINALISING HIV TRANSMISSION

    African Journals Online (AJOL)

    Esem

    should be adopted to expand targeted efforts in preventing new HIV infections in Zambia. ... result of sexual intercourse between an HIV positive and. HIV negative person and ..... countries have not criminalized HIV infection. To this end, those ...

  19. Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection.

    Directory of Open Access Journals (Sweden)

    Masahiko Mori

    Full Text Available The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naïve female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female; and children not meeting criteria to start ART by >5 yrs were more frequently female (59%; p<0.001. Among ART-treated children, immune reconstitution of CD4 T-cells was more rapid and more complete in female children, even after adjustment for pre-ART absolute CD4 count or CD4% (p=0.011, p=0.030, respectively. However, while ART was initiated as a result of meeting CD4 criteria less often in females (45%, ART initiation as a result of clinical disease in children whose CD4 counts were above treatment thresholds occurred more often in females (57%, p<0.001. The main sex difference in morbidity observed in children initiating ART above CD4 thresholds, above that of TB disease, was as a result of wasting and stunting observed in females with above-threshold CD4 counts (p=0.002. These findings suggest the possibility that optimal treatment of HIV-infected children might incorporate differential CD4 treatment thresholds for ART initiation according to sex.

  20. Modeling HIV Cure

    Science.gov (United States)

    Perelson, Alan; Conway, Jessica; Cao, Youfang

    A large effort is being made to find a means to cure HIV infection. I will present a dynamical model of post-treatment control (PTC) or ``functional cure'' of HIV-infection. Some patients treated with suppressive antiviral therapy have been taken off of therapy and then spontaneously control HIV infection such that the amount of virus in the circulation is maintained undetectable by clinical assays for years. The model explains PTC occurring in some patients by having a parameter regime in which the model exhibits bistability, with both a low and high steady state viral load being stable. The model makes a number of predictions about how to attain the low PTC steady state. Bistability in this model depends upon the immune response becoming exhausted when over stimulated. I will also present a generalization of the model in which immunotherapy can be used to reverse immune exhaustion and compare model predictions with experiments in SIV infected macaques given immunotherapy and then taken off of antiretroviral therapy. Lastly, if time permits, I will discuss one of the hurdles to true HIV eradication, latently infected cells, and present clinical trial data and a new model addressing pharmacological means of flushing out the latent reservoir. Supported by NIH Grants AI028433 and OD011095.

  1. A Novel Class of HIV-1 Antiviral Agents Targeting HIV via a SUMOylation-Dependent Mechanism.

    Science.gov (United States)

    Madu, Ikenna G; Li, Shirley; Li, Baozong; Li, Haitang; Chang, Tammy; Li, Yi-Jia; Vega, Ramir; Rossi, John; Yee, Jiing-Kuan; Zaia, John; Chen, Yuan

    2015-12-08

    We have recently identified a chemotype of small ubiquitin-like modifier (SUMO)-specific protease (SENP) inhibitors. Prior to the discovery of their SENP inhibitory activity, these compounds were found to inhibit HIV replication, but with an unknown mechanism. In this study, we investigated the mechanism of how these compounds inhibit HIV-1. We found that they do not affect HIV-1 viral production, but significantly inhibited the infectivity of the virus. Interestingly, virions produced from cells treated with these compounds could gain entry and carry out reverse transcription, but could not efficiently integrate into the host genome. This phenotype is different from the virus produced from cells treated with the class of anti-HIV-1 agents that inhibit HIV protease. Upon removal of the SUMO modification sites in the HIV-1 integrase, the compound no longer alters viral infectivity, indicating that the effect is related to SUMOylation of the HIV integrase. This study identifies a novel mechanism for inhibiting HIV-1 integration and a new class of small molecules that inhibits HIV-1 via such mechanism that may contribute a new strategy for cure of HIV-1 by inhibiting the production of infectious virions upon activation from latency.

  2. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids- ... HIV, STD, and TB Prevention. What Is HIV? ( http://www.cdc.gov/hiv/pubs/faq/faq1.htm ). ...

  3. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids- ... HIV, STD, and TB Prevention. What Is HIV? ( http://www.cdc.gov/hiv/pubs/faq/faq1.htm ). ...

  4. Significant impact of non-B HIV-1 variants genetic diversity in Gabon on plasma HIV-1 RNA quantitation.

    Science.gov (United States)

    Mouinga-Ondémé, Augustin; Mabika-Mabika, Arsène; Alalade, Patrick; Mongo, Arnaud Delis; Sica, Jeanne; Liégeois, Florian; Rouet, François

    2014-01-01

    Evaluations of HIV-1 RNA viral load assays are lacking in Central Africa. The main objective of our study was to assess the reliability of HIV-1 RNA results obtained with three different assays for samples collected in Gabon. A total of 137 plasma specimens were assessed for HIV-1 RNA using the Abbott RealTime HIV-1® and Nuclisens HIV-1 EasyQ® version 2.0 assays. It included HIV-1 non-B samples (n = 113) representing six subtypes, 10 CRFs and 18 URFs from patients infected with HIV-1 and treated with antiretrovirals that were found HIV-1 RNA positive (≥300 copies/ml) with the Generic HIV viral load® assay; and samples (n = 24) from untreated individuals infected with HIV-1 but showing undetectable (<300 copies/ml) results with the Biocentric kit. For samples found positive with the Generic HIV viral load® test, correlation coefficients obtained between the three techniques were relatively low (R = 0.65 between Generic HIV viral load® and Abbott RealTime HIV-1®, 0.50 between Generic HIV viral load® and Nuclisens HIV-1 EasyQ®, and 0.66 between Abbott RealTime HIV-1® and Nuclisens HIV-1 EasyQ®). Discrepancies by at least one log10 were obtained for 19.6%, 33.7%, and 20% of samples, respectively, irrespective of genotype. Most of samples (22/24) from untreated study patients, found negative with the Biocentric kit, were also found negative with the two other techniques. In Central Africa, HIV-1 genetic diversity remains challenging for viral load testing. Further studies are required in the same area to confirm the presence of HIV-1 strains that are not amplified with at least two different viral load assays.

  5. HIV among Women

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Women Format: Select One File [155K] Recommend ...

  6. HIV among Transgender People

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Transgender People Format: Select One PDF [227K] ...

  7. Living with HIV

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Syndicated Content Website Feedback HIV/AIDS Living With HIV Language: English (US) Español (Spanish) Recommend on ...

  8. HIV Among Asians

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Asians in the United States Format: Select ...

  9. In search of optimal DBS paradigms to treat epilepsy: bilateral versus unilateral hippocampal stimulation in a rat model for temporal lobe epilepsy

    NARCIS (Netherlands)

    Van Nieuwenhuyse, B.; Raedt, R.; Delbeke, J.; Wadman, W.J.; Boon, P; Vonck, K.

    2015-01-01

    BACKGROUND: In many temporal lobe epilepsy (TLE) patients both hippocampi are seizure onset zones. These patients are unsuitable candidates for epilepsy surgery but may be amenable to hippocampal deep brain stimulation (DBS). The optimal DBS parameters for these patients are unknown. Recent observat

  10. Incidence of chemotherapy-induced neutropenia in HIV-infected and ...

    African Journals Online (AJOL)

    Journal Home > Vol 107, No 7 (2017) > ... To establish the incidence of CIN in HIV-infected and uninfected patients undergoing ... stage II - IV breast cancer and known HIV status treated with neoadjuvant chemotherapy ... from 32 Countries:.

  11. [Dental treatment of HIV-infected and AIDS patients in the dental office in The Netherlands].

    Science.gov (United States)

    Sjamsoedin, D A; Molendijk, G; Schulten, E A; ten Kate, R W; van der Waal, I

    1991-09-01

    Every dentist should accept the responsibility of treating HIV-infected and AIDS' patients in his own office. By taking the appropriate hygienic measures, the risk of HIV-transmission in the dental office can be almost completely eliminated.

  12. Evaluation of a Systems Analysis and Improvement Approach to Optimize Prevention of Mother-To-Child Transmission of HIV Using the Consolidated Framework for Implementation Research

    Science.gov (United States)

    Rustagi, Alison S.; Robinson, Julia; Kouyate, Seydou; Coutinho, Joana; Nduati, Ruth; Pfeiffer, James; Gloyd, Stephen; Sherr, Kenneth; Granato, S. Adam; Kone, Ahoua; Cruz, Emilia; Manuel, Joao Luis; Zucule, Justina; Napua, Manuel; Mbatia, Grace; Wariua, Grace; Maina, Martin

    2016-01-01

    Background: Despite large investments to prevent mother-to-child-transmission (PMTCT), pediatric HIV elimination goals are not on track in many countries. The Systems Analysis and Improvement Approach (SAIA) study was a cluster randomized trial to test whether a package of systems engineering tools could strengthen PMTCT programs. We sought to (1) define core and adaptable components of the SAIA intervention, and (2) explain the heterogeneity in SAIA's success between facilities. Methods: The Consolidated Framework for Implementation Research (CFIR) guided all data collection efforts. CFIR constructs were assessed in focus group discussions and interviews with study and facility staff in 6 health facilities (1 high-performing and 1 low-performing site per country, identified by study staff) in December 2014 at the end of the intervention period. SAIA staff identified the intervention's core and adaptable components at an end-of-study meeting in August 2015. Two independent analysts used CFIR constructs to code transcripts before reaching consensus. Results: Flow mapping and continuous quality improvement were the core to the SAIA in all settings, whereas the PMTCT cascade analysis tool was the core in high HIV prevalence settings. Five CFIR constructs distinguished strongly between high and low performers: 2 in inner setting (networks and communication, available resources) and 3 in process (external change agents, executing, reflecting and evaluating). Discussion: The CFIR is a valuable tool to categorize elements of an intervention as core versus adaptable, and to understand heterogeneity in study implementation. Future intervention studies should apply evidence-based implementation science frameworks, like the CFIR, to provide salient data to expand implementation to other settings. PMID:27355497

  13. Vpr14-88-Apobec3G fusion protein is efficiently incorporated into Vif-positive HIV-1 particles and inhibits viral infection.

    Directory of Open Access Journals (Sweden)

    Zhujun Ao

    Full Text Available BACKGROUND: APOBEC3G (A3G, a deoxycytidine deaminase, is a potent host antiviral factor that can restrict HIV-1 infection. During Vif-negative HIV-1 replication, A3G is incorporated into HIV-1 particles, induces mutations in reverse transcribed viral DNA and inhibits reverse transcription. However, HIV-1 Vif counteracts A3G's activities by inducing its degradation and by blocking its incorporation into HIV-1 particles. Thus, it is interesting to elucidate a mechanism that would allow A3G to escape the effects of Vif in order to rescue its potent antiviral activity and to provide a possible novel therapeutic strategy for treating HIV-1 infection. METHODS AND FINDINGS: In this study, we generated an R88-A3G fusion protein by fusing A3G to a virion-targeting polypeptide (R14-88 derived from HIV-1 Vpr protein and compared its antiviral effects relative to those of HA-tagged native A3G (HA-A3G. Our study showed that transient expression of the R88-A3G fusion protein in both Vif(- and Vif(+ HIV-1 producing cells drastically inhibited viral infection in HeLa-CD4-CCR5-cells, CD4(+ C8166 T cells and human primary PBMCs. Moreover, we established CD4(+ C8166 T cell lines that stably express either R88-A3G or HA-A3G by transduction with VSV-G-pseudotyped lentiviral vector that harbor expression cassettes for R88-A3G or HA-A3G, respectively, and tested their susceptibility to Vif(+ HIV-1 infection. Our results clearly reveal that expression of R88-A3G in transduced CD4(+ C8166 cells significantly blocked Vif(+ HIV-1 infection. In an attempt to understand the mechanism underlying the antiviral activity of R88-A3G, we demonstrated that R88-A3G was efficiently incorporated into viral particles in the presence of Vif. Moreover, PCR analysis revealed that R88-A3G significantly inhibited viral cDNA synthesis during the early stage of Vif(+ virus infection. CONCLUSIONS: Our results clearly indicate that R88 delivers A3G into Vif(+ HIV-1 particles and inhibits

  14. Is there a subset of patients with recurrent cancer in the vagina who are not candidates for interstitial brachytherapy that can be treated with multichannel vaginal brachytherapy using graphic optimization?

    Science.gov (United States)

    Singh, Deepinder P; Bylund, Kevin C; Matloubieh, Ahmad; Mazloom, Ali; Gray, Alexander; Sidhu, Ravinder; Barrette, Lucille; Chen, Yuhchyau

    2015-04-01

    To evaluate recurrent vaginal cancer treated with vaginal brachytherapy (VBT) using graphic optimization in patients not amenable to surgery and interstitial brachytherapy (ISBT). We retrospectively reviewed the records of 5 patients with recurrent cancer in the vagina that were deemed not to be good candidates for ISBT implant because of medical reasons. All patients received computed tomography/magnetic resonance imaging (CT/MRI) based evaluation in addition to a detailed clinical examination, and were noted to have recurrent nodules in the vagina with size ranging from 10-25 mm. Four of the 5 patients had recurrent disease in the vaginal apex, whereas one patient had recurrence in the lateral vaginal wall. Subsequently, all patients were treated with external beam radiation therapy (EBRT) followed by multichannel vaginal cylinder (MVC)-based VBT using graphic optimization for shaping the isodose to improve the clinical target volume (CTV) coverage, as well as to spare the organs at risk (OAR). The dose to the bladder and rectum with regard to 0.1 cc, 1 cc, and 2 cc were recorded. Median age of the patients was 78 years (range 58-86 years). Thickness of the lesions before VBT ranged from 6-15 mm. All patients were followed up with MRI at 3 months. All patients but one demonstrated complete clinical/ radiological response of the tumor. No patient had any grade III/IV toxicity at 24 months. MVC-based VBT using graphic optimization is safe and yields favorable results if used judiciously.

  15. Profile of the HIV epidemic in Cape Verde: molecular epidemiology and drug resistance mutations among HIV-1 and HIV-2 infected patients from distinct islands of the archipelago.

    Science.gov (United States)

    de Pina-Araujo, Isabel Inês M; Guimarães, Monick L; Bello, Gonzalo; Vicente, Ana Carolina P; Morgado, Mariza G

    2014-01-01

    HIV-1 and HIV-2 have been detected in Cape Verde since 1987, but little is known regarding the genetic diversity of these viruses in this archipelago, located near the West African coast. In this study, we characterized the molecular epidemiology of HIV-1 and HIV-2 and described the occurrence of drug resistance mutations (DRM) among antiretroviral therapy naïve (ARTn) patients and patients under treatment (ARTexp) from different Cape Verde islands. Blood samples, socio-demographic and clinical-laboratory data were obtained from 221 HIV-positive individuals during 2010-2011. Phylogenetic and bootscan analyses of the pol region (1300 bp) were performed for viral subtyping. HIV-1 and HIV-2 DRM were evaluated for ARTn and ARTexp patients using the Stanford HIV Database and HIV-GRADE e.V. Algorithm Homepage, respectively. Among the 221 patients (169 [76.5%] HIV-1, 43 [19.5%] HIV-2 and 9 [4.1%] HIV-1/HIV-2 co-infections), 67% were female. The median ages were 34 (IQR = 1-75) and 47 (IQR = 12-84) for HIV-1 and HIV-2, respectively. HIV-1 infections were due to subtypes G (36.6%), CRF02_AG (30.6%), F1 (9.7%), URFs (10.4%), B (5.2%), CRF05_DF (3.0%), C (2.2%), CRF06_cpx (0.7%), CRF25_cpx (0.7%) and CRF49_cpx (0.7%), whereas all HIV-2 infections belonged to group A. Transmitted DRM (TDRM) was observed in 3.4% (2/58) of ARTn HIV-1-infected patients (1.7% NRTI, 1.7% NNRTI), but not among those with HIV-2. Among ARTexp patients, DRM was observed in 47.8% (33/69) of HIV-1 (37.7% NRTI, 37.7% NNRTI, 7.4% PI, 33.3% for two classes) and 17.6% (3/17) of HIV-2-infections (17.6% NRTI, 11.8% PI, 11.8% both). This study indicates that Cape Verde has a complex and unique HIV-1 molecular epidemiological scenario dominated by HIV-1 subtypes G, CRF02_AG and F1 and HIV-2 subtype A. The occurrence of TDRM and the relatively high level of DRM among treated patients are of concern. Continuous monitoring of patients on ART, including genotyping, are public policies to be implemented.

  16. Combination antiretroviral therapy and chronic HIV infection affect serum retinoid concentrations: longitudinal and cross-sectional assessments

    Directory of Open Access Journals (Sweden)

    Loignon Maude

    2012-02-01

    Full Text Available Abstract Background Several lines of evidence suggest that retinoids (retinol-ROL or vitamin A, and its active metabolites, retinoic acids-RAs play important pathogenic roles in HIV infection and combination antiretroviral therapy (cART-related events. We previously reported that antiretrovirals alter RAs synthesis in vitro. We hypothesised that in vivo serum retinoid concentrations are affected by both cART and HIV infection. This might explain several clinical and laboratory abnormalities reported in HIV-infected patients receiving cART. Methods The effects of optimal cART and chronic HIV on serum retinoids were firstly assessed longitudinally in 10 HIV-infected adults (group1 = G1: twice while on optimal cART (first, during long-term and second, during short term cART and twice during 2 cART interruptions when HIV viral load (VL was detectable. Retinoid concentrations during optimal long term cART in G1 were compared with cross-sectional results from 12 patients (G2 with suboptimal cART (detectable VL and from 28 healthy adults (G3. Serum retinoids were measured by HPLC with ultraviolet detection. Retinoid concentrations were correlated with VL, CD4+ T- cell count and percentages, CD8+38+ fluorescence, triglycerides, cholesterol and C-peptide serum levels. Results During optimal cART, G1 participants had drastically reduced RAs (0.5 ± 0.3 μg/dL; P + T- cell count, CD8+38+ fluorescence, VL. ROL correlated with triglycerides and cholesterol in G1 (rs = 0.8; P = 0.01. Conclusions Serum RAs levels are significantly diminished by cART, whereas ROL concentrations significantly decreased during uncontrolled HIV infection but augmented with optimal cART. These alterations in retinoid concentrations may affect the expression of retinoid-responsive genes involved in metabolic, hormonal and immune processes and be responsible for some adverse events observed in HIV-infected persons treated with antiretrovirals. Further studies should assess

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... late 1980s, research has shown that treating drug abuse is an effective way to prevent the spread of HIV. Drug abusers in treatment stop or reduce their drug use and related risk behaviors, including drug injection and unsafe sexual practices. Drug treatment programs also serve an important ...

  18. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naive HIV-mono-infected and HIV/HCV-co-infected Chinese.

    Directory of Open Access Journals (Sweden)

    Lai He

    Full Text Available Human Immunodeficiency Virus (HIV infection and the resultant Acquired Immunodeficiency Syndrome (AIDS epidemic are major global health challenges; hepatitis C virus (HCV co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27, a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  19. Treating depression in terminally ill patients can optimize their physical comfort at the end of life and provide them the opportunity to confront and prepare for death.

    Science.gov (United States)

    Braun, Ursula K; Kunik, Mark E; Pham, Catherine

    2008-06-01

    The dying process is characterized by feelings of sadness and fear. It is normal for patients at the end of life to worry and grieve the loss of their health. However, when these feelings become excessive and interfere with all aspects of the patient's life, they are abnormal responses to the stress of terminal illness. Screening for depression in terminally ill patients can optimize their physical comfort at the end of life and provide them the opportunity to confront and prepare for death.

  20. "If You Tell People That You Had Sex with a Fellow Man, It Is Hard to Be Helped and Treated": Barriers and Opportunities for Increasing Access to HIV Services among Men Who Have Sex with Men in Uganda.

    Directory of Open Access Journals (Sweden)

    Rhoda K Wanyenze

    Full Text Available Despite the high HIV prevalence among men who have sex with men (MSM in sub-Saharan Africa, little is known about their access to HIV services. This study assessed barriers and opportunities for expanding access to HIV services among MSM in Uganda.In October-December 2013, a cross-sectional qualitative study was conducted in 12 districts of Uganda. Semi-structured in-depth interviews were conducted with 85 self-identified MSM by snowball sampling and 61 key informants including HIV service providers and policy makers. Data were analysed using manifest content analysis and Atlas.ti software.Three quarters of the MSM (n = 62, 72.9% were not comfortable disclosing their sexual orientation to providers and 69 (81.1% felt providers did not respect MSM. Half (n = 44, 51.8% experienced difficulties in accessing health services. Nine major barriers to access were identified, including: (i unwelcoming provider behaviours; (ii limited provider skills and knowledge; (iii negative community perceptions towards MSM; (iv fear of being exposed as MSM; (v limited access to MSM-specific services; (vi high mobility of MSM, (vii lack of guidelines on MSM health services; viii a harsh legal environment; and ix HIV related stigma. Two-thirds (n = 56, 66% participated in MSM social networks and 86% of these (48 received support from the networks to overcome barriers to accessing services.Negative perceptions among providers and the community present barriers to service access among MSM. Guidelines, provider skills building and use of social networks for mobilization and service delivery could expand access to HIV services among MSM in Uganda.

  1. Decrease in immune activation in HIV-infected patients treated with highly active antiretroviral therapy correlates with the function of hematopoietic progenitor cells and the number of naive CD4+ cells

    DEFF Research Database (Denmark)

    Nielsen, S D; Sørensen, T U; Ersbøll, A K;

    2000-01-01

    determined. During the study period, the naive CD4+ count and the cloning efficiency increased significantly. Immune activation was found in HIV-infected patients and decreased during HAART. The level of immune activation correlated negatively with both the naive CD4+ count and the function of progenitor...... cells. A negative correlation was found between apoptosis and the naive CD4+ count. Alterations in cytokine production during HAART or correlation between cytokine production and the naive CD4+ count or the cloning efficiency of progenitor cells were not detected. In conclusion, immune activation in HIV...

  2. Optimization of thermophysical properties of Pacific white shrimp (Litopenaeus vannamei) previously treated with freezing-point regulators using response surface methodology

    OpenAIRE

    Wang, Liang; Liu, Zunying; Zhao, Yuanhui; Dong, Shiyuan; Zeng, Mingyong; Yang, HuiCheng

    2014-01-01

    Three freezing-point regulators (glycine, sodium chloride and D-sorbitol) were employed to optimize thermophysical properties of Pacific white shrimp (Litopenaeus vannamei) using response surface methodology (RSM). The independent variables were glycine content (0.250–1.250 %), sodium chloride content (0.500–2.500 %) and D-sorbitol content (0.125–0.625 %) and analysis of variance showed that the effects of glycine, sodium chloride and D-sorbitol on the thermophysical properties were statistic...

  3. SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Yu, V; Nguyen, D; Pajonk, F; Kaprealian, T; Kupelian, P; Steinberg, M; Low, D; Sheng, K [Department of Radiation Oncology, UCLA, Los Angeles, CA (United States)

    2015-06-15

    Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to explore the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work

  4. Formative research to optimize respondent-driven sampling surveys among hard-to-reach populations in HIV behavioral and biological surveillance: lessons learned from four case studies.

    Science.gov (United States)

    Johnston, Lisa Grazina; Whitehead, Sara; Simic-Lawson, Milena; Kendall, Carl

    2010-06-01

    Respondent-driven sampling (RDS) is widely adopted as a method to assess HIV and other sexually transmitted infection prevalence and risk factors among hard-to-reach populations. Failures to properly implement RDS in several settings could potentially have been avoided, had formative research been conducted. However, to date there is no published literature addressing the use of formative research in preparing for RDS studies. This paper uses examples from Banja Luka, Bosnia and Herzegovina; Bangkok, Thailand; Podgorica, Montenegro; and St Vincent's and Grenadine Islands, Eastern Caribbean; among populations of men who have sex with men, female sex workers, and injecting drug users to describe how formative research was used to plan, implement, and predict outcomes of RDS surveys and to provide a template of RDS-specific questions for conducting formative research in preparation for RDS surveys. We outline case studies to illustrate how formative research may help researchers to determine whether RDS methodology is appropriate for a particular population and sociocultural context, and to decide on implementation details that lead to successful study outcomes.

  5. Optimization of effects-assessment of greenside darter (Etheostoma blennioides) exposed to tertiary treated municipal wastewater based on seasonal changes of reproductive endpoints.

    Science.gov (United States)

    Tetreault, Gerald R; Bennett, Charles J; Servos, Mark Roy; McMaster, Mark E

    2014-05-01

    The present study describes the seasonal changes in reproductive endpoints of the greenside darter (Etheostoma blennioides) and its implications for environmental monitoring. Fish collections conducted at the appropriate time for the site-specific sentinel fish species can provide a wide variety of population-level information including recruitment, reproduction, and energy storage. The objectives of the present study were to: 1) characterize seasonal changes in reproductive endpoints of the greenside darter (both sexes) to determine the appropriate period for monitoring of this sentinel species; and 2) evaluate the effect of exposure of this sentinel species to tertiary treated municipal effluent at the selected monitoring period. Based on the selected parameters (gonadosomatic index [GSI], liver somatic index [LSI], condition factor, and in vitro gonadal steroid production [testosterone (T) in both sexes; estradiol (E2) in females; and 11-ketotestosterone (11KT) in males]), the present study provides evidence for the value of collecting darters during recrudescence (late fall/early winter) to ensure temporal stability, minimum variability, and stable steroid production capacity. Darters exposed to tertiary treated municipal effluent tended to be larger and heavier relative to reference fish but did not demonstrate any consistent responses in terms of condition or relative liver size. No effect on gonadal development was observed, even though these tertiary-effluent-exposed fish demonstrated a significant reduction in the ability to produce hormones. The present study suggests that although fish exposed to tertiary treated effluent demonstrate no population-level effects, they are still responding at a physiological level. Documentation of the reproductive cycle of sentinel species allows for selection of the most appropriate sampling period to reduce variability and greatly enhances the reliability and interpretation of biological responses.

  6. HIV-related stigma, social norms, and HIV testing in Soweto and Vulindlela, South Africa: National Institutes of Mental Health Project Accept (HPTN 043).

    Science.gov (United States)

    Young, Sean D; Hlavka, Zdenek; Modiba, Precious; Gray, Glenda; Van Rooyen, Heidi; Richter, Linda; Szekeres, Greg; Coates, Thomas

    2010-12-15

    HIV testing is necessary to curb the increasing epidemic. However, HIV-related stigma and perceptions of low likelihood of societal HIV testing may reduce testing rates. This study aimed to explore this association in South Africa, where HIV rates are extraordinarily high. Data were taken from the Soweto and Vulindlela, South African sites of Project Accept, a multinational HIV prevention trial. Self-reported HIV testing, stigma, and social norms items were used to study the relationship between HIV testing, stigma, and perceptions about societal testing rates. The stigma items were broken into 3 factors: negative attitudes, negative perceptions about people living with HIV, and perceptions of fair treatment for people living with HIV (equity). Results from a univariate logistic regression suggest that history of HIV testing was associated with decreased negative attitudes about people living with HIV/AIDS, increased perceptions that people living with HIV/AIDS experience discrimination, and increased perceptions that people with HIV should be treated equitably. Results from a multivariate logistic regression confirm these effects and suggest that these differences vary according to sex and age. Compared with people who had never tested for HIV, those who had previously tested were more likely to believe that the majority of people have tested for HIV. Data suggest that interventions designed to increase HIV testing in South Africa should address stigma and perceptions of societal testing.

  7. STD Clinic Patients' Awareness of Non-AIDS Complications of HIV Infection

    Science.gov (United States)

    Castro, José Guillermo; Granovsky, Inna; Jones, Deborah; Weiss, Stephen M.

    2016-01-01

    Participants were recruited from a sexually transmitted disease (STD) clinic in Florida and were assessed regarding the knowledge and awareness of non-AIDS conditions associated with HIV infection. Questionnaires were administered before and after a brief information session on non-AIDS conditions associated with HIV infection. Participants included men (n = 46) and women (n = 51). Prior to the information session, at baseline, only 34% of the participants were worried about HIV infection. Most participants (82%) agreed that HIV could be treated with antiretroviral therapy (ART), while only 38% were aware that HIV-associated conditions cannot be easily treated with ART. After the information session, almost all participants reported they were concerned regarding the risk of HIV infection. High-risk patients may have limited knowledge about the consequences of HIV infection beyond the traditional AIDS-associated conditions. Increased awareness of these less known consequences of HIV infection may decrease the potential for complacency regarding acquiring HIV infection. PMID:25331221

  8. Probiotics Differently Affect Gut-Associated Lymphoid Tissue Indolamine-2,3-Dioxygenase mRNA and Cerebrospinal Fluid Neopterin Levels in Antiretroviral-Treated HIV-1 Infected Patients: A Pilot Study

    Science.gov (United States)

    Scagnolari, Carolina; Corano Scheri, Giuseppe; Selvaggi, Carla; Schietroma, Ivan; Najafi Fard, Saeid; Mastrangelo, Andrea; Giustini, Noemi; Serafino, Sara; Pinacchio, Claudia; Pavone, Paolo; Fanello, Gianfranco; Ceccarelli, Giancarlo; Vullo, Vincenzo; d’Ettorre, Gabriella

    2016-01-01

    Recently the tryptophan pathway has been considered an important determinant of HIV-1 infected patients’ quality of life, due to the toxic effects of its metabolites on the central nervous system (CNS). Since the dysbiosis described in HIV-1 patients might be responsible for the microbial translocation, the chronic immune activation, and the altered utilization of tryptophan observed in these individuals, we speculated a correlation between high levels of immune activation markers in the cerebrospinal fluid (CSF) of HIV-1 infected patients and the over-expression of indolamine-2,3-dioxygenase (IDO) at the gut mucosal surface. In order to evaluate this issue, we measured the levels of neopterin in CSF, and the expression of IDO mRNA in gut-associated lymphoid tissue (GALT), in HIV-1-infected patients on effective combined antiretroviral therapy (cART), at baseline and after six months of probiotic dietary management. We found a significant reduction of neopterin and IDO mRNA levels after the supplementation with probiotic. Since the results for the use of adjunctive therapies to reduce the levels of immune activation markers in CSF have been disappointing so far, our pilot study showing the efficacy of this specific probiotic product should be followed by a larger confirmatory trial. PMID:27689995

  9. Periodontal status of HIV-infected patients undergoing antiretroviral therapy compared to HIV-therapy naive patients: a case control study

    National Research Council Canada - National Science Library

    Fricke, Ulrich; Geurtsen, Werner; Staufenbiel, Ingmar; Rahman, Alexander

    2012-01-01

    ... with human immunodeficiency virus (HIV). The objective of the present investigation was to determine possible differences in periodontal parameters between antiretroviral treated and untreated patients...

  10. Optimization of Enzyme-Mediated Calcite Precipitation as a Soil-Improvement Technique: The Effect of Aragonite and Gypsum on the Mechanical Properties of Treated Sand

    Directory of Open Access Journals (Sweden)

    Heriansyah Putra

    2017-02-01

    Full Text Available The effectiveness of magnesium as a substitute material in enzyme-mediated calcite precipitation was evaluated. Magnesium sulfate was added to the injecting solution composed of urea, urease, and calcium chloride. The effect of the substitution on the amount of precipitated materials was evaluated through precipitation tests. X-ray powder diffraction and scanning electron microscopy analyses were conducted to examine the mineralogical morphology of the precipitated minerals and to determine the effect of magnesium on the composition of the precipitated materials. In addition to calcite, aragonite and gypsum were formed as the precipitated materials. The effect of the presence of aragonite and gypsum, in addition to calcite, as a soil-improvement technique was evaluated through unconfined compressive strength tests. Soil specimens were prepared in polyvinyl chloride cylinders and treated with concentration-controlled solutions, which produced calcite, aragonite, and gypsum. The mineralogical analysis revealed that the low and high concentrations of magnesium sulfate effectively promoted the formation of aragonite and gypsum, respectively. The injecting solutions which produced aragonite and calcite brought about a significant improvement in soil strength. The presence of the precipitated materials, comprising 10% of the soil mass within a treated sand, generated a strength of 0.6 MPa.

  11. Treatment optimization in low- and middle-income countries

    Directory of Open Access Journals (Sweden)

    Cooper D

    2012-11-01

    Full Text Available The unprecedented, successful collaborative international effort to provide universal access to HIV care, including effective antiretroviral therapy (ART, has reached a critical time point. The global economic downturn, changing donor priorities and competing priorities in the health sector threaten the capacity of various agencies to maintain support for the continued scale-up of access toward the UN General Assembly-agreed target of 15 million people with HIV/AIDS receiving ART by 2015. This aspiration has recently received added impetus as we have come to understand that treatment acts as prevention by reducing the infectiousness of treated individuals. It is now necessary to review the elements of the success to date, in order to be able to do more with less. These elements include efforts to optimize delivery of HIV care, including ART, in low- and middle-income countries (LMIC; the emergence of new agents and drug classes which have simplified HIV treatment and made broader successful management more achievable; and changes to commencement protocols. Recent studies have indicated that earlier commencement of HIV therapy is beneficial, leading to changes in the recommended ART initiation threshold in LMIC to <350 CD4 T cells/µL. Studies currently underway are investigating approaches to second-line ART in LMIC. The results from these studies will better inform the rollout of effective second-line therapy. In addition, the financial cost of ART makes optimization of dosing an important consideration in LMIC, in order to maximize effectiveness while limiting costs. ART monitoring is also an important priority in LMIC. Efforts to develop simple and reliable technologies that can provide rapid results in the field are underway. The final priority is ope