Full Text Available Objective : The main objective of the current study is to monitor the auditory status in a group of adults with AIDS, receiving Highly Active Antiretroviral Therapy (HAART (3TC -lamivudine, D4T - stavudine, and efavirenz in a hospital outpatient clinic in Gauteng. A total sample of 54 adults (between the ages of 18 and 50 years in the experimental group and 16 in the control group were assessed prospectively following a repeated measures design. All participants were assessed at baseline at three months, and at six months into the treatment. Materials and Methods : The participants underwent case history interviews and medical record reviews, otoscopy, and tympanometry, as well as conventional pure tone audiometry and distortion product otoacoustic emission testing. Both descriptive and inferential statistics were used to analyze the data. Results : On audiological monitoring, statistically significant changes (P<0.05 were established, only in the experimental group, for pure tone audiometry - with clinically significant changes found at high frequencies. Statistically significant changes with clinically significant changes were obtained for distortion product otoacoustic emissions (DPOAEs in the experimental group, particularly at high frequencies - implying subclinical hearing function changes; while lack of statistically significant changes with no clinically significant changes were found in the control group. The subclinical hearing changes in the experimental group were also evident in the findings of the subclinical hearing loss group, who, although they had normal pure tone function after six months of follow up, presented with clinical changes on DPOAEs at 6 and 8 kHz. Conclusions : Findings highlight the need for closer monitoring of the effects of antiretroviral drugs (ARVs on hearing, through the use of more sensitive tools of assessment when conducting drug trials.
Nilssen, D E; Øktedalen, O; Brandtzaeg, P
Background: It is well documented that highly active antiretroviral therapy (HAART) restores systemic immunity to human immunodeficiency virus (HIV) but the effect of this treatment on the mucosal immune system is less clear.
ZHOU Hua-ying; ZHENG Yu-huang; ZHANG Chun-ying; DING Pei-pei; ZOU Wen
@@ Antiretroviral therapy is a key determinant in the treatment and prevention of human immunodeficiency virus (HIV) infection. Initial treatment for patients with HIV infection generally includes two nucleoside reverse transcriptase inhibitors (NRTI) and a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI). The combination antiretroviral therapy (refers to highly active antiretroviral therapy or HAART) showed a significant effect upon reducing morbidity and mortality of HIV disease. Cao and colleagues1 began the clinical application of HAART in 1999 and completed the first clinical trial in China using a combination of two NRTIs and one PI. The result in using combivir (AZT+3TC) and indinavir (2 NRTIs+1 PI) are consistent with those reported in the literature.2 In this study, we report the first virological and immunological outcomes in HIV infected Chinese patients treated with a combination of didanosine, stavudine and nevirapine (2 NRTIs+1 NNRTI) for 52 weeks.
Takeshi Kato Segundo; Giovanna Ribeiro Souto; Ricardo Alves Mesquita; Fernando Oliveira Costa
The aim of this study was to assess and compare quantitatively the presence of S100+ Langerhans cells (LC) by immunochemistry techniques in HIV+ and HIV- gingivitis and periodontitis subjects. Additionally, it aimed to evaluate the correlation among densities of these cells with CD4+ and CD8+ T cells, and viral load levels in HIV+ subjects, all using Highly Active Antiretroviral Therapy (HAART). The samples were allocated into four groups: 1) 15 subjects with moderate chronic periodontitis (M...
Brewinski, Margaret; Megazzini, Karen; Freimanis Hance, Laura; Cruz, Miguel Cashat; Pavia-Ruz, Noris; Della Negra, Marinella; Ferreira, Flavia Gomes Faleiro; Marques, Heloisa; Hazra, Rohan
In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercho...
Castilho, Jessica L; Melekhin, Vlada V.; Sterling, Timothy R
To assess sex disparities in AIDS clinical and laboratory outcomes in the highly active antiretroviral therapy (HAART) era we conducted a systematic review of the published literature on mortality, disease progression, and laboratory outcomes among persons living with HIV and starting HAART. We performed systematic PubMed and targeted bibliographic searches of observational studies published between January, 1998, and November, 2013, that included persons starting HAART and reported analyses ...
Full Text Available Rebecca Pavlos, Elizabeth J PhillipsInstitute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, AustraliaAbstract: Antiretroviral therapy (ART has evolved considerably over the last three decades. From the early days of monotherapy with high toxicities and pill burdens, through to larger pill burdens and more potent combination therapies, and finally, from 2005 and beyond where we now have the choice of low pill burdens and once-daily therapies. More convenient and less toxic regimens are also becoming available, even in resource-poor settings. An understanding of the individual variation in response to ART, both efficacy and toxicity, has evolved over this time. The strong association of the major histocompatibility class I allele HLA-B*5701 and abacavir hypersensitivity, and its translation and use in routine HIV clinical practice as a predictive marker with 100% negative predictive value, has been a success story and a notable example of the challenges and triumphs in bringing pharmacogenetics to the clinic. In real clinical practice, however, it is going to be the exception rather than the rule that individual biomarkers will definitively guide patient therapy. The need for individualized approaches to ART has been further increased by the importance of non-AIDS comorbidities in HIV clinical practice. In the future, the ideal utilization of the individualized approach to ART will likely consist of a combined approach using a combination of knowledge of drug, virus, and host (pharmacogenetic and pharmacoecologic [factors in the individual's environment that may be dynamic over time] information to guide the truly personalized prescription. This review will focus on our knowledge of the pharmacogenetics of the efficacy and toxicity of currently available antiretroviral agents and the current and potential utility of such information and approaches in present and future HIV clinical care.Keywords: HIV
Pravin S. Rathod; Praveenkumar T Patil; Rekha P. Lohar; A.W. Patil
Background: Highly active anti-retroviral therapy (HAART) became the keystone of national AIDS program. There is lack of awareness and inadequate training about drug safety monitoring among health care professionals in India. Hence, the present study was carried out to study current trends in HAART and pattern of associated adverse drug reactions. Methods: A retrospective observational study was conducted at an anti-retroviral therapy (ART) Centre. A total of 151 HIV/AIDS Patients (old and...
Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L; Gerstoft, Jan; Ostrowski, Sisse R
The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART).......The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART)....
Sashindran, V K; Chauhan, Rajeev
HIV/AIDS has been an extremely difficult pandemic to control. However, with the advent of antiretroviral therapy (ART), HIV has now been transformed into a chronic illness in patients who have continued treatment access and excellent long-term adherence. Existing indications for ART initiation in asymptomatic patients were based on CD4 levels; however, recent evidence has broken the shackles of CD4 levels. Early initiation of ART in HIV patients irrespective of CD4 counts can have profound positive impact on morbidity and mortality. Early initiation of ART has been found not only beneficial for patients but also to community as it reduces the risk of transmission. There have been few financial concerns about providing ART to all HIV-positive people but various studies have proven that early initiation of ART not only proves to be cost-effective but also contributes to economic and social growth of community. A novel multidisciplinary approach with early initiation and availability of ART at its heart can turn the tide in our favor in future. Effective preexposure prophylaxis and postexposure prophylaxis can also lower transmission risk of HIV in community. New understanding of HIV pathogenesis is opening new vistas to cure and prevention. Various promising candidate vaccines and drugs are undergoing aggressive clinical trials, raising optimism for an ever-elusive cure for HIV. This review describes various facets of tectonic shift in management of HIV. PMID:26900224
Full Text Available Injection drug users (IDUs continue to comprise a major risk group for HIV infection throughout the world and represent the focal population for HIV epidemics in Asia and Eastern Europe/Russia. HIV prevention programs have ranged from HIV testing and counseling, education, behavioral and network interventions, drug abuse treatment, bleach disinfection of needles, needle exchange and expanded syringe access, as well as reducing transition to injection and primary substance abuse prevention. With the advent of highly active antiretroviral therapy (HAART in 1996, dramatic clinical improvements have been seen. In addition, the treatment's impact on reducing HIV viral load (and therefore transmission by all routes provides a stronger rationale for an expansion of the focus on prevention to emphasize early identification and treatment of HIV infected individuals. However, treatment of IDUs has many challenges including adherence, resistance and relapse to high risk behaviors, all of which impact issues of access and ultimately effectiveness of potent antiretroviral treatment. A major current challenge in addressing the HIV epidemic revolves around an appropriate approach to HIV treatment for IDUs.
Full Text Available Injection drug users (IDUs continue to comprise a major risk group for HIV infection throughout the world and represent the focal population for HIV epidemics in Asia and Eastern Europe/Russia. HIV prevention programs have ranged from HIV testing and counseling, education, behavioral and network interventions, drug abuse treatment, bleach disinfection of needles, needle exchange and expanded syringe access, as well as reducing transition to injection and primary substance abuse prevention. With the advent of highly active antiretroviral therapy (HAART in 1996, dramatic clinical improvements have been seen. In addition, the treatment's impact on reducing HIV viral load (and therefore transmission by all routes provides a stronger rationale for an expansion of the focus on prevention to emphasize early identification and treatment of HIV infected individuals. However, treatment of IDUs has many challenges including adherence, resistance and relapse to high risk behaviors, all of which impact issues of access and ultimately effectiveness of potent antiretroviral treatment. A major current challenge in addressing the HIV epidemic revolves around an appropriate approach to HIV treatment for IDUs.
Tramarin, A; Parise, N; Campostrini, S; Yin, DD; Postma, MJ; Lyu, R; Grisetti, R; Capetti, A; Cattelan, AM; Di Toro, MT; Mastroianni, A; Pignattari, E; Mondardini, [No Value; Calleri, G; Raise, E; Starace, F
Diarrhea is a common symptom that many HIV patients experience either as a consequence of HIV infection or of highly active antiretroviral therapy (HAART). A multicenter, prospective observational study was conducted in 11 AIDS clinics in Italy to determine the effect of diarrhea on health-related q
Nieuwkerk, PT; Sprangers, MAG; Burger, DM; Hoetelmans, RMW; Hugen, PWH; Danner, SA; van der Ende, Marchina E.; Schneider, MME; Schrey, G; Meenhorst, PL; Sprenger, HG; Kauffmann, RH; Jambroes, M; Chesney, MA; de Wolf, F; Lange, JMA
Background: Adherence to highly active antiretroviral therapy (HAART) for human immunodeficiency syndrome type 1 (HIV-1) infection is essential to sustain viral suppression and prevent drug resistance. We investigated adherence to HAART among patients in a clinical cohort study. Methods: Patients re
Lundgren, Jens Dilling; Mocroft, Amanda; Gatell, Jose M; Ledergerber, Bruno; D'Arminio Monforte, Antonella; Hermans, Philippe; Goebel, Frank-Detlef; Blaxhult, Anders; Kirk, Ole; Phillips, Andrew N; NN, NN
The risk of clinical progression for human immunodeficiency virus (HIV)-infected persons receiving treatment with highly active antiretroviral therapy (HAART) is poorly defined. From an inception cohort of 8457 HIV-infected persons, 2027 patients who started HAART during prospective follow-up wer...
Price, Jennifer C; Seaberg, Eric C; Phair, John P; Witt, Mallory D; Koletar, Susan L; Thio, Chloe L
To determine the impact of highly active antiretroviral therapy (HAART) on liver disease, we analyzed changes in the aspartate aminotransferase to platelet ratio index (APRI) pre- and post-HAART initiation among 441 HIV-monoinfected and 53 HIV-viral hepatitis-coinfected men. Before HAART, APRI increased 17% and 34% among the HIV-monoinfected and coinfected men, respectively. With HAART initiation, APRI decreased significantly in men who achieved HIV RNA of <500 copies per milliliter: 16% for HIV-monoinfected and 22% for coinfected men. Decreases in APRI were dependent on HIV suppression. This protective effect of HAART decreased after 2 years, particularly in the HIV-monoinfected men. PMID:26945179
Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum
This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients. PMID:15255240
The outcome of HIV infection has improved since the widespread availability of highly active antiretroviral therapy (HAART). Some patients, however, develop a clinical and radiological deterioration following initiation of HAART due to either the unmasking of occult subclinical infection or an enhanced inflammatory response to a treated infection. This phenomenon is believed to result from the restored ability to mount an immune response and is termed immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution disease. IRIS is widely reported in the literature in adult patients, most commonly associated with mycobacterial infections. There is, however, a paucity of data documenting the radiological findings of IRIS in children. Radiologists need to be aware of this entity. As a diagnosis of exclusion it is essential that the radiological findings be assessed in the context of the clinical presentation. This article reviews the common clinical and radiological manifestations of IRIS in HIV-infected children. (orig.)
Kilborn, Tracy [Red Cross War Memorial Children' s Hospital, Department of Paediatric Radiology, Cape Town (South Africa); Zampoli, Marco [Red Cross War Memorial Children' s Hospital, Department of Paediatric Pulmonology, Cape Town (South Africa)
The outcome of HIV infection has improved since the widespread availability of highly active antiretroviral therapy (HAART). Some patients, however, develop a clinical and radiological deterioration following initiation of HAART due to either the unmasking of occult subclinical infection or an enhanced inflammatory response to a treated infection. This phenomenon is believed to result from the restored ability to mount an immune response and is termed immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution disease. IRIS is widely reported in the literature in adult patients, most commonly associated with mycobacterial infections. There is, however, a paucity of data documenting the radiological findings of IRIS in children. Radiologists need to be aware of this entity. As a diagnosis of exclusion it is essential that the radiological findings be assessed in the context of the clinical presentation. This article reviews the common clinical and radiological manifestations of IRIS in HIV-infected children. (orig.)
Sadikalmahdi Hussen Abdella
Full Text Available Background: The combination of antiretroviral therapy is the corner stone of management of patients with human immune deficiency virus infection. Although antiretroviral therapy can reduce viral load to undetectable level, improve the immunity and prolong survival of patients, antiretroviral drugs are associated with many adverse effects that may be severe and affect patient adherence and quality of life. Aims : The aim of this study was to assess management strategies under taken in patient′s experienced common adverse effects of highly active antiretroviral therapy in Goba Hospital antiretroviral clinic. Patients and Methods: A cross sectional study of patient record chart of patients who had follow-up during data collection period was done followed by patient interview. Data was filled on well structured questionnaire and analyzed using SPSS for window version 16.0. Results: The common adverse effects were Rash (48.8%, Peripheral neuropathy (36.9% and Anemia (20.24%. The rate of management was 39.3%. Pyridoxine (36.8% was commonly prescribed drug for management of Peripheral neuropathy. Chlorphenarimine gel and Iron gluconate were common drugs for management of Rash and Anemia respectively. Use of traditional healers (57.7% was leading reason for non-management. Conclusion: Rate of management for common adverse effect is low. Education should be given on adverse effects for patients.
Montoya Carlos J
Full Text Available Abstract Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection. Methods/design Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients or placebo (55 patients. Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals. Discussion Preliminary descriptive studies have suggested that statins (lovastatin may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on
Full Text Available Antiretroviral therapy (ART has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in disease progression. The various factors affecting success of ART are social aspects like motivation to begin therapy, ability to adhere to therapy, lifestyle pattern, financial support, family support, pros and cons of starting therapy and pharmacological aspects like tolerability of the regimen, availability of the drugs. Also, the regimen′s pill burden, dosing frequency, food requirements, convenience, toxicity and drug interaction profile compared with other regimens are to be considered before starting ART. The lack of trust between clinician and patient, active drug and alcohol use, active mental illness (e.g. depression, lack of patient education and inability of patients to identify their medications, lack of reliable access to primary medical care or medication are considered to be predictors of inadequate adherence. Interventions at various levels, viz. patient level, medication level, healthcare level and community level, boost adherence and overall outcome of ART.
van der Merwe Karin
Full Text Available Abstract Background Use of highly active antiretroviral therapy (HAART, a triple-drug combination, in HIV-infected pregnant women markedly reduces mother to child transmission of HIV and decreases maternal morbidity. However, there remains uncertainty about the effects of in utero exposure to HAART on foetal development. Methods Our objectives were to investigate whether in utero exposure to HAART is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV disease. A retrospective observational study was performed on women with CD4 counts ≤250 cells/mm3 attending antenatal antiretroviral clinics in Johannesburg between October 2004 and March 2007. Low birth weight ( Results Among HAART-unexposed infants, 27% (60/224 were low birth weight compared with 23% (90/388 of early HAART-exposed (exposed 3 increase, 95% CI 0.45-0.71, p 3 increase, 95% CI 0.55-0.85, p = 0.001. HAART exposure was associated with an increased preterm birth rate (15%, or 138 of 946, versus 5%, or seven of 147, in unexposed infants, p = 0.001, with early nevirapine and efavirenz-based regimens having the strongest associations with preterm birth (AOR 5.4, 95% CI 2.1-13.7, p Conclusions In this immunocompromised cohort, in utero HAART exposure was not associated with low birth weight. An association between NNRTI-based HAART and preterm birth was detected, but residual confounding is plausible. More advanced immunosuppression was a risk factor for low birth weight and preterm birth, highlighting the importance of earlier HAART initiation in women to optimize maternal health and improve infant outcomes.
Killian, M. Scott; Roop, Jeremy; Ng, Sharon; Frederick M Hecht; Levy, Jay A.
CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course. In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment. CD8+ lymphocytes from subjects with untreated primary HIV-1 in...
Faria Farhat; Jhansi Gajjala; Robert Delapenha; Syeda Mehreen Zahra; Samad Rasul
Graves' disease after the initiation of highly active antiretroviral therapy (HAART) in certain HIV-1-infected individuals has been described as an immune reconstitution inflammatory syndrome (IRIS). This phenomenon should be suspected in individuals who present with clinical deterioration and a presentation suggestive of hyperthyroidism despite good virological and immunological response to HAART. Signs and symptoms of hyperthyroidism may be discrete or overt and typically develop 8–33 month...
Popovic, Mikulas; Tenner-Racz, Klara; Pelser, Colleen; Stellbrink, Hans-Jurgen; van Lunzen, Jan; Lewis, George; Kalyanaraman, Vaniambadi S.; Gallo, Robert C.; Racz, Paul
Here we report a long-term persistence of HIV-1 structural proteins and glycoproteins in germinal centers (GCs) of lymph nodes (LNs) in the absence of detectable virus replication in patients under highly active antiretroviral therapy (HAART). The persistence of viral structural proteins and glycoproteins in GCs was accompanied by specific antibody responses to HIV-1. Seven patients during the chronic phase of HIV-1 infection were analyzed for the presence of the capsid protein (HIV-1p24), ma...
HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts 100 cells/μL for a minimum of three months. Despite HAART, patients with a CD4 count PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients. PMID:24756590
Kaio, Daniella J. Itinoseki; Rondó, Patricia Helen C.; Luzia, Liania Alves; Souza, José Maria P.; Firmino, Aline Vale; Santos, Sigrid Sousa
HIV/AIDS patients are probably more predisposed to vitamin E deficiency, considering that they are more exposed to oxidative stress. Additionally, there are an extensive number of drugs in the highly active antiretroviral therapy (HAART) regimens that may interfere with vitamin E concentrations. The objective of this study was to compare serum concentrations of alpha-tocopherol in 182 HIV/AIDS patients receiving different HAART regimens. The patients were divided into three groups according to regimen: nucleoside analog reverse-transcriptase inhibitors (NRTIs) + non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs); NRTIs + protease inhibitors + ritonavir; NRTIs + other classes. Alpha-tocopherol was assessed by high-performance liquid chromatography. Multiple linear regression analysis was used to evaluate the effects of HAART regimen, time of use, and compliance with the regimen on alpha-tocopherol concentrations. Alpha-tocopherol concentrations were on average 4.12 μmol/L lower for the NRTIs + other classes regimen when compared to the NRTIs + NNRTIs regimen (p = 0.037). A positive association (p < 0.001) was observed between alpha-tocopherol and cholesterol concentrations, a finding due, in part, to the relationship between liposoluble vitamins and lipid profile. This study demonstrated differences in alpha-tocopherol concentrations between patients using different HAART regimens, especially regimens involving the use of new drugs. Long-term prospective cohort studies are needed to monitor vitamin E status in HIV/AIDS patients since the beginning of treatment. PMID:25225815
Takeshi Kato Segundo
Full Text Available The aim of this study was to assess and compare quantitatively the presence of S100+ Langerhans cells (LC by immunochemistry techniques in HIV+ and HIV- gingivitis and periodontitis subjects. Additionally, it aimed to evaluate the correlation among densities of these cells with CD4+ and CD8+ T cells, and viral load levels in HIV+ subjects, all using Highly Active Antiretroviral Therapy (HAART. The samples were allocated into four groups: 1 15 subjects with moderate chronic periodontitis (MCP, HIV+; 2 15 subjects with MCP, HIV-; 3 10 subjects with gingivitis (G, HIV+; and 4 10 subjects with G, HIV-. The S100+ cells were assessed in the pocket epithelium, gingival epithelium, and lamina propria. A statistically significant increase of total S100+ cells in HIV+ periodontitis subjects was observed in relation to HIV- periodontitis subjects. No increase of S100+ cells with increased inflammation was observed. No statistically significant correlation among S100+ cells and blood levels of CD4, CD8, and viral load was observed. In conclusion, the use of HAART can aid in achieving viral loads, and it is suggested that it may prevent the destruction of the LC.
Full Text Available Franco Maggiolo,1 Giorgio L Colombo,2,3 Sergio Di Matteo,3 Giacomo M Bruno,3 Noemi Astuti,1 Elisa Di Filippo,1 Giulia Masini,1 Claudia Bernardini1 1Division of Infectious Diseases, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; 2University of Pavia, Department of Drug Sciences, Pavia, Italy; 3SAVE Studi Analisi Valutazioni Economiche, Milan, Italy Objectives: Costs may play a role in deciding how and when to start highly active antiretroviral therapy (HAART in a naïve patient. The aim of the present study was to assess the cost- effectiveness of treatment with HAART in a large clinical cohort of naïve adults to determine the potential role of single-tablet regimens in the management of patients with human immunodeficiency virus (HIV. An incremental cost-effectiveness ratio analysis was performed, including a quality-adjusted life year approach. Results: In total, 741 patients (females comprising 25.5% were retrospectively included. The mean age was 39 years, the mean CD4 cell count was 266 cells/µL, and the mean viral load was 192,821 copies/mL. The most commonly used backbone was tenofovir + emtricitabine (77.6%; zidovudine + lamivudine was used in 10%, lamivudine + abacavir in 3%, and other nucleoside reverse transcriptase inhibitor (NRTI or NRTI-free regimens in 9.4% of patients. NNRTIs were used in 52.8% of cases, boosted protease inhibitors in 44.1%, and unboosted protease inhibitors and integrase inhibitors in 0.7% and 2.4%, respectively. Starting therapy at CD4 >500 cells/µL and CD4 351–500 cells/µL rather than at <201 cells/µL was the more cost-effective approach. The same consideration was not true comparing current indications with the possibility to start HAART at any CD4 value (eg, >500 cells per µL; in this case, the incremental cost-effectiveness ratio value was €199,130 per quality-adjusted life year gained, a higher value than the one suggested in guidelines. The single-tablet regimen (STR invariably
Hansen, Ann-Brit Eg; Obel, N; Nielsen, H;
The aim of the study was to compare changes in bone mineral density (BMD) over 144 weeks in HIV-infected patients initiating nucleoside reverse transcriptase inhibitor (NRTI)-sparing or protease inhibitor-sparing highly active antiretroviral therapy (HAART).......The aim of the study was to compare changes in bone mineral density (BMD) over 144 weeks in HIV-infected patients initiating nucleoside reverse transcriptase inhibitor (NRTI)-sparing or protease inhibitor-sparing highly active antiretroviral therapy (HAART)....
Full Text Available Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%. Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p < 0.001 and persistently lower CD4+ cell count (p < 0.001 compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4+ cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy.
Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L; Gerstoft, Jan; Sisse R Ostrowski
Objective The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART). Methods Inflammation and endothelial activation were assessed by measuring levels of immunoglobulins, β2-microglobulin, interleukin (IL) 8, tumor necrosis factor α (TNFα), vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), sE-Selectin, and sP-Selectin. Results HIV infected p...
Full Text Available These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in 2012. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART in southern Africa has continued. Cohort studies from the region show excellent clinical outcomes; however, ART is still being initiated late (in advanced disease in some patients, resulting in relatively high early mortality rates. New data on antiretroviral drugs have become available. Although currently few, there are patients in the region who are failing protease-inhibitor-based second-line regimens. To address this, guidelines on third-line therapy have been expanded.Please find a link to the update of this guideline: http://sajhivmed.org.za/index.php/hivmed/article/view/428
Nischal K; Khopkar Uday; Saple D
Antiretroviral therapy (ART) has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in dise...
Felix F. Widjaja
Full Text Available Background: Highly active antiretroviral therapy (HAART can reduce morbidity and mortality of HIV-infected patients. However, it depends upon adherence to medication. The objective of this study was to examine the adherence to HAART and to evaluate individual patient characteristics i.e. self-efficacy, depression level, and social support and to finally determine HAART adherence in selected regions in Indonesia.Methods: This cross-sectional study was conducted in Jakarta, Malang, Bandung, Makasar and Banda Aceh. The subject of the study was HIV-infected patients who were older than 13 years old and had taken HAART for at least a month. They were recruited consecutively then asked how many pills they had missed during the previous month. Poor adherence can be stated if the percentage of adherence rate is below 95%. HIV treatment adherence self-efficacy scale (HIVASES, Beck Depression Inventory (BDI-II and Interpersonal Support Evaluation List (ISEL was adapted to assess self-efficacy, depression level and social support, respectively.Results: We found that 96% (n=53 of the subjects adhered to HAART. There were no associations between adherence with self-efficacy, depression level, and social support. The main cause of non-adherence in this study was ‘simply forget’.Conclusion: Adherence to HAART was found to be high and not associated with self-efficacy, depression level and social support in some central regions in Indonesia. (Med J Indones 2011; 20:50-5Keywords: adherence, depression, HAART, HIV, self-efficacy, social support
Full Text Available The use of highly active antiretroviral therapy (HAART in HIV-infected patients has been associated with the development of risk factors for cardiovascular diseases (CD including dyslipidemia and insulin resistance, hypertriglyceridemia being the most frequent metabolic disturbance in these patients. Fibrates are indicated when hypertriglyceridemia is accentuated and persists for over six months. We evaluated the efficacy and safety of bezafibrate for the treatment of hypertriglyceridemia in HIV-infected individuals on HAART. All patients received 400mg/day of bezafibrate and were evaluated three times: Mo (pre-treatment, M1 (one month after treatment, and M2 (six months after treatment. Fifteen adult individuals, eight males and seven females with mean age = 41.2 ± 7.97 years and triglyceride serum levels > 400mg/dL were included in the study. Smoking, alcohol ingestion and sedentarism rates were 50%, 6.66% and 60%, respectively. Family history of CD, hypertension and diabetes mellitus was reported in 33.3%, 40% and 46.7% of the cases, respectively, while dyslipidemia was reported by only 13.3%. More than half of the patients were using a protease inhibitor plus a nucleotide analog transcriptase inhibitor. Eutrophy and tendency toward overweight were observed at all three study time points. There were significant reductions in triglyceride serum levels from Mo to M1 and from Mo to M2. No significant changes were observed in the serum levels of creatine phosphokinase, hepatic enzymes, CD4+, CD8+ and viral load. Therefore, bezafibrate seems to be safe and effective for the reduction of hypertriglyceridemia in HIV-infected patients on HAART.
Full Text Available There is limited data on the prevalence of depression in HIV and AIDS patients in Sub- Saharan Africa and little resources have been allocated to address this issue. Depression affects patient adherence to treatment and predisposes patients to resistance which poses a public health threat. It also affects quality of life and productivity of patients. From August 2008 to March 2009, 731 patient adherence surveys were administered to assess disease, treatment knowledge and services received. The primary variable of interest was patients’ level of depressive symptoms score, constructed using factor analysis from five survey questions relating to: sadness, need to be alone, hopelessness and confusion and was categorized as no depressive symptoms (score 0, low depressive symptoms (score 1-2, moderate depressive symptoms (score 3-4 and high depressive symptoms (score 5-10. Majority of the patients on highly active antiretroviral therapy (HAART (59% were found to have depressive symptoms and this was more among women than men (66% vs 43%. There was some association of depressive symptoms with non-disclosure (70% of those who had not disclosed had depressive symptoms compared to 53% among those who had disclosed. There is a high prevalence of depressive symptoms among adult patients on HAART. There is need for in-depth evaluation to find out the root causes of depressive symptoms among HAART patients in AIDSRelief clinics. There is need to integrate mental health management in HIV care and treatment as well as training the existing health workers on mental health management.
Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred M;
Strategies for use of antiretroviral therapy (ART) have traditionally focused on providing treatment to persons who stand to benefit immediately from initiating the therapy. There is global consensus that any HIV+ person with CD4 counts less than 350 cells/μl should initiate ART. However, it...... remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/μl. The question of when the best time is to initiate ART during early HIV infection has...
Full Text Available BACKGROUND: Little information exists on the impact of highly active antiretroviral therapy (HAART on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices. METHODS AND FINDINGS: Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3 and 27 with AIDS (WHO stage 4 receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group. Costs of service provision (January 2004 prices, US$1 = 7.6 Rand included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY, whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97-1.19 for the HAART group versus 3.73 (95% CI: 3.55-3.97 for the No-ART group, and 8.71 (95% CI: 8.40-9.03 versus 4.35 (95% CI: 4.12-5.61, respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63-2.52 for the HAART versus 15.36 (95% CI: 13.97-16.85 for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81-8.49 compared with 6.60 (95% CI: 5.69-7.62 respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964
Beharu Woldemedhin; Nasir Tajure Wabe
Background: Highly active antiretroviral therapy (HAART) has markedly decreased the morbidity and mortality due to HIV disease. However, toxicities, comorbidity, pregnancy, and treatment failure, among others, would result in frequent initial HAART regimen change. Aim : The study was designed to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on HAART. Materials and Methods: The study was conducted using a retrospective institution-based st...
Background. Health related quality of life (HRQOL) is an important outcome measure for highly active antiretroviral treatment program. In Ethiopia, studies revealed that there are improved qualities of life among adults living with the viruses taking antiretroviral therapy but there is no explicit data showing gender differences in health related quality of life. Aim. To assess gender differences in HRQOL and its associated factors among people living with HIV and on highly active antiretrovi...
Full Text Available Objective: Introduction of new approaches for the treatment of human immunodeficiency virus (HIV infection such as anti-retroviral medicines has resulted in an increase in the life expectancy of HIV patient. Evaluating the dental health status as a part of their general health care is needed in order to improve the quality of life in these patients. The aim of this study was to compare the root and crown caries rate in HIV patients receiving highly active antiretroviral therapy (HAART with that rate in HIV patients without treatment option. Materials and Methods: This cross sectional study consisting of 100 individuals of both genders with human immunodeficiency virus were divided into two groups: i. group 1 (treatment group including 50 patients with acquired immunodeficiency syndrome (AIDS receiving HAART and ii. group 2 (control group including 50 HIV infected patients not receiving HAART. Dental examinations were done by a dentist under suitable light using periodontal probe. For each participant, numbers of decay (D, missed (M, filled (F, Decayed missed and filled teeth (DMFT, decay surface (Ds, missed surface (Ms, filled surface (Fs, Decayed missed and filled surfaces (DMFS, and tooth and root caries were recorded. Data were analyzed using Chi-square test and independent t test using SPSS 13.0, while p-value of <0.05 was considered statistically significant in all analysis. Results: The mean and standard deviation (SD of decayed, missed and filled teeth of those who were on highly active antiretroviral therapy was 6.86 ± 3.57, 6.39 ± 6.06 and 1.89 ± 1.93, respectively. There was no significant difference between these values regarding to the treatment of patients. The mean and standard deviation of DMFT, DMFS and the number of decayed root surfaces were 15.14 ± 6.09, 56.79 ± 28.56, and 4.96 ± 2.89 in patients treated by anti-retroviral medicine which were not significantly different compared to those without this treatment
Montaner, J S; Montessori, V; Harrigan, R; O'Shaughnessy, M; Hogg, R
The field of antiretroviral therapy is evolving at a very rapid pace. At this time, the initiation and optimization of antiretroviral therapy is based on serial plasma viral load determinations which aim to suppress viral replication to as low as possible for as long as possible, thus preventing disease progression. Currently available antiretrovirals require combination therapy with at least three agents to achieve this goal. Increasing availability of newer and more potent antiretroviral regimens will continue to enhance and simplify the number of therapeutic options available in the not too distant future. PMID:10337460
Tsibris, Athe M. N.; Hirsch, Martin S.
Antiretroviral therapy in the developed world has resulted in substantial reductions in HIV-associated morbidity and mortality, changing an HIV diagnosis from a likely death sentence into a manageable chronic infection (F. J. Palella, Jr., K. M. Delaney, A. C. Moorman, M. O. Loveless, J. Fuhrer, G. A. Satten, D. J. Aschman, and S. D. Holmberg, N. Engl. J. Med. 338:853-860, 1998). Several million years of life have been saved by effective anti-HIV treatment, although these successes should not...
Kirk, O; Pedersen, C; Cozzi-Lepri, A;
incidences of NHL and subtypes (Burkitt, immunoblastic, primary brain lymphoma [PBL], and other/unknown histology) were determined according to calendar time of follow-up, and for those who initiated HAART (> or =3 drugs) also time on HAART. Potential predictive factors of NHL were evaluated in Cox......This study was designed to assess the influence of highly active antiretroviral therapy (HAART) on non-Hodgkin lymphoma (NHL) among patients infected with human immunodeficiency virus (HIV). Within EuroSIDA, a multicenter observational cohort of more than 8500 patients from across Europe, the...
Lipodystrophy (LD) is a serious complication of highly active anti-retroviral therapy, characterized by peripheral fat wasting, central adiposity and metabolic changes. Since the disfiguration caused by LD is permanent, the focus of management is on early detection to arrest progression. We report a case where ancillary finding of increased fluorine-18 fluoro-2-deoxyglucose (F-18 FDG) uptake in the sub-cutaneous fat helped early detection of LD and led to early intervention to arrest progression. Though F-18 FDG positron emission tomography/computed tomography scan is not recommended to diagnose LD, conscious reporting of this finding when present can greatly influence patient management
Donoghoe, Martin C; Bollerup, Annemarie R; Lazarus, Jeff;
Providing equitable access to highly active antiretroviral treatment (HAART) to injecting drug users (IDUs) is both feasible and desirable. Given the evidence that IDUs can adhere to HAART as well as non-IDUs and the imperative to provide universal and equitable access to HIV/AIDS treatment for all...... injecting status of those initiating HAART and the use of opioid substitution therapy among HAART patients, and discuss how HAART might be better delivered to injecting drug users. Our data adds to the evidence that IDUs in Europe have poor and inequitable access to HAART, with only a relatively small...
Full Text Available Objective: To evaluate whether or not highly active antiretroviral therapy is associated with carotid artery stiffness in human immunodeficiency virus-positive patients in Henan Province, China. Method: Fifty human immunodeficiency virus-positive patients with at least a 5-year history of highly active antiretroviral therapy use and 50 human immunodeficiency virus-positive patients without a history of highly active antiretroviral therapy use were enrolled in this study. Carotid artery intima-media thickness and stiffness were determined by quantitative inter-media thickness and quantitative artery stiffness, respectively. Results: No statistically significant difference in carotid artery intima-media thickness and stiffness was observed between groups. A significant association between human immunodeficiency virus infection time and carotid artery stiffness was observed, but no significant association between human immunodeficiency virus infection time and intima-media thickness was found. No significant association between intima-media thickness, stiffness, and CD4+ and CD8+ T-cell counts were observed. Conclusion: The first-line highly active antiretroviral therapy currently used in China is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients with good highly active antiretroviral therapy compliance. Human immunodeficiency virus may play a role in the development of atherosclerosis.
Full Text Available Katie Yoganathan1, David Brown2, Kathir Yoganathan31Cardiff Medical School, Cardiff, Wales, UK; 2Virus Reference Department, Microbiology Services, Health Protection Agency, London, UK; 3Singleton Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UKAbstract: A 43-year-old Caucasian homosexual man with AIDS presented with blurring of vision, change of personality, and memory loss in March 1999. He had first been admitted 2 months previously for treatment of Pneumocystis jiroveci pneumonia. A magnetic resonance imaging scan on admission showed multiple white matter lesions involving both subcortical cerebral hemispheres and cerebellar regions, with no mass effect or surrounding edema. JC virus was detected by nested polymerase chain reaction in the cerebrospinal fluid. These findings were diagnostic of progressive multifocal leukoencephalopathy (PML. His CD4 count was 34 cells/mL, and his HIV ribonucleic acid level was 800,789 copies/mL. He was treated with a combination antiretroviral therapy. He was last reviewed in October 2011. He was fully independent socially and mentally, but he still had some residual neurologic signs with right-sided homonymous hemianopia and visual agnosia. His HIV ribonucleic acid level was undetectable, and his CD4 count was 574 cells/mm3. Although the median survival of patients with PML was poor before the antiretroviral therapy era, our patient, who is now aged 55 years, is still alive 12 years after the diagnosis. The diagnosis of PML and differential diagnosis of focal neurologic signs in HIV-positive patients are discussed in this case report.Keywords: HIV, focal neurologic signs, cerebral toxoplasmosis, primary brain lymphoma, ischaemic stroke
Full Text Available Plasmablastic lymphoma is a rare and aggressive malignancy strongly associated with HIV infection. The refractory/relapsed disease rate is high, and the survival rate is characteristically poor. There are no satisfactory salvage regimens for relapsed cases. We successfully performed autologous stem cell transplantation using a regimen consisting of MCNU (ranimustine, etoposide, cytarabine, and melphalan in a Japanese patient with relapsed AIDS-related plasmablastic lymphoma of the oral cavity. Highly active antiretroviral therapy continued during the therapy. Therapy-related toxicity was tolerable, and a total of 40 Gy of irradiation was administered after autologous stem cell transplantation. The patient has remained in complete remission for 16 months since transplantation.
Wakibi Samwel N
Full Text Available Abstract Background Antiretroviral therapy (ART requires high-level (> 95% adherence. Kenya is rolling out ART access programmes and, issue of adherence to therapy is therefore imperative. However, published data on adherence to ART in Kenya is limited. This study assessed adherence to ART and identified factors responsible for non adherence in Nairobi. Methods This is a multiple facility-based cross-sectional study, where 416 patients aged over 18 years were systematically selected and interviewed using a structured questionnaire about their experience taking ART. Additional data was extracted from hospital records. Patients were grouped into adherent and non-adherent based on a composite score derived from a three questions adherence tool developed by Center for Adherence Support Evaluation (CASE. Multivariate regression model was used to determine predictors of non-adherence. Results Overall, 403 patients responded; 35% males and 65% females, 18% were non-adherent, and main (38% reason for missing therapy were being busy and forgetting. Accessing ART in a clinic within walking distance from home (OR = 2.387, CI.95 = 1.155-4.931; p = 0.019 and difficulty with dosing schedule (OR = 2.310, CI.95 = 1.211-4.408, p = 0.011 predicted non-adherence. Conclusions The study found better adherence to HAART in Nairobi compared to previous studies in Kenya. However, this can be improved further by employing fitting strategies to improve patients' ability to fit therapy in own lifestyle and cue-dose training to impact forgetfulness. Further work to determine why patients accessing therapy from ARV clinics within walking distance from their residence did not adhere is recommended.
Frederikke F Rönsholt
Full Text Available OBJECTIVE: The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART. METHODS: Inflammation and endothelial activation were assessed by measuring levels of immunoglobulins, β2-microglobulin, interleukin (IL 8, tumor necrosis factor α (TNFα, vascular cell adhesion molecule-1 (sVCAM-1, intercellular adhesion molecule-1 (sICAM-1, sE-Selectin, and sP-Selectin. RESULTS: HIV infected patients had higher levels of β2-microglobulin, IL-8, TNFα, and sICAM-1 than uninfected controls, and HIV infected patients lacked correlation between platelet counts and sP-Selectin levels found in uninfected controls. CONCLUSION: Discrete signs of systemic and vascular inflammation persist even after very long term cART.
Lindhardt, Bjarne Ø.; Kronborg, Gitte; Hansen, Ann-Brit E.;
BACKGROUND: Coinfection with hepatitis C virus (HCV) in human immunodeficiency virus (HIV) type 1-infected patients may decrease the effectiveness of highly active antiretroviral therapy. We determined the impact of HCV infection on response to highly active antiretroviral therapy and outcome among...... <0.3, from acquired immunodeficiency syndrome-related disease, and if they had a history of alcohol abuse. Although we observed no difference in viral load between the HCV-positive and HCV-negative groups, the HCV-positive group had a marginally lower absolute CD4+ cell count. CONCLUSIONS: HIV...
Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C;
Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive functi...
Kolte, Lilian; Dreves, Anne-Mette; Ersbøll, Annette K; Strandberg, Charlotte; Jeppesen, Dorthe L; Nielsen, Jens O; Ryder, Lars P; Nielsen, Susanne D
To examine the impact of thymic size on immune recovery in patients with human immunodeficiency virus (HIV) infection, the thymus was visualized, using computed tomographic scans, in 25 HIV-infected patients who had received highly active antiretroviral therapy (HAART) for 6-18 months and had...
Weis, Nina Margrethe; Lindhardt, Bjarne Ø.; Kronborg, Gitte;
Danish patients with HIV-1 infection. METHODS: This prospective cohort study included all adult Danish HIV-1-infected patients who started highly active antiretroviral therapy from 1 January 1995 to 1 January 2004. Patients were classified as HCV positive (positive HCV serological test and/or HCV PCR...
Dragsted, Ulrik Bak; Mocroft, Amanda; Vella, Stefano; Viard, Jean-Paul; Hansen, Ann-Britt E; Panos, George; Mercey, Danielle; Machala, Ladislav; Horban, Andrzej; Lundgren, Jens Dilling
BACKGROUND: Factors that determine the immunological response to highly active antiretroviral therapy (HAART) are poorly defined. OBJECTIVE: Our aim was to investigate predictors of immunological failure after initial CD4(+) response. METHODS: Data were from EuroSIDA, a prospective, international...
Ostrowski, Sisse R; Katzenstein, Terese L; Piironen, Timo;
High blood levels of the soluble urokinase receptor (suPAR) strongly predict increased mortality in human immunodeficiency virus-1 (HIV-1)-infected patients. This study investigated the plasma concentration of suPAR in 29 treatment-naive HIV-1-infected patients during 5 years treatment with highly...... active antiretroviral therapy (HAART). Plasma suPAR decreased after introducing HAART, most pronounced during the first treatment year. The change in plasma suPAR was independent of changes in viral replication and CD4+ cells but it was strongly correlated with plasma levels of the soluble TNF receptor...... II. Compared with healthy individuals, plasma suPAR and sTN-FrII was increased in untreated patients. After initiating HAART, plasma sTNFrII remained increased whereas plasma suPAR decreased to a level comparable with healthy individuals. The present data indicate that the circulating suPAR level is...
Marina Hjertquist Tremeschin
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.
Stengaard, Annemarie Rinder; Lazarus, Jeff; Donoghoe, Martin C;
assessed by comparing the percentage of reported HIV cases with the percentage of HAART recipients in women at the end of 2002 and 2006 and in children at the end of 2004 and 2006. Findings. Overall, the data suggest that there is equivalence of access to antiretroviral therapy by gender and age in Europe...
Manisha Rajian; Paramjeet S. Gill; Uma Chaudhary
Background: In resource limited settings in India, monitoring of treatment in HIV patients taking highly active antiretroviral therapy is done by six monthly CD4 count instead of highly sensitive plasma viral load. Patients are subjected to viral load only when their CD4 count is low for the last 12 months. This protocol has a huge disadvantage as treatment failure is detected much later than it has actually occurred and switch over to second line therapy gets delayed by approximately one yea...
Hendrickson, Sher L.; Kingsley, Lawrence A; Ruiz-Pesini, Eduardo; Poole, Jason C.; Jacobson, Lisa P.; Palella, Frank J.; Bream, Jay H.; Wallace, Douglas C.; O’Brien, Stephen J.
Although highly active retroviral therapy (HAART) has been extremely effective in lowering AIDS incidence among patients infected with HIV, certain drugs included in HAART can cause serious mitochondrial toxicities. One of the most frequent adverse events is lipoatrophy, which is the loss of subcutaneous fat in the face, arms, buttocks and/or legs as an adverse reaction to nucleoside reverse transcriptase inhibitors (NRTIs). The clinical symptoms of lipoatrophy resemble those of inherited mit...
ZHANG Zi-ning; SHANG Hong; JIANG Yong-jun; LIU Jing; DAI Di; DIAO Ying-ying; GENG Wen-qing; JIN Xin; WANG Ya-nan
Background At the end of 2005, 650 000 people lived with human immunodeficiency virus type-1 (HIV-1) in (HAART) supported by the "China CARES" program but the immune responses of HAART were seldom reported. This study investigated the effect of HAART on the activation and coreceptor expression of T lymphocytes in Chinese HIV/AIDS patients and evaluated its effect on immune reconstitution.Methods Seventeen HIV/AIDS patients were enrolled and three-color-flow cytometry was used to detect the activation of HLA-DR CD38 and the coreceptor CCR5, CXCR4 expression on T lymphocytes in whole blood samples taken from the patients before and after 3- or 6-month HAART.Results The activation percents of CD4+, CD8+ T lymphocytes were significantly higher before therapy than the normal controls (HLA-DR/CD4: 40.47± 18.85 vs 11.54±4.10; CD38/CD4: 81.34± 10.86 vs 53.34± 11.44;HLA-DR/CD8:63.94±12.71 vs 25.67±9.18; CD38/CD8:86.56±11.41 vs 58.84±6.16, all P＜0.01). After 6-month combined antiretroviral treatment, the activation of T lymphocytes in HIV/AIDS patients was significantly decreased (HLA-DR/CD4:28.31 ± 13.48; CD38/CD4:69.88 ± 12.64; HLA-DR/CD8: 46.56±18.64;CD38/CD8: 70.17± 14.54, all P＜0.01 compared with the pre-treatment values). Before the treatment, CCR5 expression on CD8+ T lymphocytes was up-regulated while CXCR4 expression on CD8+ T lymphocytes downregulated in HIV/AIDS patients compared with the normal controls (CD8/CCR5:70.9 1± 10.03 vs 52.70 ±7.68; CD8/CXCR4: 24.14± 11.08 vs 50.05± 11.68, all P＜0.01). After 6-month HAART, CCR5 expression on CD8+ T lymphocytes significantly decreased (56.35±12.96, P＜0.01), while CXCR4 expression on CD8+ T lymphocytes increased (36.95±9.96, P＜0.05) compared with the pre-treatment and the normal controls. A significant statistical relationship was observed between the expression of activation markers, CCR5 and the CD4+ T lymphocyte counts after HAART (P＜0.05).Conclusions Reduced activation of T lymphocytes
Tenorio, Allan R.; Chan, Ellen S; Bosch, Ronald J.; Macatangay, Bernard J.C.; Read, Sarah W.; Yesmin, Suria; Taiwo, Babafemi; Margolis, David M.; Jacobson, Jeffrey M.; Landay, Alan L.; Wilson, Cara C.; Mellors, John W.; Keshavarzian, Ali; Rodriguez, Benigno; Aziz, Mariam
Background. Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART).
Ibrahim Abdu Wakawa; Jidda Mohammed Said; Wakil Musa Abba; Saleh Shehu; Isa Bukar Rabbebe; Omeiza Beida
Background: Globally, depression compromises the quality of life (QOL) of people suffering from it. We assessed the impact of comorbid depression on the health-related quality of life (HRQOL) of adults on highly active antiretroviral therapy (HAART) in northeastern Nigeria in this study. Materials and Methods: Three hundred and three adults on HAART were recruited for this study from the ART clinic of the University of Maiduguri Teaching Hospital in northeastern Nigeria. The depressive disord...
Chiang, Hou-Hsien; Hung, Chien-Ching; Lee, Chang-Min; Chen, Hsuan-Yu; Chen, Mao-Yuan; Sheng, Wang-Huei; Hsieh, Szu-Min; Sun, Hsin-Yun; Ho, Chao-Chi; Yu, Chong-Jen
Introduction Although access to highly active antiretroviral therapy (HAART) has prolonged survival and improved life quality, HIV-infected patients with severe immunosuppression or comorbidities may develop complications that require critical care support in intensive care units (ICU). This study aimed to describe the etiology and analyze the prognostic factors of HIV-infected Taiwanese patients in the HAART era. Methods Medical records of all HIV-infected adults who were admitted to ICU at ...
Duff, Putu; Rubaale, Tom; Kipp, Walter
Background The aim of this study was to describe the perceptions of married men about barriers to accessing and accepting highly active antiretroviral therapy (HAART) by pregnant/postnatal women positive for human immunodeficiency virus (HIV) and registered in Kabarole District’s Program for the Prevention of HIV from Mother to Child (PMTCT-Plus). Materials and methods Our study was a qualitative descriptive exploratory study using thematic analysis. Four focus group discussions were held wit...
Duff P; Rubaale T; Kipp W.
Putu Duff,1 Tom Rubaale,2 Walter Kipp1,21School of Public Health, University of Alberta, Edmonton, Canada; 2Community ARV Project, Fort Portal, UgandaBackground: The aim of this study was to describe the perceptions of married men about barriers to accessing and accepting highly active antiretroviral therapy (HAART) by pregnant/postnatal women positive for human immunodeficiency virus (HIV) and registered in Kabarole District’s Program for the Prevention of HIV from Mother to Child ...
Venkatesh, Kartik K.; Srikrishnan, A.K.; Mayer, Kenneth H.; Kumarasamy, N; Raminani, Sudha; Thamburaj, E.; Prasad, Lakshmi; Triche, Elizabeth W.; Solomon, Suniti; Safren, Steven A.
In light of the increasing availability of generic highly active antiretroviral therapy (HAART) in India, further data are needed to examine variables associated with HAART nonadherence among HIV-infected Indians in clinical care. We conducted a cross-sectional analysis of 198 HIV-infected South Indian men and women between January and April 2008 receiving first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART. Nonadherence was defined as taking less than 95% of HAART d...
María F Villafañe
Full Text Available Cutaneous B-cell lymphoma (CBCL is an unusual skin neoplasm with a great range of clinical presentations. Here, we report a case of CBCL in an AIDS patient presented as a single and nodular/ulcerative lesion in the perianal area. The patient was started on highly active antiretroviral therapy alone with a good clinical and oncological response. Two years later, the patient is asymptomatic with undetectable viral load and immune reconstitution.
Ling, Paul D.; Vilchez, Regis A.; Keitel, Wendy A.; Poston, David G.; Peng, Rong Sheng; White, Zoe S.; Visnegarwala, Fehmida; Lewis, Dorothy E.; Butel, Janet S.
Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.
Tello-Velásquez, Jorge Renzo; Díaz-Llanes, Bruno Eduardo; Mezones-Holguín, Edward; Rodríguez-Morales, Alfonso J; Huamaní, Charles; Hernández, Adrián V; Arévalo-Abanto, Jorge
This cross-sectional study analyzed the association between poor quality of sleep and adherence to highly active antiretroviral therapy (HAART) in 389 Peruvian patients with HIV/AIDS. Poor quality of sleep was measured with the Pittsburgh Sleep Quality Index (PSQI) and adherence with the CEAT-VIH (Peruvian adaptation). A Poisson generalized linear model with robust standard errors was used to estimate prevalence ratios and 95%CI. A crude model showed that mild, moderate, and severe poor quality of sleep were associated with inadequate treatment adherence. In the adjusted model for variables associated in the bivariate analysis or variables theoretically associated with adherence, only moderate/severe poor quality of sleep remained associated (PR = 1.34, 95%CI: 1.17-1.54; and PR = 1.34, 95%CI: 1.16-1.57, respectively). The study concluded that moderate/severe poor quality of sleep was independently associated with adherence to HAART. Assessing quality of sleep may be helpful in the comprehensive evaluation of HIV patients. PMID:26083174
Full Text Available Purpose: The aim of our study was to evaluate whether perirenal fat thickness (PRFT, a parameter of central obesity, is related to kidney function and intrarenal artery resistive index (IARI in human immunodeficiency virus (HIV-1-infected patients. Materials and Methods: We enrolled 102 consecutive HIV-1-infected patients receiving highly active antiretroviral therapy for more than 12 months in a prospective cohort study. Echographically, the PRFT and IARI were measured and the serum metabolic parameters were evaluated. PRFT and IARI were measured using a 3.75 MHz convex linear probe. Results: The mean of PRFT and IARI in HIV-1-infected patients with visceral obesity was considerably higher than that in patients without it (P <0.001 and <0.01, respectively. Using the average IARI as the dependent variable, age (odds ratio, 1.07; 95% confidence interval [CI], 1.01-1.14; P < 0.5 and PRFT (odds ratio, 1.28; 95% CI, 1.08-1.51; P<0.01 were independent factors associated with IARI. Conclusion: Our data indicate that ultrasonographic assessment of PRFT may have a potential to be a marker of increased endothelial damage with specific involvement of the renal vascular district in HIV-1-infected patients.
Caroline E Omoti; Chiedozie K Ojide; Patrick V Lofor; Emeka Eze; Joy C Eze
Objective:To investigate the malaria parasitemia,CD4+ cell counts and some haematological indices amongHIV-malaria co-infected adult patients with highly active antiretroviral therapy (HAART).Methods:A total of342 adultHIV positive subjects were recruited at the consultant outpatientHIV/AIDS clinic,University ofBeninTeachingHospital,BeninCity,Nigeria between June2011 toNovember2011.Blood samples were taken for malaria parasite count,CD4+ cell count and other haematological counts.Results:Out of the342 adultHIV positive subjects a total of254 patients (74.3%) were found to have malaria parasitemia.The incidence of malaria parasitemia increased with advancing clinical stage ofHIV infection and this was statistically significant (P=0.002).There was no statistical significance when gender was compared with the HIV-malaria status (P>0.05).Of the254 co-infected patients,134 (52.8%) had high parasitemia (>1.25×109/L).Sixty patients were found to be hyperparasitemic (>2.5 parasites/L).There was a significant association betweenCD4+ cell count and having significant parasitemia (P 0.05).Conclusions:The prevalence of parasitemia is high among theHIV/AIDS infected patients.
Michael, OG; Kirk, O; Mathiesen, Lars Reinhardt;
Current antiretroviral therapy can induce considerable, sustained viral suppression followed by immunological recovery, in which naive CD4 + cells are important. Long-term immunological recovery was investigated during the first 3 y of highly active antiretroviral therapy (HAART) in 210 HIV-1...... immunological recovery that can be obtained from treatment. Surprisingly, the naive CD4 + cell count tended to stabilize at a subnormal level after 18 months of HAART. This finding merits further investigation.......-infected patients. The focus was on the naive CD4 + cell time course and associations between naive CD4 + cell counts and established prognostic markers. Total and naive CD4 + cell counts were measured using flow cytometry. The HIV-RNA detection limit was 20 copies/ml. During 36 months of HAART, the total...
Full Text Available Amid numerous complications that plague the health and quality of life of people living with HIV, neurocognitive and psychiatric illnesses pose unique challenges. While there remains uncertainty with respect to the pathophysiology surrounding these disorders, their adverse implications are increasingly recognized. Left undetected, they have the potential to significantly impact patient well being, adherence to antiretroviral treatment and overall health outcomes. As such, early identification of HIV-associated neurocognitive disorders (HAND and psychiatric illnesses will be paramount in the proactive management of affected patients. The present review focuses on strategies to ensure optimal screening and detection of HAND, depression and substance abuse in routine practice. For each topic, currently available screening methods are discussed. These include identification of risk factors, recognition of relevant symptomatology and an update on validated screening tools that can be efficiently implemented in the clinical setting. Specifically addressed in the present review are the International HIV Dementia Scale, a novel screening equation and algorithm for HAND, as well as brief, validated, verbal questionnaires for detection of depression and substance abuse. Adequate understanding and usage of these screening mechanisms can ensure effective use of resources by distinguishing patients who require referral for more extensive diagnostic procedures from those who likely do not.
Holst Helga L
Full Text Available Abstract Background Few studies address the use of paediatric highly active antiretroviral therapy (HAART in Africa. Methods We performed a retrospective cohort study to investigate preliminary outcomes of all children eligible for HAART at Sinikithemba HIV/AIDS clinic in KwaZulu-Natal, South Africa. Immunologic, virologic, clinical, mortality, primary caregiver, and psychosocial variables were collected and analyzed. Results From August 31, 2003 until October 31, 2005, 151 children initiated HAART. The median age at HAART initiation was 5.7 years (range 0.3–15.4. Median follow-up time of the cohort after HAART initiation was 8 months (IQR 3.5–13.5. The median change in CD4% from baseline (p 95%adherence. Seventeen patients (11.3% had a regimen change; two (1.3% were due to antiretroviral toxicity. The Kaplan-Meier one year survival estimate was 90.9% (95%confidence interval (CI 84.8–94.6. Thirteen children died during follow-up (8.6%, one changed service provider, and no children were lost to follow-up. All 13 deaths occurred in children with advanced HIV disease within 5 months of treatment initiation. In multivariate analysis of baseline variables against mortality using Cox proportional-hazards model, chronic gastroenteritis was associated with death [hazard ratio (HR, 12.34; 95%CI, 1.27–119.71 and an HIV-positive primary caregiver was found to be protective against mortality [HR, 0.12; 95%CI, 0.02–0.88. Age, orphanhood, baseline CD4%, and hemoglobin were not predicators of mortality in our cohort. Fifty-two percent of the cohort had at least one HIV-positive primary caregiver, and 38.4% had at least one primary caregiver also on HAART at Sinikithemba clinic. Conclusion This report suggests that paediatric HAART can be effective despite the challenges of a resource-limited setting.
Full Text Available Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV and tuberculosis (TB co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART when co-administered with rifampicin-containing antituberculosis treatment (ATT and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1% patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83 at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10, 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08, 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10 respectively and 3.04 μg/ml (in cases. Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in
B Akshaya Srikanth
Full Text Available To estimate the incidence of adverse drug reactions (ADRs in Human immune deficiency virus (HIV patients on highly active antiretroviral therapy (HAART. To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%. The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52% was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/μl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm 3 with comorbid conditions.
Srikanth, B Akshaya; Babu, S Chandra; Yadav, Harlokesh Narayan; Jain, Sunil Kumar
To estimate the incidence of adverse drug reactions (ADRs) in Human immune deficiency virus (HIV) patients on highly active antiretroviral therapy (HAART). To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%). The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52%) was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/μl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm(3) with comorbid conditions. PMID:22470896
Matsukura, Motoi; Chu, Fanny F S; Au, May; Lu, Helen; Chen, Jennifer; Rietkerk, Sonja; Barrios, Rolando; Farley, John D; Montaner, Julio S; Montessori, Valentina C; Walker, David C; Côté, Hélène C F
Liver mitochondrial toxicity is a concern, particularly in HIV/hepatitis C virus (HCV) coinfection. Liver biopsies from HIV/HCV co-infected patients, 14 ON-highly active antiretroviral therapy (HAART) and nine OFF-HAART, were assessed by electron microscopy quantitative morphometric analyses. Hepatocytes tended to be larger ON-HAART than OFF-HAART (P = 0.05), but mitochondrial volume, cristae density, lipid volume, mitochondrial DNA and RNA levels were similar. We found no evidence of increased mitochondrial toxicity in individuals currently on HAART, suggesting that concomitant HAART should not delay HCV therapy. PMID:18525271
Izabel Galhardo Demarchi; Daniela Maira Cardozo; Sandra Mara Alessi Aristides; Ricardo Alberto Moliterno; Thaís Gomes Verzignassi Silveira; Rosilene Fressatti Cardoso; Dennis Armando Bertolini; Terezinha Inez Estivalet Svidzinski; Jorge Juarez Vieira Teixeira; Maria Valdrinez Campana Lonardoni
Highly active antiretroviral therapy (HAART) is used in patients infected with HIV. This treatment has been shown to significantly decrease opportunist infections such as those caused by viruses, fungi and particularly, protozoa. The use of HAART in HIV-positive persons is associated with immune reconstitution as well as decreased prevalence of oral candidiasis and candidal carriage. Antiretroviral therapy benefits patients who are co-infected by the human immunodeficiency virus (HIV), human ...
Full Text Available Abstract Background The efficacy of highly active antiretroviral therapy (HAART determined by simultaneous monitoring over 100 cell-surface antigens overtime has not been attempted. We used an antibody microarray to analyze changes in the expression of 135 different cell-surface antigens overtime on PBMC from HIV+ patients on HAART. Two groups were chosen, one (n = 6 achieved sustainable response by maintaining below detectable plasma viremia and the other (n = 6 responded intermittently. Blood samples were collected over an average of 3 years and 5–8 time points were selected for microarray assay and statistical analysis. Results Significant trends over time were observed for the expression of 7 cell surface antigens (CD2, CD3epsilon, CD5, CD95, CD36, CD27 and CD28 for combined patient groups. Between groups, expression levels of 10 cell surface antigens (CD11a, CD29, CD38, CD45RO, CD52, CD56, CD57, CD62E, CD64 and CD33 were found to be differential. Expression levels of CD9, CD11a, CD27, CD28 and CD52, CD44, CD49d, CD49e, CD11c strongly correlated with CD4+ and CD8+ T cell counts, respectively. Conclusion Our findings not only detected markers that may have potential prognostic/diagnostic values in evaluating HAART efficacy, but also showed how density of cell surface antigens could be efficiently exploited in an array-like manner in relation to HAART and HIV-infection. The antigens identified in this study should be further investigated by other methods such as flow cytometry for confirmation as biological analysis of these antigens may help further clarify their role during HAART and HIV infection.
AIM: To describe the radiological appearances of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected patients with mycobacterial infections starting highly active anti-retroviral therapy (HAART). MATERIALS AND METHODS: Five consecutive HIV infected patients with IRIS due to mycobacterial infection were studied. Intercurrent infection and poor drug compliance were excluded as causes of presentation. The chest radiological appearances at the time of starting HAART and at the time of diagnosis of IRIS were compared. RESULTS: In these five patients there was clinical and radiological deterioration, occurring between 10 days and 7 months after starting HAART, leading to unmasking of previously undiagnosed mycobacterial infection or to worsening of mycobacterial disease. All five patients had HAART-induced increases in CD4+ T lymphocyte counts and reductions in peripheral blood HIV 'viral load'. Chest radiographic abnormalities due to IRIS included marked mediastinal lymphadenopathy in three patients--severe enough to produce tracheal compression in two patients (one of whom had stridor)--and was associated with new pulmonary infiltrates in two patients. The other two patients had new infiltrates, which in one patient was associated with a pleural effusion. CONCLUSION: These cases illustrate the diverse chest radiographic appearances of IRIS occurring after HAART in patients with mycobacterial and HIV co-infection. Marked mediastinal lymphadenopathy occurred in three of these five patients (with associated tracheal narrowing in two patients); four patients developed pulmonary infiltrates and one had an effusion. The cases further highlight that the onset of IRIS may be delayed for several months after HAART is started
Buckingham, S.J.; Haddow, L.J.; Shaw, P.J.; Miller, R.F. E-mail: firstname.lastname@example.org
AIM: To describe the radiological appearances of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected patients with mycobacterial infections starting highly active anti-retroviral therapy (HAART). MATERIALS AND METHODS: Five consecutive HIV infected patients with IRIS due to mycobacterial infection were studied. Intercurrent infection and poor drug compliance were excluded as causes of presentation. The chest radiological appearances at the time of starting HAART and at the time of diagnosis of IRIS were compared. RESULTS: In these five patients there was clinical and radiological deterioration, occurring between 10 days and 7 months after starting HAART, leading to unmasking of previously undiagnosed mycobacterial infection or to worsening of mycobacterial disease. All five patients had HAART-induced increases in CD4+ T lymphocyte counts and reductions in peripheral blood HIV 'viral load'. Chest radiographic abnormalities due to IRIS included marked mediastinal lymphadenopathy in three patients--severe enough to produce tracheal compression in two patients (one of whom had stridor)--and was associated with new pulmonary infiltrates in two patients. The other two patients had new infiltrates, which in one patient was associated with a pleural effusion. CONCLUSION: These cases illustrate the diverse chest radiographic appearances of IRIS occurring after HAART in patients with mycobacterial and HIV co-infection. Marked mediastinal lymphadenopathy occurred in three of these five patients (with associated tracheal narrowing in two patients); four patients developed pulmonary infiltrates and one had an effusion. The cases further highlight that the onset of IRIS may be delayed for several months after HAART is started.
Woo, Victoria G; Liegler, Teri; Cohen, Craig R; Sawaya, George F; Smith-McCune, Karen; Bukusi, Elizabeth A; Huchko, Megan J
HIV-1 genital shedding is associated with increased HIV-1 transmission risk. Inflammation and ulceration are associated with increased shedding, while highly active antiretroviral therapy (HAART) has been shown to have a protective effect. We sought to examine the impact of cervical biopsies, a routine component of cervical cancer screening, on HIV-1 genital RNA levels in HIV-infected women on HAART. We enrolled HIV-1-infected women undergoing cervical biopsy for diagnosis of cervical intraepithelial neoplasia (CIN) 2/3 in this prospective cohort study. All were stable on HAART for at least 3 months. Clinical and demographic information as well as plasma HIV-1 viral load were collected at the baseline visit. Specimens for cervical HIV-1 RNA were collected immediately prior to biopsy, and 2 and 7 days afterward. Quantitative PCR determined HIV-1 concentration in cervical specimens at each time point to a lower limit of detection of 40 copies/specimen. Among the 30 participants, five (16.6%) women had detectable cervical HIV-1 RNA at baseline, of whom four (80%) had detectable HIV-1 RNA after cervical biopsy, with no significant increase in viral load in the follow-up specimens. Only one woman (3.3%) with undetectable baseline cervical HIV-1 RNA had detection postbiopsy. Detectable plasma HIV-1 RNA was the only factor associated with baseline cervical HIV-1 RNA. In women on HAART, an increase in cervical HIV-1 RNA detection or concentration was not associated with cervical biopsy. These findings help provide safety data regarding cervical cancer screening and diagnosis in HIV-infected women and inform postprocedure counseling. PMID:23594240
Paul C. Inyang-Etoh
Full Text Available Opportunistic and intestinal parasite infections are common health problem among HIV/AIDS patients. Early detection and treatment of these parasites are important to improve the quality of life of this category of patients. The occurrence of intestinal parasites among 400 patients on highly active anti-retroviral drug therapy (HAART aged 11-60 years was investigated. Standard parasitological techniques like direct microscopy, formol ether concentration and modified Ziehl- Neelsen staining techniques were used to analyze the stool samples. Intestinal parasite infections were positive in 116 (29% of the subjects on HAART while control subjects had 12 (12% and the difference was statistically significant (P<0.05. Subjects in the age group 21-30 years had the highest infection rate 54 (35.1%. There was no statistically significant difference in infection according to age (P>0.05. Females 76 (32.5% had a higher prevalence rate than males 40 (24.1%. But there was no statistically significant difference in infection according to gender (P<0.05. Patients with CD4 count of less than 200 cells/mm3 were observed to be more infected than those with CD4 count of more than 200 cells/mm3. There was a strong positive correlation (r=0.94 between CD4 count and the occurrence of intestinal parasite infection. Protozoan parasites 84 (21.0% accounted for a higher prevalence rate than helminthic parasites 32 (8.0%. These findings has revealed a high prevalence of intestinal parasite infection among patients on HAART thus the routine screening of stool samples from these category of patients for intestinal parasites is advocated for effective management of the disease.
Full Text Available These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in January 2008. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART in Southern Africa has continued to grow. Cohort studies from the region show excellent clinical outcomes; however, ART is still being started late (in advanced disease, resulting in relatively high early mortality rates. New data on antiretroviral (ARV tolerability in the region and several new ARV drugs have become available. Although currently few in number, some patients in the region are failing protease inhibitor (PI-based second-line regimens. To address this, guidelines on third-line (or ‘salvage’ therapy have been expanded.
Martinez-Picado, Javier; Deeks, Steven G
Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on ef...
Fitzgerald Daniel W; Atwood Sidney; Severe Patrice; Leger Paul; Riviere Cynthia; Koenig Serena P; Pape Jean W; Schackman Bruce R
Abstract Background We determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART) to patients with AIDS in Haiti. Methods We examined data from 218 treatment-naïve adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART. Results The mean total cost of treatme...
Aim: Altered thyroid function parameters have been reported in HIV patients also during therapy. We further investigated whether thyroid disorders occur in HIV patients both naive or on HAART. Materials and Methods: We enrolled 168 HIV patients aged 20 to 62 yrs, 110M and 58F: 95 patients (G1) were on HAART including protease inhibitors-PI (36.89±13.0 mths); 58 (G2) were on HAART (Nevirapine or Efavirenz) without PI (13.22±8.68 mths) and previously submitted to other HAART regimens (28.10±12.3 mths); 15 (G3) were naive. In all patients and in 44 age-sex matched normal subjects (C) we measured in serum by IRMA, FT3 and FT4 (pg/ml), TSH (μU/ml), antithyroid peroxidase (TPO) and hTG (U/ml) antibodies (Ab). Results: Thyroid function test abnormalities were found in 18/153 patients treated with HAART (11.7%), 9 G1 and 9 G2 patients, while the tests were normal in naive cases. Both FT3 and FT4 were above normal range and TSH suppressed in one G1 patient with clinical signs of hyperthyroidism; FT4 was low and TSH elevated in 2 G2 cases with slight clinical signs of hypothyroidism. Moreover, TSH values >3.5 μU/ml and normal FT3 and FT4 levels were ascertained in 7 further cases as probable subclinical hypothyroidism. Only FT4 was low in 3 further cases and FT3 high in 5 others, all asymptomatic. hTG-Ab were present in 2 subclinical hypothyroidism patients and in 3 further cases with normal thyroid tests. Mean TSH levels were higher but not significantly in G1 than in G2; both were higher than in G3 and C. FT4 levels were significantly lower in G1 (12.294±2.938; p<0.002), G2 (11.091±2.453; p<0.00002) and G3 (10.186±2.537; p<0.00004) than in C (13.734±2.205). FT4 was significantly lower in G2 (p<0.006) and G3 ( p<0.01) than in G1; there was no difference between G2 and G3. FT3 was higher in G1 (3.711±0.559) and G2 (3.60±0.581) than in G3 (3.42±0.549) and C (3.452±0.343); the difference was significant (p<0.01) only between G1 and C. Neither FT3, FT4 nor TSH
Han, Junyan; Zhao, Hongxin; Ma, Yaluan; Zhou, Haiwei; Hao, Yu; Li, Yanmei; Song, Chuan; Han, Ning; Liu, Xiangyi; Zeng, Hui; QIN, MINGZHAO
Abstract As cellular reservoirs, CD16+ monocyte subsets play important roles in the progression of HIV infection. Previous studies have shown that highly active antiretroviral therapy (HAART) reduced the percentages of CD14highCD16+ monocyte subsets, but did not recover the percentages of CD14lowCD16+ subsets. Eighty-four chronic HIV-infected, HAART-naïve individuals and 55 HIV-negative subjects (31 without hyperlipidemia and 24 with hypertriglyceridemia) were enrolled. Plasma HIV-1 RNA level...
Full Text Available Knowledge of mortality trends and predictors among HIV-positive patients in the era of highly active antiretroviral therapy (HAART in resource poor settings is still limited. The aim of this study was to describe trends and predictors of mortality among HIV-positive patients in the era of HAART in Uganda. Data from 2004 to 2013 for adult HIV-positive patients (≥15 years obtaining care and treatment from the AIDS Support Organization in Uganda were reviewed for mortality. Descriptive statistics were analyzed by frequencies and cross tabulations. Calendar period was used as a proxy measure for HAART exposure and a time plot of the proportion of HIV-positive patients reporting dead per year was used to describe the trends. Logistic regression was used to determine the predictors of mortality at bivariate and multivariate levels, respectively. We included in the analysis 95,857 HIV positive patients; 64% were female with median age of 33 years (interquartile range 27-40. Of these 36,133 (38% were initiated on ART and a total of 4279 (4.5% died; 19.5% (835/4279 of those who died had an opportunistic infection. Overall, mortality first increased between 2004 and 2006 and thereafter substantially declined (X2trend=211.9, P<0.001. Mortality was relatively higher in Eastern Uganda compared to other geographical areas. Male gender, older age (>45 years, being from Eastern or Northern Uganda, having none or primary education, being unemployed, advanced immunodeficiency (CD4 count <100 cell/μL or WHO stage III or IV and underweight (<45 kg weight at HAART initiation and calendar period 2004-2008 were significant predictors of mortality (P<0.001. Overall, the expanding coverage of HAART is associated with a declining trend in mortality among HIV positive patients in Uganda. However, mortality trends differed significantly by geographical area and men remain potentially at higher risk of death probably because of delayed initiation on ART. There is urgent
Martinez-Picado, Javier; Deeks, Steven G.
Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on efficiently targeting these three aspects. The degree to which HIV replicates during ART remains controversial. Most studies have failed to find any evidence of HIV evolution in blood, even with samples collected over many years, although a recent very intensive study of three individuals suggested that the virus population does shift, at least during the first few months of therapy. Stronger but still not definitive evidence for replication comes from a series of studies in which standard regimens were intensified with an integration inhibitor, resulting in changes in episomal DNA (blood) and cell-associated RNA (tissue). Limited drug penetration within tissues and the presence of immune sanctuaries have been argued as potential mechanisms allowing HIV to spread during ART. Mathematical models suggest that HIV replication and evolution is possible even without the selection of fully drug-resistant variants. As persistent HIV replication could have clinical consequences and might limit the efficacy of curative interventions, determining if HIV replicates during ART and why, should remain a key focus of the HIV research community. Summary Residual viral replication likely persists in lymphoid tissues, at least in a subset of individuals. Abnormal levels of immune activation might contribute to sustain virus replication. PMID:27078619
Chao, Linda L.; Cardenas, Valerie A.; Meyerhoff, Dieter J.; Rothlind, Johannes C.; Flenniken, Derek L.; Lindgren, Joselyn A.; Weiner, Michael W.
The contingent negative variation, an event-related potential related to neural activity in the frontal lobe and basal ganglia, neuropsychological tests and structural MRI were used to examine CNS function and structure in HIV-positive patients receiving antiretroviral therapy. Relative to controls, HIV patients had smaller thalamic volume and reduced late contingent negative variation amplitude that correlated with caudal atrophy. Behaviorally, viremic patients were more impaired than virall...
Full Text Available Patients with human immunodeficiency virus (HIV infection receiving antiretroviral therapy (ART, despite a reduced viral load and improved immune responses, may experience clinical deterioration. This so called "immune reconstitution inflammatory syndrome (IRIS" is caused by inflammatory response to both intact subclinical pathogens and residual antigens. Cytomegalovirus retinitis is common in HIV-infected patients on ART with a cluster differentiation 4 (CD4+ counts less than 50 cells/mm3. We reported a patient with blurred vision while receiving ART. She had an unmasking classic CMV retinitis after ART.
Hansen, Birgitte Rønde; Petersen, J; Haugaard, S B;
OBJECTIVES: The prevalence of metabolic syndrome (MS) in HIV-infected patients on highly active antiretroviral therapy (HAART) is a subject of debate. We investigated the prevalence of MS in a cohort of Danish HIV-infected patients and estimated the effect of the various classes of antiretroviral...
Abdu Wakawa Ibrahim
Full Text Available Clinical depression is a highly debilitating illness, which is often under-diagnosed and negatively impacts on the quality of life of its sufferers. When it co-exists with other medical conditions, its effect is even more incapacitating. Undiagnosed depression in the context of HIV infection leads to accelerated decline in CD4+ cell counts with concomitant increase in the viral load and poor adherence to the antiretroviral medications which lead to viral mutation and the evolution of resistant strains. This study examined the prevalence of depression, its correlates and the frequency of the diagnosis of the condition among HIV+ subjects on highly active antiretroviral therapy (HAART by the internists and general physicians at the University of Maiduguri Teaching Hospital in Northeastern Nigeria. Three hundred and fifty representative samples of HIV+ adults on HAART were drawn from the Antiretroviral Therapy Clinic of the Institution. Diagnosis of depression was made using the International Classification of Diseases-10 criteria based on Composite International Diagnostic Interview generated data. Socio-demographic and clinical variables were also analyzed for their correlation with depression in the subjects. About 20% of the respondents were diagnosed with clinical depression and no diagnosis of the condition was hitherto entertained in all the respondents. The independent determinants of depression in the participants were: female gender [odds ratio (OR=3.87 (95% confidence interval, CI: 2.089-7.183], past history of psychiatric illness [OR=43.81 (95% CI: 9.731-197.30] and family history of psychiatric illness in first-degree relatives of the subjects [OR=14.364 (95% CI=5.327- 38.729]. Depression is a relatively common psychiatric condition among adults on HAART, there is therefore the need for routine screening of this condition among HIV+ subjects in order to optimize patient care and improve clinical outcomes.
Berretta, Massimiliano; Caraglia, Michele; Martellotta, Ferdinando; Zappavigna, Silvia; Lombardi, Angela; Fierro, Carla; Atripaldi, Luigi; Muto, Tommaso; Valente, Daniela; De Paoli, Paolo; Tirelli, Umberto; Di Francia, Raffaele
The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has dramatically changed the natural approach of HIV-related cancers. Several studies have shown that intensive antiblastic chemotherapy (AC) is feasible in HIV-infected patients with cancer, and that the outcome is similar to that of HIV-negative patients receiving the same AC regimens. However, the concomitant use of HAART and AC can result in drug accumulation or possible toxicity with consequent decreased efficacy of one or both classes of drugs. In fact, many AC agents are preferentially metabolized by CYP450 and drug-drug interactions (DDIs) with HAART are common. Therefore, it is important that HIV patients with cancer in HAART receiving AC treatment at the same time receive an individualized cancer management plan based on their liver and renal functions, their level of bone marrow suppression, their mitochondrial dysfunction, and their genotype profile. The rationale of this review is to summarize the existing data on the impact of HAART on the clinical management of cancer patients with HIV/AIDS and DDIs between antiretrovirals and AC. In addition, in order to maximize the efficacy of antiblastic therapy and minimize the risk of drug-drug interaction, a useful list of pharmacogenomic markers is provided. PMID:27065862
Purpose: To report the clinical outcomes of chemoradiotherapy (CRT) for anal carcinoma in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy. Patients and Methods: Between 1997 and 2008, 21 HIV-positive patients who were receiving highly active antiretroviral therapy were treated with CRT (50.4 Gy at 1.8 Gy/fraction plus a 5.4-10.8-Gy external boost; 5-fluorouracil, 1,000 mg/m2, Days 1-4 and 29-32; and mitomycin C, 10 mg/m2, Days 1 and 29). A retrospective analysis was performed with respect to the tumor response, local control, cancer-specific and overall survival, and toxicity. The immunologic parameters, including pre- and post-treatment CD4 count, viral load, and acquired immunodeficiency syndrome-specific morbidity was recorded during follow-up (median, 53 months; range, 10-99). Results: CRT could be completed in all 21 patients with a reduction in the chemotherapy dose and/or interruption of radiotherapy in 5 and 5 cases, respectively. Acute Grade 3 toxicity occurred in 8 (38%) of the 21 patients. A complete response was achieved in 17 patients (81%), and tumor persistence or early progression was noted in 4 (19%). Six patients (29%) died, 5 of cancer progression and 1 of treatment-related toxicity. The 5-year local control, cancer-specific, and overall survival rate was 59%, 75%, and 67%, respectively. The median CD4 count significantly decreased from 347.5 cells/μL before CRT to 125 cells/μL 3-7 weeks after CRT completion (p <.001). In 6 (32%) of 19 patients, an increase of the HIV viral load was noted. Both parameters returned to the pretreatment values with additional follow-up. Conclusion: Our data have confirmed that in the highly active antiretroviral therapy era, HIV-related anal cancer can be treated with standard CRT without dose reductions. Close surveillance of the immunologic parameters is necessary.
D. Bezemer; F. de Wolf; M.C. Boerlijst; A. van Sighem; T.D. Hollingsworth; M. Prins; R.B. Geskus; L. Gras; R.A. Coutinho; C. Fraser
Objective: Reducing viral load, highly active antiretroviral therapy has the potential to limit onwards transmission of HIV-1 and thus help contain epidemic spread. However, increases in risk behaviour and resurgent epidemics have been widely reported post-highly active antiretroviral therapy. The a
Abdool Karim, Salim S.; Naidoo, Kogieleum; Grobler, Anneke; Padayatchi, Nesri; Baxter, Cheryl; Gray, Andrew L.; Gengiah, Tanuja; Gengiah, Santhanalakshmi; Naidoo, Anushka; Jithoo, Niraksha; Nair, Gonasagrie; El-Sadr, Wafaa M.; Friedland, Gerald; Abdool Karim, Quarraisha
Background We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, optimal time to initiate ART during tuberculosis treatment remains contentious. Methods To address this, we conducted a 3-arm, open-label randomized controlled trial in South Africa in acid-fast bacilli smear positive patients (n=642) with HIV and CD4+ counts IRIS) incidence rates were 20.2 (early) and 7.7 (late) per 100 person-years (IRR=2.62; 95%CI: 1.48,4.82; PIRIS and ART-related adverse events, support early ART initiation in patients with CD4+ counts <50 cells/mm3 and deferred ART initiation to the continuation phase of tuberculosis treatment when CD4+ counts are higher. PMID:22010915
Vladusić, Ivona; Krajinović, Vladimir; Begovac, Josip
Before highly active antiretroviral therapy (HAART) has become available, antibiotic treatment was usually unable to eradicate Rhodococcus (R.) equi infection in HIV-infected patients, although some clinical improvement could be observed in most cases. There are limited data on the outcome of treatment of R. equi pneumonia in the HAART era. We report on a 52-year-old HIV-infected man who presented in poor general condition with an extensive lung cavitation lesion caused by R. equi. The patient recalled exposure to horses on several occasions. R. equi was cultured from the sputum and the isolate was sensitive to imipenem vancomycin, co-trimoxazole, erythromycin, azithromycin, ciprofloxacin and rifampicin. The CD4+ lymphocyte count was 5 cells/mm3 (0.9%) and his plasma HIV-1 RNA viral load was 101000 copies/mL. The patient was successfully treated with a combination of antibiotics that included azithromycin both as part of an initial and suppressive regimen together with antiretroviral treatment. Surgery was not needed and the patient had no relapse for more than five years after the diagnosis and for more than 3 years of suppressive therapy discontinuation. Our literature search revealed 27 patients treated for R. equi infection in the HAART era. However, details on antimicrobial treatment were given in only 3 cases. The optimal drug regimen and duration of treatment for R. equi pneumonia have not yet been established. Because drug resistance may occur during single agent therapy, it has been suggested that at least two antibiotics to which R. equi is susceptible be given. The recommended choices usually include imipenem, antipseudomonal aminoglycosides, erythromycin or azithromycin, vancomycin, rifampin, and levofloxacin. To our knowledge this is the first documented case of long term remission of R. equi pneumonia in an HIV-infected man treated with azithromycin as part of his antibiotic regimen and HAART. PMID:16933840
Walter de Araujo Eyer-Silva
Full Text Available Immune reconstitution inflammatory syndrome (IRIS in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.
Obel, Niels; Farkas, D K; Kronborg, G;
OBJECTIVE: The aim of the study was to examine whether exposure to abacavir increases the risk for myocardial infarction (MI). DESIGN, SETTING AND SUBJECTS: This was a prospective nationwide cohort study which included all Danish HIV-infected patients on highly active antiretroviral therapy (HAART......) from 1995 to 2005 (N = 2952). Data on hospitalization for MI and comorbidity were obtained from Danish medical databases. Hospitalization rates for MI after HAART initiation were calculated for patients who used abacavir and those who did not. We used Cox's regression to compute incidence rate ratios...... (IRR) as a measure of relative risk for MI, while controlling for potential confounders (as separate variables and via propensity score) including comorbidity. MAIN OUTCOME: Relative risk of hospitalization with MI in abacavir users compared with abacavir nonusers. RESULTS: Hospitalization rates for MI...
Kirk, O; Gatell, J M; Mocroft, A;
year; HR = 0.58 [95% confidence intervals: 0.45-0.74], whereas this was not the case for TB; 0.95 [0.74-1.22]). In conclusion, we documented marked decreases in the incidence of TB and to an even larger extent of MAC among HIV-infected patients from 1994 to 1999. The decrease in TB was associated with......The impact of highly active antiretroviral therapy (HAART) among human immunodeficiency virus (HIV)-infected patients on the incidences of mycobacterial infections has not been studied in detail. We assessed incidences of mycobacterial diseases among HIV- infected patients following the...... introduction of HAART, using data from the EuroSIDA study, a European, multicenter observational cohort of more than 7,000 patients. Overall incidences of Mycobacterium tuberculosis (TB) and Mycobacterium avium complex (MAC) were 0.8 and 1.4 cases/100 person-years of follow-up (PYF), decreasing from 1.8 (TB...
Røge, B T; Barfod, T S; Kirk, O;
OBJECTIVES: To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens. METHODS: We retrospectively identified 56 verified primary virological failures (viral load >400 HIV-1 RNA...... copies/mL) among 293 patients randomized to two nucleoside reverse transcriptase inhibitors (NRTIs)+ritonavir+saquinavir (RS-arm) (n=115), two NRTIs+nevirapine+nelfinavir (NN-arm) (n=118), or abacavir+stavudine+didanosine (ASD-arm) (n=60) followed up for a median of 90 weeks. Data on adherence were...... collected from patient files, and genotyping was performed on plasma samples collected at time of failure. RESULTS: Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing...
Full Text Available The introduction of highly active antiretroviral therapy (HAART has caused a marked reduction in the occurrence and severity of parasitic infections, including the toxoplasmic encephalitis (TE. These changes have been attributed to the restoration of cell-mediated immunity. This study was developed to examine the activity of six antiretroviral protease inhibitors (API on Toxoplasma gondii tachyzoites. The six API showed anti-Toxoplasma activity, with IC50 value between 1.4 and 6.6 µg/mL. Further studies at the molecular level should be performed to clarify if the use of API could be beneficial or not for AIDS patients with TE.
Full Text Available Lawrence Mbuagbaw1,2, Renée Cécile Bonono-Momnougui1, Lehana Thabane2,31Centre for the Development of Best Practices in Health (CDBPH, Yaoundé Central Hospital, Yaoundé, Cameroon; 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; 3Biostatistics Unit, Father Sean O'Sullivan Research Centre, St Joseph's Healthcare, Hamilton, Ontario, CanadaAbstract: Poor adherence to highly active antiretroviral therapy (HAART is a major hindrance to the reduction of mortality and morbidity due to HIV. This qualitative study used focus groups to explore the views and experiences of HIV patients on HAART with adherence reminders, especially the text message (SMS [short message service]. The ethnographic data obtained were used to design a clinical trial to assess the effect of motivational text messages versus usual care to enhance adherence to HAART among HIV patients in Yaoundé, Cameroon. Participants appreciated the idea of a timely SMS reminder, and cited the physician as a role model. They expressed concerns about privacy. Long-term life goals were a motivating factor to adhere. Overall, text messaging was viewed positively as a tool with a dual function of reminder and motivator. Messages coming from the attending physician may have a stronger impact. Trials investigating the use of text messages to improve adherence to HAART need to consider the content and timing of SMS, taking into account technical challenges and privacy.Keywords: focus groups, adherence, highly active antiretroviral therapy (HAART, text message, short message service (SMS, human immunodeficiency virus (HIV
Full Text Available The most recent version of the Southern African HIV Clinicians Society’s adult antiretroviral therapy (ART guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomised controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults. The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/μL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.
Fitzgerald Daniel W
Full Text Available Abstract Background We determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART to patients with AIDS in Haiti. Methods We examined data from 218 treatment-naïve adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART. Results The mean total cost of treatment per patient was $US 982 including $US 846 in direct costs, $US 114 for overhead, and $US 22 for societal costs. The direct cost per patient included generic ART medications $US 355, lab tests $US 130, nutrition $US 117, hospitalizations $US 62, pre-ART evaluation $US 58, labor $US 51, non-ART medications $US 39, outside referrals $US 31, and telephone cards for patient retention $US 3. Higher treatment costs were associated with hospitalization, change in ART regimen, TB treatment, and survival for one year. We estimate that 1.5 doctors and 2.5 nurses are required to treat 1000 patients in the first year after initiating ART. Conclusion Initial ART treatment in Haiti costs approximately $US 1,000 per patient per year. With generic first-line antiretroviral drugs, only 36% of the cost is for medications. Patients who change regimens are significantly more expensive to treat, highlighting the need for less-expensive second-line drugs. There may be sufficient health care personnel to treat all HIV-infected patients in urban areas of Haiti, but not in rural areas. New models of HIV care are needed for rural areas using assistant medical officers and community health workers.
Full Text Available Aims: To ascertain and compare between highly active antiretroviral therapy (HAART and non-HAART patients, the stimulated salivary flow rates and unstimulated salivary flow rates (USFR and SSFR and to correlate the salivary flow rates with immune suppression. Materials and Methods: One hundred human-immuno deficiency virus seropositive patients attending RAGAS-YRG CARE were examined and divided into two groups, a HAART group (patients on combination antiretroviral therapy comprising 50 patients and a non-HAART group comprising 50 patients. The HAART group was followed every 3 months after the baseline visit (0 for a period of 9 months, during which a clinical oral examination and collection of unstimulated and stimulated saliva was done. Their salivary gland function was assessed using a xerostomia inventory during each visit. The study on non-HAART group was cross-sectional. Statistical Analysis: Statistical analysis were performed with the aid of the Statistical Package for the Social Sciences (SPSS version 10.05 software. Results: There was no significant difference in mean SSFR and USFR between the two groups at baseline. In the HAART group, the mean stimulated salivary flow rate increased from baseline to 3 months ( P = 0.02, with the increase being maintained at 6 months and 9 months. When salivary flow rates were correlated with Cluster of Differentiation, CD4 counts, patients in the HAART group with a CD4 ≤ 200 at 6 months visit had a higher mean stimulated salivary flow rate when compared with patients with CD4 ≥ 200 ( P = 0.02. The xerostomia inventory did not reveal any significant difference between the two groups and HAART was not significantly associated with xerostomia. Conclusion: In our study HAART was neither associated with xerostomia nor a reduction in salivary flow rate and immune suppression was not a significant factor for decreasing the salivary flow rate.
Carlos J Montoya
Full Text Available Given that highly active antiretroviral therapy (HAART has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40 against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.
Full Text Available Background: Acquired immune deficiency syndrome (AIDS is now considered as a manageable chronic illness. There has been a dramatic reduction in human immunodeficiency virus (HIV related morbidity and mortality due to antiretroviral therapy. A high level of adherence (>95% is required for antiretroviral therapy to be effective. There are many barriers to adherence in both developed and developing countries. Aim: The aim of our study was to determine adherence levels and factors influencing adherence to antiretroviral therapy among people living with HIV. Materials and Methods: Using a cross-sectional study design, 116 HIV positive patients receiving antiretroviral therapy for at least 1 year were interviewed using a semi structured questionnaire. The collected data was analyzed using Statistical Product and Service Solutions (SPSS version 11.5. Chi-square test was done. A P value of < 0.05 was considered statistically significant. Results: Of 116 participants, 63.7% reported adherence ≥ 95%. Mean adherence index was 91.25%. Financial constraints, forgetting to take medication, lack of family care, depression, alcohol use, social stigma and side effects to antiretroviral therapy were barriers for adherence in our study. Conclusion: Adherence to antiretroviral therapy in south India is suboptimal. Intensive adherence counseling should be provided to all patients before initiation ofantiretroviral therapy. Health care providers must identify possible barriers to adherence at the earliest and provide appropriate solutions.
Mark F Cotton
Full Text Available This articles provides a background for antiretroviral therapy in infants and children, incorporating both old and new data. There is increasing data favouring early therapy for all age groups. Below a year of age, all HIV-infected infants should commence therapy and thereafter at higher CD4 thresholds than previous recommendations
C D Aniji
Full Text Available Background.The majority of HIV-positive women in South Africa are of reproductive age, and pregnancies among women using antiretroviral therapy (ART are common. However, there are mixed data regarding the impact of ART on pregnancy outcomes.Objective. To examine the impact of ART on pregnancy outcome according to the timing of initiation of treatment.Methods. A retrospective cohort study was conducted among women delivering at a tertiary hospital from 1 October 2008 to 31 March 2009.Results. A total of 245 mothers were receiving ART: 76 mothers (31% started ART pre-conception and 169 mothers (69% started ART after the first trimester. No significant differences were observed in the rates of preterm delivery and low birth weight (LBW between the pre- and post-conception groups (21% v. 24% and 21% v. 25%, respectively.Conclusion. In this cohort of women receiving ART in pregnancy, timing of ART initiation did not have any adverse effect on the measured pregnancy outcomes such as preterm delivery and LBW.
Bruce L GILLIAM; Robert R REDFIELD
China has recognized the threat of HIV to its population and responded with a national antiretroviral treatment (ART)program. However, high ART failure rates and the spread of resistance within populations are important realities to consider when developing and managing ART programs in China and worldwide. Concepts which will define treatment success and local and national programmatic goals are 1) access to ART, 2) durability of ART at the patient level, 3)scalability of treatment modalities, and the 4) sustainability of the program at the community or national level. In the face of limited resources, China must also consider when to start ARV therapy, which agents to use, when to switch them, and how to treat highly experienced patients with drug resistance. The optimal ARV regimen to start with is changing frequently with the introduction of new agents and the presentation of new data. Currently, a regimen including tenofovir, emtricitabine or lamivudine and a nonnucleoside reverse transcriptase inhibitor appears to have optimal characteristics to treat HIV/AIDS in China. However, critical to all of these choices is the evaluation of programs implemented to insure wide scale success. China has wisely begun this process of evaluating the performance of local programs through systematic monitoring and evaluation of treatment outcomes. This will allow regimens and programs that work to be expanded, and programs with high failure rates to be eliminated. In the end,evidence based data supporting treatment strategies will allow China to successfully confront its AIDS epidemic early and prevent its tragic consequences
Ladjane Santos Wolmer de Melo
Full Text Available Introduction of highly active antiretroviral therapy has resulted in a significant reduction in morbimortality and significant changes in the causes of death among HIV/AIDS patients. For this reason, it has become essential to monitor survival and causes of death. We constructed a survival curve based on 597 adult patients notified as AIDS cases between 1997 and 2004, at the Hospital das Clínicas, Federal University of Pernambuco, Recife, Brazil. Among those patients, 150 (25% progressed to death by December, 2005. Of these, 119 were studied in detail. The data were collected from notification files of the State Health Department and the State Mortality Information System, and were complemented by analysis of medical records. These 597 patients had a survival rate of 88%, 86% and 82% after one, two and five years, respectively, and a 75% likelihood of surviving to 1,984 days (66 months. Most of the deaths occurred during the first months after the diagnosis (median, 129 days. Patients who died were predominantly young men who had sexual exposure and came from Recife (the state capital or its metropolitan region. When the patients were first seen, a large proportion had already presented severe signs of immunodeficiency. Comparing the patients within this group, the characteristics that were associated with lower survival were: male sex, hemoglobin < 10 mg/dL, lymphocytes < 1,000/mm³, use of fewer therapeutic drugs and antiretroviral regimens and non-introduction of protease inhibitors. Most of them died from AIDS-related diseases, particularly undefined respiratory infections.
Zhang, Shun; Rust, George; Cardarelli, Kathryn; Felizzola, Jesus; Fransua, Mesfin; Stringer, Harold G.
We examined the impact of antiretroviral treatment adherence among Hepatitis C co-infected HIV patients on survival and clinical outcomes. We analyzed Medicaid claims data from fourteen southern states from 2005-2007, comparing survival and clinical outcomes and cost of treatment for HIV and hepatitis-C co-infected patients (N=4,115) at different levels of adherence to antiretroviral therapy.More than one in five patients (20.5%) showed less than 50% adherence to antiretroviral treatment, but there were no racial-ethnic or gender disparities. Significant survival benefit was demonstrated at each incremental level of adherence to antiretroviral therapy (one-year mortality ranging from 3.5% in the highest adherence group to 26.0% in the lowest). Low adherence patients also had higher rates of hospitalization and emergency department visits. Relative to patients with high (>95%) ART-adherence, those with less than 25% treatment adherence had four-fold greater risk of death (adjusted odds ratio 4.22 [95% CI, 3.03,5.87]). Non-drug Medicaid expenditures were lower for high adherence patients, but cost of medications drove total Medicaid expenditures higher for high-adherence patients. Cost per quality-adjusted life year (QALY) saved (relative to the <25% low-adherence group) ranged from $21,874 for increasing adherence to 25-50% to $37,229 for increasing adherence to 75-95%. Adherence to antiretroviral therapy for patients with HIV and hepatitis C co-infection is associated with lower adverse clinical outcomes at a Medicaid cost per QALY commensurate with other well-accepted treatment and prevention strategies. Further research is needed to identify interventions which can best achieve optimal ART adherence at a population scale. PMID:25814041
Full Text Available Immunization with a pandemic influenza A H1N1 2009 was recommended for HIV-infected patients. However, there is limited information concerning the impact of immunization with this vaccine on immune activation and HIV viral replication. In this study, 45 HIV-infected children and adolescents receiving antiretroviral therapy were immunized with a 2-dose series of nonadjuvated monovalent influenza A H1N1 2009 vaccine upon enrollment and approximately 1 month later. Immunogenicity was determined by haemagglutination inhibition assay. The level of immune activation was determined by identification of CD38 and HLA-DR on CD8+ T cells. Patients were divided into 2 groups which include patients who had an undetectable HIV viral load (HIV detectable group and patients who show virological failure (HIV nondetectable group. The results showed seroconversion rate of 55.2% in HIV nondetectable group, whereas 31.3% was found in HIV detectable group. Both groups of patients showed no major increase in immune activation after immunization. Interestingly, a decrease in the frequency of CD8+ T cells that coexpressed CD38 and HLA-DR was observed after immunization in both groups of patients. We suggested that immunization with influenza A H1N1 2009 vaccine can induce immune response to the pandemic virus without major impact on HIV viral replication and immune activation.
Isoniazid-resistant Mycobacterium kansasii in an HIV-positive patient, and possible development of immune reconstitution inflammatory syndrome after initiation of highly active antiretroviral therapy: case report
Full Text Available Non-tuberculous mycobacteria are rare but important causes of infection in HIV-positive individuals. A 28-year-old HIV-positive male presented with a high fever, non-productive cough, right subcostal pain, splenomegaly, a very low CD4 count, elevated C-reactive protein and erythrocyte sedimentation rate, and a normal white blood cell count. The suspicion of tuberculosis (TB was very high, and sputum samples were positive for acid-fast bacilli. Standard quadruple anti-TB therapy was initiated, but once culture of the sample revealed Mycobacterium kansasii, pyrazinamide was withdrawn. Highly active antiretroviral therapy (HAART was initiated soon after, consisting of abacavir/lamivudine and efavirenz. The patient's general condition deteriorated 2 weeks after HAART initiation, which could have been due to the development of immune reconstitution inflammatory syndrome (IRIS. The patient recovered and was discharged in good condition. However, the results of resistance testing of the isolated organism arrived after discharge, and showed isoniazid and streptomycin resistance. This is the first case report of M. kansasii infection from Serbia and shows the difficulties encountered during the course of treatment.
Isoniazid-resistant Mycobacterium kansasii in an HIV-positive patient, and possible development of immune reconstitution inflammatory syndrome after initiation of highly active antiretroviral therapy: case report.
Despotovic, A; Savic, B; Salemovic, D; Ranin, J; Jevtovic, Dj
Non-tuberculous mycobacteria are rare but important causes of infection in HIV-positive individuals. A 28-year-old HIV-positive male presented with a high fever, non-productive cough, right subcostal pain, splenomegaly, a very low CD4 count, elevated C-reactive protein and erythrocyte sedimentation rate, and a normal white blood cell count. The suspicion of tuberculosis (TB) was very high, and sputum samples were positive for acid-fast bacilli. Standard quadruple anti-TB therapy was initiated, but once culture of the sample revealed Mycobacterium kansasii, pyrazinamide was withdrawn. Highly active antiretroviral therapy (HAART) was initiated soon after, consisting of abacavir/lamivudine and efavirenz. The patient's general condition deteriorated 2 weeks after HAART initiation, which could have been due to the development of immune reconstitution inflammatory syndrome (IRIS). The patient recovered and was discharged in good condition. However, the results of resistance testing of the isolated organism arrived after discharge, and showed isoniazid and streptomycin resistance. This is the first case report of M. kansasii infection from Serbia and shows the difficulties encountered during the course of treatment. PMID:26603644
Manuela G. Neuman
Full Text Available The present paper describes possible connections between antiretroviral therapies (ARTs used to treat human immunodeficiency virus (HIV infection and adverse drug reactions (ADRs encountered predominantly in the liver, including hypersensitivity syndrome reactions, as well as throughout the gastrointestinal system, including the pancreas. Highly active antiretroviral therapy (HAART has a positive influence on the quality of life and longevity in HIV patients, substantially reducing morbidity and mortality in this population. However, HAART produces a spectrum of ADRs. Alcohol consumption can interact with HAART as well as other pharmaceutical agents used for the prevention of opportunistic infections such as pneumonia and tuberculosis. Other coinfections that occur in HIV, such as hepatitis viruses B or C, cytomegalovirus, or herpes simplex virus, further complicate the etiology of HAART-induced ADRs. The aspect of liver pathology including liver structure and function has received little attention and deserves further evaluation. The materials used provide a data-supported approach. They are based on systematic review and analysis of recently published world literature (MedLine search and the experience of the authors in the specified topic. We conclude that therapeutic and drug monitoring of ART, using laboratory identification of phenotypic susceptibilities, drug interactions with other medications, drug interactions with herbal medicines, and alcohol intake might enable a safer use of this medication.
Ostrowski, S R; Ullum, H; Pedersen, B K;
highly active antiretroviral therapy (HAART), low-level viraemia, proviral-DNA or immune activation in HIV-1 infected patients. A total of 101 HAART-treated HIV-1 infected patients with < or = 200 HIV-RNA copies/ml were followed prospectively for 24 months. HIV-RNA was investigated 3-monthly and 2B4...... expression on CD3- CD16+ NK cells and CD3+ CD8+ cells, proviral-DNA and plasma soluble tumour necrosis factor receptor (sTNFr)-II were investigated 6-monthly. For comparison, 2B4 expression was investigated in 20 healthy individuals. The concentration of 2B4+ NK cells was initially reduced in HIV-1 infected...... follow-up (both P < 0.001). Higher levels of proviral-DNA carrying cells and plasma sTNFrII were associated with reductions in the concentration of 2B4+ NK cells (all P < 0.05). HIV-RNA had no effect on 2B4 expression on NK cells or CD3+ CD8+ cells. These findings demonstrate that the concentration of 2B...
Read, T; Mijch, A; Fairley, C K
Adherence to antiretroviral therapy is a powerful predictor of response to therapy. For optimal antiretroviral therapy response, individuals need to take more than 95% of their prescribed medication. The most widely used method for measuring adherence is self-report of the number of missed doses and this should be done at every clinic visit. There are several well-recognized predictors of poor adherence, such as illicit drug use, depression, limited knowledge or ambivalence about starting treatment. Adherence can be improved by addressing these issues or through other means such as pill boxes or electronic reminders. PMID:12752896
Full Text Available Abstract Background The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART. Results Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy. In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.
Adherence to highly active antiretroviral therapy and associated factors among children at the University of Gondar Hospital and Gondar Poly Clinic, Northwest Ethiopia: a cross-sectional institutional based study
Dachew, Berihun Assefa; Tesfahunegn, Tadis Brhane; Birhanu, Anteneh Messele
Background The efficacy of antiretroviral therapy (ART) in suppressing viral replication and delaying the progress of the acquired immunodeficiency syndrome (AIDS) is related to optimal adherence. Adherence is a challenge in all HIV infected people on ART. It is especially a concern in children because of factors relating to children such as age, disclosure status of HIV sero status, and understanding of the medication. This study assessed the level of adherence to highly active antiretrovira...
Hansen, Ab; Obel, N; Nielsen, H;
Objective The aim of the study was to compare changes in bone mineral density (BMD) over 144 weeks in HIV-infected patients initiating nucleoside reverse transcriptase inhibitor (NRTI)-sparing or protease inhibitor-sparing highly active antiretroviral therapy (HAART). Methods Sixty-three HAART......, compared with -3.2% (95% CI -4.4 to -2.1) and -1.9% (95% CI -3.5 to -0.3) in the protease inhibitor-sparing arm. Hip BMD declined until week 48 before stabilizing. In the NRTI-sparing arm, BMD had decreased by -5.1% (95% CI -7.1 to -3.1) at week 48 and -4.5% (95% CI -6.9 to -2.1) at week 144, compared with...... -6.1% (95% CI -8.2 to -4.0) and -5.0% (95% CI -6.8 to -3.1) in the protease inhibitor-sparing arm. There were no significant differences between arms. Low baseline CD4 cell count was independently associated with spine (P=0.007) and hip (P=0.04) BMD loss and low body mass index with hip BMD loss (P=0...
Richard K. D. Ephraim
Full Text Available Background: Crystalluria is associated with some highly active anti-retroviral therapies (HAART′s used in the management of HIV/AIDS. Aims: This study used light microscopy to establish the prevalence of crystalluria among HIV/AIDS patients on HAART and identified the routine crystals present in their urine. Materials and Methods: In this simple randomised cross-sectional study, 200 HIV/AIDS participants, comprising 150 on HAART and 50 HAART-naοve were recruited from the HIV clinic at the Komfo Anokye Teaching Hospital (KATH. Urine and blood samples were collected, for urinalysis and the determination of the CD4 count, respectively. A well-structured pre-tested questionnaire was used to obtain socio-demographic data and clinical history of the participants. Results: The prevalence of crystalluria was higher among HIV-infected persons on HAART than those not on HAART (6.7% vs 4%; P = 0.733. Calcium oxalate and triple phosphate crystals were the crystal types present in their urine (3.5% and 2.5%, respectively and was present only in HIV subjects on first line of treatment (without protease inhibitors. Participants aged between 40-50 years and those with hypersthenuria and acidic urine had the highest amount of crystalluria (41.6%, 83.3%, and 58.3%, respectively. Conclusion: HAART is associated with crystalluria in HIV patients. Light microscopy will be of disgnostic value in resource limited settings.
Randé, H; Rouffy, D
Since 2010, the Pharmacie et Aide Humanitaire (PAH) in Casamance (Senegal) has been maintaining a software package (Tacojo) that allows monthly monitoring of the distribution of treatment to every patient with HIV infection receiving highly active antiretroviral therapy (HAART). We used this program to set up measures to prevent the loss to follow-up of patients receiving HAART. Our involvement focused on two main areas. First, each patient is routinely contacted after inclusion, to help us to understand the patient's experience of the disease and the treatment. This process aims to improve adherence to the treatment. Then, all patients who miss an appointment are routinely contacted by telephone within seven days of that appointment. The goal is to understand the reasons for the absence and to encourage patients to continue their treatment. Despite the lack of distance due to the relative newness of this program, these preventive measures have shown hopeful results (80% of the patients came back after a call). It would be interesting to apply it in a sustainable manner and in more medical facilities. PMID:27412981
May, M; Sterne, J; Costagliola, D;
BACKGROUND: Highly active antiretroviral therapy (HAART) for the treatment of HIV infection was introduced a decade ago. We aimed to examine trends in the characteristics of patients starting HAART in Europe and North America, and their treatment response and short-term prognosis. METHODS: We......, 1998, 1999, 2000, 2001, and 2002-03. The primary endpoints were the hazard ratios for AIDS and for death from all causes in the first year of HAART, which were estimated using Cox regression. RESULTS: The proportion of heterosexually infected patients increased from 20% in 1995-96 to 47% in 2002...... 83% in 2002-03. Compared with 1998, adjusted hazard ratios for AIDS were 1.07 (95% CI 0.84-1.36) in 1995-96 and 1.35 (1.06-1.71) in 2002-03. Corresponding figures for death were 0.87 (0.56-1.36) and 0.96 (0.61-1.51). INTERPRETATION: Virological response after starting HAART improved over calendar...
Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred;
BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS: We randomly assigned HIV......-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or...... another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. RESULTS: A total of 4685 patients were followed for a mean of 3.0 years. At study...
OBJECTIVE: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. SUBJECTS:: Forty-nine thousand nine hundred and twenty-one antiretroviral-naive indiv......OBJECTIVE: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. SUBJECTS:: Forty-nine thousand nine hundred and twenty-one antiretroviral...... using survival methods. Ten age strata were chosen: less than 2, 2-5, 6-12, 13-17, 18-29, 30-39 (reference group), 40-49, 50-54, 55-59 and 60 years or older; those aged 6 years or more were included in multivariable analyses. RESULTS: The four youngest age groups had 223, 184, 219 and 201 individuals...... and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and immunological...
Rönsholt, Frederikke F; Ostrowski, Sisse Rye; Katzenstein, Terese Lea;
Immune activation is decreased by combination antiretroviral therapy (cART) in patients infected with human immunodeficiency virus (HIV), but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T-cell...
Bracher, Linda; Valerius, Niels Henrik; Rosenfeldt, Vibeke;
children treated with HAART. Initial HAART included 2 nucleoside reverse-transcriptase inhibitors in combination with either a protease inhibitor (n =38) or a non-nucleoside reverse-transcriptase inhibitor (n =12). 19 (39%) patients were previously treated with mono- or dual therapy. Baseline...
Full Text Available BACKGROUND: Access to highly active antiretroviral therapy (HAART is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. METHODS: Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. RESULTS: Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3% failed a second line regimen and 44 (0.8% received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18-2.00, p = 0.001, younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86-4.10, p<0.001, and prior AIDS (HR = 2.17, 95% CI 1.62-2.90, p<0.001. CONCLUSIONS: Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.
Cesar, Carina; Shepherd, Bryan E.; Jenkins, Cathy A.; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P.; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro
Background Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. Methods Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. Results Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001). Conclusions Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted. PMID:25221931
Iroezindu, M O
Opportunistic infections (OIs) cause significant morbidity/mortality in human immunodeficiency virus (HIV)-infected individuals globally. Disparities between high-income countries (HICs) and low/middle-income countries (LMICs) in the magnitude of HIV-related OIs in pre-highly active antiretroviral therapy (HAART) populations was reviewed, and HAART-induced decline in OIs was further compared between the two settings. Studies published in English from onset of HIV epidemic up to December 2013 were searched in PubMed, Google, Google Scholar, and African Journal online. An article was included if (a) the study was conducted in HIC or LMIC, (b) the age of the participants was ≥12 years, (c) the HAART status of the participants was stated, and (d) various types of OIs were investigated. In predominantly pre-HAART populations, the incidence and prevalence of overall HIV-related OIs in HIC ranged from 5.5 to 50.0 per 100 person-years (PY) and 27.4-56.7%, respectively. In LMIC, the respective overall incidence and prevalence of OIs were 12.2-93.9 per 100 PY and 32.0-77.7%. Pneumocystis jirovecii pneumonia, candidiasis, Cytomegalovirus disease, Mycobacterium avium complex disease, and Kaposi's sarcoma were the most frequent OIs in HICs while tuberculosis, candidiasis, chronic diarrhea, and cryptococcosis were predominant in LMICs. The introduction of HAART led to substantial reduction in the incidence of OIs with more impressive percentage decline in HICs (43-97%) compared to 30-79% in LMICs. Disparities in the magnitude of HIV-related OIs between HICs and LMICs are evident both in the pre-HAART and post-HAART era. Efforts to optimize HAART-induced decline in HIV-related OIs should become a global health priority irrespective of prevailing socioeconomic circumstances. PMID:27144071
Opportunistic infections (OIs) cause significant morbidity/mortality in human immunodeficiency virus (HIV)-infected individuals globally. Disparities between high-income countries (HICs) and low/middle-income countries (LMICs) in the magnitude of HIV-related OIs in pre-highly active antiretroviral therapy (HAART) populations was reviewed, and HAART-induced decline in OIs was further compared between the two settings. Studies published in English from onset of HIV epidemic up to December 2013 were searched in PubMed, Google, Google Scholar, and African Journal online. An article was included if (a) the study was conducted in HIC or LMIC, (b) the age of the participants was ≥12 years, (c) the HAART status of the participants was stated, and (d) various types of OIs were investigated. In predominantly pre-HAART populations, the incidence and prevalence of overall HIV-related OIs in HIC ranged from 5.5 to 50.0 per 100 person-years (PY) and 27.4-56.7%, respectively. In LMIC, the respective overall incidence and prevalence of OIs were 12.2-93.9 per 100 PY and 32.0-77.7%. Pneumocystis jirovecii pneumonia, candidiasis, Cytomegalovirus disease, Mycobacterium avium complex disease, and Kaposi's sarcoma were the most frequent OIs in HICs while tuberculosis, candidiasis, chronic diarrhea, and cryptococcosis were predominant in LMICs. The introduction of HAART led to substantial reduction in the incidence of OIs with more impressive percentage decline in HICs (43-97%) compared to 30-79% in LMICs. Disparities in the magnitude of HIV-related OIs between HICs and LMICs are evident both in the pre-HAART and post-HAART era. Efforts to optimize HAART-induced decline in HIV-related OIs should become a global health priority irrespective of prevailing socioeconomic circumstances.
Eduardo Milton Ramos-Sanchez
Full Text Available Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.
Valerie J. Ehlers; Esther Kip; Van der Wal, Dirk M.
Anti-retroviral drugs (ARVs) are supplied free of charge in Botswana. Lifelong adherence to anti-retroviral therapy (ART) is vital to improve the patient’s state of well-being and to prevent the development of strains of the human immunodef ciency virus (HIV) that are resistant to ART. Persons with ART-resistant strains of HIV can spread these to other people, requiring more expensive ART with more severe side-effects and poorer health outcomes. The purpose of this exploratory, descriptive, q...
Pepper, Dominique J.; Marais, Suzaan; Wilkinson, Robert J.; Bhaijee, Feriyl; De Azevedo, Virginia; Meintjes, Graeme
Background In the developing world, the principal cause of death among HIV-infected patients is tuberculosis (TB). The initiation of antiretroviral therapy (ART) during TB therapy significantly improves survival, however it is not known which barriers prevent eligible TB patients from initiating life-saving ART. Method Setting. A South African township clinic with integrated tuberculosis and HIV services. Design. Logistic regression analyses of a prospective cohort of HIV-1 infected adults (≥...
Full Text Available Human immunodeficiency virus type 1 (HIV-1 and type 2 (HIV-2 are the causative agents of AIDS. HIV-2 is prevalent at moderate to high rates in West African countries, such as Senegal, Guinea, Gambia, and Cape Verde. Diagnosis of HIV-2 is made with a positive HIV-1/HIV-2 ELISA or simple/rapid assay, followed by one or two confirmatory tests specific for HIV-2. Following CD4+ T cell counts, HIV-2 viral burden and clinical signs and symptoms of immunodeficiency are beneficial in monitoring HIV-2 disease progression. Although non-nucleoside reverse transcriptase inhibitors are ineffective in treating HIV-2, nucleoside reverse transcriptase inhibitors and protease inhibitors can be effective in dual and triple antiretroviral regimens. Their use can decrease HIV-2 viral load, increase CD4+ T cell counts and improve AIDS-related symptoms. HIV-2 resistance to various nucleoside reverse transcriptase inhibitors and protease inhibitors, including zidovudine, lamivudine, ritonavir and indinavir, has been identified in some HIV-2 infected patients on antiretroviral therapy. The knowledge of HIV-2 peculiarities, when compared to HIV-1, is crucial to helping diagnose and guide the clinician in the choice of the initial antiretroviral regimen and for monitoring therapy success.
developed countries. These findings have implications for decision makers in designing safe strategies that maintain HIV-1 suppression at lower costs.Keywords: health economics, cost analysis, antiretroviral agents economics, antiretroviral therapy highly active, protease inhibitor monotherapy
Full Text Available Abstract Background The psychosocial development of pediatric HIV patients has not been extensively evaluated. The study objectives were to evaluate whether emotional and social functions are differentially associated with HIV-related complications. Methods A matched case-control study design was conducted. The case group (n = 20 consisted of vertically infected children with HIV (aged 3-18 years receiving HAART in Greece. Each case was matched with two randomly selected healthy controls from a school-based population. CNS imaging and clinical findings were used to identify patients with HIV-related neuroimaging abnormalities. The Wechsler Intelligence Scale III and Griffiths Mental Abilities Scales were applied to assess cognitive abilities. The age specific Strengths and Difficulties Questionnaire was used to evaluate emotional adjustment and social skills. The Fisher's exact test, student's t-test, and Wilcoxon rank sum test were used to compare categorical, continuous, and ordinal scores, respectively, of the above scales between groups. Results HIV patients without neuroimaging abnormalities did not differ from patients with neuroimaging abnormalities with respect to either age at HAART initiation (p = 0.306 or months of HAART treatment (p = 0.964. While HIV patients without neuroimaging abnormalities had similar cognitive development with their healthy peers, patients with neuroimaging abnormalities had lower mean General (p = 0.027 and Practical (p = 0.042 Intelligence Quotient scores. HIV patients without neuroimaging abnormalities had an increased likelihood of both Abnormal Emotional Symptoms (p = 0.047 and Hyperactivity scores (p = 0.0009. In contrast, HIV patients with neuroimaging abnormalities had an increased likelihood of presenting with Abnormal Peer Problems (p = 0.033. Conclusions HIV patients without neuroimaging abnormalities are more likely to experience maladjustment with respect to their emotional and activity spheres
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.
Ferreira Rosa Maria Carvalho
Full Text Available The aim of this study was to determine the prevalence of non-tuberculous mycobacteria (NTM isolates at University Hospital, Reference Center for Aids in Rio de Janeiro, Brazil, during one year. We used standard biochemical tests for species identification and IS1245 PCR amplification was applied as a Mycobacterium avium specific identification marker. Four hundred and four specimens from 233 patients yielded acid-fast bacilli growth. M. tuberculosis was identified in 85% of the patients and NTM in 15%. NTM disseminated infection was a common event correlated with human immunodeficiency virus (HIV infected patients and only in HIV negative patients the source of NTM was non sterile site. M. avium complex (MAC was biochemically identified in 57.8% (49/83 of NTM isolates, most of them from sterile sites (75.5%, and in 94% (46/49 the IS 1245 marker specific for M. avium was present. Twenty NTM strains showed a MAC biochemical pattern with the exception of a urease-positive (99% of MAC are urease-negative, however IS1245 was detected in 96% of the strains leading to their identification as M. avium. In this group differences in NTM source was not significant. The second most frequently isolated NTM was identified as M. scrofulaceum (7.2%, followed by M. terrae (3.6%, M. gordonae (2.4%, M. chelonae (1.2%, M. fortuitum (1.2% and one strain which could not be identified. All were IS1245 negative except for one strain identified as M. scrofulaceum. It is interesting to note that non-sterile sites were the major source of these isolates (92.8%. Our finding indicated that M. avium is still the major atypical species among in the MAC isolates recovered from Brazilian Aids patients without highty active antiretroviral therapy schema. Some discrepancies were seen between the identification methods and further investigations must be done to better characterize NTM isolates using other phenotypic and genotypic methods.
Full Text Available Abstract Background Highly active antiretroviral therapy (HAART improves the immune function and decreases morbidity, mortality and opportunistic infections (OIs in HIV-infected patients. However, since the use of HAART, immune restoration disease (IRD has been described in association with many OIs. Our objective was to determine the proportion of IRD, changes in CD4+ T-cell count and possible risk factors of IRD in HIV-infected patients. Methods A retrospective study of all HIV- infected patients starting HAART between September 1, 2005 and August 31, 2006 at Zewditu memorial hospital HIV clinic, Addis Ababa, Ethiopia was conducted. All laboratory and clinical data were extracted from computerized clinic records and patient charts. Results A total of 1166 HIV- infected patients with mean ± SD age of 36 ± 9.3 years were on HAART. IRD was identified in 170 (14.6% patients. OIs diagnosed in the IRD patients were tuberculosis (66.5%, 113/170, toxoplasmosis (12.9%, 22/170, herpes zoster rash (12.9%, 22/170, Pneumocystis jirovecii pneumonia (4.1%, 7/170, and cryptococcosis (3.5%, 6/170. Of the 170 patients with IRD, 124 (72.9% patients developed IRD within the first 3 months of HAART initiation. Low baseline CD4+ T-cell count (odds ratio [OR], 3.16, 95% confidence interval [CI], 2.19-4.58 and baseline extra pulmonary tuberculosis (OR, 7.7, 95% CI, 3.36-17.65 were associated with development of IRD. Twenty nine (17.1% of the IRD patients needed to use systemic anti-inflammatory treatment where as 19(11.2% patients required hospitalization associated to the IRD occurrence. There was a total of 8 (4.7% deaths attributable to IRD. Conclusions The proportion and risk factors of IRD and the pattern of OIs mirrored reports from other countries. Close monitoring of patients during the first three months of HAART initiation is important to minimize clinical deterioration related to IRD.
Full Text Available Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV. In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known.HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030 and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg. At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log(10 IU/mL and 4.47 log(10 copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24% lost HBsAg and 7 of 8 (88% HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months. HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L.All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of co-infected patients
This paper examines the effects of antiretroviral therapy (ART) on demand for HIV testing and of ART-induced testing on demand for risky sexual behavior. I provide a model of sexual behavior decision-making under uncertainty and estimate the structural parameters of the model using nationally representative survey data from Zambia on HIV testing decisions before and after the introduction of ART. The empirical results indicate that although the introduction of ART increased demand for HIV tes...
Canter, Jeffrey A.; Robbins, Gregory K.; Selph, Doug; Clifford, David B.; Kallianpur, Asha R.; Shafer, Robert; Levy, Shawn; Murdock, Deborah G.; Ritchie, Marylyn D.; Haas, David W.; Hulgan, Todd
Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs) was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine if NRTI-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic blacks with genomic data, 51 (33%) develope...
Byakika-Tusiime, Jayne; Polley, Eric C.; Oyugi, Jessica H.; Bangsberg, David R.
Objective: To estimate the population-level causal effect of source of payment for HIV medication on treatment adherence using Marginal Structural Models. Methods: Data were obtained from an observational cohort of 76 HIV-infected individuals with at least 24 weeks of antiretroviral therapy treatment from 2002 to 2007 in Kampala, Uganda. Adherence was the primary outcome and it was measured using the 30-day visual analogue scale. Marginal structural models (MSM) were used to estimate the effe...
Chun, Tae-Wook; Shawn Justement, J.; Murray, Danielle; Kim, Connie J.; Blazkova, Jana; Hallahan, Claire W.; Benko, Erika; Costiniuk, Cecilia T.; Kandel, Gabor; Ostrowski, Mario; Kaul, Rupert; Moir, Susan; Casazza, Joseph P.; Koup, Richard A.; Kovacs, Colin; Fauci, Anthony S.
Elite controllers suppress human immunodeficiency virus (HIV) viremia to below the limit of detection in the absence of antiretroviral therapy (ART). However, precise frequencies of CD4+ T cells carrying replication-competent HIV and/or the dynamics of the infectious viral reservoirs in response to initiation and discontinuation of ART in elite controllers are unknown. We show that the size of the pool of CD4+ T cells harboring infectious HIV diminished significantly after initiation of ART and rebounded to baseline upon cessation of therapy. Our data provide compelling evidence that persistent viral replication occurs in untreated elite controllers even in the absence of detectable plasma viremia. PMID:23847057
Full Text Available OBJECTIVES: To investigate the duration of sequential HAART regimens and predictors of first-line regimen discontinuation among HIV-1 vertically infected children and adolescents. DESIGN: Multicentre survey of antiretroviral-naïve patients enrolled in the HIV-Paediatric Cohor,t CoRISpeS-Madrid Cohort, Spain. METHODS: Patients with a follow-up of ≥ 1 month spent on HAART, with available baseline CD4 count and HIV-viral load (VL were included. Time spent on sequential HAART regimens was estimated and multivariable regression was used to identify predictors of time to first-line regimen discontinuation. RESULTS: 104 patients were followed for a median 8 years after starting HAART among 1996-2012; baseline %CD4 was 21.5 (12.3-34.0and viral load was 5.1 (4.6-5.6 log10 copies/mL. Patients received a mean of 1.9 regimens. Median time on first-line HAART (n = 104 was 64.5 months; second HAART (n = 56 69.8 months; and third HAART (n = 21 66.5 months. Eleven (11% patients were lost to follow-up while on first-line HAART and 54% discontinued (cumulative incidence of 16% and 38% by 1 and 3-year, respectively. The main predictor of first-line regimen discontinuation was suboptimal adherence to antiretrovirals (AHR: 2.60; 95% CI: 1.44-4.70. CONCLUSIONS: Adherence to therapy was the main determinant of the duration of the first-line HAART regimen in children. It is important to identify patients at high risk for non-adherence, such as very young children and adolescents, in provide special care and support to those patients.
Yang, Tina Yang
AIM The aim was to explore the experiences of HIV-positive individuals before and after gaining access to antiretroviral therapy in Wakiso District, Uganda and how antiretroviral therapy impacts certain aspects of those living with HIV, such as sexual behavior, support systems, faith and personal identity. METHODS Based on secondary data analysis of “Life On Antiretroviral Therapy: People’s Adaptive Coping And Adjustment To Living With HIV As A Chronic Condition In Wakiso District, Uganda” by...
Hartman, Tracy L.; Buckheit, Robert W.
During the past three decades, over thirty-five anti-HIV-1 therapies have been developed for use in humans and the progression from monotherapeutic treatment regimens to today's highly active combination antiretroviral therapies has had a dramatic impact on disease progression in HIV-1-infected individuals. In spite of the success of AIDS therapies and the existence of inhibitors of HIV-1 reverse transcriptase, protease, entry and fusion, and integrase, HIV-1 therapies still have a variety of...
Lodi, Sara; Dray-Spira, Rosemary; Touloumi, Giota;
nine HIV cohorts within COHERE in Austria, France, Greece, Italy, Spain and Switzerland, collecting data on level of education in categories of the UNESCO/International Standard Classification of Education standard classification: non-completed basic, basic, secondary and tertiary education. We......OBJECTIVES: In Europe and elsewhere, health inequalities among HIV-positive individuals are of concern. We investigated late HIV diagnosis and late initiation of combination antiretroviral therapy (cART) by educational level, a proxy of socioeconomic position. DESIGN AND METHODS: We used data from...
Kalapila, Aley G; Marrazzo, Jeanne
Human immunodeficiency virus (HIV) infection is considered a chronic medical condition. Several new drugs are available, including fixed-dose combination tablets, that have greatly simplified combination antiretroviral therapy (ART) regimens to treat HIV, while increasing the life-expectancy of infected individuals. In the last decade, multiple well-regarded studies have established the benefits of using ART in high-risk, HIV-negative persons to prevent HIV acquisition. The primary care provider must not only understand commonly encountered issues pertaining to ART, such as toxicities and drug interactions, but also needs to be aware of using ART for HIV prevention. PMID:27235622
Carlos del Rio; Jack DeHovitz; Kenrad Nelson; Akaki Abutidze; Pati Gabunia; Natia Dvali; Otar Chokoshvili; Nikoloz Chkhartishvili; Lali Sharvadze; Tengiz Tsertsvadze
Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/mm3. During followup, 152 (...
April, Michael D; Wood, Robin; Berkowitz, Bethany K.; Paltiel, A David; Anglaret, Xavier; LOSINA, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.
Background. We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), secon...
Full Text Available We report 2 cases illustrating that it is too simplistic to link nevirapine (NVP toxicity exclusively to individuals with immune preservation. Not enough is known about the mechanism of hepatotoxicity or cutaneous eruption to predict these events. This type of hypersensitivity reaction occurs rarely among HIV-exposed infants taking NVP prophylaxis or antiretroviral therapy (ART-experienced adults with complete plasma viral load suppression. Conversely, HIV-uninfected adults and ART-naive pregnant women appear to be disproportionately affected by the adverse effects of NVP.
Hasitha Diana Manohar; Smita Shenoy; Muralidhar Varma; Asha Kamath; Chaithanya Malalur; Kurady Laxminarayana Bairy; Amod Tilak; Kavitha Saravu
Background: Human immunodeficiency virus (HIV) presently accounts for the highest number of deaths due to any infective agent in the world. The present study assessed the one year treatment outcome following antiretroviral therapy in HIV positive, treatment na and iuml;ve patients in a tertiary care hospital. Methods: Adult HIV positive, antiretroviral treatment naive patients who were started on antiretroviral therapy (ART) between 1st January 2011 and 31st May 2013 were included in the s...
Dhaka Ram Bhandari
Full Text Available The diminution of CD4 lymphocytes is the diagnostic characteristic of human immunodeficiency virus (HIV infection. Since the discovery of the disease 35 years ago, the infection has become one of the greatest menaces for the modern civilization. There are many individual drug toxicities and a number of class-specific or therapy-related toxicities of anti-HIV agents. Hepatotoxicity is a well-recognized side effect developing asymptomatic mild elevation of transaminases. It is known that the incidence of adverse reactions is high in long-term reactions such as lipodystrophy, paresthesia, and neuromotor disorders. Antiretroviral (ARV therapy is not only effective but also complex. There are many adverse effects of the therapy, which affect varieties of the organ system. To optimize the treatment, health professionals should focus on preventing the adverse effect of ARV agents.
Full Text Available BACKGROUND: Although women of reproductive age are the largest group of HIV-infected individuals in sub-Saharan Africa, little is known about the impact of pregnancy on response to highly active antiretroviral therapy (HAART in that setting. We examined the effect of incident pregnancy after HAART initiation on virologic response to HAART. METHODS AND FINDINGS: We evaluated a prospective clinical cohort of adult women who initiated HAART in Johannesburg, South Africa between 1 April 2004 and 30 September 2009, and followed up until an event, death, transfer, drop-out, or administrative end of follow-up on 31 March 2010. Women over age 45 and women who were pregnant at HAART initiation were excluded from the study; final sample size for analysis was 5,494 women. Main exposure was incident pregnancy, experienced by 541 women; main outcome was virologic failure, defined as a failure to suppress virus to ≤ 400 copies/ml by six months or virologic rebound >400 copies/ml thereafter. We calculated adjusted hazard ratios using marginal structural Cox proportional hazards models and weighted lifetable analysis to calculate adjusted five-year risk differences. The weighted hazard ratio for the effect of pregnancy on time to virologic failure was 1.34 (95% confidence limit [CL] 1.02, 1.78. Sensitivity analyses generally confirmed these main results. CONCLUSIONS: Incident pregnancy after HAART initiation was associated with modest increases in both relative and absolute risks of virologic failure, although uncontrolled confounding cannot be ruled out. Nonetheless, these results reinforce that family planning is an essential part of care for HIV-positive women in sub-Saharan Africa. More work is needed to confirm these findings and to explore specific etiologic pathways by which such effects may operate.
Mocroft, Amanda; Wyatt, Christina; Szczech, Lynda;
continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. METHODS: Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random...
E. Martinez; F. Visnegarwala; B. Grund; A. Thomas; C. Gibert; J. Shlay; F. Drummond; D. Pearce; S. Edwards; P. Reiss; W. El-Sadr; A. Carr
Objective: To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters. Design: Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or t
Bangani, Nonzwakazi; Goliath, Rene; Kampmann, Beate; Wilkinson, Katalin A.; Wilkinson, Robert J.; Martineau, Adrian R.
Rationale: Experimental and epidemiological evidence suggests that neutrophils are important in the host response to tuberculosis. HIV infection, which increases the risk of tuberculosis, adversely affects neutrophil function. Objectives: To determine the impact of HIV and antiretroviral therapy on neutrophil antimycobacterial activity. Methods: We performed a cross-sectional comparison of neutrophil functions in 20 antiretroviral-naive HIV-infected and 20 HIV-uninfected individuals using luminescence-, flow cytometry–, and ELISA-based assays. We then conducted a prospective study in the HIV-infected individuals investigating these parameters during the first 6 months of antiretroviral therapy. Surface markers of neutrophil activation were investigated in a separate cohort using flow cytometry. Measurements and Main Results: HIV infection impaired control of Mycobacterium tuberculosis by neutrophils (mean ratio of mycobacterial luminescence in neutrophil samples vs. serum controls at 1 hour in HIV-infected participants, 0.88 ± 0.13 vs. HIV-uninfected participants, 0.76 ± 0.14; P = 0.01; at 24 hours, 0.82 ± 0.13 vs. 0.71 ± 0.13; P = 0.01). The extent of impairment correlated with log[HIV viral load]. Neutrophil cell death after 24 hours’ incubation with M. tuberculosis was higher in the HIV-infected cohort (85.3 ± 11.8% vs. 57.9 ± 22.4% necrotic cells; P < 0.0001). Neutrophils from HIV-infected participants demonstrated significantly more CD62L-negative cells (median, 23.0 vs. 8.5%; P = 0.008) and CD16-negative cells (3.2 vs. 1.3%, P = 0.03). Antiretroviral therapy restored mycobacterial restriction and pattern of neutrophil death toward levels seen in HIV-uninfected persons. Conclusions: Neutrophils in antiretroviral-naive HIV-infected persons are hyperactivated, eliminate M. tuberculosis less effectively than in HIV-uninfected individuals, and progress rapidly to necrotic cell death. These factors are
The neurologic events related to antiretroviral therapy (ART) in HIV-infected ART-naive patients are relatively common. Side effects of ART and complications of HIV infection may overlap significantly. Establishing etiology of neurologic (neuropathy and neuropathic pain, changes in cognition, dementia, and myelopathy) and psychiatric (neurocognitive disorders, depression, anxiety, substance abuse and dependence, and others) complications can present a significant challenge. It has long been documented that neurologic and psychological side effects can occur with many of the agents used to treat HIV infection. Particularly, efavirenz from the non-nucleoside reverse transcriptase inhibitor (NNRTI) has been associated with neurologic and psychological complaints that may be difficult to differentiate from pre-existing mental illness, substance abuse, and HIV-related neuropsychiatric symptoms. Peripheral neuropathy (PN) of at least 6 different types is a well-known adverse effect of treatment with nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-infected patients. Lack of dealing with early stages of neurologic and psychological side effects of HIV infection and Highly Active Anti-retroviral Therapy (HAART) are observed in daily practice. The purpose of this article is to identify the neurologic, neuropsychiatric and psychiatric complications related to HIV and anti-retroviral therapy, to discuss current knowledge about these disorders, and to suggest strategies for their diagnosis and management. PMID:24013599
Dominique J Pepper
Full Text Available BACKGROUND: In the developing world, the principal cause of death among HIV-infected patients is tuberculosis (TB. The initiation of antiretroviral therapy (ART during TB therapy significantly improves survival, however it is not known which barriers prevent eligible TB patients from initiating life-saving ART. METHOD: Setting. A South African township clinic with integrated tuberculosis and HIV services. Design. Logistic regression analyses of a prospective cohort of HIV-1 infected adults (≥18 years who commenced TB therapy, were eligible for ART, and were followed for 6 months. FINDINGS: Of 100 HIV-1 infected adults eligible for ART during TB therapy, 90 TB patients presented to an ART clinic for assessment, 66 TB patients initiated ART, and 15 TB patients died. 34% of eligible TB patients (95%CI: 25-43% did not initiate ART. Male gender and younger age (<36 years were associated with failure to initiate ART (adjusted odds ratios of 3.7 [95%CI: 1.25-10.95] and 3.3 [95%CI: 1.12-9.69], respectively. Death during TB therapy was associated with a CD4+ count <100 cells/µL. CONCLUSION: In a clinic with integrated services for tuberculosis and HIV, one-third of eligible TB patients--particularly young men--did not initiate ART. Strategies are needed to promote ART initiation during TB therapy, especially among young men.
Primary parotid B-cell lymphoma successfully treated with chemotherapy plus highly active antiretroviral therapy with prolonged survival and immune reconstitution in an acquired immunodeficiency syndrome patient: Case report and review of the literature
Full Text Available Non-Hodgkin′s lymphoma (NHL is the second most common acquired immunodeficiency syndrome (AIDS-defining cancer. In this population, up to 70-80% of cases may present as extranodal location as the primary clinical manifestation of the neoplasm disease. Gastrointestinal tract is the most frequent location of AIDS-associated NHL. However, salivary gland involvement, including the parotid gland is a rare complication in human immunodeficiency virus (HIV-patients. Here, we describe a patient seropositive for the HIV, who developed a primary NHL of the parotid gland histologically classified as a high-grade diffuse large B-cell lymphoma. Patient was treated with a combination of chemotherapy plus highly active antiretroviral therapy with a good clinical, virological and immunological response and a prolonged survival, more than 5 years, without evidence of neoplasm relapse.
Full Text Available Abstract Background To increase access to antiretroviral therapy in resource-limited settings, several experts recommend "task shifting" from doctors to clinical officers, nurses and midwives. This study sought to identify task shifting that has already occurred and assess the antiretroviral therapy training needs among clinicians to whom tasks have shifted. Methods The Infectious Diseases Institute, in collaboration with the Ugandan Ministry of Health, surveyed health professionals and heads of antiretroviral therapy clinics at a stratified random sample of 44 health facilities accredited to provide this therapy. A sample of 265 doctors, clinical officers, nurses and midwives reported on tasks they performed, previous human immunodeficiency virus training, and self-assessment of knowledge of human immunodeficiency virus and antiretroviral therapy. Heads of the antiretroviral therapy clinics reported on clinic characteristics. Results Thirty of 33 doctors (91%, 24 of 40 clinical officers (60%, 16 of 114 nurses (14% and 13 of 54 midwives (24% who worked in accredited antiretroviral therapy clinics reported that they prescribed this therapy (p Conclusion Training initiatives should be an integral part of the support for task shifting and ensure that antiretroviral therapy is used correctly and that toxicity or drug resistance do not reverse accomplishments to date.
Liver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy.
Audsley, Jennifer; Robson, Christopher; Aitchison, Stacey; Matthews, Gail V; Iser, David; Sasadeusz, Joe; Lewin, Sharon R
Background. Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment. Methods. We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (≥F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined. Results. The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7%-20.4%) over a median of 31 months. Conclusions. The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression. PMID:27006960
De Clercq, Erik
In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one. PMID:20471318
Sorensen, JL; Haug, NA; Larios, S; Gruber, VA; Tulsky, J; Powelson, E; Logan, DP; Shapiro, B.
Devising interventions to provide integrated treatment for addiction and medical problems is an urgent issue. This study piloted a structural intervention, Directly Administered Antiretroviral Therapy (DAART), to assist methadone-maintenance patients in HIV medication adherence. Twenty-four participants received: (1) antiretroviral medications at the methadone clinic daily before receiving their methadone; (2) take-home antiretroviral medication for days they were not scheduled to attend the ...
May, Margaret; Sterne, Jonathan A C; Shipley, Martin;
Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors...
Full Text Available Optic neuropathy in HIV-infected patients results from the HIV infection itself, post-infectious auto-immune disease, opportunistic infections and drugs. Nucleoside reverse transcriptase inhibitors (NRTIs such as zidovudine and stavudine have known mitochondrial toxicity and can cause mitochondrial myopathies, neuropathies, hyperlactataemia, and can induce mitochondrial genetic disorders. Individuals with the mutation for Leber’s hereditary optic neuropathy (LHON, a mitochondrial disorder, are usually asymptomatic but develop visual loss when exposed to external triggers such as smoking. We report on two HIV-infected patients with LHON mutations (m.14484T>C and m.11778G>A who developed profound visual loss with antiretroviral therapy. We postulate that the phenotypic expression of LHON in these genetically predisposed individuals was triggered by NRTI drugs lamivudine and tenofovir when used in combination, despite their relatively weak mitochondrial toxic effects.
This paper examines the effects of antiretroviral therapy (ART) on demand for HIV testing and of ART-induced testing on demand for risky sexual behavior. I provide a model of sexual behavior decision-making under uncertainty and estimate the structural parameters of the model using nationally representative survey data from Zambia on HIV testing decisions before and after the introduction of ART. The empirical results indicate that although the introduction of ART appears to have increased HIV testing rates by upwards of 50 percent, the ART allocation process may have limited the prevention benefit of ART-induced testing. Simulation results show that eliminating this prevention inefficiency while holding the supply of ART constant would increase the prevention impact of ART-induced testing more than four-fold. More generally, the analysis indicates that existing studies which examine "universal" testing or quasi-experimental testing programs understate the efficacy of standard voluntary counseling and testing programs. PMID:26970992
Rupak Shivakoti; Nikhil Gupte; Wei-Teng Yang; Noluthando Mwelase; Cecilia Kanyama; Tang, Alice M.; Sandy Pillay; Wadzanai Samaneka; Cynthia Riviere; Sima Berendes; Lama, Javier R.; Cardoso, Sandra W.; Patcharaphan Sugandhavesa; Richard D Semba; Parul Christian
A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic...
Bannister, W; Kirk, O; Gatell, J;
BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS: Vi...
Bannister, Wendy P; Kirk, Ole; Gatell, Jose M;
BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS: Vi...
Bannister, WP; Ruiz, L; Loveday, C; Vella, S; Zilmer, K; Kjær, Jesper; Knysz, B; Phillips, AN; Mocroft, A; Lundgren, Jens Dilling
BACKGROUND: Combination antiretroviral therapy (cART) may vary in ability to suppress viral load and increase CD4+ T-cell count in people infected with different HIV-1 subtypes, possibly due to differences in resistance development. Antiretroviral drugs have predominantly been developed in Western...
Wainberg, M A; Friedland, G
Widespread use of antiretroviral agents and increasing occurrence of human immunodeficiency virus (HIV) strains resistant to these drugs have given rise to a number of important issues. Some of these concerns are distinct from the obvious question of the relationship between drug resistance and treatment failure and have potentially widespread public health implications. The relevant issues include but are not limited to the following: (1) frequency with which drug-resistant virus may be transmitted via sexual, intravenous, or mother-to-child routes; (2) ability of drug-resistant variants to be transmitted, a question that relates, in part, to the relative fitness of such strains; (3) effectiveness of antiviral therapy in diminishing viral burden in both blood and genital secretions, and whether this may be compromised in persons harboring resistant virus; and (4) importance of patient adherence to antiviral therapy and its relationship to sustained reduction in viral load to minimize the appearance in and transmission of drug-resistant virus from both blood and genital secretions. Thus, prevention of both development of HIV drug resistance as well as transmission of drug-resistant variants is a central issue of public health importance. Unless this topic is appropriately addressed, the likelihood is that drug-resistant variants of HIV, if able to successfully replicate, will sustain the epidemic and limit the effectiveness of antiviral therapy. PMID:9643862
Crothers, Kristina; Huang, Laurence; Goulet, Joseph L.; Goetz, Matthew Bidwell; Brown, Sheldon T.; Rodriguez-Barradas, Maria C.; Oursler, Krisann K.; Rimland, David; Gibert, Cynthia L.; Butt, Adeel A.; Justice, Amy C.
Rationale: In aging HIV-infected populations comorbid diseases are important determinants of morbidity and mortality. Pulmonary diseases have not been systematically assessed in the combination antiretroviral therapy (ART) era.
Tenorio, Allan R.; Chan, Ellen S.; Bosch, Ronald J.; Macatangay, Bernard J. C.; Read, Sarah W.; Yesmin, Suria; Taiwo, Babafemi; Margolis, David M.; Jacobson, Jeffrey M.; Landay, Alan L.; Wilson, Cara C.; Mellors, John W.; Keshavarzian, Ali; Rodriguez, Benigno; Aziz, Mariam; Presti, Rachel; Deeks, Steven; Ebiasah, Ruth; Myers, Laurie; Borowski, LuAnn; Plants, Jill; Palm, David A.; Weibel, Derek; Putnam, Beverly; Lindsey, Elizabeth; Player, Amy; Albrecht, Mary; Kershaw, Andrea; Sax, Paul; Keenan, Cheryl; Walton, Patricia; Baum, Jane; Stroberg, Todd; Hughes, Valery; Coster, Laura; Kumar, Princy N.; Yin, Michael T.; Noel-Connor, Jolene; Tebas, Pablo; Thomas, Aleshia; Davis, Charles E.; Redfield, Robert R.; Sbrolla, Amy; Flynn, Teri; Davis, Traci; Whitely, Kim; Singh, Baljinder; Swaminathan, Shobha; McGregor, Donna; Palella, Frank; Aberg, Judith; Cavanagh, Karen; Santana Bagur, Jorge L.; Flores, Olga Méndez; Fritsche, Janice; Sha, Beverly; Slamowitz, Debbie; Valle, Sandra; Tashima, Karen; Patterson, Helen; Harber, Heather; Para, Michael; Eaton, Molly; Maddox, Dale; Currier, Judith; Cajahuaringa, Vanessa; Luetkemeyer, Annie; Dwyer, Jay; Fichtenbaum, Carl J.; Saemann, Michelle; Ray, Graham; Campbell, Thomas; Fischl, Margaret A.; Bolivar, Hector; Oakes, Jonathan; Chicurel-Bayard, Miriam; Tripoli, Christine; Weinman, D. Renee; Adams, Mary; Hurley, Christine; Dunaway, Shelia; Storey, Sheryl; Klebert, Michael; Royal, Michael
Background. Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART). Methods. HIV-positive adults receiving ART for ≥96 weeks with undetectable viremia for ≥48 weeks and CD4+ T-cell counts <350 cells/mm3 were randomized 2:1 to rifaximin versus no study treatment for 4 weeks. T-cell activation, LPS, and soluble CD14 were measured at baseline and at weeks 2, 4, and 8. Wilcoxon rank sum tests compared changes between arms. Results. Compared with no study treatment (n = 22), rifaximin (n = 43) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8+T-cell activation (median change, 0.0% with rifaximin vs +0.6% with no treatment; P = .03). This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm. Similarly, although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14, there were no significant changes within the rifaximin arm. Conclusions. In immune nonresponders to ART, rifaximin minimally affected microbial translocation and CD8+T-cell activation. Trial registration number. NCT01466595. PMID:25214516
Full Text Available Human immunodeficiency virus type 1 (HIV-1 is undoubtedly the primary cause of the acquired immunodeficiency syndrome (AIDS, which is a slow, progressive and degenerative disease of the human immune system. The pathogenesis of HIV-1 is complex and characterized by the interplay of both viral and host factors. Practically every stage in the viral life cycle and every viral gene product is a potential target. Although HAART has made long-term suppression of HIV a reality, drug resistance, drug toxicity, drug penetration, adherence to therapy, low levels of continued viral replication in cellular reservoirs and augmentation of host immune responses are some of the most important challenges that remain to be sorted out. Novel targets for the management of HIV infection have become increasingly relevant in view of extensive drug resistance, side effects and high pill burden of some of the conventional anti-retroviral agents. These agents include chemokine receptor antagonists, integrase inhibitors, maturation inhibitors, zinc finger inhibitors, pharmacological CDK inhibitors, Tate-TAR interaction inhibitors, anti-CD4 monoclonal antibodies and antisense oligonucleotides. In this review we gave a basic overview of the virology of HIV-1 including the functions of the different HIV-1 proteins required for effective viral replication, various obstacles to HIV therapy, perspectives related to the issues that are critical in determining the success or failure of HAART, current methods for detecting HIV-1 drug resistance and various novel targets for the management of HIV infection
Full Text Available Abstract Background Although severe oral opportunistic infections decreased with the implementation of highly active antiretroviral therapy, periodontitis is still a commonly described problem in patients infected 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. Methods The study population comprised 80 patients infected with HIV divided into two groups. The first group was receiving antiretroviral therapy while the second group was therapy naive. The following parameters were examined: probing pocket depth, gingival recession, clinical attachment level, papilla bleeding score, periodontal screening index and the index for decayed, missed and filled teeth. A questionnaire concerning oral hygiene, dental care and smoking habits was filled out by the patients. Results There were no significant differences regarding the periodontal parameters between the groups except in the clinical marker for inflammation, the papilla bleeding score, which was twice as high (P Conclusion There is no indication for advanced periodontal damage in HIV-infected versus non-infected patients in comparable age groups. Due to their immunodeficiency, HIV-infected patients should be monitored closely to prevent irreversible periodontal damage. Periodontal monitoring and early therapy is recommended independent of an indication for highly active antiretroviral therapy.
Tukei, Vincent J; Murungi, Miriam; Asiimwe, Alice R; Migisha, Daniella; Maganda, Albert; Bakeera-Kitaka, Sabrina; Kalyesubula, Israel; Musoke, Philippa; Kekitiinwa, Adeodata
Background Antiretroviral therapy (ART) is known to save lives. Among HIV-infected infants living in resource constrained settings, the short and long term benefits of ART are only partially known. This study was designed to determine the virologic, immunologic and clinical outcomes of antiretroviral therapy in a cohort of HIV-infected infants receiving care from an outpatient clinic in Kampala, Uganda. Methods A prospective cohort of HIV-infected infants receiving treatment at the Baylor-Uga...
Achappa, Basavaprabhu; Madi, Deepak; Shetty, Nishitha; Mahalingam, Soundarya
The Immune Reconstitution Inflammatory Syndrome (IRIS) is an exaggerated pathological inflammatory reaction which occurs after the initiation of the antiretroviral therapy, due to the exuberant immune responses to the occult or the apparent opportunistic infections. The hallmark of the syndrome is the paradoxical worsening of an existing infection or a disease process or the appearance of a new infection or a disease process soon after the initiation of the antiretroviral therapy.
Nyanzi-Wakholi, B; Lara, AM; Munderi, P.; Gilks, C.; Dart Trial Team, (incl. Grosskurth, H. )
: Antiretroviral therapy (ART) improves the quality of life of people living with HIV/AIDS. However, adherence remains a challenge. A total of eight focus group discussions (FGD) were conducted with participants from a randomised controlled trial that monitored strategies for managing ART in African adults: Development of Antiretroviral Therapy. All FGD participants had received ART for at least one year. Perceived benefits of ART were key motivators for adherence. These benefits included imp...
Suleiman IA; Momo A
Background: A high level of adherence is required to achieve the desired outcomes of antiretroviral therapy. There is paucity of information about adherence to combined antiretroviral therapy in Bayelsa State of southern Nigeria. Objectives: The objectives of the study were to determine the level of adherence to combined antiretroviral therapy among the patients, evaluate the improvement in their immune status and identify reasons for sub-optimal adherence to therapy. Methods: The cross...
Cole, Stephen R.; Jacobson, Lisa P.; Tien, Phyllis C.; Kingsley, Lawrence; Chmiel, Joan S.; Anastos, Kathryn
To estimate the net effect of imperfectly measured highly active antiretroviral therapy on incident acquired immunodeficiency syndrome or death, the authors combined inverse probability-of-treatment-and-censoring weighted estimation of a marginal structural Cox model with regression-calibration methods. Between 1995 and 2007, 950 human immunodeficiency virus–positive men and women were followed in 2 US cohort studies. During 4,054 person-years, 374 initiated highly active antiretroviral thera...
Increased levels of regulatory T cells (T(regs)) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive T(regs)
Kolte, L; Gaardbo, J C; Skogstrand, K;
Summary This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores...... if naive T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38......(+)human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly...
Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs
Kolte, L.; Gaardbo, J.C.; Skogstrand, K.;
This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive...... T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38(+)human...... leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly higher in...
Shalihu, Nauyele; Pretorius, Louise; van Dyk, Agnes; Vander Stoep, Ann; Hagopian, Amy
Little is available in scholarly literature about how HIV-positive prisoners, especially in low-income countries, access antiretroviral therapy (ART) medication. We interviewed 18 prisoners at a large prison in Namibia to identify barriers to medication adherence. The lead nurse researcher was a long-standing clinic employee at the prison, which afforded her access to the population. We identified six significant barriers to adherence, including (1) the desire for privacy and anonymity in a setting where HIV is strongly stigmatized; (2) the lack of simple supports for adherence, such as availability of clocks; (3) insufficient access to food to support the toll on the body of ingesting taxing ART medications; (4) commodification of ART medication; (5) the brutality and despair in the prison setting, generally leading to discouragement and a lack of motivation to strive for optimum health; and (6) the lack of understanding about HIV, how it is transmitted, and how it is best managed. Because most prisoners eventually transition back to communitysettings when their sentences are served, investments in prison health represent important investments in public health. PMID:24499371
Cribbs, Sushma K; Fontenot, Andrew P
Despite the introduction of antiretroviral therapy (ART), human immunodeficiency virus-1 (HIV) continues to cause a major impact worldwide. HIV-induced lung disease continues to represent a significant source of morbidity and mortality, although the spectrum of pulmonary diseases has changed. HIV significantly affects the lung, causing acute and chronic cellular changes in the alveolar space. The impact of ART on lung immunology still needs to be fully elucidated. Similar to the periphery, ART affects HIV viral load and reconstitutes CD4(+) T cells in the lung. ART has been associated with significant decreases in bronchoalveolar lavage lymphocytes and increases in B-cell numbers and functionality, resulting in improved immune responses to vaccinations. There are substantial clinical implications of these ART-induced alterations, including the emergence of immune reconstitution inflammatory syndrome and the increased incidences of noninfectious lung diseases, such as lung cancer and chronic obstructive lung disease. There continues to be many unanswered questions regarding the effects of ART on lung health and, in particular, the immune system. Growing knowledge in this area will hopefully diminish the incidence of these noninfectious lung diseases and further improve the health of individuals living with HIV. PMID:26974295
Full Text Available BACKGROUND: Substantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU and non-adherence to ART in a large treatment cohort in Nigeria. METHODS AND FINDINGS: We reviewed clinic records of adult patients initiating ART between March 2005 and July 2006 at five health facilities. Patients were classified as LTFU if they did not return >60 days from their expected visit. Pharmacy refill rates were calculated and used to assess non-adherence. We identified risk factors associated with LTFU and non-adherence using Cox and Generalized Estimating Equation (GEE regressions, respectively. Of 5,760 patients initiating ART, 26% were LTFU. Female gender (p 350 and 2 hours to the clinic (p = 0.03, had total ART duration of >6 months (p200 at ART initiation were at a higher risk of non-adherence. Patients who disclosed their HIV status to spouse/family (p = 0.01 and were treated with tenofovir-containing regimens (p < or = 0.001 were more likely to be adherent. CONCLUSIONS: These findings formed the basis for implementing multiple pre-treatment visit preparation that promote disclosure and active community outreaching to support retention and adherence. Expansion of treatment access points of care to communities to diminish travel time may have a positive impact on adherence.
Valerie J. Ehlers
Full Text Available Anti-retroviral drugs (ARVs are supplied free of charge in Botswana. Lifelong adherence to anti-retroviral therapy (ART is vital to improve the patient’s state of well-being and to prevent the development of strains of the human immunodef ciency virus (HIV that are resistant to ART. Persons with ART-resistant strains of HIV can spread these to other people, requiring more expensive ART with more severe side-effects and poorer health outcomes. The purpose of this exploratory, descriptive, qualitative study was to determine nurses’ perspectives on Botswana patients’ anti-retroviral therapy (ART adherence, and to identify factors which could promote or hinder ART adherence. Four ART sites were randomly selected and all 16 nurses providing ART services at these sites participated in semi-structured interviews. These nurses indicated that patients’ ART adherence was inf uenced by service-related and patient-related factors. Service-related factors included the inaccessibility of ART clinics, limited clinic hours, health workers’ inability to communicate in patients’ local languages, long waiting times at clinics and delays in being informed about their CD4 and viral load results. Nurses could not trace defaulters nor contact them by phone, and also had to work night shifts, disrupting nurse-patient relationships. Patient-related factors included patients’ lack of education, inability to understand the significance of CD4 and viral load results, financial hardships, non-disclosure and non-acceptance of their HIV positive status, alcohol abuse, the utilisation of traditional medicines and side effects of ART. The challenges of lifelong ART adherence are multifaceted involving both patient-related and service-related factors. Supplying free ARVs does not ensure high levels of ART adherence.
Anti-retrovirale middels (ARMs word gratis verskaf in Botswana. Lewenslange getroue nakoming van ARM voorskrifte is
Gulick, Roy M
There is general consistency among US and European guidelines regarding the initiation of antiretroviral therapy for HIV-infected individuals. Recent and ongoing trials comparing regimens may lead to reevaluation of initial treatment choices. The choice of antiretroviral regimen will also likely be affected by development, evaluation, and availability of newer drugs. This article reviews currently recommended regimens and characteristics of selected current investigational drugs, including the nucleotide analogue reverse transcriptase inhibitor tenofovir alafenamide, the nonnucleoside reverse transcriptase inhibitor doravirine, the integrase strand transfer inhibitor cabotegravir, the HIV entry inhibitor BMS-663068, and the HIV maturation inhibitor BMS-955176. This article summarizes a presentation by Roy M. Gulick, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in New York, New York, in March 2015 and September 2015. PMID:26713502
Vichitvejpaisal, Pornpattana; Reeponmahar, Somporn; Tantisiriwat, Woraphot
Typical progressive outer retinal necrosis (PORN) is an acute ocular infectious disease in acquired immunodeficiency syndrome (AIDS) patients with extremely low CD4+ T-cell counts. It is a form of the Varicella- zoster virus (VZV) infection. This destructive infection has an extremely rapid course that may lead to blindness in affected eyes within days or weeks. Attempts at its treatment have had limited success. We describe the case of a bilateral PORN in an AIDS patient with an initial CD4+ T-cell count >100 cells/microL that developed after initiation of highly active antiretroviral therapy (HAART). A 29-year-old Thai female initially diagnosed with human immunodeficiency virus (HIV) in 1998, presented with bilaterally decreased visual acuity after initiating HAART two months earlier. Multiple yellowish spots appeared in the deep retina without evidence of intraocular inflammation or retinal vasculitis. Her CD4+ T-cell count was 127 cells/microL. She was diagnosed as having PORN based on clinical features and positive VZV in the aqueous humor and vitreous by polymerase chain reaction (PCR). Despite combined treatment with intravenous acyclovir and intravitreous ganciclovir, the patient's visual acuity worsened with no light-perception in either eye. This case suggests that PORN should be included in the differential diagnosis of reduced visual acuity in AIDS patients initiating HAART with higher CD4+ T-cell counts. PORN may be a manifestation of the immune reconstitution syndrome. PMID:19702067
Thomford, Nicholas E; Awortwe, Charles; Dzobo, Kevin; Adu, Faustina; Chopera, Denis; Wonkam, Ambroise; Skelton, Michelle; Blackhurst, Dee; Dandara, Collet
Highly active antiretroviral therapy (HAART) has greatly improved health parameters of HIV infected individuals. However, there are several challenges associated with the chronic nature of HAART administration. For populations in health transition, dual use of medicinal plant extracts and conventional medicine poses a significant challenge. There is need to evaluate interactions between commonly used medicinal plant extracts and antiretroviral drugs used against HIV/AIDS. Efavirenz (EFV) and nevirapine (NVP) are the major components of HAART both metabolized by CYP2B6, an enzyme that can potentially be inhibited or induced by compounds found in medicinal plant extracts. The purpose of this study was to evaluate the effects of extracts of selected commonly used medicinal plants on CYP2B6 enzyme activity. Recombinant human CYP2B6 was used to evaluate inhibition, allowing the assessment of herb-drug interactions (HDI) of medicinal plants Hyptis suaveolens, Myrothamnus flabellifolius, Launaea taraxacifolia, Boerhavia diffusa and Newbouldia laevis. The potential of these medicinal extracts to cause HDI was ranked accordingly for reversible inhibition and also classified as potential time-dependent inhibitor (TDI) candidates. The most potent inhibitor for CYP2B6 was Hyptis suaveolens extract (IC50 = 19.09 ± 1.16 µg/mL), followed by Myrothamnus flabellifolius extract (IC50 = 23.66 ± 4.86 µg/mL), Launaea taraxacifolia extract (IC50 = 33.87 ± 1.54 µg/mL), and Boerhavia diffusa extract (IC50 = 34.93 ± 1.06 µg/mL). Newbouldia laevis extract, however, exhibited weak inhibitory effects (IC50 = 100 ± 8.71 µg/mL) on CYP2B6. Launaea taraxacifolia exhibited a TDI (3.17) effect on CYP2B6 and showed a high concentration of known CYP450 inhibitory phenolic compounds, chlorogenic acid and caffeic acid. The implication for these observations is that drugs that are metabolized by CYP2B6 when co-administered with these herbal medicines and when adequate amounts of the extracts
Tavel, Jorge A; Babiker, Abdel; Fox, Lawrence;
BACKGROUND: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4(+) counts compared to no therapy. METHODOLOGY: Participants not on continuous ART...
Oluwafemi O OguntibejuOxidative Stress Research Centre, Cape Peninsula University of Technology, Bellville, South AfricaAbstract: The development of antiretroviral drugs has significantly changed the perception of HIV/AIDS from a very fatal to a chronic and potentially manageable disease, and the availability and administration of antiretroviral therapy (ART) has significantly reduced mortality and morbidity associated with HIV and AIDS. There is a relationship between ART and quality of life...
Cristiane A. Menezes de Pádua; Cibele C. César; Palmira F. Bonolo; Francisco A. Acurcio; Mark Drew C. Guimarães
A cross-sectional analysis was carried out to describe adverse reactions to antiretroviral therapy (ART) reported by HIV-infected patients initiating treatment at two public health AIDS referral centers in Belo Horizonte, Brazil, 2001-2003 and to verify their association with selected variables. Adverse reactions were obtained through interview at the first follow-up visit (first month) after the antiretroviral prescription. Socio-demographic and behavioral variables related to ART were obtai...
Antiretroviral therapy (ART) represents a significant milestone in the battle against AIDS. However, we continue learning about HIV and confronting challenges 30 years after its discovery. HIV has cleverly tricked both the host immune system and ART. First, the many HIV subtypes and recombinant forms have different susceptibilities to antiretroviral drugs, which may represent an issue in countries where ART is just being introduced. Second, even under the suppressive pressures of ART, HIV sti...
Anglemyer, Andrew; Rutherford, George W.; Horvath, Tara; Baggaley, Rachel C; Egger, Matthias; Siegfried, Nandi
BACKGROUND Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). OBJECTIVES To determine if ART use in an HIV-infected member of an HIV-discordant couple is ...
Full Text Available Few studies have documented the contribution of HIV/AIDS to mortality among children under 15 years. From June 30 to October 19, 2001, all child deaths (n=588 registered to the morgue and/or hospitals of the city of Pointe-Noire, Congo, were investigated using a combined approach including an interview of relatives and postmortem clinical and biological HIV diagnosis. Twenty-one percent of children were HIV positive, while 10.5% of deaths were attributed to AIDS. The most common causes of death in HIV-infected children were pneumonia (30%, pyrexia (22%, diarrhoea (16% and wasting syndrome (16%. Infant mortality rate was estimated 6.3 times higher in children born to HIV-infected mothers compared to HIV-uninfected mothers. This study provides a direct measure of HIV/AIDS as impact on child mortality using a rapid and reliable method. A significant number of deaths could be prevented if HIV infection was diagnosed earlier and infants were provided with antiretroviral treatments.
Morgan, Melissa C; Masaba, Rose O; Nyikuri, Mary; Thomas, Timothy K
Abstract In the Kisumu Breastfeeding Study, a prevention of mother-to-child HIV transmission study, highly active antiretroviral therapy (HAART) is provided from 34 weeks gestation, through delivery to six months postpartum. The study recommends that women practice exclusive breastfeeding for six months, then wean abruptly. We sought to explore factors such as, education, family support, cultural norms, and sources of information about perinatal HIV transmission, which may influe...
Nadia Bakkour; Yea-Lih Lin; Sophie Maire; Lilia Ayadi; Florence Mahuteau-Betzer; Chi Hung Nguyen; Clément Mettling; Pierre Portales; David Grierson; Benoit Chabot; Philippe Jeanteur; Christiane Branlant; Pierre Corbeau; Jamal Tazi
Author Summary Over the two decades highly active antiretroviral therapy (HAART) for the treatment of HIV infection has led to a significant decline in morbidity and mortality rates among HIV-infected individuals. HAART uses a combination of molecules that target the virus itself. However, naturally occurring and extensive genetic variation found in the virus allow the emergence of drug-resistant viruses, which rapidly render individuals untreatable. An alternative approach for effective anti...
Melekhin, Vlada V.; Shepherd, Bryan E.; Stinnette, Samuel E.; Peter F Rebeiro; Gema Barkanic; Raffanti, Stephen P.; Sterling, Timothy R
BACKGROUND: Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed. METHODS: We conducted a retrospective cohort study from 1997-2005 among 112 pregnant HIV-infected women who started HAART before (N = 12), during (N = 70) or after pregnancy (N = 30). RESULTS: Women initiat...
El-Sadr, WM; Lundgren, Jens Dilling; Neaton, JD;
BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who...... than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic.......9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS: Episodic antiretroviral therapy guided by the CD4...
Stylianou, E; Aukrust, P; Bendtzen, K;
Interferons play an important, but incompletely understood role in HIV-related disease. We investigated the effect of HAART on plasma levels of IFN-alpha, IFN-gamma, neopterin and interferon-inducible protein 10 (IP-10) in 41 HIV-infected patients during 78 weeks of therapy. At baseline HIV...... seemed not to involve enhanced lymphocyte apoptosis. Our findings suggest a pathogenic role of IFN-alpha in HIV infection, which may be a potential target for immunomodulating therapy in combination with HAART....
Calza, Leonardo; Colangeli, Vincenzo; Manfredi, Roberto; Bon, Isabella; Re, Maria Carla; Viale, Pierluigi
The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents. PMID:26846208
G. Verweel; N.G. Hartwig (Nico); H.J. Scherpbier; R. de Groot (Ronald); T.F.W. Wolfs (Tom); A.M.C. van Rossum (Annemarie)
textabstractINTRODUCTION: Growth failure is a common feature of children with human immunodeficiency virus type 1 (HIV-1) infection. Children who are treated with mono or dual nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy show a temporary increase in weight gai
Stylianou, E; Aukrust, P; Bendtzen, K;
Interferons play an important, but incompletely understood role in HIV-related disease. We investigated the effect of HAART on plasma levels of IFN-alpha, IFN-gamma, neopterin and interferon-inducible protein 10 (IP-10) in 41 HIV-infected patients during 78 weeks of therapy. At baseline HIV-infec...
Analysis of HIV- type 1 protease and reverse transcriptase in Brazilian children failing highly active antiretroviral therapy (HAART Análise da protease e transcriptase reversa do HIV-1 em crianças com falha terapêutica em uso de terapia anti-retroviral altamente eficaz (HAART
Daisy Maria Machado
Full Text Available The aim of this study was to evaluate the genotypic resistance profiles of HIV-1 in children failing highly active antiretroviral therapy (HAART. Forty-one children (median age = 67 months receiving HAART were submitted to genotypic testing when virological failure was detected. cDNA was extracted from PBMCs and amplified by nested PCR for the reverse transcriptase and protease regions of the pol gene. Drug resistance genotypes were determined from DNA sequencing. According to the genotypic analysis, 12/36 (33.3% and 6/36 (16.6% children showed resistance and possible resistance, respectively, to ZDV; 5/36 (14% and 4/36 (11.1%, respectively, showed resistance and possible resistance to ddI; 4/36 (11.1% showed resistance to 3TC and D4T; and 3/36 (8.3% showed resistance to Abacavir. A high percentage (54% of children exhibited mutations conferring resistance to NNRTI class drugs. Respective rates of resistance and possible resistance to PIs were: RTV (12.2%, 7.3%; APV (2.4%, 12.1%; SQV(0%, 12.1%; IDV (14.6%, 4.9%, NFV (22%, 4.9%, LPV/RTV (2.4%, 12.1%. Overall, 37/41 (90% children exhibited virus with mutations related to drug resistance, while 9% exhibited resistance to all three antiretroviral drug classes.O objetivo deste estudo foi avaliar o perfil de resistência genotípica do HIV-1 em crianças com falha terapêutica ao tratamento anti-retroviral (HAART. Quarenta e uma crianças (idade mediana = 67 meses em uso de HAART foram submetidas ao teste de genotipagem no momento da detecção de falha ao tratamento. Foi realizada extração de cDNA de células periféricas mononucleares e amplificação do mesmo (regiões da transcriptase reversa e protease do gene pol através de PCR-nested. O perfil genotípico foi determinado através do seqüenciamnto de nucleotídeos. De acordo com a análise genotípica, 12/36 (33,3% e 6/36 (16,6% crianças apresentaram, respectivamente, resistência e possível resistência ao AZT; 5/36 (14% e 4/36 (11
Baker, Jason V; Neuhaus, Jacqueline; Duprez, Daniel;
Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compa...
Jarrin, Inma; Pantazis, Nikos; Gill, M John; Geskus, Ronald; Perez-Hoyos, Santiago; Meyer, Laurence; Prins, Maria; Touloumi, Giota; Johnson, Anne; Hamouda, Osamah; de Olalla, Patricia García; Porter, Kholoud; del Amo, Julia; Kirk, Ole
We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART).......We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART)....
Full Text Available Introduction: Adherence to antiretroviral therapy (ART plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh in the first 24 months of ART in an Asian HIV cohort. Methods: As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i 14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results: Out of 1316 patients, 32% ever reported 2 assessments per patient per year had an odds ratio (OR=0.7 (95% confidence interval (CI (0.55 to 0.90, p=0.006, compared to sites with ≤2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs (OR=1.92, 95% CI (1.23 to 3.00, p=0.004 and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71, p<0.001. Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67, p=0.001 compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI combination. SubAdh decreased with increasing time on ART (all p<0.001. Similar associations were found with adherence <95% as the outcome. Conclusions: We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social
Full Text Available Jean B Nachega,1,2,4 Chelsea Morroni,1 Richard E Chaisson,2–4 Rene Goliath,1 Anne Efron,4 Malathi Ram,2 Gary Maartens11University of Cape Town, Department of Medicine, Division of Clinical Pharmacology, Cape Town, South Africa; 2Johns Hopkins University, Bloomberg School of Public Health, Departments of International Health and Epidemiology, 3Johns Hopkins University, School of Medicine, Department of Medicine, Division of Infectious Diseases, 4Johns Hopkins University, Center for Tuberculosis Research, Baltimore, Maryland, USAObjective: We determined the impact of immune reconstitution inflammatory syndrome (IRIS on antiretroviral therapy (ART adherence in a cohort of 274 human immunodeficiency virus (HIV-infected South African adults initiating ART.Methods: We carried out a secondary analysis of data from a randomized controlled trial of partially supervised ART in Cape Town, South Africa. Monthly pill count adherence, viral suppression (HIV viral load < 50 c/mL, and IRIS events were documented. Poisson regression was used to identify variables associated with ART adherence below the median in the first 6 months of ART.Results: We enrolled 274 patients: 58% women, median age 34 years, median CD4 count 98 cells/µL, 46% World Health Organization clinical stage IV, and 40% on treatment for tuberculosis (TB. IRIS and TB-IRIS developed in 8.4% and 6.6% of patients, respectively. The median cumulative adherence at 6 months for those with an IRIS event vs no IRIS was 95.5% vs 98.2% (P = 0.04. Although not statistically significant, patients developing IRIS had a lower 6-month viral load suppression than those without IRIS (68% vs 80%, P = 0.32. ART adherence below the median of 98% was independently associated with alcohol abuse (relative risk [RR] 1.5; 95% confidence interval [CI] 1.2–1.9; P = 0.003 and IRIS events (RR 1.7; 95% CI 1.2–2.2; P = 0.001.Conclusion: Although IRIS events were associated with slightly lower adherence rates, overall
Full Text Available Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART, yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher's exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7% vs.11/153 (7.2%, p<0.001 and frank diabetes mellitus (27/150 (18.0% vs. 8/153 (5.2%, p = 0.001 than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78-11.77, p<0.001. Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.
Carey, Vincent J.; Pahwa, Savita; Weinberg, Adriana
Our objective was to develop data-based algorithms for definition of immunologic response to AIDS therapies in pediatric patients, taking account of T-cell subset measurement errors. The study design involved cross-protocol analysis of 2,148 enrollees in six completed Pediatric AIDS Clinical Trials Group trials. We used standard quantitation of T-cell subsets; linear modeling with mean-dependent measurement error variance was used to develop 95% tolerance limits for change in CD4%. For indivi...
Menéndez-Arias, Luis; Alvarez, Mar
One to two million people worldwide are infected with the human immunodeficiency virus type 2 (HIV-2), with highest prevalences in West African countries, but also present in Western Europe, Asia and North America. Compared to HIV-1, HIV-2 infection undergoes a longer asymptomatic phase and progresses to AIDS more slowly. In addition, HIV-2 shows lower transmission rates, probably due to its lower viremia in infected individuals. There is limited experience in the treatment of HIV-2 infection and several antiretroviral drugs used to fight HIV-1 are not effective against HIV-2. Effective drugs against HIV-2 include nucleoside analogue reverse transcriptase (RT) inhibitors (e.g. zidovudine, tenofovir, lamivudine, emtricitabine, abacavir, stavudine and didanosine), protease inhibitors (saquinavir, lopinavir and darunavir), and integrase inhibitors (raltegravir, elvitegravir and dolutegravir). Maraviroc, a CCR5 antagonist blocking coreceptor binding during HIV entry, is active in vitro against CCR5-tropic HIV-2 but more studies are needed to validate its use in therapeutic treatments against HIV-2 infection. HIV-2 strains are naturally resistant to a few antiretroviral drugs developed to suppress HIV-1 propagation such as nonnucleoside RT inhibitors, several protease inhibitors and the fusion inhibitor enfuvirtide. Resistance selection in HIV-2 appears to be faster than in HIV-1. In this scenario, the development of novel drugs specific for HIV-2 is an important priority. In this review, we discuss current anti-HIV-2 therapies and mutational pathways leading to drug resistance. PMID:24345729
Friis-Moller, N; Sabin, CA; Weber, R; Monforte, AD; El-Sadr, WM; Reiss, P; Thiebaut, R; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Lundgren, JD; Lundgren, JD; Weber, R; Monteforte, AD; Bartsch, G; Reiss, P; Dabis, F; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Houyez, F; Loeliger, E; Tressler, R; Weller, I.; Friis-Moller, N; Sabin, CA; Sjol, A; Lundgren, JD; Sawitz, A; Rickenbach, M; Pezzotti, P; Krum, E; Meester, R; Lavignolle, V.; Sundstrom, A; Poll, B; Fontas, E; Torres, F; Petoumenos, K; Kjaer, J; Hammer, S; Neaton, J; Sjol, A; de Wolf, F; van der Ven, E; Zaheri, S; Van Valkengoed, L; Meester, R; Bronsveld, W; Weigel, H; Brinkman, K; Frissen, P; ten Veen, J; Hillbrand, M; Schieveld, S; Mulder, J; van Gorp, E; Meenhorst, P; Danner, S; Claessen, F; Perenboom, R; Schattenkerk, JKE; Godfried, M; Lange, J; Lowe, S; van der Meer, J; Nellen, F; Pogany, K; van der Poll, T; Reiss, R; Ruys, T; Wit, F; Richter, C; van Leusen, R; Vriesendorp, R; Jeurissen, F; Kauffmann, R; Koger, E; Brevenboer, B; Sprenger, HG; Law, G; ten Kate, RW; Leemhuis, M; Schippers, E; Schrey, G; van der Geest, S; Verbon, A; Koopmans, P; Keuter, M; Telgt, D; van der Ven, A; van der Ende, Marchina E.; Gyssens, I.; de Marie, S; Juttmann, J; van der Heul, C; Schneider, M; Borleffs, J; Hoepelman, I.; Jaspers, C; Matute, A; Schurink, C; Blok, W; Salamon, R; Beylot, J; Dupon, M; Le Bras, M; Pellegrin, JL; Ragnaud, JM; Dabis, F; Chene, G; Jacqmin-Gadda, H; Rhiebaut, R; Lawson-Ayayi, S; Lavignolle, V.; Balestre, E; Blaizeau, MJ; Decoin, M; Formaggio, AM; Delveaux, S; Labarerre, S; Uwamaliya, B; Vimard, E; Merchadou, L; Palmer, G; Touchard, D; Dutoit, D; Pereira, F; Boulant, B; Beylot, J; Morlat, P; Bonarek, M; Bonnet, F; Coadou, B; Gelie, P; Jaubert, D; Nouts, C; Lacoste, D; Dupon, M; Dutronc, H; Cipriano, G; Lafarie, S; Chossat, I.; Lacut, JY; Leng, B; Pellegrin, JL; Mercie, P; Viallard, JF; Faure, I.; Rispal, P; Cipriano, C; Tchamgoue, S; Le Bras, M; Djossou, F; Malvy, D; Pivetaud, JP; Ragnaud, JM; Chambon, D; De La Taille, C; Galperine, T; Lafarie, S; Neau, D; Ochoa, A; Beylot, C; Doutre, MS; Bezian, JH; Moreau, JF; Taupin, JL; Conri, C; Constans, J; Couzigou, P; Castera, L; Fleury, H; Lafon, ME; Masquelier, B; Pellegrin, I.; Trimoulet, P; Moreau, F; Mestre, C; Series, C; Taytard, A; Law, M; Petoumenos, K; Bal, J; Mijch, A; Watson, K; Roth, N; Wood, H; Austin, D; Gowers, A; Baker, B; McFarlane, R; Carr, A; Cooper, D; Chuah, J; Fankhauser, W; Mallal, S; Skett, J; Calvo, G; Torres, F; Mateau, S; Domingo, P; Sambeat, MA; Gatell, J; Del Cacho, E; Cadafalch, J; Fuster, M; Codina, C; Sirera, G; Vaque, A; Clumeck, N; De Wit, S; Gerard, M; Hildebrand, M; Kabeya, K; Konopnicki, D; Payen, MC; Poll, B; Van Laethem, Y; Neaton, J; Bartsch, G; El-Sadr, WM; Krum, E; Thompson, G; Wentworth, D; Luskin-Hawk, R; Telzak, E; El-Sadr, WM; Abrams, DI; Cohn, D; Markowitz, N; Arduino, R; Mushatt, D; Friedland, G; Perez, G; Tedaldi, E; Fisher, E; Gordin, F; Crane, LR; Sampson, J; Baxter, J; Kirk, O; Mocroft, A; Phillips, AN; Lundgren, JD; Vetter, N; Clumeck, N; Hermans, P; Colebunders, R; Machala, L; Nielsen, J; Benfield, T; Gerstoft, J; Katzenstein, T; Roge, B; Skinhoj, P; Pedersen, C; Katlama, C; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Miller, V.; Staszewski, S; Bieckel, M; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Karydis, I.; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, I.; Turner, D; Pollack, S; Ben-Ishai, Z; Bentwich, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, V.; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Finazzi, R; Monforte, VO; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, V.; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Boron-Kaczmarska, A; Pnyka, M; Beniowski, M; Trocha, H; Antunes, F; Mansinho, K; Proenca, R; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, V.; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Blaxhult, A; Heidemann, B; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Telenti, A; Hirschel, B; Soravia-Dunand, V.; Furrer, H; Fisher, M; Brettle, R; Barton, S; Johnson, AM; Mercey, D; Loveday, C; Johnson, MA; Pinching, A; Parkin, J; Weber, J; Scullard, G; Morfeldt, L; Thulin, G; Sunstrom, A; Akerlund, B; Koppel, K; Karlsson, A; Flamholc, L; Hakangard, C; Monforte, AD; Pezzotti, P; Moroni, M; Monforte, AD; Cargnel, A; Merli, S; Vigevani, GM; Pastecchia, C; Lazzarin, A; Novati, R; Caggese, L; Moioli, C; Mura, MS; Mannazzu, M; Suter, F; Arici, C; Manconi, PE; Piano, P; Mazzotta, F; Lo Caputo, S; Poggio, A; Bottari, G; Pagano, G; Alessandrini, A
Background: It remains controversial whether exposure to combination antiretroviral treatment increases the risk of myocardial infarction. Methods: In this prospective observational study, we enrolled 23,468 patients from 11 previously established cohorts from December 1999 to April 2001 and collect
Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for anal carcinoma: Are there differences between HIV-positive and HIV-negative patients in the era of highly active antiretroviral therapy?
Purpose: To report treatment compliance, toxicity and clinical outcome of chemoradiotherapy (CRT) for anal carcinoma in HIV-negative vs. HIV-positive patients treated with highly active antiretroviral therapy. Material and methods: Between 1997 and 2008, 25 HIV-positive and 45 HIV-negative patients received CRT (50.4 Gy at 1.8 Gy/fraction plus 5.4-10.8 Gy boost; 5-fluorouracil, 1000 mg/m2, Days 1-4 and 29-32, mitomycin C, 10 mg/m2, Days 1 and 29). Median follow-up was 51 (range, 3-235) months. Results: HIV-positive patients were significantly younger (mean age, 47 vs. 57 years, p < 0.001) and predominantly male (92% vs. 29%, p < 0.001). CRT could be completed in all patients with a reduction of chemotherapy and/or RT-interruption in 28% and 8%, respectively, in HIV-positive patients, and in 9% and 11%, respectively, in HIV-negative patients. Acute Grade 3/4-toxicity occurred in 44% vs. 49% (p = 0.79). Initial complete response (84% vs. 93%, p = 0.41), 5-year rates of local control (65% vs. 78%, p = 0.44), cancer-specific (78% vs. 90%, p = 0.17) and overall survival (71% vs. 77%, p = 0.76) were not significantly different. Conclusion: HIV-positive patients with anal cancer can be treated with standard CRT, with the same tolerability and toxicity as HIV-negative patients. Long-term local control and survival rates are not significantly different between these groups.
Lebech, Anne-Mette; Kristoffersen, Ulrik Sloth; Mehlsen, Jesper; Wiinberg, Niels; Petersen, Claus Leth; Hesse, Birger; Gerstoft, Jan; Kjaer, Andreas
BACKGROUND: The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Introduction of highly active antiretroviral combination therapy (ART) has dramatically changed the course of the disease and improved prognosis and...... decreased morbidity. At present it is not known whether introduction of ART also has decreased autonomic dysfunction. AIM: To evaluate whether autonomic dysfunction is present in an ART-treated HIV population. METHODS: HIV patients receiving ART for at least 3 years (n = 16) and an age-matched control group...... [294 (161-602) versus 946 (711-1668) ms(2); P<0.01]. High frequency power as well as systolic and diastolic blood pressure did not differ between the groups. CONCLUSIONS: The HIV patients in ART have increased resting heart rate and decreased short-term heart rate variability indicating parasympathetic...
Full Text Available The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16 that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.
Full Text Available Pharmacist’s interventions (also known as pharmaceutical care plans are means of solving the drug therapy problems identified in pharmaceutical care. Outcomes are the results of pharmacists’ intervention activities. Patients’ satisfaction refers to patients’ feeling of fulfillment, pleasure or happiness with the services they have received. This study was designed to determine the types of pharmacist interventions applied in the pharmaceutical care of HIV patients receiving treatment at a tertiary hospital in southeast Nigeria, the types of outcomes of such interventions and level of patients’ satisfaction with their drug therapy. The components of the American society of health-system pharmacists (ASHP guidelines on ‘standardized method for pharmaceutical care was used as a data collection instrument to evaluate, document and intervene in the antiretroviral therapy of about one thousand four hundred and seventy three (1,473 patients. The results showed significant reductions in the frequency of the various interventions and parameters measured after the interventions. The study concluded that pharmaceutical interventions influences patients’ adherence, optimizes their drug therapy and improves rational prescribing and care resulting in significant improvements in the outcomes of their treatment and levels of satisfaction.
Conclusions: HBV co-infection can affect late immunological and virological responses to ART and increase the risk of hepatotoxicity. Mortality due to liver disease was high among HIV/HBV co-infected individuals in this study, despite HBV-active ART. As long as HIV/HBV co-infected persons need anti-HBV therapy, they should be recommended ART that includes agents with activity against both HIV and HBV, regardless of the CD4 cell count level.
Sevelius, Jae M.; Carrico, Adam; Johnson, Mallory O.
Despite disproportionate rates of HIV among transgender women and evidence that medication adherence is necessary for treatment success and increased likelihood of survival, there has been little investigation into antiretroviral treatment (ART) adherence issues among transgender women. This study examined rates of self-reported ART adherence among transgender women on ART (n = 35) and well-established correlates of nonadherence including depression, adherence self-efficacy, patient perceptio...
Cristiane A. Menezes de Pádua
Full Text Available A cross-sectional analysis was carried out to describe adverse reactions to antiretroviral therapy (ART reported by HIV-infected patients initiating treatment at two public health AIDS referral centers in Belo Horizonte, Brazil, 2001-2003 and to verify their association with selected variables. Adverse reactions were obtained through interview at the first follow-up visit (first month after the antiretroviral prescription. Socio-demographic and behavioral variables related to ART were obtained from baseline and follow-up interviews and clinical variables from medical charts. Patients with four or more reactions were compared to those with less than four. Odds ratio with 95% confidence interval were estimated using logistic regression model for both univariate and multivariate analyses. At least one adverse reaction was reported by 92.2% of the participants while 56.2% reported four or more different reactions. Antiretroviral regimens including indinavir/ritonavir, irregular use of antiretrovirals and switch in regimens were independently associated with four or more adverse reactions (OR=7.92, 5.73 and 2.03, respectively. The initial period of ARV treatment is crucial and patients´ perception of adverse reactions should be carefully taken into account. Strategies for monitoring and management of adverse reactions including the choice of regimens and the prevention of irregular ART should be developed in AIDS/HIV referral centers in Brazil to promote better adherence to antiretroviral therapy.
Full Text Available In Mozambique, the evaluation of retention in HIV care and ART programmes is limited. To assess rate and predictors of attrition (no retention in care and HAART effectiveness in HIV-1 infected patients who pay for medication and laboratory testing in Mozambique, we conducted a multicenter survey of HIV-1-infected patients who started HAART during 2002-2006. Cox proportional hazard models were used to assess risk of attrition and of therapy failure. Overall, 142 patients from 16 healthcare centers located in the capital city Maputo were followed-up for 22.2 months (12.1-46.7. The retention rate was 75%, 48% and 37% after one, two and three years, respectively. Risk of attrition was lower in patients with higher baseline CD4 count (P = 0.022 and attending healthcare center 1 (HCC1 (P = 0.013. The proportion of individuals with CD4 count ≤ 200 cells/µL was 55% (78/142 at baseline and decreased to 6% (3/52 at 36 months. Among the patients with available VL, 86% (64/74 achieved undetectable VL levels. The rate of immunologic failure was 17.2% (95% CI: 12.6-22.9 per 100 person-years. Risk of failure was associated to higher baseline CD4 count (P = 0.002, likely reflecting low adherence levels, and decreased with baseline VL ≥ 10,000 copies/mL (P = 0.033. These results suggest that HAART can be effective in HIV-1 infected patients from Mozambique that pay for their medication and laboratory testing. Further studies are required to identify the causes for low retention rates in patients with low CD4 counts and to better understand the association between healthcare setting and attrition rate.
LI Zai-cun; LI Hong-jun; DAI Li-li; GAO Yan-qing; CAI Wei-ping; LI Hai-ying; HUANG Xiao-jie; ZHANG Tong; WU Hao
Background Liver injury is one of the most important adverse effects of antiretroviral therapy, leading to therapy changing or discontinuation. Data on liver injury in human immunodeficiency virus-1-infected patients receiving antiretroviral therapy are limited in China. The purpose of this study was to investigate the features of liver injury in human immunodeficiency virus type 1-infected patients receiving non-nucleosides reverse transcriptase inhibitors-based antiretroviral therapy in China.Methods Seventy-five patients on antiretroviral therapy containing non-nucleosides reverse transcriptase inhibitors were retrospectively studied. The patients were divided into 2 groups: group 1 (with liver injury, n=45) and group 2(without liver injury, n=30). The features of liver injury were analyzed. The sex, age, baseline CD4 counts, hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection, hepatotoxic drug use and nevirapine or efavirenz use were compared between two groups.Results Forty-five patients (60.0%), 31 (68.9%) males and 14 (31.1%) females, aged 12 to 52 years (averaged (3g±9)years), experienced at least one episode of liver injury. Forty (53.3%) patients were co-infected with HBV and/or HCV, 42 (56%) patients had concomitant use of antituberculosis drugs or cotrimoxazole, 46 (61.3%) and 29 (38.7%) patients received regimen containing nevirapine and efavirenz, respectively. Grade 1 liver injuries were observed in 26 (57.8%)patients, grade 2 in 16 (35.6%), grade 3 in 2 (4.0%) and grade 4 in 1 (2.2%). Three (6.7%) patients discontinued highly active antiretroviral therapy (HAART) due to liver injury. In group 1, there were 29 (64.4%) patients co-infected with HBV and/or HCV, 32 (71.1%) patients received regimen containing nevirapine, and 30 (66.7%) patients had concomitant use of anti-tuberculosis drugs or cotrimoxazole, respectively, significantly higher than those in group 2 (11 (36.7%), 14 (46.7%)and 12 (40%), respectively; P=0.018, 0.033, 0
Ana Celia Oliveira dos Santos
Full Text Available Introduction Even with current highly active antiretroviral therapy, individuals with AIDS continue to exhibit important nutritional deficits and reduced levels of albumin and hemoglobin, which may be directly related to their cluster of differentiation 4 (CD4 cell counts. The aim of this study was to characterize the nutritional status of individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS and relate the findings to the albumin level, hemoglobin level and CD4 cell count. Methods Patients over 20 years of age with AIDS who were hospitalized in a university hospital and were receiving antiretroviral therapy were studied with regard to clinical, anthropometric, biochemical and sociodemographic characteristics. Body mass index, percentage of weight loss, arm circumference, triceps skinfold and arm muscle circumference were analyzed. Data on albumin, hemoglobin, hematocrit and CD4 cell count were obtained from patient charts. Statistical analysis was performed using Fisher's exact test, Student's t-test for independent variables and the Mann-Whitney U-test. The level of significance was set to 0.05 (α = 5%. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS 17.0 software for Windows. Results Of the 50 patients evaluated, 70% were male. The prevalence of malnutrition was higher when the definition was based on arm circumference and triceps skinfold measurement. The concentrations of all biochemical variables were significantly lower among patients with a body mass index of less than 18.5kg/m2. The CD4 cell count, albumin, hemoglobin and hematocrit anthropometric measures were directly related to each other. Conclusions These findings underscore the importance of nutritional follow-up for underweight patients with AIDS, as nutritional status proved to be related to important biochemical alterations.
Houston, Eric; McKirnan, David J.; Cervone, Daniel; Matthew S. Johnson; Sandfort, Theo G. M.
Using multidimensional scaling analysis (MDS), this study examined how patient conceptualisations of treatment motivation compare with theoretically-based assumptions used in current assessment approaches. Patients undergoing antiretroviral therapy for HIV/AIDS (n = 39) rated for similarity all possible pairings of 23 treatment descriptions, including descriptors of intrinsic, extrinsic, approach, and avoidance motivation. MDS analyses revealed that patient perceptions of intrinsic and extrin...
Oosterhout, J.J. van; Bodasing, N.; Kumwenda, J.J.; Nyirenda, C.; Mallewa, J.; Cleary, P.R.; Baar, M.P. de; Schuurman, R.; Burger, D.M.; Zijlstra, E.E
OBJECTIVE: To evaluate treatment results of the paying antiretroviral therapy (ART) clinic of Queen Elizabeth Central Hospital, a large public and teaching hospital in Blantyre, Malawi. The only ART was a fixed drug combination of stavudine, lamivudine and nevirapine. METHODS: Cross sectional study
Lampe, Fiona C; Duprez, Daniel A; Kuller, Lewis H;
The effect of interruption of antiretroviral therapy (ART) on lipoprotein particle subclasses has not been studied. We examined short-term changes in lipids and lipoprotein particles among 332 HIV-infected individuals randomized to interrupt or continue ART in the "Strategies for Management of...
Poveda, Eva; Tabernilla, Andrés
Current combinations of antiretroviral drugs for the treatment of HIV infection can successfully achieve and maintain long-term suppression of HIV-1 replication in plasma. Still, none of these therapies is capable of eradicating the virus from the long-lived cellular reservoir that represents the major barrier to HIV cure. PMID:27028272
Bannister, Wendy P; Cozzi-Lepri, Alessandro; Kjær, Jesper;
Estimating the prevalence of accumulated HIV drug resistance in patients receiving antiretroviral therapy (ART) is difficult due to lack of resistance testing at all occasions of virological failure and in patients with undetectable viral load. A method to estimate this for 6498 EuroSIDA patients...
Lodi, Sara; Del Amo, Julia; Moreno, Santiago; Bucher, Heiner C.; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Olson, Ashley; Van Sighem, Ard; Reiss, Peter; Sabin, Caroline; Jose, Sophie; Justice, Amy; Goulet, Joseph; Miró, José M.; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Vourli, Georgia; Antoniadou, Anastasia; Dabis, Francois; Vandenhede, Mari-Anne; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A.; Hernan, Miguel; Bansi, L.; Hill, T.; Sabin, C.; Dunn, D.; Porter, K.; Glabay, A.; Orkin, C.; Thomas, R.; Jones, K.; Fisher, M.; Perry, N.; Pullin, A.; Churchill, D.; Gazzard, B.; Nelson, M.; Asboe, D.; Bulbeck, S.; Mandalia, S.; Clarke, J.; Delpech, V.; Anderson, J.; Munshi, S.; Post, F.; Easterbrook, P.; Khan, Y.; Patel, P.; Karim, F.; Duffell, S.; Gilson, R.; Man, S.-L.; Williams, I.; Gompels, M.; Dooley, D.; Schwenk, A.; Ainsworth, J.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Ismajani Puradiredja, D.; Bansi, L.; Hill, T.; Phillips, A.; Sabin, C.; Walsh, J.; Weber, J.; Kemble, C.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Bezemer, D.O.; Gras, L.A.J.; Kesselring, A.M.; Van Sighem, A.I.; Zaheri, S.; Van Twillert, G.; Kortmann, W.; Branger, J.; Prins, J.M.; Kuijpers, T.W.; Scherpbier, H.J.; Van Der Meer, J.T.M.; Wit, F.W.M.N.; Godfried, M.H.; Reiss, P.; Van Der Poll, T.; Nellen, F.J.B.; Lange, J.M.A.; Geerlings, S.E.; Van Vugt, M.; Pajkrt, D.; Bos, J.C.; van der Valk, M.; Grijsen, M.L.; Wiersinga, W.J.; Brinkman, K.; Blok, W.L.; Frissen, P.H.J.; Schouten, W.E.M.; Van Den Berk, G.E.L.; Veenstra, J.; Lettinga, K.D.; Mulder, J.W.; Vrouenraets, S.M.E.; Lauw, F.N.; Van Eeden, A.; Verhagen, D.W.M.; Van Agtmael, M.A.; Perenboom, R.M.; Claessen, F.A.P.; Bomers, M.; Peters, E.J.G.; Richter, C.; Van Der Berg, J.P.; Gisolf, E.H.; Schippers, E.F.; Van Nieuwkoop, C.; Van Elzakker, E.P.; Leyten, E.M.S.; Gelinck, L.B.S.; Pronk, M.J.H.; Bravenboer, B.; Kootstra, G.J.; Delsing, C.E.; Sprenger, H.G.; Doedens, R.; Scholvinck, E.H.; Van Assen, S.; Bierman, W.F.W.; Soetekouw, R.; Ten Kate, R.W.; Van Vonderen, M.G.A.; Van Houte, D.P.F.; Kroon, F.P.; Van Dissel, J.T.; Arend, S.M.; De Boer, M.G.J.; Jolink, H.; Ter Vollaard, H.J.M.; Bauer, M.P.; Weijer, S.; El Moussaoui, R.; Lowe, S.; Schreij, G.; Oude Lashof, A.; Posthouwer, D.; Koopmans, P.P.; Keuter, M.; Van Der Ven, A.J.A.M.; Ter Hofstede, H.J.M.; Dofferhoff, A.S.M.; Warris, A.; Van Crevel, R.; van der Ende, Marchina E.; De Vries-Sluijs, T.E.M.S.; Schurink, C.A.M.; Nouwen, J.L.; Nispen Tot Pannerden, M.H.; Verbon, A.; Rijnders, B.J.A.; Van Gorp, E.C.M.; Hassing, R.J.; Smeulders, A.W.M.; Hartwig, N.G.; Driessen, G.J.A.; Den Hollander, J.G.; Pogany, K.; Juttmann, J.R.; Van Kasteren, M.E.E.; Hoepelman, A.I.M.; Mudrikova, T.; Schneider, M.M.E.; Jaspers, C.A.J.J.; Ellerbroek, P.M.; Oosterheert, J.J.; Arends, J.E.; Wassenberg, M.W.M.; Barth, R.E.; Geelen, S.P.M.; Wolfs, T.F.W.; Bont, L.J.; Van Den Berge, M.; Stegeman, A.; Groeneveld, P.H.P.; Alleman, M.A.; Bouwhuis, J.W.; Barin, F.; Burty, C.; Duvivier, C.; Enel, P.; Fredouille-Heripret, L.; Gasnault, J.; Khuong, M.A.; Mahamat, A.; Pilorgé, F.; Tattevin, P.; Salomon, Valérie; Jacquemet, N.; Abgrall, S.; Costagliola, D.; Grabar, S.; Guiguet, M.; Lanoy, E.; Lièvre, L.; Mary-Krause, M.; Selinger-Leneman, H.; Lacombe, J.M.; Potard, V.; Bricaire, F.; Herson, S.; Katlama, C.; Simon, A.; Desplanque, N.; Girard, P.M.; Meynard, J.L.; Meyohas, M.C.; Picard, O.; Cadranel, J.; Mayaud, C.; Pialoux, G.; Clauvel, J.P.; Decazes, J.M.; Gerard, L.; Molina, J.M.; Diemer, M.; Sellier, P.; Bentata, M.; Honoré, P.; Jeantils, V.; Tassi, S.; Mechali, D.; Taverne, B.; Bouvet, E.; Crickx, B.; Ecobichon, J.L.; Matheron, S.; Picard-Dahan, C.; Yeni, P.; Berthé, H.; Dupont, C.; Chandemerle, C.; Mortier, E.; De Truchis, P.; Tisne-Dessus, D.; Weiss, L.; Salmon, D.; Auperin, I.; Gilquin, J.; Roudière, L.; Viard, J.P.; Boué, F.; Fior, R.; Delfraissy, J.F.; Goujard, C.; Jung, C.; Lesprit, Ph.; Vittecoq, D.; Fraisse, P.; Lang, J.M.; Rey, D.; Beck-Wirth, G.; Stahl, J.P.; Lecercq, P.; Gourdon, F.; Laurichesse, H.; Fresard, A.; Lucht, F.; Bazin, C.; Verdon, R.; Chavanet, P.; Arvieux, C.; Michelet, C.; Choutet, P.; Goudeau, A.; Maître, M.F.; Hoen, B.; Eglinger, P.; Faller, J.P.; Borsa-Lebas, F.; Caron, F.; Reynes, J.; Daures, J.P.; May, T.; Rabaud, C.; Berger, J.L.; Rémy, G.; Arlet-Suau, E.; Cuzin, L.; Massip, P.; Thiercelin Legrand, M.F.; Pontonnier, G.; Viget, N.; Yasdanpanah, Y.; Dellamonica, P.; Pradier, C.; Pugliese, P.; Aleksandrowicz, K.; Quinsat, D.; Ravaux, I.; Tissot-Dupont, H.; Delmont, J.P.; Moreau, J.; Gastaut, J.A.; Poizot-Martin, I.; Retornaz, F.; Soubeyrand, J.; Galinier, A.; Ruiz, J.M.; Allegre, T.; Blanc, P.A.; Bonnet-Montchardon, D.; Lepeu, G.; Granet-Brunello, P.; Esterni, J.P.; Pelissier, L.; Cohen-Valensi, R.; Nezri, M.; Chadapaud, S.; Laffeuillade, A.; Billaud, E.; Raffi, F.; Boibieux, A.; Peyramond, D.; Livrozet, J.M.; Touraine, J.L.; Cotte, L.; Trepo, C.; Strobel, M.; Bissuel, F.; Pradinaud, R.; Sobesky, M.; Cabié, A.; Gaud, C.; Contant, M.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Haerry, D.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Hasse, B.; Hirsch, H.H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez De Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.; Casabona, J.; Gallois, A.; Esteve, A.; Podzamczer, D.; Murillas, J.; Gatell, J.M.; Manzardo, C.; Tural, C.; Clotet, B.; Ferrer, E.; Riera, M.; Segura, F.; Navarro, G.; Force, L.; Vilaró, J.; Masabeu, A.; García, I.; Guadarrama, M.; Cifuentes, C.; Dalmau, D.; Jaen, À.; Agustí, C.; Montoliu, A.; Pérez, I.; Gargoulas, Freyra; Blanco, J.L.; Garcia-Alcaide, F.; Martínez, E.; Mallolas, J.; López-Dieguez, M.; García-Goez, J.F.; Sirera, G.; Romeu, J.; Jou, A.; Negredo, E.; Miranda, C.; Capitan, M.C.; Saumoy, M.; Imaz, A.; Tiraboschi, J.M.; Murillo, O.; Bolao, F.; Peña, C.; Cabellos, C.; Masó, M.; Vila, A.; Sala, M.; Cervantes, M.; Jose Amengual, Ma.; Navarro, M.; Penelo, E.; Barrufet, P.; Bejarano, G.; Molina, J.; Guadarrama, M.; Alvaro, M.; Mercadal, J.; Fernandez, Juanse; Ospina, Jesus E.; Muñoz, M.A.; Caro-Murillo, A.M.; Sobrino, P.; Jarrín, I.; Gomez Sirvent, J.L.; Rodríguez, P.; Aleman, M.R.; Alonso, M.M.; Lopez, A.M.; Hernandez, M.I.; Soriano, V.; Labarga, P.; Barreiro, P.; Medrano, J.; Rivas, P.; Herrero, D.; Blanco, F.; Vispo, M.E.; Martín, L.; Ramírez, G.; De Diego, M.; Rubio, R.; Pulido, F.; Moreno, V.; Cepeda, C.; Hervás, Rl.; Iribarren, J.A.; Arrizabalaga, J.; Aramburu, M.J.; Camino, X.; Rodrí-guez-Arrondo, F.; Von Wichmann, M.A.; Pascual, L.; Goenaga, M.A.; 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Masozera, N.; Goetz, M.; Leaf, D.; Simberkoff, M.; Blumenthal, D.; Leung, J.; Butt, A.; Hoffman, E.; Gibert, C.; Peck, R.; Mattocks, K.; Braithwaite, S.; Brandt, C.; Bryant, K.; Cook, R.; Conigliaro, J.; Crothers, K.; Chang, J.; Crystal, S.; Day, N.; Erdos, J.; Freiberg, M.; Kozal, M.; Gandhi, N.; Gaziano, M.; Gerschenson, M.; Good, B.; Gordon, A.; Goulet, J.L.; Hernán, M.A.; Kraemer, K.; Lim, J.; Maisto, S.; Miller, P.; Mole, L.; O'Connor, P.; Papas, R.; Robins, J.M.; Rinaldo, C.; Roberts, M.; Samet, J.; Tierney, B.; Whittle, J.; Babiker, A.; Brettle, R.; Darbyshire, J.; Gilson, R.; Goldberg, D.; Hawkins, D.; Jaffe, H.; Johnson, A.; McLean, K.; Pillay, D.; Cursley, Adam; Ewings, Fiona; Fairbrother, Keith; Louisa Gnatiuc, S.L.; Murphy, Brendan; Douglas, G.; Kennedy, N.; Pritchard, J.; Andrady, U.; Rajda, N.; Maw, R.; McKernan, S.; Drake, S.; Gilleran, G.; White, D.; Ross, J.; Toomer, S.; Hewart, R.; Wilding, H.; Woodward, R.; Dean, G.; Heald, L.; Horner, P.; Glover, S.; Bansaal, D.; Eduards, S.; 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Ong, E.; Das, R.; Grey, R.; Meaden, J.; Bignell, C.; Loay, D.; Peacock, K.; Girgis, M.R.; Morgan, B.; Palfreeman, A.; Wilcox, J.; Tobin, J.; Tucker, L.; Saeed, A.M.; Chen, F.; Deheragada, A.; Williams, O.; Lacey, H.; Herman, S.; Kinghorn, D.; Devendra, V.S.; Wither, J.; Dawson, S.; Rowen, D.; Harvey, J.; Wilkins, E.; Bridgwood, A.; Singh, G.; Chauhan, M.; Kellock, D.; Young, S.; Dannino, S.; Kathir, Y.; Rooney, G.; Currie, J.; Fitzgerald, M.; Devendra, S.; Keane, F.; Booth, G.; Green, T.; Arumainayyagam, J.; Chandramani, S.; Rajamanoharan, S.; Robinson, T.; Curless, E.; Gokhale, R.; Tariq, A.; Roberts, M.; Williams, O.; Luzzi, G.; FitzGerald, M.; Fairley, I.; Wallis, F.; Smit, E.; Ward, F.; Molina, J.M.; Loze, B.; Morlat, P.; Bonarek, M.; Bonnet, F.; Nouts, C.; Louis, I.; Raffi, F.; Reliquet, V.; Sauser, F.; Biron, C.; Mounoury, O.; Hue, H.; Brosseau, D.; Delfraissy, J.F.; Goujard, C.; Ghosn, J.; Rannou, M.T.; Bergmann, J.F.; Badsi, E.; Rami, A.; Diemer, M.; Parrinello, M.; Girard, P.M.; Samanon-Bollens, D.; Campa, P.; Tourneur, M.; Desplanques, N.; Livrozet, J.M.; Jeanblanc, F.; Chiarello, P.; Makhloufi, D.; Blanc, A.P.; Allègre, T.; Reynes, J.; Baillat, V.; Lemoing, V.; Merle De Boever, C.; Tramoni, C.; Cabié, A.; Sobesky, G.; Abel, S.; Beaujolais, V.; Pialoux, G.; Slama, L.; Chakvetadze, C.; Berrebi, V.; Yeni, P.; Bouvet, E.; Fournier, I.; Gerbe, J.; Trepo, C.; Koffi, K.; Augustin-Normand, C.; Miailhes, P.; Thoirain, V.; Brochier, C.; Thomas, R.; Souala, F.; Ratajczak, M.; Beytoux, J.; Jacomet, C.; Gourdon, F.; Rouveix, E.; Morelon, S.; Dupont, C.; Olivier, C.; Lortholary, O.; Dupont, B.; Viard, J.P.; Maignan, A.; Ragnaud, J.M.; Raymond, I.; Leport, C.; Jadand, C.; Jestin, C.; Longuet, P.; Boucherit, S.; Sereni, D.; Lascoux, C.; Prevoteau, F.; Sobel, A.; Levy, Y.; Lelièvre, J.D.; Lascaux, A.S.; Dominguez, S.; Dumont, C.; Aumâitre, H.; Delmas, B.; Saada, M.; Medus, M.; Guillevin, L.; Salmon, D.; Tahi, T.; Yazdanpanah, Y.; Pavel, S.; Marien, M.C.; Drenou, B.; Beck-Wirth, G.; Beck, C.; Benomar, M.; Katlama, C.; Tubiana, R.; Ait Mohand, H.; Chermak, A.; Ben Abdallah, S.; Bentata, M.; Touam, F.; Hoen, B.; Drobacheff, C.; Folzer, A.; Massip, P.; Obadia, M.; Prudhomme, L.; Bonnet, E.; Balzarin, F.; Pichard, E.; Chennebault, J.M.; Fialaire, P.; Loison, J.; Galanaud, P.; Boué, F.; Bornarel, D.; Verdon, R.; Bazin, C.; Six, M.; Ferret, P.; Weiss, L.; Batisse, D.; Gonzales-Canali, G.; Tisne-Dessus, D.; Devidas, A.; Chevojon, P.; Turpault, I.; Lafeuillade, A.; Cheret, A.; Philip, G.; Morel, P.; Timsit, J.; Herson, S.; Amirat, N.; Simon, A.; Brancion, C.; Cabane, J.; Picard, O.; Tredup, J.; Stein, A.; Ravault, I.; Chavanet, C.; Buisson, M.; Treuvetot, S.; Choutet, P.; Nau, P.; Bastides, F.; May, T.; Boyer, L.; Wassoumbou, S.; Oksenhendeler, E.; Gérard, L.; Bernard, L.; De Truchis, P.; Berthé, H.; Domart, Y.; Merrien, D.; Greder Belan, A.; Gayraud, M.; Bodard, L.; Meudec, A.; Beuscart, C.; Daniel, C.; Pape, E.; Vinceneux, P.; Simonpoli, A.M.; Zeng, A.; Fournier, L.; Fuzibet, J.G.; Sohn, C.; Rosenthal, E.; Quaranta, M.; Dellamonica, P.; Chaillou, S.; Sabah, M.; Audhuy, B.; Schieber, A.; Moreau, P.; Niault, M.; Vaillant, O.; Huchon, G.; Compagnucci, A.; De Lacroix Szmania, I.; Richier, L.; Lamaury, I.; Saint-Dizier, F.; Garipuy, D.; Gastaut, J.A.; Drogoul, M.P.; Poizot Martin, I.; Fabre, G.; Lambert De Cursay, G.; Abraham, B.; Perino, C.; Lagarde, P.; David, F.; Roche-Sicot, J.; Saraux, J.L.; Leprêtre, A.; Fampin, B.; Uludag, A.; Morin, A.S.; Bletry, O.; Zucman, D.; Regnier, A.; Girard, J.J.; Quinsat, D.T.; Heripret, L.; Grihon, F.; Houlbert, D.; Ruel, M.; Chemlal, K.; Caron, F.; Debab, Y.; Tremollieres, F.; Perronne, V.; Lepeu, G.; Slama, B.; Perré, P.; Miodovski, C.; Guermonprez, G.; Dulioust, A.; Boudon, P.; Malbec, D.; Patey, O.; Semaille, C.; Deville, J.; Remy, G.; Béguinot, I.; Galanaud, P.; Boue, F.; Chambrin, V.; Pignon, C.; Estocq, G.A.; Levy, A.; Delfraissy, J.F.; Goujard, C.; Duracinsky, M.; Le Bras, P.; Ngussan, M.S.; Peretti, D.; Medintzeff, N.; Lambert, T.; 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Quaranta, M.; Krivitsky, J.A.; Bentata, M.; Bouchaud, O.; Honore, P.; Sereni, D.; Lascoux, C.; Delgado, J.; Rouzioux, C.; Burgard, M.; Boufassa, L.; Peynet, J.; Pérez-Hoyos, S.; Del Amo, J.; Alvarez, D.; Monge, S.; Muga, R.; Sanvisens, A.; Clotet, B.; Tor, J.; Bolao, F.; Rivas, I.; Vallecillo, G.; Del Romero, J.; Raposo, P.; Rodríguez, C.; Vera, M.; Hurtado, I.; Belda, J.; Fernandez, E.; Alastrue, I.; Santos, C.; Tasa, T.; Juan, A.; Trullen, J.; Garcia De Olalla, P.; Cayla, J.; Masdeu, E.; Knobel, H.; Mirò, J.M.; Sambeat, M.A.; Guerrero, R.; Rivera, E.; Guerrero, R.; Marco, A.; Quintana, M.; Gonzalez, C.; Castilla, J.; Guevara, M.; De Mendoza, C.; Zahonero, N.; Ortíz, M.; Paraskevis, D.; Touloumi, G.; Pantazis, N.; Bakoyannis, G.; Gioukari, V.; Antoniadou, A.; Papadopoulos, A.; Petrikkos, G.; Daikos, G.; Psichogiou, M.; Gargalianos-Kakolyris, P.; Xylomenos, G.; Katsarou, O.; Kouramba, A.; Ioannidou, P.; Kordossis, T.; Kontos, A.; Lazanas, M.; Chini, M.; Tsogas, N.; Panos, G.; Paparizos, V.; Leuow, K.; Kourkounti, S.; Sambatakou, H.; Mariolis, I.; Skoutelis, A.; Papastamopoulos, V.; Baraboutis, I.
Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacteri
XIAO Jian; LI Ming-yuan; WANG Ying; QIAN Ke-lei; CAO Qing-hua; QIU Chen-li; QIU Cao; XUE Yi-le; ZHANG Xiao-yan; ZHONG Ping; XU Jian-qing
Background The frequencies of regulatory T cells (Tregs) increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4+CD25+CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. ResultsCompared to HIV-1 seronegative donors, the levels of HLA-DR on CD4+CD25+CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads (r=0.3163,P=0.004) and negatively with CD4 T-cell counts (r=-0.4153, P<0.0001). In addition, significant associations between HLA-DR expression on CD4+CD25+CD127lo/-Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4+ and CD8+ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.
Full Text Available Objectives: To estimate the percentage of adherence to highly-active antiretroviral therapy (HAART in Spanish observational studies and to identify the variables associated with adherence. Methods: Seven electronic databases were used to locate the studies. Six inclusion criteria were established. Two coders codified the variables independently. Intercoder reliability was calculated. Publication bias was analyzed through the Begg, Egger and Trim and Fill tests. Homogeneity was evaluated using the Q test and the l² index. A random effects model was assumed to estimate both the overall percentage of adherence and to explain heterogeneity. Results: This meta-analysis included 23 observational studies, yielding a total of 34 adherence estimates. The sample was composed of 9,931 HIV-positive individuals (72% men older than 18 years under treatment with HAART. The percentage of patients adhering to an intake of >90% of the prescribed antiretroviral drugs was 55%. Wide heterogeneity was detected (I²=91.20; 95%CI: 88.75-93.13. Adherence was mainly measured using a single strategy (47.8%, the most widely used being self-report (48.7%. In the univariate analysis, the following factors were significant: infection stages A (β=0.68, p 200 copies/ml (β=-0.41, p Objetivo: Calcular el porcentaje de adherencia al TARGA en estudios observacionales españoles, así como identificar las variables asociadas a ella. Métodos: Para localizar los estudios se emplearon siete bases bibliográficas. Se establecieron seis criterios de inclusión. Dos codificadores realizaron la codificación de forma independiente. Se calculó la fiabilidad intercodificadores. El sesgo de publicación se evaluó mediante los tests de Begg y de Egger, y Trim & Fill. La homogeneidad se estimó mediante la prueba Q y el índice I². Se asumió un modelo de efectos aleatorios tanto para la estimación del porcentaje global de adherencia como para explicar la heterogeneidad. Resultados: El
Full Text Available Introduction: These guidelines are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the French health authorities in September 2013. The objective was to provide updated recommendations for antiretroviral treatment (ART of HIV-positive adults. Guidelines included the following topics: when to start, what to start, specific situations for the choice of the first session of antiretroviral therapy, optimization of antiretroviral therapy after virologic suppression, and management of virologic failure. Methods: Ten members of the French HIV 2013 expert group were responsible for guidelines on ART. They systematically reviewed the most recent literature. The chairman of the subgroup was responsible for drafting the guidelines, which were subsequently discussed within, and finalized by the whole expert group to obtain a consensus. Recommendations were graded for strength and level of evidence using predefined criteria. Economic considerations were part of the decision-making process for selecting preferred first-line options. Potential conflicts of interest were actively managed throughout the whole process. Results: ART should be initiated in any HIV-positive person, whatever his/her CD4 T-cell count, even when >500/mm3. The level of evidence of the individual benefit of ART in terms of mortality or progression to AIDS increases with decreasing CD4 cell count. Preferred initial regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine plus a non-nucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine, or a ritonavir-boosted protease inhibitor (atazanavir or darunavir. Raltegravir, lopinavir/r, and nevirapine are recommended as alternative third agents, with specific indications and restrictions. Specific situations such as HIV infection in women, primary HIV infection, severe immune suppression
Pelosi, Giorgio; Bisceglie, Franco; Bignami, Fabio; Ronzi, Paola; Schiavone, Pasqualina; Re, Maria Carla; Casoli, Claudio; Pilotti, Elisabetta
Thiosemicarbazones display a wide antimicrobial activity by targeting bacteria, fungi, and viruses. Here, we report our studies on the antiviral activity of two thiosemicarbazone metal complexes, [bis(citronellalthiosemicarbazonato)nickel(II)] and [aqua(pyridoxalthiosemicarbazonato)copper(II)] chloride monohydrate, against the retroviruses HIV-1 and HTLV-1/-2. Both compounds exhibit antiviral properties against HIV but not against HTLVs . In particular, the copper complex shows the most potent anti-HIV activity by acting at the post-entry steps of the viral cycle. PMID:21121632
Marra, C.M.; Lockhart, D.; Zunt, J. R.; Perrin, M.; Coombs, R.W.; Collier, A.C.
The authors assessed CSF and plasma HIV-1 RNA and neuropsychological test performance (composite neuropsychological test Z score [NPZ-4]) in 25 HIV-1–infected subjects 4 and 8 weeks after beginning potent antiretroviral therapy that included a protease inhibitor. In the 14 subjects who entered the study on no antiretroviral treatment, NPZ-4 improvement was associated with decline in CSF HIV-1 RNA at both visits (p = 0.001 and p = 0.02), and those treated with zidovudine or indinavir had great...
Thanawuth, Nattasiri; Rojpibulstit, Malee
The objective of this study was to examine the extent of unprotected sex among patients already established in HIV-medical care and their associated factors. Sexually active patients who were receiving antiretroviral therapy (ART) from five public hospitals in Trang province, Southern Thailand, were interviewed. Of 279 studied patients, 37.3% had unprotected sex in the prior 3 months and 27.2% did not disclose their serostatus to sexual partners. The median duration interquartile range (IQR) of using ART was 47 (27-60) months and 26.7% were non-adherent to ART (i.e., taking less than 95% of the prescribed doses). More than one-third had the perception that ART use would protect against HIV transmission even with unprotected sex. About 36.6% reported that they were unaware of their current CD4 counts and nearly one-third did not receive any safe sex counseling at each medical follow-up. After adjustment for potential confounders, non-adherence to ART and HIV-nondisclosure were strongly associated with an increase in the risk of unprotected sex with the adjusted odds ratio (aOR) of 5.03 (95% CI 2.68-9.44) and 3.89 (95% CI 1.57-9.61), respectively. In contrast, the risk for engaging in unprotected sex was less likely among patients having a negative-serostatus partner (aOR = 0.30; 95% CI 0.12-0.75), a longer duration of the use of ART (aOR = 0.98; 95%CI 0.97-0.99) and an unawareness of their current CD4 levels (aOR = 0.54; 95% CI 0.30-0.99). To maximize the benefits from ART, there should be a bigger emphasis on the "positive prevention" program and more efforts are needed to target the population at risk for unprotected sex. Strategies to encourage adherence to ART and for disclosure of serostatus are also required. PMID:26666292
The cameroon mobile phone sms (CAMPS trial: a protocol for a randomized controlled trial of mobile phone text messaging versus usual care for improving adherence to highly active anti-retroviral therapy
Full Text Available Abstract Background This trial aims at testing the efficacy of weekly reminder and motivational text messages, compared to usual care in improving adherence to Highly Active Antiretroviral Treatment in patients attending a clinic in Yaoundé, Cameroon. Methods and Design This is a single-centered randomized controlled single-blinded trial. A central computer generated randomization list will be generated using random block sizes. Allocation will be determined by sequentially numbered sealed opaque envelopes. 198 participants will either receive the mobile phone text message or usual care. Our hypothesis is that weekly motivational text messages can improve adherence to Highly Active Antiretroviral Treatment and other clinical outcomes in the control group by acting as a reminder, a cue to action and opening communication channels. Data will be collected at baseline, three months and six months. A blinded program secretary will send out text messages and record delivery. Our primary outcomes are adherence measured by the visual analogue scale, self report, and pharmacy refill data. Our secondary outcomes are clinical: weight, body mass index, opportunistic infections, all cause mortality and retention; biological: Cluster Designation 4 count and viral load; and quality of life. Analysis will be by intention-to-treat. Covariates and subgroups will be taken into account. Discussion This trial investigates the potential of SMS motivational reminders to improve adherence to Highly Active Antiretroviral Treatment in Cameroon. The intervention targets non-adherence due to forgetfulness and other forms of non-adherence. Trial Registration Pan-African Clinical Trials Registry PACTR201011000261458 http://clinicaltrials.gov/NCT01247181
Murphy, Patricia; Cocohoba, Jennifer; Tang, Andrew; Pietrandoni, Glen; Hou, John; Guglielmo, B. Joseph
Patient adherence (the degree to which patients follow their therapeutic regimen as prescribed within a set period of time) and persistence (the time to treatment discontinuation, with a permissible gap) with drug therapy are essential components of HIV/AIDS treatment. Select community pharmacies offer specialized services for HIV/AIDS patients to help combat some of the barriers to adherence and persistence. We assessed adherence and persistence with antiretroviral therapy (ART) for patients...
Becker, James T.; Cuesta, Pablo; Fabrizio, Melissa; Sudre, Gustavo; Vergis, Emanuel N.; Douaihy, Antoine; Bajo Breton, Ricardo; Schubert, Allie; Lopez, Oscar L.; Parkkonen, Lauri; Maestú, Fernando; Bagic, Anto
NeuroAIDS persists in the era of combination antiretroviral therapies. We describe here the recovery of brain structure and function following 6 months of therapy in a treatment-naive patient presenting with HIV-associated dementia. The patient’s neuropsychological test performance improved and his total brain volume increased by more than 5 %. Neuronal functional connectivity measured by magnetoencephalography changed from a pattern identical to that observed in other HIV-infected individual...
Full Text Available HIV-2 contributes approximately a third to the prevalence of HIV in West Africa and is present in significant amounts in several low-income countries outside of West Africa with historical ties to Portugal. It complicates HIV diagnosis, requiring more expensive and technically demanding testing algorithms. Natural polymorphisms and patterns in the development of resistance to antiretrovirals are reviewed, along with their implications for antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitors, crucial in standard first-line regimens for HIV-1 in many low-income settings, have no effect on HIV-2. Nucleoside analogues alone are not sufficiently potent enough to achieve durable virologic control. Some protease inhibitors, in particular those without ritonavir boosting, are not sufficiently effective against HIV-2. Following review of the available evidence and taking the structure and challenges of antiretroviral care in West Africa into consideration, the authors make recommendations and highlight the needs of special populations.