PrayGod, George; Blevins, M; Woodd, Susannah;
Antiretroviral therapy (NUSTART) trial in Tanzania and Zambia from 2011 to 2013. SUBJECTS/METHODS: HIV-infected, ART-eligible adults with body mass index (BMI) of ...BACKGROUND/OBJECTIVES: The effects of inflammation on nutritional rehabilitation after starting antiretroviral therapy (ART) are not well understood. We assessed the relationship between inflammation and body composition among patients enrolled in the Nutritional Support for African Adults Starting...
Douglas C Heimburger
Full Text Available BACKGROUND: Patients starting antiretroviral therapy (ART for acquired immunodeficiency syndrome (AIDS in sub-Saharan Africa have high rates of mortality in the initial weeks of treatment. We assessed the association of serum phosphate with early mortality among HIV-infected adults with severe malnutrition and/or advanced immunosuppression. METHODOLOGY/PRINCIPAL FINDINGS: An observational cohort of 142 HIV-infected adults initiating ART in Lusaka, Zambia with body mass index (BMI <16 kg/m(2 or CD4(+ lymphocyte count <50 cells/microL, or both, was followed prospectively during the first 12 weeks of ART. Detailed health and dietary intake history, review of systems, physical examination, serum metabolic panel including phosphate, and serum ferritin and high-sensitivity C-reactive protein (hsCRP were monitored. The primary outcome was mortality. Baseline serum phosphate was a significant predictor of mortality; participants alive at 12 weeks had a median value of 1.30 mmol/L (interquartile range [IQR]: 1.04, 1.43, compared to 1.06 mmol/L (IQR: 0.89, 1.27 among those who died (p<0.01. Each 0.1 mmol/L increase in baseline phosphate was associated with an incremental decrease in mortality (AHR 0.83; 95% CI 0.72 to 0.95. The association was independent of other metabolic parameters and known risk factors for early ART-associated mortality in sub-Saharan Africa. While participant attrition represented a limitation, it was consistent with local program experience. CONCLUSIONS/SIGNIFICANCE: Low serum phosphate at ART initiation was an independent predictor of early mortality among HIV patients starting ART with severe malnutrition or advanced immunosuppression. This may represent a physiologic phenomenon similar to refeeding syndrome, and may lead to therapeutic interventions that could reduce mortality.
Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred M
, 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......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...
Olsen, Mette Frahm; Abdissa, Alemseged; Kæstel, Pernille
Objectives: To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months...... delay. Design: Randomised controlled trial. Setting: Three public ART facilities in Jimma, Oromia region, Ethiopia. Participants: Adults with HIV eligible for ART with body mass index (BMI) >16. Intervention: Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either...... and CD3 and CD8 counts. Results: Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg...
Full Text Available Abstract Background The scarcity of physicians in sub-Saharan Africa – particularly in rural clinics staffed only by non-physician health workers – is constraining access to HIV treatment, as only they are legally allowed to start antiretroviral therapy in the HIV-positive patient. Here we present a pilot study from Uganda assessing agreement between non-physician clinicians (nurses and clinical officers and physicians in their decisions as to whether to start therapy. Methods We conducted the study at 12 government antiretroviral therapy sites in three regions of Uganda, all of which had staff trained in delivery of antiretroviral therapy using the WHO Integrated Management of Adult and Adolescent Illness guidelines for chronic HIV care. We collected seven key variables to measure patient assessment and the decision as to whether to start antiretroviral therapy, the primary variable of interest being the Final Antiretroviral Therapy Recommendation. Patients saw either a clinical officer or nurse first, and then were screened identically by a blinded physician during the same clinic visit. We measured inter-rater agreement between the decisions of the non-physician health workers and physicians in the antiretroviral therapy assessment variables using simple and weighted Kappa analysis. Results Two hundred fifty-four patients were seen by a nurse and physician, while 267 were seen by a clinical officer and physician. The majority (> 50% in each arm of the study were in World Health Organization Clinical Stages I and II and therefore not currently eligible for antiretroviral therapy according to national antiretroviral therapy guidelines. Nurses and clinical officers both showed moderate to almost perfect agreement with physicians in their Final Antiretroviral Therapy Recommendation (unweighted κ = 0.59 and κ = 0.91, respectively. Agreement was also substantial for nurses versus physicians for assigning World Health Organization Clinical
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.
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.
Kesselring, Anouk M; Wit, Ferdinand W; Sabin, Caroline A;
BACKGROUND: This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). METHODS: Patients starting NVPc after 1...... to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year...... of starting NVPc and mode of transmission. RESULTS: Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high...
Full Text Available We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes.
BACKGROUND: Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European...... factor, detectable HIV-1 RNA viral load becomes an increasingly important risk factor in patients who started cART several years earlier, independently of immunodeficiency....
Minga, Albert; Gabillard, Delphine; Ouassa, Timothée; Messou, Eugene; Morris, Brandon; Traore, Moussa; Coulibaly, Ali; Freedberg, Kenneth A.; Lewden, Charlotte; Ménan, Hervé; Abo, Yao; Dakoury-Dogbo, Nicole; Toure, Siaka; Seyler, Catherine
Background. In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell count–specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)–infected adults with high CD4 cell counts. In sub–Saharan Africa, these CD4 cell count–specific estimates are scarce. Methods. From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Côte d’Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200 cells/μL once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count–specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum. Results. Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ≥650, 500–649, 350–499, 200–349, 100–199, 50–99, and 0–49 cells/μL CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ≥200 CD4 cells/μL, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200–349 and ≥650 cells/μL, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY). Conclusions. Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ≥200 cells/μL. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub–Saharan Africa. PMID:22173233
Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.......Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load....
Filteau, Suzanne; PrayGod, George; Kasonka, Lackson;
BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study was ...
Scott, Christopher; Staughton, Richard C D; Bunker, Christopher J; Asboe, David
Immune reconstitution disease (IRD) has been widely reported following the commencement of antiretrovirals. We report a case series from a cohort of HIV-1-infected patients of whom four developed acne vulgaris and one developed acne rosacea after the initiation of antiretroviral therapy. Acne vulgaris, as part of IRD, has been reported only once in the literature, whereas acne rosacea has not, to our knowledge, previously been described. This serves as a reminder not to overlook dermatological manifestations of disease in patients with HIV infection after starting antiretrovirals.
May, Margaret T.; Vehreschild, Janne; Obel, Niels; Gill, Michael John; Crane, Heidi; Boesecke, Christoph; Samji, Hasina; Grabar, Sophie; Cazanave, Charles; Cavassini, Matthias; Shepherd, Leah; d’Arminio Monforte, Antonella; Smit, Colette; Saag, Michael; Lampe, Fiona; Hernando, Vicky; Montero, Marta; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy; Miro, Jose; Ingle, Suzanne; Sterne, Jonathan A. C.
Objectives To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996–1999 and survived for more than ten years. Methods We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. Results During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years. Conclusions Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes. PMID:27525413
Baxter, J D; Dunn, D; White, E;
of resistance testing in START trial participants. METHODS: In the Strategic Timing of AntiRetroviral Treatment (START) trial, baseline genotypic resistance testing results were collected at study entry and analysed centrally to determine the prevalence of TDR in the study population. Resistance was based...
Full Text Available BACKGROUND: In adults it is well documented that there are substantial losses to the programme between HIV testing and start of antiretroviral therapy (ART. The magnitude and reasons for loss to follow-up and death between HIV diagnosis and start of ART in children are not well defined. METHODS: We searched the PubMed and EMBASE databases for studies on children followed between HIV diagnosis and start of ART in low-income settings. We examined the proportion of children with a CD4 cell count/percentage after after being diagnosed with HIV infection, the number of treatment-eligible children starting ART and predictors of loss to programme. Data were extracted in duplicate. RESULTS: Eight studies from sub-Saharan Africa and two studies from Asia with a total of 10,741 children were included. Median age ranged from 2.2 to 6.5 years. Between 78.0 and 97.0% of HIV-infected children subsequently had a CD4 cell count/percentage measured, 63.2 to 90.7% of children with an eligibility assessment met the eligibility criteria for the particular setting and time and 39.5 to 99.4% of the eligible children started ART. Three studies reported an association between low CD4 count/percentage and ART initiation while no association was reported for gender. Only two studies reported on pre-ART mortality and found rates of 13 and 6 per 100 person-years. CONCLUSION: Most children who presented for HIV care met eligibility criteria for ART. There is an urgent need for strategies to improve the access to and retention to care of HIV-infected children in resource-limited settings.
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
Trickey, Adam; May, Margaret T; Vehreschild, Janne
OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing to the Antiretro...
Jeffrey K Hom
Full Text Available OBJECTIVE: To estimate the prevalence of drug-resistant tuberculosis (TB and describe the resistance patterns in patients commencing antiretroviral therapy (ART in an HIV clinic in Durban, South Africa. DESIGN: Cross-sectional cohort study. METHODS: Consecutive HIV-infected adults (≥ 18y/o initiating HIV care were enrolled from May 2007-May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium. Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed. RESULTS: 1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42-150/µl. 267 subjects (26% reported a prior history of TB and 210 (20% were receiving TB treatment at enrollment; 191 (18% subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0-12.4. Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9-30.5 compared to 5.2% (95% CI 2.1-8.9 among those with no prior TB. 5.1% (95% CI 2.4-9.5 had rifampin or rifampin plus INH resistance. CONCLUSIONS: The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence.
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.
Sharma, S; Babiker, A G; Emery, S;
OBJECTIVES: The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation...
Filteau, Suzanne; PrayGod, George; Kasonka, Lackson
BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study...... was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) ... was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART...
Leroi, Charline; Balestre, Eric; Messou, Eugene; Minga, Albert; Sawadogo, Adrien; Drabo, Joseph; Maiga, Moussa; Zannou, Marcel; Seydi, Moussa; Dabis, Francois; Jaquet, Antoine
Background In sub-Saharan Africa, antiretroviral therapy (ART) including drugs with potential toxicity such as Zidovudine (ZDV) are routinely prescribed. This study aimed at estimating the incidence of severe neutropenia and associated factors after ART initiation in five West African countries. Methods A retrospective cohort analysis was conducted within the international epidemiologic database to evaluate AIDS (IeDEA) collaboration in West Africa. All HIV-infected adults, initiating ART between 2002 and 2014, with a baseline and at least one follow-up absolute neutrophil count (ANC) measurement were eligible. Incidence of severe neutropenia (ANC <750 cells/mm3) was estimated with 95% confidence interval (CI) according to age, gender, HIV clinic, hemoglobin, CD4 count, clinical stage, and ART duration. A Cox proportional hazard model was used to identify factors associated with severe neutropenia, expressed with their adjusted hazard ratios (aHR). Results Between 2002 and 2014, 9,426 HIV-infected adults were enrolled. The crude incidence rate of a first severe neutropenia was 9.1 per 100 person-years (95% CI: 8.6–9.8). Factors associated with severe neutropenia were exposure to ZDV <6 months (aHR = 2.2; 95% CI: 1.8–2.6), ≥6–12 months (aHR = 2.1; 95% CI: 1.6–2.8) and ≥12 months (aHR = 1.6; 95% CI: 1.2–2.2) [Ref. no ZDV exposure], CD4 count <350 cells/mm3 (aHR = 1.3; 95% CI: 1.1–1.5) and advanced clinical stage at ART initiation (aHR = 1.2; 95% CI: 1.0–1.4). Conclusion The incidence of severe neutropenia after ART initiation in West Africa is high and associated with ZDV exposure and advanced HIV disease. In this context, efforts are needed to scale-up access to less toxic first-line ART drugs and to promote early ART initiation. PMID:28122041
Full Text Available Purpose: Bone turnover markers (BTM - aminoterminal propeptide of type 1 collagen (P1NP and C-terminal telopeptide of type 1 collagen (β-CTX - are related to bone density and fracture risk. A high prevalence of osteopenia/osteoporosis and hypovitaminosis D has been reported in HIV patients, however there are few data about BTM in this population. Our aim was to analyse the prevalence of elevated serum levels of BTM in HIV patients before starting antiretroviral therapy (ART, and related factors. Methods: Cross-sectional study of a series of HIV-patients who started ART during June/11–June/12 in our hospital. Patients with presence of diseases or treatments known to affect bone metabolism were excluded. Epidemiological, clinical, and immunovirological data in addition to serum fasting levels of glucose, lipid profile, calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D3 (25OHD, parathyroid hormone (PTH, P1NP, and β-CTX were collected. Definitions: hypovitaminosis D if 25OHD<30 ng/ml, vitamin D deficiency if 25OHD<20 ng/ml; elevated levels of BTM if β-CTX (ng/ml >0.64 (men<70 years,>0.85 (men >70 years,>0.58 (pre-menopause women, >0.99 (post-menopause women, or P1NP (ng/mL>69.4 (men <60 years, >71.1 (men>60 years, >55.7 (pre-menopause women, >61.2 (post-menopause women. Results: 47 patients were included, 91.5% men, median age 37.1 years (30.0–44.3, and 93.6% sexual transmission of HIV (34 HMX, 10 HTX. Median time since the diagnosis of HIV was 3.4 months (1.4–31.7; there were 7 (14.9% Aids cases, median CD4 count was 277/mm3 (155–433, and HIV-VL 4.8 log10 (4.1–5.2. Median serum 25OHD was 29 µg/L (21.9–41.1, with a prevalence of hypovitaminosis of 52.2%, and deficiency of 17.4%. PTH was in range in all cases. Median serum P1NP was 33.3 ng/mL (24.5–52.5 and β-CTX 0.25 ng/mL (0.20–0.45; five (11.4% patients presented high levels of BTM: 4 men, median age 37.1 years, median CD4 count 247/mm3, median HIV-VL 5.18 log10
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
SA HIV Clinicians Society
Full Text Available This document serves to guide clinicians and programme managers on how to switch from 3 separate antiretroviral (ARV drugs to the new, single, fixed-dose combination (FDC tablet containing tenofovir (TDF, emtricitabine (FTC and efavirenz (EFV. Summary Transitioning from individual drugs to an FDC tablet needs to be managed carefully, particularly regarding stock management, ordering processes, supply-chain integrity and comprehensive patient counselling. Priority groups • Initially, FDC supply will be insufficient to provide for all FDC-suitable patients • Therefore, the National Department of Health (NDoH has recommended that the following patient groups be prioritized for FDC initiation/switch: • Priority group 1: All HIV-positive patients newly initiating ART – adults, adolescents and pregnant women (regardless of CD4 count (amendment to the guidelines for the prevention of mother-to-child transmission of HIV (PMTCT anticipated in April 2013 – and who do not have contra-indications to the FDC component drugs • Priority group 2: HIV-positive pregnant women and breastfeeding mothers currently stable on lamivudine (3TC, TDF and EFV • Priority group 3: Virologically suppressed patients on a stavudine (d4T-based regimen and who have normal renal function • Priority group 4: Stable patients receiving individual TDF, 3TC and EFV and who have tuberculosis (TB co-infection • Priority group 5: Stable patients receiving individual TDF, 3TC and EFV and who have other co-morbidites (e.g. hypertension, diabetes • Priority group 6: Patients receiving individual TDF, 3TC and EFV and who request to switch to the FDC treatment • Priority group 7: Patients receiving individual TDF, 3TC and EFV and who, after counselling, agree to switch to the FDC treatment. Important: Clinic staff must co-ordinate this process and only switch as many patients to the FDC tablet as stock allows. This should avoid patients being switched back and forth
Rehman, Andrea M; Woodd, Susannah; PrayGod, George
in malnourished patients starting ART and that vitamin and mineral supplementation would improve appetite and permit nutritional recovery. DESIGN:: The randomised controlled Nutritional Support for Africans Starting Antiretroviral Therapy (NUSTART) trial was conducted in Mwanza, Tanzania and Lusaka, Zambia. ART......-naïve adults referred for ART and with body mass index (BMI)supplements either without (LNS) or with added vitamins and minerals (LNS-VM), beginning prior to ART initiation. Participants were given 30 g/day LNS from recruitment until 2 weeks after starting ART...
Nabeta, Henry W; Okia, Richard; Rhein, Joshua; Lukande, Robert
Histoplasmosis is the most common endemic mycoses among HIV-infected people. Patients with suppressed cell immunity mainly due to HIV are at increased risk of disseminated disease. Dermatological manifestations of immune reconstitution inflammatory syndrome (IRIS) and cutaneous manifestations of histoplasmosis similar to an IRIS event have been previously described. We report the case of a 43-year-old male who presented with cutaneous disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum 4 months after the onset of the antiretroviral therapy and some improvement in the immune reconstitution. After 2 weeks of amphotericin B and itraconazole therapy, the scheduled treatment involved fluconazole maintenance therapy, which resulted in an improvement of his skin lesions. PMID:28210571
Eaton, Jeffrey W; Menzies, Nicolas A; Stover, John
BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral th...
Babiker, Abdel G; Emery, Sean; Fätkenheuer, Gerd
Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an incr...... is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals....... with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication...
Full Text Available Dermatophyte infection may present in the form of concentric rings caused by Trichophyton concentricum, known as Tinea Imbricata. In immunosuppressed patients, there are reports of lesions in the form of concentric rings caused by dermatophytes other than Trichophyton concentricum too, mostly by Trichophyton tonsurans, known as Tinea indesiciva or Tinea pseudoimbricata. We report a case of tinea capitis in a HIV-positive adult woman on antiretroviral therapy, who presented with concentric rings of papules and pustules with slight scaling on the scalp along with diffuse thinning of hair. Both Potassium hydroxide mount and culture showed the presence of Dermatophytes. Tinea capitis is considered rare in adults, but new cases are being reported in immunocompromised as well as in immunocompetent patients. The pertinent features of this case are: HIV-positive adult female on antiretroviral therapy, presenting with tinea capitis in the form of concentric rings; culture from the lesion grew Microsporum audouinii; responding to oral Terbinafine.
Martin W G Brinkhof
Full Text Available BACKGROUND: Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa. METHODS AND FINDINGS: Patients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs with 95% confidence intervals (CIs. Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67% patients were female, and 10,811 of 12,720 patients (85% with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1 per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO stage III/IV, compared to 1.00 (0.55-1.81 per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6 and 3.44 (1.91-6.17. Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94 per 100 person-years and the SMR was 1.14 (0.47-2.77. CONCLUSIONS: Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the
Full Text Available Commencement of antiretroviral treatment (ART in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4% patients were diagnosed with TB during followup. Eight (3.8% patients had ART-associated TB (incidence rate of 4.3 per 100 person years; of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years. A body mass index of less than 18.5 kg/m2 BMI (HR 5.85 95% CI 1.24–27.46, P=.025 and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36–38.33, P=.020 were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray, the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence.
Worodria, William; Massinga-Loembe, Marguerite; Mayanja-Kizza, Harriet; Namaganda, Jane; Kambugu, Andrew; Manabe, Yukari C; Kestens, Luc; Colebunders, Robert
Commencement of antiretroviral treatment (ART) in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB) disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI) consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4%) patients were diagnosed with TB during followup. Eight (3.8%) patients had ART-associated TB (incidence rate of 4.3 per 100 person years); of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years). A body mass index of less than 18.5 kg/m(2) BMI (HR 5.85 95% CI 1.24-27.46, P = .025) and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36-38.33, P = .020) were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray), the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence.
Bohlius, Julia; Schmidlin, Kurt; Costagliola, Dominique
enrolled in cohorts participating in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who were aged 16 years or older, started cART at some point after 1 January 1998 and developed NHL after 1 January 1998. Patients had to have a CD4 cell count after 1 January 1998 and one...
Buckingham, S.J.; Haddow, L.J.; Shaw, P.J.; Miller, R.F. E-mail: email@example.com
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.
Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K
The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general
Filteau, Suzanne; PrayGod, George; Kasonka, Lackson;
BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study...... was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART...... in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased...
Nyirenda, Christopher; Zulu, Isaac; Kabagambe, Edmond K; Bagchi, Shashwatee; Potter, Dara; Bosire, Claire; Krishnasami, Zipporah; Heimburger, Douglas C
High mortality rates have been reported in the first 90 days of antiretroviral therapy in Zambia and other low-income countries. We report a case of acute hypophosphataemia and hypokalaemia in the first week of antiretroviral therapy in a patient with extreme AIDS wasting. Given its occurrence in an extremely wasted patient, it may be physiologically similar to refeeding syndrome but other causes could be relevant as well. Acute hypophosphataemia may contribute to early antiretroviral therapy associated mortality in low-income countries.
Full Text Available BACKGROUND: Improved survival among HIV-infected individuals on antiretroviral therapy (ART has focused attention on AIDS-related cancers including Kaposi sarcoma (KS. However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART. METHODS: We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment. RESULTS: Between January 2001-January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2% were similar to those without KS (n = 13600,98% with respect to age (35 vs. 35yrs, presenting CD4 count (74 vs. 85cells/mm³ and proportion on TB treatment (37% vs. 30%. In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71-4.84 than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95-5.55 and attenuated thereafter (HR: 2.30; 95% CI: 1.08-4.89. Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7-52cells/mm³ and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99-2.06 within the first 6-months of treatment. CONCLUSIONS: HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS
Outlaw, Angulique Y; Naar-King, Sylvie; Tanney, Mary; Belzer, Marvin E; Aagenes, Anna; Parsons, Jeffrey T; Merlo, Lisa J
Young people represent the largest number of new HIV infections, thus youth living with HIV (YLH) are likely to be the largest group to initiate antiretroviral treatment (ART). Adherence patterns for behaviorally infected YLH are not adequate to effectively manage the disease; therefore, novel interventions are needed to improve medication adherence. The purpose of the current study, which will precede a randomized controlled trial, was to assess the initial feasibility of an individually tailored computer-based two-session interactive motivational interviewing (MI) intervention for YLH newly recommended to start ART. Intervention development occurred in collaboration with three youth advisory groups. Ten youth (ages 18-24) were recruited to participate in this study. Participants completed the intervention online. Intervention components focused on medication adherence (rating perceived importance and confidence, and goal setting). Retention was 100% for both intervention sessions. All participants (n=10) felt medication adherence was important, but 80% felt confident they could manage their adherence to HIV medications. Ninety percent of participants set the goal of taking their HIV medications exactly as prescribed and reported success achieving this goal at follow-up. Additionally, participants were satisfied with the quality of the sessions and the amount of assistance they received for managing their adherence to HIV medications (90% participants for Session 1; 89% for Session 2). Per exit interview responses, participants felt that the intervention made them think more about their health and was a motivator for them to take better care of their health. In conclusion, the intervention was feasible for YLH enrolled in the study.
Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults : 48-week results from the antiretroviral regimen evaluation study (ARES)
Lowe, SH; Wensing, AMJ; Hassink, EAM; ten Kate, RW; Richter, C; Schreij, G; Koopmans, PP; Juttmann, J.; van der Tweel, I.; Lange, JMA; Borleffs, JCC
Background: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. Method: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida
Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults: 48-week results from the Antiretroviral Regimen Evaluation Study (ARES).
Lowe, S.H.; Wensing, B.M.; Hassink, E.A.M.; Kate, R.W. ten; Richter, C.; Schreij, G.; Koopmans, P.P.; Juttmann, J.R.; Tweel, I. van de; Lange, J.M.A.; Borleffs, J.C.
BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. METHOD: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida
Williams, Ian; Churchill, Duncan; Anderson, Jane; Boffito, Marta; Bower, Mark; Cairns, Gus; Cwynarski, Kate; Edwards, Simon; Fidler, Sarah; Fisher, Martin; Freedman, Andrew; Geretti, Anna Maria; Gilleece, Yvonne; Horne, Rob; Johnson, Margaret; Khoo, Saye; Leen, Clifford; Marshall, Neal; Nelson, Mark; Orkin, Chloe; Paton, Nicholas; Phillips, Andrew; Post, Frank; Pozniak, Anton; Sabin, Caroline; Trevelion, Roy; Ustianowski, Andrew; Walsh, John; Waters, Laura; Wilkins, Edmund; Winston, Alan; Youle, Mike
The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii)support of patients on treatment; (iii) management of patients experiencing virological failure; and (iv) recommendations in specific patient populations where other factors need to be taken into consideration. The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.
Marzocchetti, Angela; Schwarz, Jessica; Di Giambenedetto, Simona; Colafigli, Manuela; Bracciale, Laura; Fabbiani, Massimilliano; Fantoni, Massimo; Trecarichi, Enrico; Cauda, Roberto; De Luca, Andrea
We investigated whether polymorphisms in human candidate genes could be associated with a different risk of developing lipodystrophy and dyslipidemia in HIV-infected patients starting combination antiretroviral therapy (cART). Genomic DNA samples from white HIV-1-infected patients were analyzed for seven polymorphisms located in the MDR1, TNF-α, APM1, APOE, and LPL genes. Lipid data were retrospectively collected beginning with the initiation of cART. Lipodystrophy was assessed cross-sectionally and then prospectively. The association with lipodystrophy and National Cholesterol Evaluation Program Adult Treatment Panel III-defined lipid thresholds was analyzed using survival analysis and logistic regression. One-hundred and seventy-four patients were genotyped. In 151 patients assessed for lipodystrophy, MDR1 3435 T homozygosis was associated with a higher hazard (adjusted hazard ratio, aHR, versus CT 0.25; p=0.02) and tumor necrosis factor (TNF)-α 308 G homozygosis with a lower hazard (vs. AA aHR 2.14; p=0.04) of developing trunk fat accumulation after adjusting for gender and initial cART type. The TNF 238 GG genotype was associated with a higher risk of developing low HDL-cholesterol levels (adjusted odd ratio, aOR, 5.91; p=0.01) while patients carrying the LPL S477X mutation were at lower risk of reaching high non-HDL-cholesterol levels (aOR 0.39; p=0.05). The APOEe3/3 genotype patients were at lower risk (aOR 0.26, p=0.015), whereas the adiponectin 276 GT carriers were at higher risk of developing hypertriglyceremia (vs. GG aOR 3.10; p=0.04). Knowledge of the effect of genetic determinants on dyslipidemia and lipodystrophy may prompt the investigation of potential pathogenetic mechanisms and might eventually be used for guiding individualized treatment decisions.
Cohen Stuart, James; Hamann, Dörte; Borleffs, Jan; Roos, Marijke; Miedema, Frank; Boucher, Charles; de Boer, Rob
OBJECTIVE: To determine the influence of age on the regeneration rate of naive and memory T cells in the blood of 45 adults on highly active antiretroviral therapy (HAART). METHODS: The age of the patients ranged from 25 to 57 years. Naive cells were defined as CD45RA+CD27+. Cells negative for CD45R
Since the roll-out of antiretroviral therapy (ART), few data have been generated on outcomes and outcome predictors of ART in adults and children in Rwanda. Equally, the extent of chronic hepatitis virus infections and their impact on the ART outcomes in the country are not known. This information i
Chagoma, Newton; Mallewa, Jane; Kaunda, Symon; Njalale, Yasin; Kampira, Elizabeth; Mukaka, Mavuto; Heyderman, Robert S; van Oosterhout, Joep J
Introduction Stavudine is still widely used in under-resourced settings such as Malawi due to its low price. It frequently causes peripheral neuropathy and lipodystrophy and increases the risk of lactic acidosis and other high lactate syndromes. Methods We studied the association of longitudinal lactate levels, obtained by routine, 3-monthly point-of-care monitoring, with peripheral neuropathy, lipodystrophy and high lactate syndromes in adult Malawians who were in the second year of stavudine containing antiretroviral therapy (ART). Results Point-of-care lactate measurements were feasible in a busy urban ART clinic. Of 1170 lactate levels collected from 253 patients over the course of one year, 487 (41.8%) were elevated (>2.2mg/dl), 58 (5.0%) were highly elevated (>3.5mg/dl). At least one elevated lactate level occurred in 210 (83.0%) of patients and sustained hyperlactatemia in 65 (26.4%). In random effects analyses lipodystrophy and peripheral neuropathy were associated with higher lactate levels. Only five patients developed high lactate syndromes (one lactic acidosis) of whom no preceding lactate measurements were available because events had started before enrolment. Lactate levels significantly decreased over time and no high lactate syndromes were observed after the 15th month on ART. Conclusion Lipodystrophy and peripheral neuropathy were associated with higher lactate levels. Lactate levels decreased over time, coinciding with absence of new high lactate syndromes after the 15th month on ART. PMID:23926161
Jeannette Y. Lee
Full Text Available The objective of this study was to explore the cancer incidence rates among HIV-infected persons with commercial insurance who were on antiretroviral therapy and compare them with those rates in the general population. Paid health insurance claims for 63,221 individuals 18 years or older, with at least one claim with a diagnostic code for HIV and at least one filled prescription for an antiretroviral medication between January 1, 2006, and September 30, 2012, were obtained from the LifeLink® Health Plan Claims Database. The expected number of cancer cases in the general population for each gender-age group (60 years was estimated using incidence rates from the Surveillance Epidemiology and End Results (SEER program. Standardized incidence ratios (SIRs were estimated using their 95% confidence intervals (CIs. Compared to the general population, incidence rates for HIV-infected adults were elevated (SIR, 95% CI for Kaposi sarcoma (46.08; 38.74–48.94, non-Hodgkin lymphoma (4.22; 3.63–4.45, Hodgkin lymphoma (9.83; 7.45–10.84, and anal cancer (30.54; 25.62–32.46 and lower for colorectal cancer (0.69; 0.52–0.76, lung cancer (0.70; 0.54, 0.77, and prostate cancer (0.54; 0.45–0.58. Commercially insured, treated HIV-infected adults had elevated rates for infection-related cancers, but not for common non-AIDS defining cancers.
Molly F Franke
Full Text Available BACKGROUND: Randomized clinical trials examining the optimal time to initiate combination antiretroviral therapy (cART in HIV-infected adults with sputum smear-positive tuberculosis (TB disease have demonstrated improved survival among those who initiate cART earlier during TB treatment. Since these trials incorporated rigorous diagnostic criteria, it is unclear whether these results are generalizable to the vast majority of HIV-infected patients with TB, for whom standard diagnostic tools are unavailable. We aimed to examine whether early cART initiation improved survival among HIV-infected adults who were diagnosed with TB in a clinical setting. METHODS AND FINDINGS: We retrospectively reviewed charts for 308 HIV-infected adults in Rwanda with a CD4 count ≤ 350 cells/µl and a TB diagnosis. We estimated the effect of cART on survival using marginal structural models and simulated 2-y survival curves for the cohort under different cART strategies:start cART 15, 30, 60, or 180 d after TB treatment or never start cART. We conducted secondary analyses with composite endpoints of (1 death, default, or lost to follow-up and (2 death, hospitalization, or serious opportunistic infection. Early cART initiation led to a survival benefit that was most marked for individuals with low CD4 counts. For individuals with CD4 counts of 50 or 100 cells/µl, cART initiation at day 15 yielded 2-y survival probabilities of 0.82 (95% confidence interval: [0.76, 0.89] and 0.86 (95% confidence interval: [0.80, 0.92], respectively. These were significantly higher than the probabilities computed under later start times. Results were similar for the endpoint of death, hospitalization, or serious opportunistic infection. cART initiation at day 15 versus later times was protective against death, default, or loss to follow-up, regardless of CD4 count. As with any observational study, the validity of these findings assumes that biases from residual confounding by
Eaton, J.W.; Menzies, N.A.; Stover, J.; Cambiano, V.; Chindelevitch, L.; Cori, A.; Hontelez, J.A.; Humair, S.; Kerr, C.C.; Klein, D.J.; Mishra, S.; Mitchell, K.M.; Nichols, B.E.; Vickerman, P.; Bakker, R; Barnighausen, T.; Bershteyn, A.; Bloom, D.E.; Boily, M.C.; Chang, S.T.; Cohen, T.; Dodd, P.J.; Fraser, C.; Gopalappa, C.; Lundgren, J.; Martin, N.K.; Mikkelsen, E.; Mountain, E.; Pham, Q.D.; Pickles, M.; Phillips, A.; Platt, L.; Pretorius, C.; Prudden, H.J.; Salomon, J.A.; Vijver, D.A. van de; Vlas, S.J. de; Wagner, B.G.; White, R.G.; Wilson, D.P.; Zhang, L.; Blandford, J.; Meyer-Rath, G.; Remme, M.; Revill, P.; Sangrujee, N.; Terris-Prestholt, F.; Doherty, M.; Shaffer, N.; Easterbrook, P.J.; Hirnschall, G.; Hallett, T.B.
BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per muL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral ther
Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette;
In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size and predict......In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size...... and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR...
Rehman, Andrea M; Woodd, Susannah; PrayGod, George;
BACKGROUND:: The evidence base for effects of nutritional interventions for malnourished HIV-infected patients starting antiretroviral therapy (ART) is limited and inconclusive. OBJECTIVE:: We hypothesised that both vitamin and mineral deficiencies and poor appetite limit weight gain in malnouris...
May, Margaret T; Vehreschild, Jorg-Janne; Trickey, Adam;
-2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0-49, 50-99, 100-199, 200-349, 350-499, ≥500 cells/µL) overall and separately according to time since start of ART. RESULTS: A total of 6344 of 37 496 patients died during 359 219...
Full Text Available Human immunodeficiency virus (HIV management of adolescents and young adults (AYAs is particularly pertinent to sub-Saharan Africa, where the pediatric HIV burden is marked. Antiretroviral treatment (ART adherence is a major challenge for AYAs. This qualitative study explored knowledge and experiences of adherence amongst AYAs attending treatment at the Perinatal HIV Research Unit (PHRU, Soweto, South Africa. Four focus group discussions (FGDs and eight in-depth interviews (IDIs were conducted with HIV-infected 15–25-year-old ART recipients. Transcripts were coded thematically. Participants (n=26 were aged median 18.5 years, 59.1% female and 69.2% virally suppressed <400 cp/ml. Three main themes emerged during FGDs and IDIs: (i correct knowledge about how to be adherent, benefits, and nonadherence consequences, (ii social, personal, and medication-related barriers to adherence, and (iii reminder, concealment, and motivational strategies to optimize adherence. Interventions to improve AYA adherence could focus on practical strategies, including status disclosure and medication concealment.
Kalichman, Seth C; Grebler, Tamar; Amaral, Christina M; McKerney, Megan; White, Denise; Kalichman, Moira O; Cherry, Chauncey; Eaton, Lisa
Food insecurity is associated with HIV treatment non-adherence and poor health outcomes for people living with HIV/AIDS. Given the poor nutritional status common to people who drink alcohol, food insecurity may be particularly problematic for HIV positive individuals who drink alcohol. To examine food insecurity among HIV positive men and women who drink alcohol and its association with antiretroviral therapy (ART) adherence, health outcomes and health service utilization. Adults living with HIV (N = 183) in Atlanta, Georgia who reported alcohol use in the previous week and were receiving ART participated in a 12-month cohort. Participants were recruited from infectious disease clinics and social services to complete computerized interviews, monthly-unannounced pill counts to monitor ART adherence, and daily cell-phone delivered interactive-text assessments for alcohol use. Forty-three percent of participants experienced food insecurity during at least one month of the study period. Food insecurity was independently associated with suboptimal ART adherence and less suppressed HIV viral load over. Individuals who experienced food insecurity also had histories of more medical and psychiatric hospitalizations, and greater mental health problems. Food insecurity is prevalent among alcohol using people receiving ART and food insecurity is associated with treatment non-adherence, poor health outcomes, and increased medical and psychiatric hospitalizations.
Full Text Available Background: The prevalence of thrombocytopenia among Chinese antiretroviral therapy (ART-naïve HIV-infected adults has not been well-described. The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-naïve HIV-infected adults. Methods: We performed a cross-sectional study of Chinese adult ART-naïve HIV-infected patients from September 2005 through August 2014. Socio-demographic variables and laboratory results including platelets, CD4+ cell count, and viral load were obtained from medical records. Factors and outcomes associated with thrombocytopenia were assessed using logistic regression. Results: A total of 1730 adult ART-naïve HIV-infected patients was included. The mean age was 38 years. The prevalence of thrombocytopenia was 4.5%. There were significant differences in the prevalence of thrombocytopenia between patients 350 cells/mm 3 (2.8% compared with patients with CD4+ counts of 50-199 cells/mm 3 (7.1% (P = 0.002 and P = 0.005, respectively. The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab seropositivity (10.2% for HCV-Ab positive vs. 3.9% for HCV-Ab negative, P = 0.001. We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection: Blood transmission (10.7% versus men who have sex with men (3.9% (P = 0.002 and versus heterosexual transmission (3.9% (P = 0.001. In binary logistic regression analyses, age ≥50 years, HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm 3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]: 1.167, 5.281, P = 0.018, 2.091 (95% CI: 1.078, 4.055, P = 0.029 and 2.259 (95% CI: 1.028, 4.962, P = 0.042, respectively. Conclusions: Thrombocytopenia is not common among adult ART-naïve HIV-infected patients in China. Older age (age over 50 years, HCV-Ab positivity and lower CD4
Full Text Available In South Africa, abacavir (ABC is currently recommended as part of first- and second-line antiretroviral therapy (ART for HIV-positive paediatric patients. Concerns about overprescribing of the drug, particularly to adults, led to an analysis of ABC use in public sector ART programmes. We investigated current prescription of the drug to adults and children accessing ART in 4 public sector programmes across Gauteng Province, South Africa. ABC was almost exclusively prescribed to children initiating ART and adults requiring regimen changes due to drug toxicities. Patterns of ABC use among HIV-positive paediatric patients followed national ART treatment guidelines on the application of the drug. Although ABC is commonly used in the private sector for adults, the current national ART treatment guidelines for adults and adolescents should include ABC as an alternative to standard first- or second-line ART.
Kasirye, Ronnie P.; Grosskurth, Heiner; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Baisley, Kathy
Introduction: Using the data of a trial on cotrimoxazole (CTX) cessation, we investigated the effect of different antiretroviral therapy (ART) regimens on the incidence of clinical malaria. Methods: During the cotrimoxazole cessation trial (ISRCTN44723643), HIV-infected Ugandan adults with CD4+ at least 250 cells/μl were randomized to receive either CTX prophylaxis or placebo and were followed for a median of 2.5 years. Blood slides for malaria microscopy were examined at scheduled visits and at unscheduled visits when the participant felt unwell. CD4+ cell counts were done 6-monthly. Malaria was defined as fever with a positive blood slide. ART regimens were categorized as nucleoside reverse transcriptase inhibitor (NRTI) only, non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing or protease inhibitor containing. Malaria incidence was calculated using random effects Poisson regression to account for clustering of events. Results: Malaria incidence in the three ART regimen groups was 9.9 (3.6-27.4), 9.3 (8.3-10.4), and 3.5 (1.6-7.6) per 100 person-years, respectively. Incidence on protease inhibitors was lower than that on the other regimens with the results just reaching significance (adjusted rate ratio 0.4, 95% confidence interval = 0.2–1.0, comparing with NNRTI regimens). Stratification by CTX/placebo use gave similar results, without evidence of an interaction between the effects of CTX/placebo use and ART regimen. There was no evidence of an interaction between ART regimen and CD4+ cell count. Conclusion: There was some evidence that protease inhibitor-containing ART regimens may be associated with a lower clinical malaria incidence compared with other regimens. This effect was not modified by CTX use or CD4+ cell count. The antimalarial properties of protease inhibitors may have clinical and public health importance. PMID:28121670
Full Text Available Purpose of the study: To identify the proportion of patients starting ARV treatment with NNRTIs or with a PI/r and to explore and compare their clinical profile establishing different factors whereby physicians select the initial ARV treatment in a Spanish clinical setting. Methods: An observational study was conducted in two different phases. In Phase I a cross-sectional registration was conducted for patients who initiated ARV treatment in a 6-month period in 65 Spanish hospitals. In Phase II clinical and social-demographic features were collected retrospectively of patients who visited HIV clinics between August and November 2010 who had started ARV treatment containing an NNRTIs or a PI/r in Phase I. Summary of results: In Phase I, 1,687 subjects who initiated ARV treatment were registered, of which 53% started with an NNRTI-based regimen whereas 42% started with a PI/r-based regimen. Two percent of the treatment initiations occurred in a clinical trial. In Phase II, 642 patients were paired consecutively and retrospectively. The group of patients was composed of predominantly male subjects (81% vs 19%. The median time between diagnosis and the start of ARV treatment was 3.6±5.3 years. At the initiation of treatment, 72% of patients had a CD4 count below 350 cells/µl. Although treatment based on NNRTIs in naïve patients is the most frequent option in Spain, the analysis of clinical profiles shows that PI/r-based therapy is more often used than NNRTIs with statistical significance in patients with high viral load, Fig. A (≥100.000 copies/ml (58% vs 42%; OR:1,75; 95% CI: 1,26–2,43; p<0,01, with CD4 cell counts <200 cells/µl, Fig. B (68% vs 31%; OR: 2,92; 95% CI: 1,99–4,27; p<0,01, and in patients at CDC stage C (65% vs 35%; OR: 2,05; CI: 1,27–3,31; p<0,01. Conclusions: In Spain, HIV is still diagnosed late (as measured by CD4 count<350 cells/µl. Treatment based on NNRTIs are more frequently used in naïve patients, although PIs
Serena P Koenig
Full Text Available BACKGROUND: In a randomized clinical trial of early versus standard antiretroviral therapy (ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial. METHODS AND FINDINGS: Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS, including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART and US$979 (standard ART. Early ART patients had higher mean costs for ART (US$398 versus US$81 but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384. The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS-US$9,979/YLS including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS-US$5,537/YLS. CONCLUSIONS: Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita after a maximum of 3 years, after excluding research-related laboratory tests. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120510.
Hong-Wei Fan; Fu-Ping Guo; Yi-Jia Li; Ning Li; Tai-Sheng Li
Background:The prevalence ofthrombocytopenia among Chinese antiretroviral therapy (ART)-na(i)ve HIV-infected adults has not been well-described.The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-na(i)ve HIV-infected adults.Methods:We performed a cross-sectional study of Chinese adult ART-na(i)ve HIV-infected patients from September 2005 through August 2014.Socio-demographic variables and laboratory results including platelets,CD4+ cell count,and viral load were obtained from medical records.Factors and outcomes associated with thrombocytopenia were assessed using logistic regression.Results:A total of 1730 adult ART-na(i)ve HIV-infected patients was included.The mean age was 38 years.The prevalence of thrombocytopenia was 4.5％.There were significant differences in the prevalence of thrombocytopenia between patients ＜30 years of age (2.8％) and 30-39 years (4.0％) compared with patients greater than 50 years (7.0％) (P =0.006 and P =0.044,respectively).The prevalence of thrombocytopenia was also significantly different between patients with CD4+ counts of 200-349 cells/mm3 (3.3％) and ＞350 cells/mm3 (2.8％) compared with patients with CD4+ counts of50-199 cells/mm3 (7.1％) (P =0.002 and P =0.005,respectively).The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab) seropositivity (10.2％ for HCV-Ab positive vs.3.9％ for HCV-Ab negative,P =0.001).We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection:Blood transmission (10.7％) versus men who have sex with men (3.9％) (P =0.002) and versus heterosexual transmission (3.9％) (P =0.001).In binary logistic regression analyses,age ≥＞50 years,HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95％ confidence interval [CI]:1.167,5.281,P=0
Siefried, Krista J.; Mao, Limin; Kerr, Stephen; Cysique, Lucette A.; Gates, Thomas M.; McAllister, John; Maynard, Anthony; de Wit, John; Carr, Andrew
Background Missing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings. Methods Adults on ART with undetectable viral load (UDVL) were recruited into a national, multi-centre cohort, completing a comprehensive survey assessing demographics, socio-economic indicators, physical health, well-being, life stressors, social supports, HIV disclosure, HIV-related stigma and discrimination, healthcare access, ART regimen, adherence, side effects, costs and treatment beliefs. Baseline data were assessed, and suboptimal adherence was defined as self-reported missing ≥1 ART dose/month over the previous 3-months; associated factors were identified using bivariate and multivariate binary logistic regression. Results We assessed 522 participants (494 [94.5%] men, mean age = 50.8 years, median duration UDVL = 3.3 years [IQR = 1.2–6.8]) at 17 sexual health, hospital, and general practice clinics across Australia. Seventy-eight participants (14.9%) reported missing ≥1 dose/month over the previous three months, which was independently associated with: being Australian-born (AOR [adjusted odds ratio] = 2.4 [95%CI = 1.2–4.9], p = 0.014), not being in a relationship (AOR = 3.3 [95%CI = 1.5–7.3], p = 0.004), reaching the “Medicare safety net” (capping annual medical/pharmaceutical costs) (AOR = 2.2 [95%CI = 1.1–4.5], p = 0.024), living in subsidised housing (AOR = 2.5 [95%CI = 1.0–6.2], p = 0.045), receiving home-care services (AOR = 4.4 [95%CI = 1.0–18.8], p = 0.046), HIV community/outreach services linkage (AOR = 2.4 [95%CI = 1.1–5.4], p = 0.033), and starting ART following self-request (AOR = 3.0 [95%CI = 1.3–7.0], p = 0.012). Conclusions In this population, 15% reported recent suboptimal ART adherence at levels associated in prospective studies with
Abioye, Ajibola I; Isanaka, Sheila; Liu, Enju; Mwiru, Ramadhani S; Noor, Ramadhani A; Spiegelman, Donna; Mugusi, Ferdinand; Fawzi, Wafaie
Human immunodeficiency virus (HIV)-infected males have poor treatment outcomes after initiation of antiretroviral therapy (ART) compared to HIV-infected women. Dietary factors might mediate the association between sex and disease progression. However, the gender difference in diet among HIV-infected individuals in sub-Saharan Africa is largely unknown. The objective of this study was to examine differences in dietary intake among HIV-infected men and women. We conducted a cross-sectional analysis of dietary questionnaire data from 2038 adults initiating ART in Dar es Salaam, Tanzania to assess whether nutrient adequacy differed by sex. We dichotomized participants' nutrient intakes by whether recommended dietary allowances (RDAs) were met and estimated the relative risk (RR) of meeting RDAs in males using binomial regression models. We also estimated the mean difference in intake of foods and food groups by gender. We found poorer dietary practices among men compared to women. Males were less likely to meet the RDAs for micronutrients critical for slowing disease progression among HIV patients: niacin (RR = 0.39, 95% confidence interval [CI]: 0.27 to 0.55), riboflavin (RR = 0.81, 95% CI: 0.73 to 0.91), vitamin C (RR = 0.94, 95% CI: 0.89 to 1.00), and zinc (RR = 0.06, 95% CI: 0.01 to 0.24). Intake of thiamine, pantothenate, vitamins B6, B12, and E did not vary by gender. Males were less likely to eat cereals (mean difference [servings per day] = -0.21, 95% CI: -0.44 to 0.001) and vegetables (mean difference = -0.47, 95% CI: -0.86 to -0.07) in their diet, but more likely to have meat (mean difference = 0.14, 95% CI: 0.06 to 0.21). We conclude that male HIV patients have poorer dietary practices than females, and this may contribute to faster progression of the disease in males.
Do, Natalie T; Phiri, Kelesitse; Bussmann, Hermann; Gaolathe, Tendani; Marlink, Richard G; Wester, C William
As increasing numbers of persons are placed on potentially life-saving combination antiretroviral therapy (cART) in sub-Saharan Africa, it is imperative to identify the psychosocial and social factors that may influence antiretroviral (ARV) medication adherence. Using an 87 question survey, the following data were collected from patients on cART in Botswana: demographics, performance (Karnofsky) score, perceived stigma and level of HIV disclosure, attitudes and beliefs concerning HIV/AIDS, substance and/or drug use, depression, and pharmacy and healthcare provider-related factors. Overall adherence rates were determined by patient self-report, institutional adherence, and a culturally modified Morisky scale. Three hundred adult patients were recruited between April and May 2005. The overall cART adherence rate was 81.3% based on 4 day and 1 month patient recall and on clinic attendance for ARV medication refills during the previous 3 months. Adults receiving cART for 1-6 months were the least adherent (77%) followed by those receiving cART for greater than 12 months (79%). Alcohol use, depression, and nondisclosure of positive HIV status to their partner were predictive of poor adherence rates (p value HIV disclosure to "at-risk" partners and provide ongoing counseling and education to help patients recognize and overcome HIV-associated stigma, alcohol abuse, and depression.
Messou, Eugène; Chaix, Marie-Laure; Gabillard, Delphine; Minga, Albert; Losina, Elena; Yapo, Vincent; Kouakou, Martial; Danel, Christine; Sloan, Caroline; Rouzioux, Christine; Freedberg, Kenneth A.; Anglaret, Xavier
Background Adherence is a strong determinant of viral suppression with antiretroviral therapy (ART), but measuring it is challenging. Medication delivery can be measured accurately in settings with computerized prescription databases. We studied the association between Medication Possession Ratio (MPR), virologic suppression, and resistance to ART in Côte d’Ivoire. Methods We conducted a prospective cohort study of HIV-1 infected adults initiating ART in three clinics using computerized monitoring systems. Patients had viral load (VL) tests at month 6 (M6) and month 12 (M12) after ART initiation, and genotype tests if VL was detectable (≥300 copies/ml). MPR was defined as the number of daily doses of antiretroviral drug actually provided divided by the total number of follow-up days since ART initiation. Results Overall, 1,573 patients started ART with stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. At M6 and M12, 996 and 942 patients were in active follow-up; 20% (M6) and 25% (M12) of patients had detectable VL, including 7% (M6) and 11% (M12) with ≥1 resistance mutation. Among patients with MPR ≥95%, 80–94%, 65–79%, 50–64% and <50% at M12, the proportion with detectable VL [resistance] was 9% [4%], 17% [7%], 45% [24%], 67% [31%], and 85% [37%]. Among patients with ≥1 mutation at M12, 86% were resistant to lamivudine/emtricitabine and/or nevirapine/efavirenz but not to other drugs. Conclusion MPR was strongly associated with virologic outcomes. Half of those with detectable VL at M12 had no resistance mutations. MPR should be used at M6 to identify patients who might benefit from early interventions to reinforce adherence. PMID:21191309
Full Text Available Abstract Background HIV and AIDS are significant and growing public health concerns in southern Africa. The majority of countries in the region have national adult HIV prevalence estimates exceeding 10 percent. The increasing availability of highly active antiretroviral therapy (HAART has potential to mitigate the situation. There is however concern that women may experience more barriers in accessing treatment programs than men. Methods A systematic review of the literature was carried out to describe the gender distribution of patients accessing highly active antiretroviral therapy (HAART in Southern Africa. Data on number of patients on treatment, their mean or median age and gender were obtained and compared across studies and reports. Results The median or mean age of patients in the studies ranged from 33 to 39 years. While female to male HIV infection prevalence ratios in the southern African countries ranged from 1.2:1 to 1.6:1, female to male ratios on HAART ranged from 0.8: 1 to 2.3: 1. The majority of the reports had female: male ratio in treatment exceeding 1.6. Overall, there were more females on HAART than there were males and this was not solely explained by the higher HIV prevalence among females compared to males. Conclusion In most Southern African countries, proportionally more females are on HIV antiretroviral treatment than men, even when the higher HIV infection prevalence in females is accounted for. There is need to identify the factors that are facilitating women's accessibility to HIV treatment. As more patients access HAART in the region, it will be important to continue assessing the gender distribution of patients on HAART.
Mocroft, A; Horban, A; Clumeck, N;
BACKGROUND: Few published studies have considered both the short- and long-term virologic or immunologic response to combination antiretroviral therapy (cART) and the impact of different cART strategies. PURPOSE: To compare time to initial virologic (200/mm3 cell...... increase) response in antiretroviral-naïve patients starting either a single protease inhibitor (PI; n = 183), a ritonavir-boosted PI regimen (n = 197), or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART regimen (n = 447) after January 1, 2000, and the odds of lack of virologic...... or immunologic response at 3 years after starting cART. METHOD: Cox proportional hazards models and logistic regression. RESULTS: After adjustment, compared to patients taking an NNRTI-regimen, patients taking a single-PI regimen were significantly less likely to achieve a viral load (VL)
Full Text Available BACKGROUND: Large HIV care programs frequently subsidize antiretroviral (ARV drugs and CD4 tests, but patients must often pay for other health-related drugs and services. We estimated the financial burden of health care for households with HIV-infected adults taking antiretroviral therapy (ART in Côte d'Ivoire. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional survey. After obtaining informed consent, we interviewed HIV-infected adults taking ART who had consecutively attended one of 18 HIV care facilities in Abidjan. We collected information on socioeconomic and medical characteristics. The main economic indicators were household capacity-to-pay (overall expenses minus food expenses, and health care expenditures. The primary outcome was the percentage of households confronted with catastrophic health expenditures (health expenditures were defined as catastrophic if they were greater than or equal to 40% of the capacity-to-pay. We recruited 1,190 adults. Median CD4 count was 187/mm(3, median time on ART was 14 months, and 72% of subjects were women. Mean household capacity-to-pay was $213.7/month, mean health expenditures were $24.3/month, and 12.3% of households faced catastrophic health expenditures. Of the health expenditures, 75.3% were for the study subject (ARV drugs and CD4 tests, 24.6%; morbidity events diagnosis and treatment, 50.1%; transportation to HIV care centres, 25.3% and 24.7% were for other household members. When we stratified by most recent CD4 count, morbidity events related expenses were significantly lower when subjects had higher CD4 counts. CONCLUSIONS/SIGNIFICANCE: Many households in Côte d'Ivoire face catastrophic health expenditures that are not attributable to ARV drugs or routine follow-up tests. Innovative schemes should be developed to help HIV-infected patients on ART face the cost of morbidity events.
Portia C Mutevedzi
Full Text Available OBJECTIVE: To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART in a large rural HIV treatment cohort. DESIGN: Retrospective cohort analysis using data from a public HIV Treatment & Care Programme. METHODS: Adults initiating ART 1(st August 2004-31(st October 2009 were stratified by age at initiation: young adults (16-24 years mid-age adults (25-49 years and older (≥50 years adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points. RESULTS: 8846 adults were included, 808 (9.1% young adults; 7119 (80.5% mid-age adults and 919 (10.4% older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004 compared to those aged 25-49 years. Overall mortality rates (MR per 100 person-years were 6.18 (95% CI 4.90-7.78; 6.55 (95% CI 6.11-7.02 and 8.69 (95% CI 7.34-10.28 for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0-3 months (MR: 27.1 vs 17.17 and 21.36 and 3-12 months (MR: 9.5 vs 4.02 and 6.02 respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1 year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0-3 months whilst immunological and virological responses were associated with mortality after 12 months. CONCLUSIONS: Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly
Tirivayi, Nyasha; Koethe, John R; Groot, Wim
BACKGROUND: There has been limited research to date on the effects of food assistance provided to HIV-infected adults in resource-constrained settings with a high prevalence of malnutrition and chronic food insecurity. We compare antiretroviral therapy (ART) adherence, weight gain, and CD4+ lymphocy
J.W. Eaton (Jeffrey); D. Menzies; J. Stover (John); V. Cambiano (Valentina); L. Chindelevitch (Leonid); A. Cori (Anne); J.A.C. Hontelez (Jan A.C.); S. Humair (Salal); C.C. Kerr (Cliff); D.J. Klein (David); S. Mishra (Sharmistha); K.M. Mitchell (Kate); B.E. Nichols (Brooke); K. Vickerman; R. Bakker (Roel); T. Bärnighausen (Till); A. Bershteyn (Anna); D.E. Bloom (David); M-C. Boily (Marie-Claude); S.T. Chang (Stewart); T. Cohen (Ted); P. Dodd (Peter); C. Fraser (Christophe); C. Gopalappa (Chaitra); J. Lundgren (Jens); N.K. Martin (Natasha); T.S. Mikkelsen; E. Mountain (Elisa); Q.D. Pham (Quang); T. Pickles (Tom); A. Phillips (Andrew); S. Platt; C. Pretorius (Carel); H.J. Prudden (Holly); J.A. Salomon (Joshua); D.A.M.C. van de Vijver (David); S.J. de Vlas (Sake); B.G. Wagner (Bradley); R.G. White (Richard); D.C. Wilson (David); L. Zhang (Lingling); J. Blandford (John); G. Meyer-Rath (Gesine); M. Remme (Michelle); P. Revill (Paul); N. Sangrujee (Nalinee); F. Terris-Prestholt (Fern); M.C. Doherty (Meg); N. Shaffer (Nathan); P.J. Easterbrook (Philippa); G. Hirnschall (Gottfried); T.B. Hallett (Timothy)
textabstractBackground: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretr
Full Text Available BACKGROUND: Despite recent changes to expand the ART eligibility criteria in sub-Saharan Africa, many patients still initiate ART in the advanced stages of HIV infection, which contributes to increased early mortality rates, poor patient outcomes, and onward transmission. METHODS: To evaluate individual and clinic-level factors associated with late ART initiation in Mozambique, we conducted a retrospective sex-specific analysis of data from 36,411 adult patients who started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique. Late ART initiation was defined as CD4 count45_vs.26-30 = 0.72, 95%CI [0.67-0.77], entry into care via PMTCT (AOR(entry_through_PMTCT_vs.VCT = 0.42, 95%CI [0.35-0.50], marital status (AOR(married/in union_vs.single = 0.87, 95%CI [0.83-0.92], education (AOR(secondary_or_higher_vs.primary = 0.87, 95%CI [0.83-0.93] and year of ART initiation were associated with a lower likelihood of late ART initiation. Clinic-level factors independently associated with a lower likelihood of late ART initiation included CD4 machine on-site (AOR(CD4_machine_onsite_vs.offsite = 0.83, 95%CI [0.74-0.94] and presence of PMTCT services onsite (AOR = 0.85, 95%CI [0.77-0.93]. CONCLUSION: The risk of starting ART late remained persistently high. Efforts are needed to ensure identification and enrollment of patients at earlier stages of HIV disease. Individual and clinic level factors identified may provide clues for upstream structural interventions.
Inzaule, Seth C.; Hamers, Raph L.; Kityo, Cissy; Rinke de Wit, Tobias F.; Roura, Maria
Background Long-term success of HIV antiretroviral therapy requires near-perfect adherence, maintained throughout one’s lifetime. However, perceptions towards ART and patterns of adherence may change during the life course. We assessed challenges to long-term adherence in adolescents and adults in three regional HIV treatment centers in Uganda. Methods We conducted 24 in-depth interviews and 2 focus group discussions with a total of 33 health-care providers and expert clients (HIV patients on long-term ART who assist with adherence support of fellow patients). Interview topics included experiences with patients on long-term treatment with either declining adherence or persistent poor adherence. Transcribed texts were coded and analyzed based on the social-ecological framework highlighting differences and commonalities between adolescents and adults. Results The overarching themes in adolescents were unstructured treatment holidays, delays in disclosure of HIV status by caretakers, stigma, which was mainly experienced in boarding schools, and diminishing or lack of clinical support. In particular, there was minimal support for early and gradual disclosure for caretakers to the infected children, diminishing clinical support for young adults during transition to adult-based care and declining peer-to-peer support group activities. The predominating theme in adults was challenges with treatment access among temporary economic migrants. Common themes to adults and adolescents were challenges with disclosure in intimate relationships, treatment related factors including side effects, supply of single tablets in place of fixed-dose combined drugs, supply of drug brands with unfavorable taste and missed opportunities for counseling due to shortage of staff. Conclusion Adherence counseling and support should be adapted differently for adolescents and adults and to the emerging life course challenges in long-term treated patients. Programs should also address constraints
Mocroft, A; Horban, A; Clumeck, N
increase) response in antiretroviral-naïve patients starting either a single protease inhibitor (PI; n = 183), a ritonavir-boosted PI regimen (n = 197), or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART regimen (n = 447) after January 1, 2000, and the odds of lack of virologic...... or immunologic response at 3 years after starting cART. METHOD: Cox proportional hazards models and logistic regression. RESULTS: After adjustment, compared to patients taking an NNRTI-regimen, patients taking a single-PI regimen were significantly less likely to achieve a viral load (VL)
Haissman, J.M.; Vestergaard, L.S.; Sembuche, S.;
OBJECTIVE: To evaluate the role immune activation leading to the production and circulation of cytokines has in the pathogenesis of HIV infection in sub-Saharan Africa and the effect of antiretroviral treatment (ART) on these parameters. METHODS: Plasma concentrations of tumor necrosis factor (TNF...... counts below 200 cells per microliter than individuals with CD4 cell counts above 200 cells per microliter. HIV RNA was the strongest predictor of all cytokine expression in multivariate analysis. ART leads to a decrease in all cytokines to levels close to those of HIV-uninfected individuals. CONCLUSIONS...
Yan, Tingjian; Wilber, Kathleen H.; Aguirre, Rosa; Trejo, Laura
Purpose: This study assessed the effectiveness of Active Start, a community-based behavior change and fitness program, designed to promote physical activity among sedentary community-dwelling older adults. Design and Methods: A quasi-experimental design was used. Data were analyzed using a within-group pretest-post-test design to calculate changes…
Robert G. Lockie
Full Text Available This study profiled beach flags start kinematics for experienced young adult sprinters. Five males and three females (age = 20.8 ± 2.1 years; height = 1.70 ± 0.06 meters [m]; mass = 63.9 ± 6.0 kilograms completed four sprints using their competition start technique. A high-speed camera, positioned laterally, filmed the start. Data included: start time; hand clearance time; posterior movement from the start line; feet spacing during the start; elbow, hip, knee, trunk lean, and trajectory angles at take-off; and first step length. Timing gates recorded 0-2, 0-5, and 0-20 m time. Spearman's correlations identified variables relating (p < 0.05 to faster start and sprint times. The beach flags start involved sprinters moving 0.18 ± 0.05 m posterior to the start line by flexing both legs underneath the body before turning. Following the turn, the feet were positioned 0.47 ± 0.07 apart. This distance negatively correlated with start (ρ = -0.647, 0-2 (ρ = -0.683, and 0-5 m (ρ = -0.766 time. Beach flags start kinematics at take-off resembled research analyzing track starts and acceleration. The elbow extension angle (137.62 ± 13.45° of the opposite arm to the drive leg correlated with 0-2 (ρ = -0.762, 0-5 (ρ = -0.810, and 0-20 m (ρ = -0.810 time. Greater arm extension likely assisted with stability during the start, leading to enhanced sprint performance. The drive leg knee extension angle (146.36 ± 2.26° correlated with start time (ρ = -0.677, indicating a contribution to a faster start completion. A longer first step following the start related to faster 0-5 m time (ρ = -0.690. Sprinters quicker over 0-2 and 0-5 m were also quicker over 20 m (ρ = 0.881-0.952. Beach flags sprinters must ensure their start is completed quickly, such that they can attain a high speed throughout the race
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.
Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette;
In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size...... and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR...... count (r = 0.083, p = 0.706), naive CD4 count (r = 0.067, p = 0.762), CD4 + TREC frequency (r = 0.028, p = 0.900) and CD4 + TCR repertoire (r = -0.057, p = 0.828). These findings show that CT remains superior for assessing thymic size in adults and is preferable to ultrasound when evaluating...
Full Text Available Complexity of antiretroviral treatment (ART is a reason for non-adherence and may impact treatment outcome. The association between daily dosing and pill burden and chance of virological success (VS of first ART has been rarely assessed. 3,674 naïve patients who started treatment after January 2000 were identified from the ICoNA cohort. Number of daily doses and pills were estimated on the basis of the drugs used to rank first ART complexity: 1–2 daily pills once a day (low-pills QD [lpQD]; 3–6 daily pills QD (high-pills QD [hpQD]; 2–5 daily pills BID (low-pills BID [lpBID]; >6 daily pills BID (high-pills BID [hpBID]. VS was the date of first HIV RNA <50 cp/ml. Follow-up was censored at the date of VS or last available HIV RNA. Kaplan-Meier curves estimated probability of achieving VS according to ART complexity. Univariable and multivariable Cox regression stratified by clinical site was used to identify variables associated with VS. ITT principle was applied, using competing risk approach for death. Population: male 75%; median age 37 y (IQR, 32–44; HIV transmission heterosexual 43%, homosexual 33%, drug use 16%; Italian origin 86%; CDC group C 17%; median pre-ART CD4 and log HIV-RNA were 271/mm3 (range, 0–1672 and 4.84 cp/ml (1.70–6.38, respectively. Regimens were started in ‘00–‘02 24%,‘03–‘05 17%,‘06–‘08 17%,‘09–‘12 42% and based on NNRTI in 40%, PI/r 43%, PI 8%, other ART 10%. Frequencies in complexity ranks were: 19% lpQD, 23% hpQD, 32% lpBID, 26% hpBID. VS was achieved by 85% of patients with an overall median time to VS of 5.6 months (95% CI: 5.4–5.8. Median months to VS were shorter with decreasing complexity: hpBID 6.5; lpBID 6.0; hpQD 5.3, lpQD 4.5. Kaplan-Meier curves are shown (Figure. After stratifying for clinical site and adjusting for age, gender, origin, transmission route, CDC group C, HCV/HBV infection, years of HIV, pre-cART CD4 and HIV-RNA, type of regimen a significantly reduced
Newcomb, Michael E; Bedoya, C Andres; Blashill, Aaron J; Lerner, Jonathan A; O'Cleirigh, Conall; Pinkston, Megan M; Safren, Steven A
There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting.
Auld, Andrew F; Agolory, Simon G; Shiraishi, Ray W; Wabwire-Mangen, Fred; Kwesigabo, Gideon; Mulenga, Modest; Hachizovu, Sebastian; Asadu, Emeka; Tuho, Moise Zanga; Ettiegne-Traore, Virginie; Mbofana, Francisco; Okello, Velephi; Azih, Charles; Denison, Julie A; Tsui, Sharon; Koole, Olivier; Kamiru, Harrison; Nuwagaba-Biribonwoha, Harriet; Alfredo, Charity; Jobarteh, Kebba; Odafe, Solomon; Onotu, Dennis; Ekra, Kunomboa A; Kouakou, Joseph S; Ehrenkranz, Peter; Bicego, George; Torpey, Kwasi; Mukadi, Ya Diul; van Praag, Eric; Menten, Joris; Mastro, Timothy; Dukes Hamilton, Carol; Swaminathan, Mahesh; Dokubo, E Kainne; Baughman, Andrew L; Spira, Thomas; Colebunders, Robert; Bangsberg, David; Marlink, Richard; Zee, Aaron; Kaplan, Jonathan; Ellerbrock, Tedd V
Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by age at enrollment: adolescents and young adults (aged 15-24 years), middle-aged adults (aged 25-49 years), and older adults (aged ≥50 years). Enrollees aged 15-24 years were predominantly female (81%-92%), commonly pregnant (3%-32% of females), unmarried (54%-73%), and, in four countries with employment data, unemployed (53%-86%). In comparison, older adults were more likely to be male (padolescents and young adults had higher LTFU rates in all seven countries, reaching statistical significance in three countries in crude and multivariable analyses. Evidence-based interventions to reduce LTFU for adolescent and young adult ART enrollees could help reduce mortality and HIV incidence in this age group.
Daniella J. Itinoseki Kaio
Full Text Available 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.
Fatai A. Fehintola
Full Text Available Background. Nevirapine- (NVP- based antiretroviral therapy (ART and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics. Methods. We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n=10 and ART-naive controls (n=11. Artesunate-amodiaquine 200/600 mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis. Results. Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P=0.03, resulting in a 45% increase in the AUC0-96 (105 versus 69 ug∗hr/L; P=0.02. The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P=0.004, but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC0-96=5.6 versuss 8.5 in NVP and control groups, respectively, P=0.008. Conclusion. Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.
Dybul, Mark; Fauci, Anthony S; Bartlett, John G; Kaplan, Jonathan E; Pau, Alice K
The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4+ T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy; 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. Treatment should
Muhula, Samuel Opondo; Peter, Memiah; Sibhatu, Biadgilign; Meshack, Ndirangu; Lennie, Kyomuhangi
Recent improvements in access to Anti-Retroviral Therapy (ART) have radically reduced hospitalizations and deaths associated with HIV infection in both developed countries and sub-Saharan Africa. Not much is known about survival of patients on ART in slums. The objective of this study was to identify factors associated with mortality among adult patients on ART in resource poor, urban, sub-Saharan African setting. A prospective open cohort study was conducted with adult patients on ART at a clinic in Kibera slums, Nairobi, Kenya. The patients' enrollment to care was between March 2005 and November 2011. Descriptive statistics were computed and Kaplan-Meier (KM) methods used to estimate survival time while Cox's proportional hazards (CPH) model fitted to determine mortality predictors. A total of 2,011 adult patients were studied, 69% being female. Female gender (p=0.0016), zidovudine-based regimen patients (p351 patients (p<0.0001), WHO stage I patients (p<0.0001) and "Working" functional status patients recorded better survival probability on ART. In CPH analysis, the hazard of dying was higher in patients on Stavudine-based regimen(hazard ratio (HR)=.8; 95% CI, 1.5-2.2; p<0.0001),CD4 count<50 cells/µl (HR=1.6; 95% CI, 1.5-1.7;p<0.0001), WHO Stage IV at ART initiation (HR=1.3; 95% CI, 1.1-1.6; p=0.016) and bedridden patients (HR=2.7; 95% CI, 1.7-4.4;p<0.0001). There was increased mortality among the males, those with advanced Immunosuppression, late WHO stage and bedridden patients. The findings further justify the need to switch patients on Stavudine-based regimen as per the WHO recommendations.
Karade, Santosh; Patil, Ajit A; Ghate, Manisha; Kulkarni, Smita S; Kurle, Swarali N; Risbud, Arun R; Rewari, Bharat B; Gangakhedkar, Raman R
In India, the roll out of the free antiretroviral therapy (ART) program completed a decade of its initiation in 2014. The success of first-line ART is influenced by prevalence of HIV pretreatment drug resistance (PDR) in the population. In this cross-sectional study, we sought to determine the prevalence of PDR among adults attending the state-sponsored free ART clinic in Pune in western India. Fifty-two individuals eligible for ART as per national guidelines with median CD4 cell count of 253 cells/mm(3) (inter quartile range: 149-326) were recruited between January 2014 and April 2015. Population-based sequencing of partial pol gene sequences from plasma specimen revealed predominant HIV-1 subtype C infection (96.15%) and presence of single-drug resistance mutations against non-nucleoside reverse transcriptase inhibitor in two sequences. The study supports the need for periodic surveillance, when offering PDR testing at individual level is not feasible.
Full Text Available Abstract Background Antiretroviral therapy (ART clinic populations have expanded enormously in the successful Malawi ART scale-up programme. Overcrowding, long waiting times and living far away from the clinic may affect the extent to which patients use their ART clinic for intercurrent illnesses. Methods We interviewed patients of a large urban ART clinic in Blantyre, Malawi, during routine visits about the choice of health care facility during recent illness episodes. Results Out of 346 enrolled adults, mean age 39.8 (range 18-70 years, 54.3% female, 202 (58% reported one or more illness in the past 6 months, during which 85 (42.1%; 95%-confidence interval: 36.9-47.3% did not utilize their own clinic. Long distance to the clinic was the main subjective reason, while low education attainment, rural residence, perceived mild illness and dissatisfaction with the ART service were associated with not using their own clinic in multivariate analyses. Of all participants, 83.6% were satisfied with the service provided; only 6.1% were aware of the full service package of the ART clinic. Conclusions ART patients often seek health care outside their own clinic, which may have detrimental effects, and has consequences for ART counseling content and reporting of ART information in health passports.
Pollack, Todd M.; Duong, Hao T.; Pham, Thuy T.; Do, Cuong D.; Colby, Donn
High HIV viral load (VL >100,000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132 cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100,000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1–10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15–3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75–2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100,000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use
Maskew, Mhairi; MacPhail, A Patrick; Whitby, Denise; Egger, Matthias; Fox, Matthew P.
Background The possible impact of co-infection with Kaposi’s sarcoma associated herpes virus on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa. Methods We enrolled a prospective cohort of HIV-infected adults initiating ART in Johannesburg, South Africa. Subjects were defined as seropositive to KSHV if reactive to either KSHV lytic K8.1 or latent Orf73 antigen or both. Subjects were followed from ART initiation until 18-months on treatment. HIV viral load and CD4 counts were tested 6 monthly. Linear generalized estimating and log-binomial regression models were used to estimate the effect of KSHV infection on immunologic recovery and response as well as HIV viral load suppression within 18-months after ART initiation. Results 385 subjects initiating ART from November 2008-March 2009 were eligible including 184 (48%) KSHV+. The KSHV+ group was similar to the KSHV− in terms of age, gender, initiating CD4 count, body mass index, tuberculosis and haemoglobin levels. The KSHV+ group gained a similar number of cells at 6- (difference of 10 cells/mm3, 95% CI: −11–31), 12- (3 cells/mm3, 95% CI: −19–25) and 18-months (24 cells/mm3, 95% CI: −13–61) compared to the KSHV− group. Adjusted relative risk of failure to suppress viral load to <400 copies/mL (1.03; 95% CI: 0.90–1.17) were similar for KSHV+ and KSHV− by 6-months on treatment. Conclusions In a population with a high KSHV prevalence, HIV-positive adults co-infected with KSHV achieved similar immunologic and virologic responses to ART early after treatment initiation compared to those KSHV−. PMID:23614996
Woodd, Susannah L; Kelly, Paul; Koethe, John R;
an increased risk in the pre-ART period. Participants on tuberculosis treatment at referral had a lower mortality rate (adjusted Rate Ratio 0.44; 95 % CI 0.31, 0.63). CONCLUSION: Among malnourished ART-eligible adults, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART...... deaths represent advanced HIV disease rather than treatment-related events. Therefore, more efforts are needed to promote earlier diagnosis and immediate initiation of ART, as recently recommended by WHO for all persons with HIV worldwide. The positive effect of tuberculosis treatment suggests...... undiagnosed tuberculosis is a contributor to mortality in this population. TRIAL REGISTRATION: Pan African Clinical Trials Registry, PACTR201106000300631 ; registered on 1st June 2011....
Full Text Available Habtamu Mitiku, Fitsum Weldegebreal, Zelalem Teklemariam Haramaya University, College of Health and Medical Sciences, Department of Medical Laboratory Sciences, Harar, Ethiopia Purpose: The aim of this study was to assess the prevalence of opportunistic infections (OIs and associated factors among HIV-infected adults on anti-retroviral therapy (ART in Hiwot Fana Specialized University Hospital, Eastern Ethiopia. Patients and methods: A hospital-based retrospective study was conducted in 358 HIV-infected adult patients on ART from April to June 2014. Data were collected through review of clinical records. The data was entered and analyzed by using SPSS version 16.0. Univariate and multivariate analyses were performed to determine the association of each independent variable with occurrence of OIs. A 95% confidence interval (CI and P-value less than 0.05 were considered as significant association. Results: A total of 358 patients were included in the study, in which majority (68.4% were females. The mean age of patients was 34 (standard deviation [SD] ±9.8 years. The overall of prevalence of OIs among HIV/AIDS patients on ART was 48%. The highest prevalent rates of OIs observed were tuberculosis (TB (21.23%, followed by Herpes zoster (11.2% and oral candidiasis (9.5%. Baseline CD4 cell count <200 cells/mm3 (adjusted odds ratio [AOR] =1.645, 95% CI =2.187, 3.983, baseline World Health Organization (WHO clinical stage III (AOR =2.801, 95% CI =1.958, 7.165 and IV (AOR =3.856; 95% CI =2.691, 10.390, and not using prophylaxis (AOR =1.912, 95% CI =1.444, 3.824 were found to have strong association with acquisition of OIs. Conclusion: There was a high prevalence of OIs observed in this study. Baselines CD4 count of <200 cells/mm3, advanced WHO clinical stages, and not using prophylaxis were found to be predictors of OIs. Interventions were aimed at promoting early HIV testing and enrollment of HIV-infected individuals into ART services needed before CD4
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.
Full Text Available Mette Frahm Olsen,1 Markos Tesfaye,2 Pernille Kæstel,1 Henrik Friis,1 Lotte Holm3 1Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark; 2Department of Psychiatry, College of Public Health and Medical Sciences, Jimma University, Jimma, Ethiopia; 3Department of Food and Resource Economics, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark Objectives: Ready-to-use supplementary foods (RUSF are used increasingly in human immunodeficiency virus (HIV programs, but little is known about how it is used and viewed by patients. We used qualitative methods to explore the use, perceptions, and acceptability of RUSF among adult HIV patients in Jimma, Ethiopia. Methods: The study obtained data from direct observations and 24 in-depth interviews with HIV patients receiving RUSF. Results: Participants were generally very motivated to take RUSF and viewed it as beneficial. RUSF was described as a means to fill a nutritional gap, to “rebuild the body,” and protect it from harmful effects of antiretroviral treatment (ART. Many experienced nausea and vomiting when starting the supplement. This caused some to stop supplementation, but the majority adapted to RUSF. The supplement was eaten separately from meal situations and only had a little influence on household food practices. RUSF was described as food with “medicinal qualities,” which meant that many social and religious conventions related to food did not apply to it. The main concerns about RUSF related to the risk of HIV disclosure and its social consequences. Conclusion: HIV patients view RUSF in a context of competing livelihood needs. RUSF intake was motivated by a strong wish to get well, while the risk of HIV disclosure caused concerns. Despite the motivation for improving health, the preservation of social networks was prioritized, and nondisclosure was often a necessary strategy. Food sharing and religious
Shoshana Y Kahana
Full Text Available The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States.The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer-assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural and Esri Crime (e.g., global crime index databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1 being on antiretroviral therapy (ART currently; (2 being on ART for at least 6 months; (3 missed HIV care appointments (not having missed any vs. having missed one or more appointments over the past 12 months; and (4 viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability.Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%; ART use for ≥6 months (n = 861, 45.53%; at least one missed HIV care appointment (n = 936, 49.50; and viral suppression (n = 577, 30.51%. After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single-headed households, percent
Koethe, John R; Blevins, Meridith; Nyirenda, Christopher K; Kabagambe, Edmond K; Chiasera, Janelle M; Shepherd, Bryan E; Zulu, Isaac; Heimburger, Douglas C
Background. Low body mass index (BMI) at antiretroviral therapy (ART) initiation is associated with early mortality, but the etiology is not well understood. We hypothesized that low pretreatment serum phosphate, a critical cellular metabolism intermediate primarily stored in skeletal muscle, may predict mortality within the first 12 weeks of ART. Methods. We prospectively studied 352 HIV-infected adults initiating ART in Lusaka, Zambia to estimate the odds of death for each 0.1 mmol/L decrease in baseline phosphate after adjusting for established predictors of mortality. Results. The distribution of phosphate values was similar across BMI categories (median value 1.2 mmol/L). Among the 145 participants with BMI refeeding syndrome. Further studies of cellular metabolism in this population are needed.
Koethe, John R.; Blevins, Meridith; Nyirenda, Christopher K.; Kabagambe, Edmond K.; Chiasera, Janelle M.; Shepherd, Bryan E.; Zulu, Isaac; Heimburger, Douglas C.
Background. Low body mass index (BMI) at antiretroviral therapy (ART) initiation is associated with early mortality, but the etiology is not well understood. We hypothesized that low pretreatment serum phosphate, a critical cellular metabolism intermediate primarily stored in skeletal muscle, may predict mortality within the first 12 weeks of ART. Methods. We prospectively studied 352 HIV-infected adults initiating ART in Lusaka, Zambia to estimate the odds of death for each 0.1 mmol/L decrease in baseline phosphate after adjusting for established predictors of mortality. Results. The distribution of phosphate values was similar across BMI categories (median value 1.2 mmol/L). Among the 145 participants with BMI refeeding syndrome. Further studies of cellular metabolism in this population are needed. PMID:23691292
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.
Heestermans, Tessa; Browne, Joyce L; Aitken, Susan C; Vervoort, Sigrid C; Klipstein-Grobusch, Kerstin
Objective The rapid scale up of antiretroviral treatment (ART) in sub-Saharan Africa (SSA) has resulted in an increased focus on patient adherence. Non-adherence can lead to drug-resistant HIV caused by failure to achieve maximal viral suppression. Optimal treatment requires the identification of pa
Raffi, François; Babiker, Abdel G; Richert, Laura;
BACKGROUND: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen. METHODS: Between August, 2010, and...
Full Text Available Objective: VIOLIN (TMC125IFD3002; NCT01422330 evaluated the safety, tolerability, and pharmacokinetics of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected patients. Methods: In a 48-week, phase IV, single-arm, multicenter study, patients on prior antiretroviral therapy (⩾8 weeks who needed to change regimen for virologic failure (viral load ⩾ 500 copies/mL or simplification/adverse events (viral load < 50 copies/mL received etravirine 200 mg bid with ⩾1 other active antiretroviral, excluding darunavir/ritonavir or only nucleoside/tide reverse transcriptase inhibitors. Results: Of 211 treated patients, 73% (n = 155 had baseline viral load ⩾ 50 copies/mL and 27% (n = 56 had baseline viral load < 50 copies/mL. Protease inhibitors were the most common background antiretrovirals (83%. Diarrhea was the most frequent adverse event (17%. Serious adverse events (no rash occurred in 5% of patients; none were etravirine related. Overall, median etravirine AUC12h was 5390 ng h/mL and C0h was 353 ng/mL (N = 199. Week 48 virologic response rates (viral load < 50 copies/mL; Food and Drug Administration Snapshot algorithm were 48% (74/155 (baseline viral load ⩾ 50 copies/mL and 75% (42/56 (baseline viral load < 50 copies/mL. Virologic failure rates were 42% and 13%, respectively. The most frequently emerging etravirine resistance-associated mutations in virologic failures were Y181C, E138A, and M230L. Virologic response rates for patients with baseline viral load ⩾ 50 copies/mL were 38% (30/79 (non-adherent versus 64% (44/69 (adherent subset. Conclusion: Etravirine 200 mg bid in combination with antiretrovirals other than darunavir/ritonavir was well tolerated in the studied treatment-experienced HIV-1-infected population. The overall etravirine safety and tolerability profile and pharmacokinetics (specifically in those patients who were adherent
Full Text Available Background: The Tanzanian national HIV care and treatment programme has provided free antiretroviral therapy (ART to HIV-positive persons since 2004. ART has been available to participants of the Kisesa open cohort study since 2005, but data to 2007 showed a slow uptake of ART and a modest impact on mortality. Additional data from the 2010 HIV serological survey provide an opportunity to update the estimated impact of ART in this setting. Methods: The Kisesa Health and Demographic Surveillance Site (HDSS has collected HIV serological data and demographic data, including verbal autopsy (VA interviews since 1994. Serological data to the end of 2010 were used to make two estimates of HIV-attributable mortality, the first among HIV positives using the difference in mortality between HIV positives and HIV negatives, and the second in the population using the difference between the observed mortality rate in the whole population and the mortality rate among the HIV negatives. Four time periods (1994–1999, 2000–2004, 2005–2007, and 2008–2010 were used and HIV-attributable mortality estimates were analysed in detail for trends over time. A computer algorithm, InterVA-4, was applied to VA data to estimate the HIV-attributable mortality for the population, and this was compared to the estimates from the serological survey data. Results: Among HIV-positive adults aged 45–59 years, high mortality rates were observed across all time periods in both males and females. In HIV-positive men, the HIV-attributable mortality was 91.6% (95% confidence interval (CI: 84.6%–95.3% in 2000–2004 and 86.3% (95% CI: 71.1%–93.3% in 2008–2010, while among women, the HIV-attributable mortality was 87.8% (95% CI: 71.1%–94.3% in 2000–2004 and 85.8% (95% CI: 59.6%–94.4% in 2008–2010. In the whole population, using the serological data, the HIV-attributable mortality among men aged 30–44 years decreased from 57.2% (95% CI: 46.9%–65.3% in 2000–2004
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...... 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...... results [443 patients [16%
Weis, Nina Margrethe; Lindhardt, Bjarne Ø.; Kronborg, Gitte;
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...... 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...... results [443 patients [16%
Newcomb, Michael E.; Bedoya, C. Andres; Blashill, Aaron J.; Lerner, Jonathan A.; O’Cleirigh, Conall; Pinkston, Megan M.; Safren, Steven A.
There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depres...
Winston, A; Stöhr, W; Antinori, A;
OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence...... Nationale de Recherche sur le SIDA (ANRS) 143 study. METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean...... and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models. RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile...
Kahana, Shoshana Y; Rohan, Jennifer; Allison, Susannah; Frazier, Thomas W; Drotar, Dennis
The relationship between adherence to antiretroviral therapy (ART) and virologic outcomes in HIV+ children, adolescents, and young adults has been notably understudied, with much of the extant research focused on specific sub-literatures, such as resource-limited regions, specific clinical outcomes and time frames. The authors sought to better characterize the relationship between adherence to ART and virologic functioning along various sample and methodological factors. The authors conducted a meta-analysis of thirty-seven studies and utilized a random effects model to generate weighted mean effect sizes. In addition, the authors conducted meta-ANOVAs to examine potential factors influencing the relationship between adherence and three categories of clinical outcomes, specifically Viral Load (VL) adolescents, and young adults. The relationship between adherence behaviors and virologic outcomes varied across different methods of measurement and analysis. The relationship between adherence and continuously measured VL was significantly larger than for dichotomously-coded VL adolescent and parent) produced significantly larger effects than caregiver report alone with adherence and VL adolescents and young adults varies across virologic outcomes and may be affected by moderating sample and methodological factors. Methodological and research recommendations for the interpretation of the current findings as well as for future HIV adherence related research are presented.
Helen van der Plas
Full Text Available BACKGROUND: HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries. METHODS: Prospective, observational cohort study of adult inpatients with HIV-associated tuberculosis starting antiretroviral therapy in a dedicated tuberculosis hospital in Cape Town, South Africa. Causes of clinical deterioration and outcome were recorded in the first 12 weeks of antiretroviral therapy. Patients with rifampicin-resistant tuberculosis were excluded. RESULTS: Between May 2009 and November 2010, 112 patients (60% female, with a median age of 32 years were enrolled. At baseline the median CD4 count was 55 cells/mm3 (IQR 31-106 and HIV viral load 5.6 log copies/mL. All patients had significant comorbidity: 82% were bed-bound, 65% had disseminated tuberculosis and 27% had central nervous system tuberculosis. Seventy six patients (68% developed 144 clinical events after starting antiretroviral therapy. TB-IRIS, hospital-acquired infections and significant drug toxicities occurred in 42%, 20.5% and 15% of patients respectively. A new opportunistic disease occurred in 15% of patients and a thromboembolic event in 8%. Mortality during the 12 week period was 10.6%. CONCLUSIONS: High rates of TB-IRIS, hospital-acquired infections and drug toxicities complicate the course of patients with HIV-associated tuberculosis starting antiretroviral therapy in hospital. Despite the high morbidity, mortality was relatively low. Careful clinical management and adequate resources are needed in hospitalised HIV-TB patients in the 1(st three
John R. Koethe
Full Text Available Background. Low body mass index (BMI at antiretroviral therapy (ART initiation is associated with early mortality, but the etiology is not well understood. We hypothesized that low pretreatment serum phosphate, a critical cellular metabolism intermediate primarily stored in skeletal muscle, may predict mortality within the first 12 weeks of ART. Methods. We prospectively studied 352 HIV-infected adults initiating ART in Lusaka, Zambia to estimate the odds of death for each 0.1 mmol/L decrease in baseline phosphate after adjusting for established predictors of mortality. Results. The distribution of phosphate values was similar across BMI categories (median value 1.2 mmol/L. Among the 145 participants with BMI <18.5 kg/m2, 28 (19% died within 12 weeks. Lower pretreatment serum phosphate was associated with increased mortality (odds ratio (OR 1.24 per 0.1 mmol/L decrement, 95% CI: 1.05 to 1.47; P=0.01 after adjusting for sex, age, and CD4+ lymphocyte count. A similar relationship was not observed among participants with BMI ≥18.5 kg/m2 (OR 0.96, 95% CI: 0.76 to 1.21; P=0.74. Conclusions. The association of low pretreatment serum phosphate level and early ART mortality among undernourished individuals may represent a variant of the refeeding syndrome. Further studies of cellular metabolism in this population are needed.
Gupta, S B; Pujari, S N; Joshi, S R; Patel, A K
With rational use of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been transformed into a chronic manageable illness like diabetes and hypertension. These guidelines provide information on state of art, evidence based approach for use of ART in Indian context. When to initiate ART? Antiretroviral therapy is indicated for all symptomatic HIV infected persons regardless of CD4 counts and plasma viral load (PVL) levels. In asymptomatic patients, ART should be offered when the CD4 counts ART. What to start with? A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen is recommended for antiretroviral naïve patients. The choice between nevirapine and efavirenz is based on differences in adverse events profiles; cost and availability of convenient fixed dose combinations and need for concomitant use of rifampicin. A backbone of 2-nucleoside reverse transcriptase inhibitors (NRTIs) is combined with the NNRTI. Various combinations and ART strategies not to be used in clinical practice has been enlisted. How to follow up? Recommendations have been made for baseline evaluation and monitoring of patients on ART. These include guidelines on laboratory and clinical evaluation. A plasma viral load at 6 months after initiation of first-line ART is strongly recommended. Yearly estimation of lipid profile has been recommended. How to identify and manage ART failure? The guidelines recognize the issue of identifying ART failure late if only CD4 counts are used for monitoring. In the absence of resistance testing various second-line regimens have been enlisted. A boosted protease inhibitor based regimen is recommended in this situation to be combined with 2-NRTIs. Special situations Recommendations have been made for use of ART in HIV-TB, HIV-HBV, and HIV-HCV co-infected patients. In patients with active TB and a CD4 count ART is recommended as soon as the anti-TB treatment is tolerated. Efavirenz is the only ARV drug, which can be
Julicristie M. Oliveira
Full Text Available Background: The benefits of antiretroviral therapy for HIV-infected subjects have been limited by an increased risk of metabolic and cardiovascular diseases. The objective of this study was to assess the effects of a low dose of marine omega-3 fatty acids on inflammatory marker concentrations in HIV-infected subjects under antiretroviral therapy (ART. Methods: This was a randomized, parallel, placebo-controlled trial that investigated the effects of 3 g fish oil/day (540 mg of eicosapentaenoic acid—EPA plus 360 mg of docosahexaenoic acid—DHA or 3 g soy oil/day (placebo for 24 weeks in 83 male and non-pregnant female HIV-infected adults on ART. Results: There were no differences between groups for the measures at baseline. Multilevel analyses revealed no statistically significant relationship between the longitudinal changes in high sensitivity-C reactive protein (hs-CRP (Wald Chi2 = 0.17, p = 0.918, fibrinogen (Wald Chi2 = 3.82, p = 0.148, and factor VIII (Wald Chi2 = 5.25, p = 0.073 with fish oil. No significant changes in interleukin-6 (IL6, interleukin-1 beta (IL1-beta and tumor necrosis factor-alpha (TNF-alpha serum concentrations were observed with fish oil supplements for 12 weeks. Conclusions: Compared to placebo, a low dose of 900 mg omega-3 fatty acids (EPA plus DHA in fish oil capsules did not change hs-CRP, fibrinogen, factor VIII, IL6, IL1-beta and TNF-alpha serum concentrations in HIV-infected subjects on ART. Further investigations should consider the assessment of more sensitive inflammatory markers or higher doses to evaluate the effects of marine omega-3 fatty acids in this population. Registered at the Nederlands Trial Register, Identifier no. NTR1798.
Yukl, Steven A.; Shergill, Amandeep; McQuaid, Kenneth; Gianella, Sara; Lampiris, Harry; Hare, C. Bradley; Pandori, Mark; Sinclair, Elizabeth; Günthard, Huldrych F.; Fischer, Marek; Wong, Joseph K.; Havlir, Diane V.
Objective To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut. Design Open-label study in HIV+ adults on ART with plasma HIV RNA<40 copies/ml. Methods Seven HIV+ adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from PBMC and 4 gut sites, T cell subsets, and activation markers. Results Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, 5 of 7 participants had a decrease in unspliced HIV RNA per 106 CD4+ T cells in the ileum. There was a trend towards decreased T cell activation in all sites, which was greatest for CD8+ T cells in the ileum and PBMC, and a trend towards increased CD4+ T cells in the ileum. Conclusion Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible. PMID:20827162
Full Text Available Objective: We aimed to describe the morbidity and mortality patterns in HIV-positive adults hospitalized in West Africa. Method: We conducted a six-month prospective multicentre survey within the IeDEA West Africa collaboration in six adult medical wards of teaching hospitals in Abidjan, Ouagadougou, Cotonou, Dakar and Bamako. From April to October 2010, all newly hospitalized HIV-positive patients were eligible. Baseline and follow-up information until hospital discharge was recorded using standardized forms. Diagnoses were reviewed by a local event validation committee using reference definitions. Factors associated with in-hospital mortality were studied with a logistic regression model. Results: Among 823 hospitalized HIV-positive adults (median age 40 years, 58% women, 24% discovered their HIV infection during the hospitalization, median CD4 count was 75/mm3 (IQR: 25–177 and 48% had previously received antiretroviral treatment (ART. The underlying causes of hospitalization were AIDS-defining conditions (54%, other infections (32%, other diseases (8% and non-specific illness (6%. The most frequent diseases diagnosed were: tuberculosis (29%, pneumonia (15%, malaria (10% and cerebral toxoplasmosis (10%. Overall, 315 (38% patients died during hospitalization and the underlying cause of death was AIDS (63%, non-AIDS-defining infections (26%, other diseases (7% and non-specific illness or unknown cause (4%. Among them, the most frequent fatal diseases were: tuberculosis (36%, cerebral toxoplasmosis (10%, cryptococcosis (9% and sepsis (7%. Older age, clinical WHO stage 3 and 4, low CD4 count, and AIDS-defining infectious diagnoses were associated with hospital fatality. Conclusions: AIDS-defining conditions, primarily tuberculosis, and bacterial infections were the most frequent causes of hospitalization in HIV-positive adults in West Africa and resulted in high in-hospital fatality. Sustained efforts are needed to integrate care of these
ter Maaten, JC
During the last decade, growth hormone deficiency (GHD) in adults has been described as a clinical syndrome. Central features of this entity include increased fat mass, reduced muscle and bone mass, as well as impaired exercise capacity and quality of life. GH replacement therapy has been initiated
Elsley, Susan; McMellon, Christina
This literature review considers the links between childhood and adult participation in cultural activities, including participation in science events. This includes attendance as members of an audience and participation in arts and cultural activities and as visitors at science attractions such as museums and science centres.
Deutsch, Nancy L.; Schmertz, Barbara
Women adult students face particular constraints when pursuing degrees. This paper uses focus group data to explore the educational pathways, barriers, and supports of women students. Women's educations are shaped by personal and structural gendered forces, including family, economic, and workplace issues. Women report conflict over short-term…
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.
Pinto Mendicino, Cássia Cristina; Reis, Edna Afonso; Carmo, Ricardo Andrade; Menezes de Pádua, Cristiane
This study estimated the incidence of and time to first antiretroviral therapy (ART) modification. This longitudinal analysis comprised a sample of 236 patients from three HIV/AIDS referral centers in Belo Horizonte, Brazil—part of a major historical cohort. Inclusion criteria were as follows: having been treatment-naive patient ≥18 years old who initiated ART between 2001 and 2005 in these three referral centers. The main endpoint was time to first ART modification. Patients were followed up for five years, covering the period 2001–2010, during which time Pearson's chi-square test was performed to compare ART modification between groups. Kaplan-Meier inverse survival curves were employed to describe the probability of ART modification and Cox proportional hazard regression was used to estimate the adjusted hazard ratio (aHR) of ART modification. Among 247 patients from the major cohort, 236 were eligible. Median follow-up time was 37.2 months and the contribution in person-months was 7,615.4 months. A total of 108 (45.8%) patients had their ART regimen modified at least once (incidence rate: 1.42 per 100 person-months). Adverse drug reactions were the main reason for ART modification. Women (aHR = 1.62; p = 0.022) and patients on protease inhibitor- (PI-) based regimens (aHR = 2.70; p < 0.001) were at higher risk of ART modification.
Yilma, Daniel; Kæstel, Pernille; Olsen, Mette F;
Low vitamin D level in HIV-positive persons has been associated with disease progression. We compared the levels of serum 25-hydroxyvitamin D (25(OH)D) in HIV-positive and HIV-negative persons, and investigated the role of nutritional supplementation and antiretroviral treatment (ART) on serum 25...... daily allowance of vitamin D (10 μg/200 g). The level of serum 25(OH)D before nutritional intervention and ART initiation was compared with serum 25(OH)D of HIV-negative individuals. A total of 348 HIV-positive and 100 HIV-negative persons were recruited. The median baseline serum 25(OH)D level......-supplemented group had a 10·8 (95 % CI 7·8, 13·9) nmol/l decrease in serum 25(OH)D level after 3 months of ART. Nutritional supplementation that contained vitamin D prevented a reduction in serum 25(OH)D levels in HIV-positive persons initiating ART. Vitamin D replenishment may be needed to prevent reduction...
Gupta Samir K
Full Text Available Abstract Background The World Health Organization (WHO has recently recommended that antiretrovirals be initiated in all individuals with CD4 counts of less than 350 cells/mm3. For countries with resources too limited to expand care to all such patients, it would be of value to able to identify and target populations at highest risk of HIV progression. Renal disease has been identified as a risk factor for disease progression or death in some populations. Methods Times to meeting combination antiretroviral therapy (cART initiation criteria (developing either a CD4 count 3 or WHO stage 3 or 4 disease and overall mortality were evaluated in cART-naïve, HIV-infected Kenyan adults with CD4 cell counts ≥200/mm3 and with WHO stage 1 or 2 disease. Cox proportional hazard regression models were used to evaluate the associations between renal function and these endpoints. Results We analyzed data of 7383 subjects with a median follow-up time of 59 (interquartile range, 27-97 weeks. In Cox regression analyses adjusted for age, sex, WHO disease stage, CD4 cell count and haemoglobin, estimated creatinine clearance (CrCl 2 was associated with shorter times to meeting cART initiation criteria (HR 1.39; 95% CI, 1.22-1.58, but not with overall mortality. CrCl and eGFR remained associated with shorter times to cART initiation criteria, but neither was associated with mortality, in weight-adjusted analyses. Conclusions In this large natural history study, reduced renal function was strongly associated with faster HIV disease progression in adult Kenyans not initially meeting cART initiation criteria. As such, renal function measurement in resource-limited settings may be an inexpensive method to identify those most in need of cART to prevent progression to AIDS. The initial association between reduced CrCl, but not reduced eGFR, and greater mortality was explained by the low weights in this population.
Shah, Seema K
Ethical guidelines recommend that experimental interventions should be tested in adults first before they are tested and approved in children. Some challenge this paradigm, however, and recommend initiating paediatric testing after preliminary safety testing in adults in certain cases. For instance, commentators have argued for accelerated testing of HIV vaccines in children. Additionally, HIV cure research on the use of very early therapy (VET) in infants, prompted in part by the Mississippi baby case, is one example of a strategy that is currently being tested in infants before it has been well tested in adults. Because infants’ immune systems are still developing, the timing of HIV transmission is easier to identify in infants than in adults, and infants who receive VET might never develop the viral reservoirs that make HIV so difficult to eradicate, infants may be uniquely situated to achieve HIV cure or sustained viral remission. Several commentators have now argued for earlier initiation of HIV cure interventions other than (or in addition to) VET in children. HIV cure research is therefore a good case for re-examining the important question of when to initiate paediatric research. I will argue that, despite the potential for HIV cure research to benefit children and the scientific value of involving children in this research, the HIV cure agenda should not accelerate the involvement of children for the following reasons: HIV cure research is highly speculative, risky, aimed at combination approaches and does not compare favourably with the available alternatives. I conclude by drawing general implications for the initiation of paediatric testing, including that interventions that have to be used in combination with others and cures for chronic diseases may not be valuable enough to justify early paediatric testing. PMID:27259546
Full Text Available To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa.Cross-sectional study nested within HIV treatment programme.Adult (≥ 18 years HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART regimen and with evidence of virological failure (one viral load >1000 copies/ml were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms.A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%; and stavudine, lamivudine and nevirapine (24%. Median duration of ART was 42 months (interquartile range (IQR 32-53 and median duration of antiretroviral failure was 27 months (IQR 17-40. One hundred and ninety one (86% had at least one drug resistance mutation. For 34 individuals (15%, the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR 5.70, 95% confidence interval (CI 2.60-12.49.There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.
Minga, Albert; Lewden, Charlotte; Dohoun, Lambert; Abo, Yao; Emieme, Arlette; Coulibaly, Ali; Salamon, Roger; Eholié, Serge; Anglaret, Xavier; Danel, Christine
Stavudine is no longer recommended for use in first-line antiretroviral therapy (ART), but it remains in high demand worldwide because it is affordable. We report the clinical presentation and incidence of severe hyperlactatemia (SL) in HIV-infected adults who initiated ART between April 2005 and May 2009 in Côte d'Ivoire, West Africa. In a prospective cohort study at the HIV care center affiliated with the National Centre for Blood Transfusion, we used standardized forms to record baseline and follow-up data. We measured serum lactate levels for all adults on ART who showed signs of hyperlactatemia. SL was defined as serum lactate >2.5 mmol/liter. Overall, 806 adults initiated ART. Among the 591 patients (73%) on stavudine-containing regimens, 394 were women (67%); the median pre-ART CD4 count was 150/mm3 and the median body mass index was 20.9 kg/m2. These patients were followed for a median of 28 months. We detected SL only among patients taking stavudine. The incidence of SL was 0.55/100 person-years (PY) (95% CI 0.47-0.63) overall and 0.85/100 PY among women (95% CI 0.75-0.95). Among the eight patients with SL, 100% lost >9% of body weight before diagnosis, 100% had serum lactate >4 mmol/liter (range 4.2-12.1), 50% had pre-ART BMI >25 kg/m2, and three patients died (38%), accounting for 6.4% of deaths among patients taking stavudine. As long as HIV clinicians continue to use stavudine in sub-Saharan Africa, they should watch out for acute unexplained weight loss in patients taking ART, particularly among women and patients with high pre-ART BMI.
Sub-optimal adherence to combination anti-retroviral therapy and its associated factors according to self-report, clinician-recorded and pharmacy-refill assessment methods among HIV-infected adults in Addis Ababa.
Mekuria, Legese A; Prins, Jan M; Yalew, Alemayehu W; Sprangers, Mirjam A G; Nieuwkerk, Pythia T
Adherence to combination antiretroviral therapy (cART) is generally high in most resource-limited settings. However, sub-optimal adherence occurs in a sizable proportion of patients, and is independently predictive of detectable viremia. We investigated sub-optimal adherence according to self-report, clinician-recorded, and pharmacy-refill assessment methods, and their associated factors among HIV-infected adults receiving cART in Addis Ababa, Ethiopia. Eight-hundred seventy patients who initiated cART between May 2009 and April 2012 were randomly selected, and 664 patients who were alive, had remained in clinical care and were receiving cART for at least six-months were included. Sub-optimal adherence was defined as patients' response of less than "all-of the time" to the self-report adherence question, or any clinician-recorded poor adherence during the six most recent clinic visits, or a pharmacy-refill of sub-optimal adherence. The average adherence level to cART, expressed as MPR, was nearly 97%. However, sub-optimal adherence occurred in 12%, 4%, and 27% of patients according to self-report, clinician-recorded, and pharmacy-refill measures, respectively. More satisfaction with social support was significantly associated with less sub-optimal adherence according to self-report and clinician-record. Younger age, lower educational level, and lower CD4 cell count at cART initiation were significantly associated with sub-optimal refill-based adherence. Findings from our large multi-center study suggest that sub-optimal adherence was present in up to a quarter of the patients, despite a high degree of average adherence to cART. Interventions aimed at preventing sub-optimal adherence should focus on improving social support, on younger patients, on patients with lower educational level, and on those who started cART at a lower CD4 cell count.
Full Text Available BACKGROUND: Generalizable data are needed on the magnitude and determinants of adherence and virological suppression among patients on antiretroviral therapy (ART in Africa. METHODS: We conducted a cross-sectional survey with chart abstraction, patient interviews and site assessments in a nationally representative sample of adults on ART for 6, 12 and 18 months at 20 sites in Rwanda. Adherence was assessed using 3- and 30-day patient recall. A systematically selected sub-sample had viral load (VL measurements. Multivariable logistic regression examined predictors of non-perfect (40 copies/ml. RESULTS: Overall, 1,417 adults were interviewed and 837 had VL measures. Ninety-four percent and 78% reported perfect adherence for the last 3 and 30 days, respectively. Eighty-three percent had undetectable VL. In adjusted models, characteristics independently associated with higher odds of non-perfect 30-day adherence were: being on ART for 18 months (vs. 6 months; younger age; reporting severe (vs. no or few side effects in the prior 30 days; having no documentation of CD4 cell count at ART initiation (vs. having a CD4 cell count of <200 cells/µL; alcohol use; and attending sites which initiated ART services in 2003-2004 and 2005 (vs. 2006-2007; sites with ≥600 (vs. <600 patients on ART; or sites with peer educators. Participation in an association for people living with HIV/AIDS; and receiving care at sites which regularly conduct home-visits were independently associated with lower odds of non-adherence. Higher odds of having a detectable VL were observed among patients at sites with peer educators. Being female; participating in an association for PLWHA; and using a reminder tool were independently associated with lower odds of having detectable VL. CONCLUSIONS: High levels of adherence and viral suppression were observed in the Rwandan national ART program, and associated with potentially modifiable factors.
Full Text Available Routine HIV viral load (VL monitoring is the standard of care for persons receiving antiretroviral therapy (ART in developed countries. Although the World Health Organization recommends annual VL monitoring of patients on ART, recognizing difficulties in conducting routine VL testing, the WHO continues to recommend targeted VL testing to confirm treatment failure for persons who meet selected immunologic and clinical criteria. Studies have measured positive predictive value (PPV, negative predictive value, sensitivity and specificity of these criteria among patients receiving first-line ART but not specifically among those on second-line or subsequent regimens. Between 2008 and 2011, adult ART patients in Nyanza, Kenya who met national clinical or immunologic criteria for treatment failure received targeted VL testing. We calculated PPV and 95% confidence intervals (CI of these criteria to detect virologic treatment failure among patients receiving a first-line ART, b second/subsequent ART, and c any regimen. Of 12,134 patient specimens tested, 2,874 (23.7% were virologically confirmed as treatment failures. The PPV for 2,834 first-line ART patients who met either the clinical or immunologic criteria for treatment failure was 34.4% (95% CI 33.2-35.7, 33.1% (95% CI 24.7-42.3 for the 40 patients on second-line/subsequent regimens, and 33.4% (95% CI 33.1-35.6 for any ART. PPV, regardless of criteria, for first-line ART patients was lowest among patients over 44 years old and highest for patients aged 15 to 34 years. PPV of immunological and clinical criteria for correctly identifying treatment failure was similarly low for adult patients receiving either first-line or second-line/subsequent ART regimens. Our data confirm the inadequacy of clinical and immunologic criteria to correctly identify treatment failure and support the implementation of routine VL testing.
Waruru, Anthony; Muttai, Hellen; Ng'ang'a, Lucy; Ackers, Marta; Kim, Andrea; Miruka, Fredrick; Erick, Opiyo; Okonji, Julie; Ayuaya, Tolbert; Schwarcz, Sandra
Routine HIV viral load (VL) monitoring is the standard of care for persons receiving antiretroviral therapy (ART) in developed countries. Although the World Health Organization recommends annual VL monitoring of patients on ART, recognizing difficulties in conducting routine VL testing, the WHO continues to recommend targeted VL testing to confirm treatment failure for persons who meet selected immunologic and clinical criteria. Studies have measured positive predictive value (PPV), negative predictive value, sensitivity and specificity of these criteria among patients receiving first-line ART but not specifically among those on second-line or subsequent regimens. Between 2008 and 2011, adult ART patients in Nyanza, Kenya who met national clinical or immunologic criteria for treatment failure received targeted VL testing. We calculated PPV and 95% confidence intervals (CI) of these criteria to detect virologic treatment failure among patients receiving a) first-line ART, b) second/subsequent ART, and c) any regimen. Of 12,134 patient specimens tested, 2,874 (23.7%) were virologically confirmed as treatment failures. The PPV for 2,834 first-line ART patients who met either the clinical or immunologic criteria for treatment failure was 34.4% (95% CI 33.2-35.7), 33.1% (95% CI 24.7-42.3) for the 40 patients on second-line/subsequent regimens, and 33.4% (95% CI 33.1-35.6) for any ART. PPV, regardless of criteria, for first-line ART patients was lowest among patients over 44 years old and highest for patients aged 15 to 34 years. PPV of immunological and clinical criteria for correctly identifying treatment failure was similarly low for adult patients receiving either first-line or second-line/subsequent ART regimens. Our data confirm the inadequacy of clinical and immunologic criteria to correctly identify treatment failure and support the implementation of routine VL testing.
Chang, Charlotte A.; Meloni, Seema Thakore; Eisen, Geoffrey; Chaplin, Beth; Akande, Patrick; Okonkwo, Prosper; Rawizza, Holly E.; Tchetgen Tchetgen, Eric; Kanki, Phyllis J.
Background. Despite the benefits of antiretroviral therapy (ART), tuberculosis (TB) is the leading cause of mortality among human immunodeficiency virus (HIV)-infected persons in Africa. Nigeria bears the highest TB burden in Africa and second highest HIV burden globally. This long-term multicenter study aimed to determine the incidence rate and predictors of TB in adults in the Harvard/AIDS Prevention Initiative in Nigeria (APIN) and President's Emergency Plan for AIDS Relief (PEPFAR) Nigeria ART program. Methods. This retrospective evaluation used data collected from 2004 to 2012 through the Harvard/APIN PEPFAR program. Risk factors for incident TB were determined using multivariate Cox proportional hazards regression with time-dependent covariates. Results. Of 50 320 adults enrolled from 2005 to 2010, 11 092 (22%) had laboratory-confirmed active TB disease at ART initiation, and 2021 (4%) developed active TB after commencing ART. During 78 228 total person-years (PY) of follow-up, the TB incidence rate was 25.8 cases per 1000 PY (95% confidence interval [CI], 24.7–27.0) overall, and it decreased significantly both with duration on ART and calendar year. Risk factors at ART initiation for incident TB included the following: earlier ART enrollment year, tenofovir-containing initial ART regimen, and World Health Organization clinical stage above 1. Time-updated risk factors included the following: low body mass index, low CD4+ cell count, unsuppressed viral load, anemia, and ART adherence below 80%. Conclusions. The rate of incident TB decreased with longer duration on ART and over the program years. The strongest TB risk factors were time-updated clinical markers, reinforcing the importance of consistent clinical and laboratory monitoring of ART patients in prompt diagnosis and treatment of TB and other coinfections. PMID:26613097
Olsen, Mette Frahm; Tesfaye, Markos; Kæstel, Pernille;
Ready-to-use supplementary foods (RUSF) are used increasingly in human immunodeficiency virus (HIV) programs, but little is known about how it is used and viewed by patients. We used qualitative methods to explore the use, perceptions, and acceptability of RUSF among adult HIV patients in Jimma, ...
Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or both in INITIO: open-label randomised trial
Yeni, P; Cooper, DA; Aboulker, J-P;
BACKGROUND: Antiretroviral therapy has greatly reduced HIV mortality and morbidity. However, the best sequence of regimens and implications of initial regimen for long-term therapeutic success are not well defined. METHODS: In INITIO, a large international randomised trial, we compared antiretrov...
Christine M Kelly
Full Text Available Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND among patients on combination antiretroviral therapy (cART in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART.HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery.One hundred and six HIV positive patients, with median (range age 39 (18-71 years, 73% female and median (range CD4 count 323.5 (68-1039 cells/µl were studied. Symptomatic neurocognitive impairment was present in 15% (12% mild neurocognitive disorder [MND], 3% HIV associated dementia [HAD]. A further 55% fulfilled Frascati criteria for asymptomatic neurocognitive impairment (ANI; however factors other than neurocognitive impairment could have confounded this estimate. Neither the symptomatic (MND and HAD nor asymptomatic (ANI forms of HAND were associated with subtherapeutic nevirapine/efavirenz concentrations, adjusted odds ratio 1.44 (CI. 0.234, 8.798; p = 0.696 and aOR 0.577 (CI. 0.09, 3.605; p = 0.556 respectively. All patients with subtherapeutic nevirapine/efavirenz levels had a GDS of less than 0.6, consistent with normal neurocognition.Fifteen percent of adult Malawians on cART had a diagnosis of MND or HAD. Subtherapeutic drug concentrations were found exclusively in patients with normal neurocognitive function suggesting HAND did not affect cART adherence. Further study of HAND requires more robust locally derived normative neurocognitive values and
Julie A Denison
Full Text Available Introduction: Worldwide, HIV-related mortality among adolescents living with HIV (ALHIV increased by 50% from 2005 to 2012 and is attributed in part to a lack of support for adolescent retention to care and adherence to antiretroviral therapy (ART. This vulnerability reinforces the need to better understand incomplete ART adherence among ALHIV, particularly in sub-Saharan Africa, where the majority of the world's 2.1 million ALHIV reside. Methods: From December 2011 to February 2012, we conducted in-depth interviews with 32 ALHIV (aged 15 to 18 and 23 of their adult caregivers in the Copperbelt Province of Zambia. Interviews were transcribed and translated. An iterative qualitative process was used to code and analyze the data and main themes were summarized regarding the barriers to and facilitators of ART adherence. Results: More than a quarter of ALHIV reported missing a day or more of ART (ranging from one day to six months. Barriers to ART adherence included fear of disclosure and anticipated stigma. Few youth were willing to take their drugs outside of the home, which led to missed doses of ART. Similarly, families tended to manage HIV within the home only. As a result, although caregivers and families were often the greatest source of emotional and instrumental support, they coped with HIV in isolation of other potential support from their communities, schools or churches. Factors that supported ART adherence included attending clinic-sponsored youth groups, wanting to maintain one's health and using phone and clock alarms. Involvement of adult caregivers in HIV management varied greatly and was often based on the age and health status of the youth. Some caregivers struggled with letting the adolescents assume responsibility for their medication, and ALHIV had few self-management skills and tools to help them regularly take ART. Conclusions: These data highlight the importance of families and home environments in supporting adherence to
Sempa, Joseph B.; Ujeneza, Eva L.; Nieuwoudt, Martin
Introduction In Sub-Saharan African (SSA) resource limited settings, Cluster of Differentiation 4 (CD4) counts continue to be used for clinical decision making in antiretroviral therapy (ART). Here, HIV-infected people often remain with CD4 counts <350 cells/μL even after 5 years of viral load suppression. Ongoing immunological monitoring is necessary. Due to varying statistical modeling methods comparing immune response to ART across different cohorts is difficult. We systematically review such models and detail the similarities, differences and problems. Methods ‘Preferred Reporting Items for Systematic Review and Meta-Analyses’ guidelines were used. Only studies of immune-response after ART initiation from SSA in adults were included. Data was extracted from each study and tabulated. Outcomes were categorized into 3 groups: ‘slope’, ‘survival’, and ‘asymptote’ models. Wordclouds were drawn wherein the frequency of variables occurring in the reviewed models is indicated by their size and color. Results 69 covariates were identified in the final models of 35 studies. Effect sizes of covariates were not directly quantitatively comparable in view of the combination of differing variables and scale transformation methods across models. Wordclouds enabled the identification of qualitative and semi-quantitative covariate sets for each outcome category. Comparison across categories identified sex, baseline age, baseline log viral load, baseline CD4, ART initiation regimen and ART duration as a minimal consensus set. Conclusion Most models were different with respect to covariates included, variable transformations and scales, model assumptions, modelling strategies and reporting methods, even for the same outcomes. To enable comparison across cohorts, statistical models would benefit from the application of more uniform modelling techniques. Historic efforts have produced results that are anecdotal to individual cohorts only. This study was able to
Full Text Available This study explores factors associated with virological detectability, and viral re-suppression after enhanced adherence counselling, in adults and children on antiretroviral therapy (ART in Swaziland.This descriptive study used laboratory data from 7/5/2012 to 30/9/2013, which were linked with the national ART database to provide information on time on ART and CD4 count; information on enhanced adherence counselling was obtained from file review in health facilities. Multivariable logistic regression was used to explore the relationship between viral load, gender, age, time on ART, CD4 count and receiving (or not receiving enhanced adherence counselling.From 12,063 patients undergoing routine viral load monitoring, 1941 (16% had detectable viral loads. Children were more likely to have detectable viral loads (AOR 2.6, 95%CI 1.5-4.5, as were adolescents (AOR 3.2, 95%CI 2.2-4.8, patients with last CD4 1000 copies/ml (AOR 0.3, 95%CI 0.1-0.7, and those with last CD4<350 cells/µl (AOR 0.4, 95%CI 0.2-0.7. Receiving (or not receiving enhanced adherence counselling was not associated with likelihood of re-suppression.Children, adolescents and those with advanced disease were most likely to have high viral loads and least likely to achieve viral suppression at retesting; receiving adherence counselling was not associated with higher likelihood of viral suppression. Although the level of viral resistance was not quantified, this study suggests the need for ART treatment support that addresses the adherence problems of younger people; and to define the elements of optimal enhanced adherence support for patients of all ages with detectable viral loads.
Fokam, Joseph; Takou, Désiré; Santoro, Maria Mercedes; Akonie, Haniel Ze; Kouanfack, Charles; Ceccherini-Silberstein, Francesca; Colizzi, Vittorio; Perno, Carlo-Federico; Ndjolo, Alexis
With ongoing earlier enrollment on and rapid scale-up of antiretroviral therapy (ART) in Cameroon, there are increasing risks of transmitted HIV drug resistance (HIVDR) at population levels. We, therefore, evaluated the threshold of HIVDR in a population initiating ART, to inform on the effectiveness of first-line regimens, considering HIV-1 diversity, plasma viral load (PVL), and CD4-based disease progression. A total of 53 adults [median (interquartile range, IQR) CD4: 162 cell/mm(3) (48-284); median (IQR) PVL: 5.34 log10 RNA (4.17-6.42) copies/ml] initiating ART in 2014 at the Yaoundé Central Hospital were enrolled for HIV-1 protease-reverse transcriptase sequencing. Drug resistance mutations (DRMs) were interpreted using the 2009 World Health Organization (WHO) list versus the Stanford HIVdb algorithm version 7.0. Level of DRMs was low (3.77%) versus moderate (7.55%), respectively, following the WHO list (T69D, K103N) versus Stanford HIVdb (T69D, A98G, K103N, K238T), respectively. Prevailing clade was CRF02_AG (71.70%). Based on Stanford HIVdb, a slightly higher proportion of patients with DRMs were found among ones infected with CRF02_AG than in those non-CRF02_AG infected (7.89% vs. 6.67%, p = 1.000), with lower PVL (7.69% population levels, despite scale-up of ART in the country, pending adherence, and closed virological monitoring. With an intent-to-diagnose approach, the discrepant levels of DRMs support using Stanford HIVdb to evaluate initial ART, while revising the WHO list for surveillance.
Woldesellassie M Bezabhe
Full Text Available BACKGROUND: Antiretroviral therapy (ART has been life saving for hundreds of thousands of Ethiopians. With increased availability of ART in recent years, achievement of optimal adherence and patient retention are becoming the greatest challenges in the management of HIV/AIDS in Ethiopia. However, few studies have explored factors influencing medication adherence to ART and retention in follow-up care among adult Ethiopian HIV-positive patients, especially in the Amhara region of the country, where almost one-third of the country's ART is prescribed. The aim of this qualitative study was to collect such data from patients and healthcare providers in the Amhara region of Ethiopia. METHODS: Semi-structured interviews were conducted with 24 patients, of whom 11 had been lost to follow-up and were non-persistent with ART. In addition, focus group discussions were performed with 15 ART nurses and 19 case managers. All interviews and focus groups were audio-recorded, transcribed, and coded for themes and patterns in Amharic using a grounded theory approach. The emergent concepts and categories were translated into English. RESULTS: Economic constraints, perceived stigma and discrimination, fasting, holy water, medication side effects, and dissatisfaction with healthcare services were major reasons for patients being non-adherent and lost to follow-up. Disclosure of HIV status, social support, use of reminder aids, responsibility for raising children, improved health on ART, and receiving education and counseling emerged as facilitators of adherence to ART. CONCLUSIONS: Improving adherence and retention requires integration of enhanced treatment access with improved job and food security. Healthcare providers need to be supported to better equip patients to cope with the issues associated with ART. Development of social policies and cooperation between various agencies are required to facilitate optimal adherence to ART, patient retention, and improved
Ekouevi, Didier K; Coffie, Patrick A.; Eugene Messou; Adrien Sawadogo; Eholie, Serge P.; Djimon Marcel Zannou; Carin Ahouada; Jocelyn Akakpo; Christelle Ahomadegbé; Jules Bashi; Alice Gougounon-Houéto; Angèle Azon-Kouanou; Fabien Houngbé; Sikiratou Koumakpaï; Florence Alihonou
Background HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). Methods We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART)...
Full Text Available Despite effective antiretroviral treatment (ART, HIV-positive individuals are at increased risk of serious non-AIDS conditions (cardiovascular, liver and renal disease, and cancers, perhaps due in part to ongoing inflammation and/or coagulation. To estimate the potential risk reduction in serious non-AIDS conditions or death from any cause that might be achieved with treatments that reduce inflammation and/or coagulation, we examined associations of interleukin-6 (IL-6, D-dimer, and high-sensitivity C-reactive protein (hsCRP levels with serious non-AIDS conditions or death in 3 large cohorts.In HIV-positive adults on suppressive ART, associations of IL-6, D-dimer, and hsCRP levels at study entry with serious non-AIDS conditions or death were studied using Cox regression. Hazard ratios (HR adjusted for age, gender, study, and regression dilution bias (due to within-person biomarker variability were used to predict risk reductions in serious non-AIDS conditions or death associated with lower "usual" levels of IL-6 and D-dimer.Over 4.9 years of mean follow-up, 260 of the 3766 participants experienced serious non-AIDS conditions or death. IL-6, D-dimer and hsCRP were each individually associated with risk of serious non-AIDS conditions or death, HR = 1.45 (95% CI: 1.30 to 1.63, 1.28 (95% CI: 1.14 to 1.44, and 1.17 (95% CI: 1.09 to 1.26 per 2x higher biomarker levels, respectively. In joint models, IL-6 and D-dimer were independently associated with serious non-AIDS conditions or death, with consistent results across the 3 cohorts and across serious non-AIDS event types. The association of IL-6 and D-dimer with serious non-AIDS conditions or death was graded and persisted throughout follow-up. For 25% lower "usual" IL-6 and D-dimer levels, the joint biomarker model estimates a 37% reduction (95% CI: 28 to 46% in the risk of serious non-AIDS conditions or death if the relationship is causal.Both IL-6 and D-dimer are independently associated with
Hosseinipour, Mina C.; Bisson, Gregory P.; Miyahara, Sachiko; Sun, Xin; Moses, Agnes; Riviere, Cynthia; Kirui, F.K.; Badal-Faesen, Sharla; Lagat, David; Nyirenda, Mulinda; Naidoo, K; Hakim, James; Mugyenyi, Peter; Henostroza, German; Leger, P.D; Lama, Javier.R; Mohapi, Lerato; Alave, Jorge; Mave, V; Veloso, Valdilea.G; Pillay, Sandy; Kumarasamy, N.; Bao, Jing; Hogg, Evelyn; Jones, Lynne; Zolopa, Andrew; Kumwenda, Johnstone; Gupta, Amita
Summary Background Mortality within the first 6 months after initiating antiretroviral therapy (ART) is common in resource-limited settings and is often due to tuberculosis (TB) among patients with advanced HIV disease. Isoniazid preventive therapy (IPT) is recommended in HIV-infected adults, but sub-clinical TB can be difficult to diagnose. We hypothesized that empiric TB treatment would reduce early mortality compared to IPT in high-burden settings. Methods We conducted a multi-country randomized clinical trial comparing empiric TB therapy (Empiric) vs. isoniazid preventive therapy (IPT) in HIV-infected outpatients initiating ART with CD4 counts <50 cells/mm3. Individuals were screened for TB using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available. The primary endpoint was survival (death or unknown status) at 24 weeks post randomization. Kaplan Meier estimates of the endpoint rates across arms were compared by the z-test. Registered at ClinicalTrials.gov (NCT01380080). Findings From October 31, 2011 until June 9, 2014, we randomized 850 participants (424 in Empiric arm and 426 in IPT arm); the median CD4 count at baseline was 18 cells/mm3 (IQR: 9, 32). At week 24, each arm had 22 primary endpoints, for rates of 5.2% in each arm (95% CI: 3.5% to 7.8% for Empiric and 3.4% to 7.8% for IPT; absolute risk difference of -0.06% (95% CI: −3.05% to 2.94%). Grade 3 or 4 signs or symptoms occurred in 50 (12%) in the Empiric arm and 46 (11%) in the IPT arm. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) in the Empiric arm and 97 (23%) in the IPT arm. Incident TB was more common in the Empiric arm (31 vs. 18 events, p=0.01). Interpretation Empiric TB therapy did not reduce mortality at 24 weeks in outpatient adults initiating ART with advanced HIV disease. The low mortality rate of the trial supports implementation of systematic TB screening and IPT in outpatients with advanced HIV disease. PMID:27025337
Nachega, Jean B; Rosenkranz, Bernd; Pham, Paul A
The recent development of once-daily antiretroviral agents and fixed-dose combination formulations has been an important development in antiretroviral regimen simplification. Recent studies indicate that once-daily antiretroviral regimens improve adherence, especially in antiretroviral-naïve patients and in difficult-to-treat populations, such as the homeless or marginally housed. However, there are potential risks with the higher peak and lower trough plasma drug concentrations that may result from certain once-daily formulations. Due to the multifactorial and complex nature of adherence behavior, clinicians’ efforts to improve patient adherence should not be limited to prescribing once-daily regimens, but should also consider social support, side effect management, and adherence support tools, such as pillbox organizers and other targeted interventions. Additional research will clarify the benefits of once-daily and fixed-dose combination regimens on clinical and virologic outcomes. Comprehensive cost-benefit analysis of regimen simplification could help facilitate evidence-based decisions regarding antiretroviral regimen choices. PMID:22259241
Bastiaans, Diane E T; Cressey, Tim R; Vromans, Herman; Burger, David M
INTRODUCTION: A multitude of antiretroviral drug formulations are now available for HIV-infected adults and children. These formulations include individual and co-formulated drugs, many of which are also supplied in generic versions. Many antiretroviral drugs have a low aqueous solubility and poor b
Full Text Available Jean B Nachega1–3, Bernd Rosenkranz4, Paul A Pham51Department of International Health, 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 3Department of Medicine and Centre for Infectious Diseases, 4Division of Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Stellenbosch, Capetown, South Africa; 5Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USAAbstract: The recent development of once-daily antiretroviral agents and fixed-dose combination formulations has been an important development in antiretroviral regimen simplification. Recent studies indicate that once-daily antiretroviral regimens improve adherence, especially in antiretroviral-naïve patients and in difficult-to-treat populations, such as the homeless or marginally housed. However, there are potential risks with the higher peak and lower trough plasma drug concentrations that may result from certain once-daily formulations. Due to the multifactorial and complex nature of adherence behavior, clinicians’ efforts to improve patient adherence should not be limited to prescribing once-daily regimens, but should also consider social support, side effect management, and adherence support tools, such as pillbox organizers and other targeted interventions. Additional research will clarify the benefits of once-daily and fixed-dose combination regimens on clinical and virologic outcomes. Comprehensive cost-benefit analysis of regimen simplification could help facilitate evidence-based decisions regarding antiretroviral regimen choices.Keywords: regimen adherence, regimen simplification, health care costs, fixed-dose combination, once-daily antiretroviral drugs
Full Text Available BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART. It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. METHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger, we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI of: 0.35 (0.30-0.40 for counts <200 cells/µl, 0.81 (0.71-0.92 for counts 200 to <350 cells/µl, 0.74 (0.66-0.83 for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99 for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. CONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.
Ekouevi, Didier K; Coffie, Patrick A; Messou, Eugene
HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework...
Grund, Birgit; Baker, Jason V; Deeks, Steven G;
BACKGROUND: Despite effective antiretroviral treatment (ART), HIV-positive individuals are at increased risk of serious non-AIDS conditions (cardiovascular, liver and renal disease, and cancers), perhaps due in part to ongoing inflammation and/or coagulation. To estimate the potential risk reduct...
Dragsted, Ulrik Bak; Mocroft, Amanda; Vella, Stefano;
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...
Petersen, Tonny; Andersen, Stig E; Gerstoft, Jan;
To determine the adherence to the national guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients.......To determine the adherence to the national guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients....
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 individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... 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...
Spivak, Adam M.; Andrade, Adriana; Eisele, Evelyn; Hoh, Rebecca; Bacchetti, Peter; Bumpus, Namandjé N.; Emad, Fatemeh; Buckheit, Robert; McCance-Katz, Elinore F.; Lai, Jun; Kennedy, Margene; Chander, Geetanjali; Siliciano, Robert F.; Siliciano, Janet D.; Deeks, Steven G.
Background. Transcriptionally silent human immunodeficiency virus type 1 (HIV-1) DNA persists in resting memory CD4+ T cells despite antiretroviral therapy. In a primary cell model, the antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4+ T cells at concentrations achieved in vivo. Methods. We conducted a single-arm pilot study to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1–infected individuals on stable suppressive antiretroviral therapy would result in reversal of HIV-1 latency with a concomitant transient increase in residual viremia or depletion of the latent reservoir in resting memory CD4+ T cells. Results. Disulfiram was safe and well tolerated. There was a high level of subject-to-subject variability in plasma disulfiram levels. The latent reservoir did not change significantly (1.16-fold change; 95% confidence interval [CI], .70- to 1.92-fold; P = .56). During disulfiram administration, residual viremia did not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69-fold; P = .13), although residual viremia was estimated to increase by 1.88-fold compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P = .04). In a post hoc analysis, a rapid and transient increase in viremia was noted in a subset of individuals (n = 6) with immediate postdose sampling (HIV-1 RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). Conclusions. Administration of disulfiram to patients on antiretroviral therapy does not reduce the size of the latent reservoir. A possible dose-related effect on residual viremia supports future studies assessing the impact of higher doses on HIV-1 production. Disulfiram affects relevant signaling pathways and can be safely administered, supporting future studies of this drug. PMID:24336828
Auer, Sonya K
Low food availability during early growth and development can have long-term negative consequences for reproductive success. Phenotypic plasticity in adult life-history decisions may help to mitigate these potential costs, yet adult life-history responses to juvenile food conditions remain largely unexplored. I used a food-manipulation experiment with female Trinidadian guppies (Poecilia reticulata) to examine age-related changes in adult life-history responses to early food conditions, whether these responses varied across different adult food conditions, and how these responses affected overall reproductive success. Guppy females reared on low food as juveniles matured at a later age, at a smaller size, and with less energy reserves than females reared on high food as juveniles. In response to this setback, they changed their investment in growth, reproduction, and fat storage throughout the adult stage such that they were able to catch up in body size, increase their reproductive output, and restore their energy reserves to levels comparable to those of females reared on high food as juveniles. The net effect was that adult female guppies did not merely mitigate but surprisingly were able to fully compensate for the potential long-term negative effects of poor juvenile food conditions on reproductive success.
Full Text Available BACKGROUND: Smear-positive pulmonary TB is the most infectious form of TB. Previous studies on the effect of HIV and antiretroviral therapy on TB treatment outcomes among these highly infectious patients demonstrated conflicting results, reducing understanding of important issues. METHODS: All adult smear-positive pulmonary TB patients diagnosed between 2008 and 2010 in Malawi's largest public, integrated TB/HIV clinic were included in the study to assess treatment outcomes by HIV and antiretroviral therapy status using logistic regression. RESULTS: Of 2,361 new smear-positive pulmonary TB patients, 86% had successful treatment outcome (were cured or completed treatment, 5% died, 6% were lost to follow-up, 1% failed treatment, and 2% transferred-out. Overall HIV prevalence was 56%. After adjusting for gender, age and TB registration year, treatment success was higher among HIV-negative than HIV-positive patients (adjusted odds ratio 1.49; 95% CI: 1.14-1.94. Of 1,275 HIV-infected pulmonary TB patients, 492 (38% received antiretroviral therapy during the study. Pulmonary TB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on ART (adjusted odds ratio : 1.83; 95% CI: 1.29-2.60. CONCLUSION: HIV co-infection was associated with poor TB treatment outcomes. Despite high HIV prevalence and the integrated TB/HIV setting, only a minority of patients started antiretroviral therapy. Intensified patient education and provider training on the benefits of antiretroviral therapy could increase antiretroviral therapy uptake and improve TB treatment success among these most infectious patients.
Mocroft, Amanda; Neuhaus, Jacqueline; Peters, Lars
Chronic kidney disease (CKD) is an important cause of morbidity and mortality in HIV-positive individuals. Hepatitis C (HCV) co-infection has been associated with increased risk of CKD, but prior studies lack information on potential mechanisms. We evaluated the association between HCV or hepatitis...... B (HBV) co-infection and progressive CKD among 3,441 antiretroviral-treated clinical trial participants. Progressive CKD was defined as the composite of end-stage renal disease, renal death, or significant glomerular filtration rate (eGFR) decline (25% decline to eGFR 800,000 IU/ml had increased...... odds (OR 3.07; 95% CI 1.60-5.90). Interleukin-6, hyaluronic acid, and the FIB-4 hepatic fibrosis index were higher among participants who developed progressive CKD, but were no longer associated with progressive CKD after adjustment. Future studies should validate the relationship between HCV viremia...
Dragsted, Ulrik Bak; Mocroft, Amanda; Vella, Stefano;
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...... diminishes with a longer time receiving treatment and is associated with pretreatment CD4(+) cell count, ongoing viral replication, and intravenous drug use......., observational human immunodeficiency virus (HIV) type 1 cohort. RESULTS: Of 2347 patients with an increase in CD4(+) cell count >or=100 cells/microL within 6-12 months of the initiation of HAART, 550 (23%) subsequently experienced immunological failure (CD4(+) count less than or equal to the pre-HAART value......], 2.05; 95% CI, 1.83-2.31; PHIV-1 risk behavior (P=.047 for a global comparison of risk groups). CONCLUSION: The risk of immunological failure in patients with an immunological response to HAART...
Jacobson, Jeffrey M; Kuritzkes, Daniel R; Godofsky, Eliot; DeJesus, Edwin; Larson, Jeffrey A; Weinheimer, Steven P; Lewis, Stanley T
Ibalizumab (formerly TNX-355) is a humanized monoclonal antibody that binds CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1), and inhibits the viral entry process. A phase lb multidose study of the safety, pharmacokinetics, and antiviral activity of ibalizumab was conducted with 22 HIV-1-infected patients. Nineteen patients were randomized to receive either 10 mg/kg of body weight weekly (arm A) or a 10-mg/kg loading dose followed by 6 mg/kg every 2 weeks (arm B) intravenously for 9 weeks. Three patients were assigned to receive 25 mg/kg every 2 weeks for five doses (arm C). During the study, the patients remained off other antiretrovirals or continued a stable failing regimen. Treatment with ibalizumab resulted in substantial reductions in HIV-1 RNA levels (0.5 to 1.7 log(10)) in 20 of 22 subjects. In most patients, HIV-1 RNA fell to nadir levels after 1 to 2 weeks of treatment and then returned to baseline despite continued treatment. Baseline viral isolates were susceptible to ibalizumab in vitro, regardless of coreceptor tropism. Emerging resistance to ibalizumab was manifested by reduced maximal percent inhibition in a single-cycle HIV infectivity assay. Resistant isolates remained CD4 dependent and were susceptible to enfuvirtide in vitro. Complete coating of CD4(+) T-cell receptors was correlated with serum ibalizumab concentrations. There was no evidence of CD4(+) T-cell depletion in ibalizumab-treated patients. Ibalizumab was not immunogenic, and no serious drug-related adverse effects occurred. In conclusion, ibalizumab administered either weekly or biweekly was safe and well tolerated and demonstrated antiviral activity. Further studies with ibalizumab in combination with standard antiretroviral treatments are warranted.
Nosik, D N; Lialina, I K; Kalnina, L B; Lobach, O A; Chataeva, M S; Rasnetsov, L D
The antiretroviral properties of Fullevir (sodium salt of fullerenepolyhydropolyaminocaproic acid) manufactured by IntelFarm Co.) were studied in the human cell culture infected with human immunodeficiency virus (HIV). The agent was ascertained to be able to protect the cell from the cytopathic action of HIV. The 90% effective concentration (EF90) was 5 microg/ml. The 50% average toxic concentration was 400 microg/ml. Testing of different (preventive and therapeutic) Fullevir dosage regimens has shown that the drug is effective when used both an hour before and an hour after infection and when administered simultaneously with cell infection. The longer contact time for the agent with the cells increased the degree of antiviral defense. Co-administration of Fullevir and the HIV reverse transcriptase inhibitor Retrovir (azidothymidine) showed a synergistic antiretroviral effect. Thus, Fullevir may be regarded as a new promising antiretroviral drug for the treatment of HIV infection.
Kristina M Bonaparte
Full Text Available Developmental stress, and individual variation in response to it, can have important fitness consequences. Here we investigated the consequences of variable dietary protein on the duration of growth and associative learning abilities of zebra finches, Taeniopygia guttata, which are obligate graminivores. The high-protein conditions that zebra finches would experience in nature when half-ripe seed is available were mimicked by the use of egg protein to supplement mature seed, which is low in protein content. Growth rates and relative body proportions of males reared either on a low-protein diet (mature seed only or a high-protein diet (seed plus egg were determined from body size traits (mass, head width, and tarsus measured at three developmental stages. Birds reared on the high-protein diet were larger in all size traits at all ages, but growth rates of size traits showed no treatment effects. Relative head size of birds reared on the two diets differed from age day 95 onward, with high-diet birds having larger heads in proportion to both tarsus length and body mass. High-diet birds mastered an associative learning task in fewer bouts than those reared on the low-protein diet. In both diet treatments, amount of sub-adult head growth varied directly, and sub-adult mass change varied inversely, with performance on the learning task. Results indicate that small differences in head growth during the sub-adult period can be associated with substantial differences in adult cognitive performance. Contrary to a previous report, we found no evidence for growth compensation among birds on the low-protein diet. These results have implications for the study of vertebrate cognition, developmental stress, and growth compensation.
HIV Treatment What to Start: Choosing an HIV Regimen (Last updated 2/24/2016; last reviewed 2/24/ ... of HIV medicines used to treat HIV infection. HIV treatment (also called antiretroviral therapy or ART) begins with ...
Full Text Available Chronic kidney disease (CKD is an important cause of morbidity and mortality in HIV-positive individuals. Hepatitis C (HCV co-infection has been associated with increased risk of CKD, but prior studies lack information on potential mechanisms. We evaluated the association between HCV or hepatitis B (HBV co-infection and progressive CKD among 3,441 antiretroviral-treated clinical trial participants. Progressive CKD was defined as the composite of end-stage renal disease, renal death, or significant glomerular filtration rate (eGFR decline (25% decline to eGFR 800,000 IU/ml had increased odds (OR 3.07; 95% CI 1.60-5.90. Interleukin-6, hyaluronic acid, and the FIB-4 hepatic fibrosis index were higher among participants who developed progressive CKD, but were no longer associated with progressive CKD after adjustment. Future studies should validate the relationship between HCV viremia and CKD.ClinicalTrials.gov NCT00027352; NCT00004978.
Przybyla, Sarahmona M; Eliseo-Arras, Rebecca K; Krawiec, Gabriela; Gower, Emily; Dermen, Kurt
While substance use is one of the most consistent predictors of poor adherence to antiretroviral therapy (ART), few studies among people living with HIV (PLH) have utilized mobile phone-based assessment of these health behaviors. PLH were recruited from primary care clinics to report ART and substance use using a smartphone application (app) for 14 consecutive days. The app's feasibility as a data collection tool was evaluated quantitatively via surveys and qualitatively via in-depth interviews to assess daily report completion, compliance, and study satisfaction. Overall, 26 participants (M = 49.5 years, 76% male) completed 95.3% of time-based daily reports. Participants reported high satisfaction with the app and expressed future interest in using smartphones to report daily behaviors. High completion rates and participant acceptability suggest that smartphones are a feasible, acceptable method for collecting substance use and ART data among PLH. Potential areas of concern such as sufficient training and assistance for those with limited smartphone experience should be considered for future app-based research studies among PLH.
Sarahmona M. Przybyla
Full Text Available While substance use is one of the most consistent predictors of poor adherence to antiretroviral therapy (ART, few studies among people living with HIV (PLH have utilized mobile phone-based assessment of these health behaviors. PLH were recruited from primary care clinics to report ART and substance use using a smartphone application (app for 14 consecutive days. The app’s feasibility as a data collection tool was evaluated quantitatively via surveys and qualitatively via in-depth interviews to assess daily report completion, compliance, and study satisfaction. Overall, 26 participants (M=49.5 years, 76% male completed 95.3% of time-based daily reports. Participants reported high satisfaction with the app and expressed future interest in using smartphones to report daily behaviors. High completion rates and participant acceptability suggest that smartphones are a feasible, acceptable method for collecting substance use and ART data among PLH. Potential areas of concern such as sufficient training and assistance for those with limited smartphone experience should be considered for future app-based research studies among PLH.
In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise 3 drugs, namely, 2 nucleoside reverse transcriptase inhibitors (NRTI), and 1 drug from another family. Four of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further 6 regimens, which are based on an INSTI, a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with cobicistat or ritonavir (PI/COBI, PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include 3 (or at least 2) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.
Nelson, Larry J; Padilla-Walker, Laura M; Carroll, Jason S; Madsen, Stephanie D; Barry, Carolyn McNamara; Badger, Sarah
The purpose of this study was (a) to identify the criteria parents of emerging adults consider necessary and important for their children to achieve adulthood, (b) to compare parents' criteria for adulthood with the criteria espoused by emerging adults, and (c) to examine how these criteria might differ on the basis of gender of the parent and gender of the child. Participants included 392 unmarried college students, ages 18-25, and at least 1 of their parents (271 fathers, 319 mothers). Results revealed that (a) as did their children, most parents did not yet view their children as adults, (b) there was disagreement between children and their parents in the emphasis they placed on various criteria for adulthood, (c) mothers and fathers did not always agree on the importance of various criteria, and (d) the gender of both the parent and the child played a role in the criteria parents deemed important for adulthood. Taken together, the findings suggest that parents and children view the transition to adulthood differently, which might have implications for the parent-child relationship during this period of development.
Fairall Lara R
Full Text Available Abstract Background Health Related Quality of Life (HRQoL is an important outcome in times of Highly Active Antiretroviral Treatment (HAART. We compared the HRQoL of HIV positive patients receiving HAART with those awaiting treatment in public sector facilities in the Free State province in South Africa. Methods A stratified random sample of 371 patients receiving or awaiting HAART were interviewed and the EuroQol-profile, EuroQol-index and Visual Analogue Scale (VAS were compared. Independent associations between these outcomes and HAART, socio-demographic, clinical and health service variables were estimated using linear and ordinal logistic regression, adjusted for intra-clinic clustering of outcomes. Results Patients receiving HAART reported better HRQoL for 3 of the 5 EuroQol-dimensions, for the VAS score and for the EuroQol index in bivariable analysis. They had a higher mean EuroQol index (0.11 difference, 95% confidence interval [CI] 0.04; 0.23, and were more likely to have a higher index (odds ratio 1.9, 95% CI 1.1; 1.3, compared to those awaiting HAART, in multivariate analysis. Higher mean VAS scores were reported for patients who were receiving HAART (6.5 difference, 95% CI 1.3; 11.7, were employed (9.1, 95% CI 4.3; 13.7 or were female (4.7, 95% CI 0.79; 8.5. Conclusion HAART was associated with improved HRQoL in patients enrolled in a public sector treatment program in South Africa. Our finding that the EuroQol instrument was sensitive to HAART supports its use in future evaluation of HIV/AIDS care in South Africa. Longitudinal studies are needed to evaluate changes in individuals' HRQoL.
The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial
Andrea A. Howard
Full Text Available Background: Initiating antiretroviral therapy (ART early during tuberculosis (TB treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. Objective: The Start TB Patients on ART and Retain on Treatment (START Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Design: Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center. The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6–9 months. Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete
The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial
Howard, Andrea A.; Hirsch-Moverman, Yael; Frederix, Koen; Daftary, Amrita; Saito, Suzue; Gross, Tal; Wu, Yingfeng; Maama, Llang Bridget
Background Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. Objective The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Design Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6–9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. Discussion The START
Adler, M W
The most recent UNAIDS figures indicate that approximately 30 million people are infected with HIV worldwide, 5.8 million of whom were newly infected during 1997. At the 10th International Conference on AIDS and Sexually Transmitted Diseases in Africa, the President and Secretary of Health of France called upon developed countries to establish a Therapeutic Assistance Fund to make antiretrovirals available to people with HIV/AIDS in sub-Saharan Africa. While the annual per capita health budget in most African countries is less than US$10, triple antiretroviral therapy against AIDS in the developed world costs $12,000-14,000 per patient per year. Calculations based upon a lower per patient cost of $7000, and treating all 1.4 million African AIDS cases, would cost US$10 billion per year for drugs alone, more than 30 times the amount currently spent annually by international donors for AIDS programs in the entire developing world. Basic infrastructural requirements would have to be met were antiretrovirals made widely available, ranging from HIV screening and counseling to the provision of clean water with which to consume the required 20-30 tablets per day. High program costs will challenge long-term sustainability. Universal access to care and treatment for HIV infection and AIDS is not a reality in the developed world, let alone feasible in developing countries. Given the competing health care priorities in developing countries, the high costs of antiretroviral agents, poor infrastructure, and inability to sustain such a program, the French initiative is ill-advised and foolish public health practice.
Full Text Available BACKGROUND: We systematically reviewed observational studies of early mortality post-antiretroviral therapy (ART initiation in low- and middle-income countries (LMIC in Asia, Africa, and Central and South America, as defined by the World Bank, to summarize what is known. METHODS AND FINDINGS: Studies published in English between January 1996 and December 2010 were searched in Medline and EMBASE. Three independent reviewers examined studies of mortality within one year post-ART. An article was included if the study was conducted in a LMIC, participants were initiating ART in a non-clinical trial setting and were ≥15 years. Fifty studies were included; 38 (76% from sub-Saharan Africa (SSA, 5 (10% from Asia, 2 (4% from the Americas, and 5 (10% were multi-regional. Median follow-up time and pre-ART CD4 cell count ranged from 3-55 months and 11-192 cells/mm(3, respectively. Loss-to-follow-up, reported in 40 (80% studies, ranged from 0.3%-27%. Overall, SSA had the highest pooled 12-month mortality probability of 0.17 (95% CI 0.11-0.24 versus 0.11 (95% CI 0.10-0.13 for Asia, and 0.07 (95% CI 0.007-0.20 for the Americas. Of 14 (28% studies reporting cause-specific mortality, tuberculosis (TB (5%-44%, wasting (5%-53%, advanced HIV (20%-37%, and chronic diarrhea (10%-25% were most common. Independent factors associated with early mortality in 30 (60% studies included: low baseline CD4 cell count, male sex, advanced World Health Organization clinical stage, low body mass index, anemia, age greater than 40 years, and pre-ART quantitative HIV RNA. CONCLUSIONS: Significant heterogeneity in outcomes and in methods of reporting outcomes exist among published studies evaluating mortality in the first year after ART initiation in LMIC. Early mortality rates are highest in SSA, and opportunistic illnesses such as TB and wasting syndrome are the most common reported causes of death. Strategies addressing modifiable risk factors associated with early death are
Nansseu, Jobert Richie N; Bigna, Jean Joel R; Kaze, Arnaud D; Noubiap, Jean Jacques N
Introduction With the new ‘test and treat’ policy of the WHO, it is obvious that the number of HIV-infected patients taking antiretroviral therapy (ART) will grow exponentially, with consequential increase in the burden of diabetes mellitus (DM). Our aim is to summarise existing data on the incidence of pre-diabetes and DM, and associated risk factors among HIV-infected adults. Methods and analysis This systematic review will include cohort studies reporting the incidence of pre-diabetes and/or DM, and associated risk factors among HIV-infected adults on ART, with these patients being free of any impaired glucose metabolism at study baseline. We will perform electronic searches in PubMed, Excerpta Medica Database (EMBASE), Web of Science and WHO Global Health Library, supplemented with manual searches. Articles published from 1 January 2000 to 31 July 2016, in English or French languages, and without any geographical restriction will be eligible for inclusion. 3 authors will independently screen, select studies, extract data and assess the risk of bias with discrepancies resolved by consensus. We will assess clinical heterogeneity by examining the study design and setting, criteria and cut-offs used to define pre-diabetes or DM, process of calculation of incidence and outcomes in each study. We will also assess statistical heterogeneity using the χ2 test of homogeneity and quantify it using the I2 statistic. A random effects meta-analysis will be used to estimate the overall cumulative incidence of pre-diabetes/DM and risk factors. Ethics and dissemination This systematic review will use data from published studies and does not require ethics approval. Its results are expected to help putting in place action plans and preventive measures to curb the growing burden of DM in the HIV population on ART. Findings will be published in a peer-reviewed journal and presented at scientific conferences. PROSPERO registration number CRD42016039651. PMID:27633645
Hamza, O.; Matee, M.I.N.; Simon, E.N.; Kikwilu, E.; Moshi, M.J.; Mugusi, F.; Mikx, F.H.M.; Verweij, P.E.; Ven, A.J.A.M. van der
ABSTRACT: BACKGROUND: The aim of the study was to compare the prevalence and types of HIV-related oral lesions between children and adult Tanzanian patients on HAART with those not on HAART and to relate the occurrence of the lesions with anti-HIV drug regimen, clinical stage of HIV disease and CD4+
Sornpaisarn, Bundit; Shield, Kevin D; Cohen, Joanna E; Schwartz, Robert; Rehm, Jürgen
The objective of this study is to assess the relationship between alcohol taxation changes and drinking initiation among adolescents and young adults (collectively "youth") in Thailand (a middle-income country). Using a survey panel, this study undertook an age-period-cohort analysis using four large-scale national cross-sectional surveys of alcohol consumption performed in Thailand in 2001, 2004, 2007 and 2011 (n=87,176 Thai youth, 15-24 years of age) to test the hypothesis that changes in the inflation-adjusted alcohol taxation rates are associated with drinking initiation. Regression analyses were used to examine the association between inflation-adjusted taxation increases and the prevalence of lifetime drinkers. After adjusting for potential confounders, clear cohort and age effects were observed. Furthermore, a 10% increase of the inflation-adjusted taxation rate of the total alcohol market was significantly associated with a 4.3% reduction in the prevalence of lifetime drinking among Thai youth. In conclusion, tax rate changes in Thailand from 2001 to 2011 were associated with drinking initiation among youth. Accordingly, increases in taxation may prevent drinking initiation among youth in countries with a high prevalence of abstainers and may reduce the harms caused by alcohol.
Full Text Available Abstract Background Use of multivitamin supplements during the pre-HAART era has been found to reduce viral load, enhance immune response, and generally improve clinical outcomes among HIV-infected adults. However, immune reconstitution is incomplete and significant mortality and opportunistic infections occur in spite of HAART. There is insufficient research information on whether multivitamin supplementation may be beneficial as adjunct therapy for HIV-infected individuals taking HAART. We propose to evaluate the efficacy of a single recommended daily allowance (RDA of micronutrients (including vitamins B-complex, C, and E in slowing disease progression among HIV-infected adults receiving HAART in Uganda. Methods/Design We are using a randomized, double-blind, placebo-controlled trial study design. Eligible patients are HIV-positive adults aged at least 18 years, and are randomized to receive either a placebo; or multivitamins that include a single RDA of the following vitamins: 1.4 mg B1, 1.4 mg B2, 1.9 mg B6, 2.6 mcg B12, 18 mg niacin, 70 mg C, 10 mg E, and 0.4 mg folic acid. Participants are followed for up to 18 months with evaluations at baseline, 6, 12 and 18 months. The study is primarily powered to examine the effects on immune reconstitution, weight gain, and quality of life. In addition, we will examine the effects on other secondary outcomes including the risks of development of new or recurrent disease progression event, including all-cause mortality; ARV regimen change from first- to second-line therapy; and other adverse events as indicated by incident peripheral neuropathy, severe anemia, or diarrhea. Discussions The conduct of this trial provides an opportunity to evaluate the potential benefits of this affordable adjunct therapy (multivitamin supplementation among HIV-infected adults receiving HAART in a developing country setting. Trial registration Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique
Eades, Chris P; Herbert, Sophie A; Edwards, Simon G; Waters, Laura J; Peake, Tabitha; Miller, Robert F; Jungmann, Eva
Among an inner London UK cohort of 147 adolescents transitioning from paediatric into adult care between 2007 and 2015, a new diagnosis of lymphoma was made in five patients; incidence rate = 0.425/100 person-years (95% confidence interval = 0.424-0.426). Previously described risk factors, including low nadir CD4 cell count and ongoing HIV-1 viraemia, appeared to be important. These data suggest that careful surveillance and a low threshold for investigating relevant symptoms continue to be essential for such patients.
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
Patou Masika Musumari
Full Text Available BACKGROUND: Food insecurity is increasingly reported as an important barrier of patient adherence to antiretroviral therapy (ART in both resource-poor and rich settings. However, unlike in resource rich-settings, very few quantitative studies to date have investigated the association of food insecurity with patient adherence to ART in Sub-Saharan Africa. The current study examines the association between food insecurity and adherence to ART among HIV-infected adults in the Democratic Republic of Congo (DRC. METHODS AND FINDINGS: This is a cross-sectional quantitative study of patients receiving ART at three private and one public health facilities in Kinshasa, DRC. Participants were consecutively recruited into the study between April and November 2012. Adherence was measured using a combined method coupling pharmacy refill and self-reported adherence. Food insecurity was the primary predictor, and was assessed using the Household Food Insecurity Access Scale (HFIAS. Of the 898 participants recruited into the study, 512 (57% were food insecure, and 188 (20.9% were not adherent to ART. Food insecurity was significantly associated with non-adherence to ART (AOR, 2.06; CI, 1.38-3.09. We also found that perceived harmfulness of ART and psychological distress were associated respectively with increased (AOR, 1.95; CI, 1.15-3.32 and decreased (AOR, 0.31; CI, 0.11-0.83 odds of non-adherence to ART. CONCLUSION: Food insecurity is prevalent and a significant risk factor for non-adherence to ART among HIV-infected individuals in the DRC. Our findings highlight the urgent need for strategies to improve food access among HIV-infected on ART in order to ensure patient adherence to ART and ultimately the long-term success of HIV treatment in Sub-Saharan Africa.
Full Text Available Abstract Background For antiretroviral therapy (ART naive human immunodeficiency virus (HIV infected adults suffering from tuberculosis (TB, there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART after starting antituberculosis treatment (ATT, in order to minimize mortality, HIV disease progression, and adverse events. Methods In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART and 62 after 8-12 weeks (delayed ART of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045. Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05. Rates of adverse events were similar. Interpretation Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Trial registration CTRI/2011/12/002260
Full Text Available With the introduction of highly active antiretroviral therapy, a number of drugs have been developed. The best choice concerning which antiretroviral analogs to start is always under discussion, especially in the choice between non-nucleoside reverse transcriptase inhibitors-based therapies and ritonavir-boosted protease inhibitors. Both are proven to control viral replication and lead to immunological gain. The choice between a non-nucleoside analog reverse transcriptase inhibitor and a protease inhibitor as a third antiretroviral drug in the therapy should consider factors related to the individual, as well as the inclusion of the best therapy in the patient's daily activities and potential adherence. The protease inhibitor-based therapies showed similar efficacy among the various inhibitors with characteristics concerning the adverse events from each medicine. For the treatment of protease-resistant patients, darunavir and tipranavir showed good efficacy with higher genetic barrier to resistance.
Introduction Risky sexual practice among people living with HIV/AIDS is a public health concern because of the risk of transmission of the virus to sero-discordant partner/s. There is also the risk of re-infection with new, drug resistant viral strains between sero-concordant partners. However, there is lack of information on risky sexual practices among HIV positive adults. Therefore, this study aimed to assess risky sexual practice and associated factors among adult HIV positive clients at Gondar University Referral Hospital, Northwest Ethiopia, 2015. Methods An institution based cross sectional study was conducted at Gondar University Referral Hospital from May to June 2015. A pretested structured questionnaire was used to collect the data. Using systematic random sampling technique, a total of 513 respondents were participated in this study. The data were entered into EPI info version 3.5.3 and transferred to SPSS version 20 for analysis. Descriptive, bivariate and multivariate analyses were done. A P-value <0.05 was considered to determine the statistical significance of the association between factors (independent variables) and risky sexual practice. The Odds ratio was also used to determine the presence and the degree of association between the dependent and independent variables. Results A total of 513 respondents were participated in this study. The prevalence of risky sexual practices in the past three months was 38% (95% CI: 33.3%, 42.3%). Being in the age range of 18–29 years (AOR = 2.63, 95% CI: 1.55, 4.47) and 30–39 years (AOR = 2.29, 95% CI: 1.48, 3.53), being single (AOR = 6.32, 95%CI: 2.43, 16.44),being married (AOR = 6.06, 95% CI: 2.81, 13.07), having no child (AOR = 2.58, 95% CI: 1.17, 5.72), and a CD4 count of greater than 500/mm3 were factors significantly associated with risky sexual practices. Conclusions A considerable number of HIV positive clients had risky sexual practices. It is strongly recommended that the Regional Health Bureau
Gundersen Svein G
Full Text Available Abstract Background HIV-associated anemia is common and associated with poor prognosis. However, its response to antiretroviral treatment (ART in rural Africa is poorly understood. Methods HIV-infected adults (≥15 years who enrolled in HIV care at Haydom Lutheran Hospital in northern Tanzania were included in the study. The effect of ART (zidovudine/stavudine + lamivudine + efavirenz/nevirapine on HIV-associated anemia was studied in a subset of patients who were anemic at the time they started ART and had a follow-up hemoglobin measurement 12 months later. Pregnant women were excluded from the study, as were women who had given birth within the past 6 weeks. Anemia was defined as hemoglobin Results At enrollment, mean hemoglobin was 10.3 g/dL, and 649 of 838 patients (77.4% were anemic. Of the anemic patients, 254 (39.1% had microcytosis and hypochromia. Among 102 patients who were anemic at ART initiation and had a follow-up hemoglobin measurement after 12 months, the mean hemoglobin increased by 2.5 g/dL (P Conclusions Most patients had anemia at enrollment, of whom nearly 40% had microcytosis and hypochromia suggestive of iron deficiency. The mean hemoglobin increased significantly in patients who received ART, but one third were still anemic 12 months after ART initiation indicating that additional interventions to treat HIV-associated anemia in rural Africa might be warranted, particularly in patients with microcytosis and those treated with zidovudine.
Full Text Available The 2013 World Health Organization’s (WHO Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART and monitoring treatment. Guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource-limited settings. The most important new clinical recommendations include: treating adults, adolescents and older children earlier – starting ART in all individuals with a CD4 cell count of 500 cells/mm3 or less (but giving priority to those with advanced clinical disease or a CD4 cell count less than 350 cells/mm3; starting ART at any CD4 cell count in certain populations, including those with active TB (existing recommendation, Hepatitis B infection and severe chronic liver disease, HIV-positive partners in serodiscordant couples (existing recommendation, pregnant and breastfeeding women, and children younger than 5 years of age; a preferred first-line ART regimen of Tenofovir+3TC or FTC+ Efavirenz as a once-daily fixed-dose combination for adults, pregnant women, and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services, including strategies to improve retention in care, and adherence to ART; task-shifting to address human resource gaps; decentralizing delivery of ART to primary health care, and integrating ART services within
Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H.; García, Felipe.; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L.; Mounzer, Karam; Swindells, Susan; Baxter, John D.; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François
Abstract The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): −0.088; 0.235]), or F4/AS01B_3 and control group (−0.096 log10 copies/mL [97.5% CI: −0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4+ T-cell responses, but did not reduce HIV-1 VL, impact CD4+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events. PMID:26871794
Gabillard, Delphine; Lewden, Charlotte; Ndoye, Ibra; Moh, Raoul; Ségéral, Olivier; Tonwe-Gold, Besigin; Etard, Jean-François; Pagnaroat, Men; Fournier-Nicolle, Isabelle; Eholié, Serge; Konate, Issouf; Minga, Albert; Mpoudi-Ngolé, Eitel; Koulla-Shiro, Sinata; Zannou, Djimon Marcel; Anglaret, Xavier; Laurent, Christian
Background In resource-limited countries, estimating CD4-specific incidence rates of mortality and morbidity among patients receiving antiretroviral therapy (ART) may help assess the effectiveness of care and treatment programmes, identify program weaknesses and inform decisions. Methods We pooled data from 13 research cohorts in five sub-Saharan African (Benin, Burkina Faso, Cameroon, Cote d'Ivoire and Senegal) and two Asian (Cambodia and Laos) countries. HIV-infected adults (≥18 years) who received ART in 1998-2008 and had at least one CD4 count available were eligible. Changes in CD4 counts over time were estimated by a linear mixed regression. CD4-specific incidence rates were estimated as the number of first events occurring in a given CD4 stratum divided by the time spent within the stratum. Results Overall 3,917 adults (62% women) on ART were followed-up during 10,154 person-years. In the ≤50, 51-100, 101-200, 201-350, 351-500, 501-650 and >650/mm3 CD4 cells strata, death rates were: 20.6, 11.8, 6.7, 3.3, 1.8, 0.9 and 0.3 per 100 person-years; AIDS rates were: 50.5, 32.9, 11.5, 4.8, 2.8, 2.2 and 2.2 per 100 person-years; and loss to follow-up rates were: 4.9, 6.1, 3.5, 3.1, 2.9, 1.7 and 1.2 per 100 person-years, respectively. Mortality and morbidity were higher during the first year following ART initiation. Conclusion In these resource-limited settings, death and AIDS rates remained substantial after ART initiation, even in individuals with high CD4 cell counts. Ensuring earlier ART initiation and optimizing case finding and treatment for AIDS-defining diseases should be seen as priorities. PMID:23274931
Wendel Mombaque dos Santos
Full Text Available ABSTRACT Objective: to investigate potential drug-drug interactions (PDDI in patients with HIV infection on antiretroviral therapy. Methods: a cross-sectional study was conducted on 161 adults with HIV infection. Clinical, socio demographic, and antiretroviral treatment data were collected. To analyze the potential drug interactions, we used the software Micromedex(r. Statistical analysis was performed by binary logistic regression, with a p-value of ≤0.05 considered statistically significant. Results: of the participants, 52.2% were exposed to potential drug-drug interactions. In total, there were 218 potential drug-drug interactions, of which 79.8% occurred between drugs used for antiretroviral therapy. There was an association between the use of five or more medications and potential drug-drug interactions (p = 0.000 and between the time period of antiretroviral therapy being over six years and potential drug-drug interactions (p < 0.00. The clinical impact was prevalent sedation and cardiotoxicity. Conclusions: the PDDI identified in this study of moderate and higher severity are events that not only affect the therapeutic response leading to toxicity in the central nervous and cardiovascular systems, but also can interfere in tests used for detection of HIV resistance to antiretroviral drugs.
Andrew F Auld
Full Text Available In Côte d'Ivoire during 2004-2007, numbers of ART enrollees increased from <5,000 to 36,943. Trends in nationally representative ART program outcomes have not yet been reported.We conducted a retrospective chart review to assess trends in patient characteristics and attrition [death or loss to follow-up (LTFU] over time, among a nationally representative sample of 3,682 adults (≥15 years initiating ART during 2004-2007 at 34 health facilities. Among ART enrollees during 2004-2007, median age was 36, the proportion female was 67%, the proportion HIV-2-infected or dually HIV-1&2 reactive was 5%, and median baseline CD4+ T-cell (CD4 count was 135 cells/µL. Comparing cohorts initiating ART in 2004 with cohorts initiating ART in 2007, median baseline weight declined from 55 kg to 52 kg (p = 0.008 and the proportion weighing <45 kg increased from 17% to 22% (p = 0.014. During 2004-2007, pharmacy-based estimates of the percentage of new ART enrollees ≥95% adherent to ART declined from 74% to 60% (p = 0.026, and twelve-month retention declined from 86% to 69%, due to increases in 12-month mortality from 2%-4% and LTFU from 12%-28%. In univariate analysis, year of ART initiation was associated with increasing rates of both LTFU and mortality. Controlling for baseline CD4, weight, adherence, and other risk factors, year of ART initiation was still strongly associated with LTFU but not mortality. In multivariate analysis, weight <45 kg and adherence <95% remained strong predictors of LTFU and mortality.During 2004-2007, increasing prevalence among ART enrollees of measured mortality risk factors, including weight <45 kg and ART adherence <95%, might explain increases in mortality over time. However, the association between later calendar year and increasing LTFU is not explained by risk factors evaluated in this analysis. Undocumented transfers, political instability, and patient dissatisfaction with crowded facilities might explain
Starting Electronics is unrivalled as a highly practical introduction for hobbyists, students and technicians. Keith Brindley introduces readers to the functions of the main component types, their uses, and the basic principles of building and designing electronic circuits. Breadboard layouts make this very much a ready-to-run book for the experimenter; and the use of multimeter, but not oscilloscopes, puts this practical exploration of electronics within reach of every home enthusiast's pocket. The third edition has kept the simplicity and clarity of the original. New material
Didier K Ekouevi
Full Text Available HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA.We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region.Data was merged for 1,754 patients (56% female, including 1,021 HIV-2 infected patients (551 on ART and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART. At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7 and 42.4 years, IQR (37.0-47.3 for dually seropositive patients (p = 0.048. Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C. The median CD4 count at the ART initiation is 166 cells/mm(3, IQR (83-247 among HIV-2 infected patients and 146 cells/mm(3, IQR (55-249 among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3 after 24 months on ART for HIV-2 patients and 169 cells/mm(3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3.This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.
Ekouevi, Didier K.; Balestre, Eric; Coffie, Patrick A.; Minta, Daouda; Messou, Eugene; Sawadogo, Adrien; Minga, Albert; Sow, Papa Salif; Bissagnene, Emmanuel; Eholie, Serge P.; Gottlieb, Geoffrey S.; Dabis, François; Zannou, Djimon Marcel; Ahouada, Carin; Akakpo, Jocelyn; Ahomadegbé, Christelle; Bashi, Jules; Gougounon-Houéto, Alice; Azon-Kouanou, Angèle; Houngbé, Fabien; Koumakpaï, Sikiratou; Alihonou, Florence; d’Almeida, Marcelline; Hodonou, Irvine; Hounhoui, Ghislaine; Sagbo, Gracien; Tossa-Bagnan, Leïla; Adjide, Herman; Drabo, Joseph; Bognounou, René; Dienderé, Arnaud; Traore, Eliezer; Zoungrana, Lassane; Zerbo, Béatrice; Sawadogo, Adrien Bruno; Zoungrana, Jacques; Héma, Arsène; Soré, Ibrahim; Bado, Guillaume; Tapsoba, Achille; Yé, Diarra; Kouéta, Fla; Ouedraogo, Sylvie; Ouédraogo, Rasmata; Hiembo, William; Gansonré, Mady; Messou, Eugène; Gnokoro, Joachim Charles; Koné, Mamadou; Kouakou, Guillaume Martial; Bosse, Clarisse Amani; Brou, Kouakou; Assi, Achi Isidore; Chenal, Henri; Hawerlander, Denise; Soppi, Franck; Minga, Albert; Abo, Yao; Bomisso, Germain; Eholié, Serge Paul; Amego, Mensah Deborah Noelly; Andavi, Viviane; Diallo, Zelica; Ello, Frédéric; Tanon, Aristophane Koffi; Koule, Serge Olivier; Anzan, Koffi Charles; Guehi, Calixte; Aka, Edmond Addi; Issouf, Koffi Ladji; Kouakou, Jean-Claude; N’Gbeche, Marie-Sylvie; Touré, Pety; Avit-Edi, Divine; Kouakou, Kouadio; Moh, Magloire; Yao, Valérie Andoblé; Folquet, Madeleine Amorissani; Dainguy, Marie-Evelyne; Kouakou, Cyrille; Méa-Assande, Véronique Tanoh; Oka-Berete, Gladys; Zobo, Nathalie; Acquah, Patrick; Kokora, Marie-Berthe; Eboua, Tanoh François; Timité-Konan, Marguerite; Ahoussou, Lucrèce Diecket; Assouan, Julie Kebé; Sami, Mabéa Flora; Kouadio, Clémence; Renner, Lorna; Goka, Bamenla; Welbeck, Jennifer; Sackey, Adziri; Owiafe, Seth Ntiri; Wejse, Christian; Silva, Zacarias José Da; Paulo, Joao; Rodrigues, Amabelia; da Silva, David; Medina, Candida; Oliviera-Souto, Ines; Østergaard, Lars; Laursen, Alex; Sodemann, Morten; Aaby, Peter; Fomsgaard, Anders; Erikstrup, Christian; Eugen-Olsen, Jesper; Maïga, Moussa Y; Diakité, Fatoumata Fofana; Kalle, Abdoulaye; Katile, Drissa; Traore, Hamar Alassane; Minta, Daouda; Cissé, Tidiani; Dembelé, Mamadou; Doumbia, Mohammed; Fomba, Mahamadou; Kaya, Assétou Soukho; Traoré, Abdoulaye M; Traoré, Hamady; Toure, Amadou Abathina; Dicko, Fatoumata; Sylla, Mariam; Berthé, Alima; Traoré, Hadizatou Coulibaly; Koïta, Anta; Koné, Niaboula; N'Diaye, Clémentine; Coulibaly, Safiatou Touré; Traoré, Mamadou; Traoré, Naïchata; Charurat, Man; Ajayi, Samuel; Dapiap, Stephen; Otu; Igbinoba, Festus; Benson, Okwara; Adebamowo, Clément; James, Jesse; Obaseki; Osakede, Philip; Olasode, John; Sow, Papa Salif; Diop, Bernard; Manga, Noël Magloire; Tine, Judicael Malick; Signate Sy, Haby; Ba, Abou; Diagne, Aida; Dior, Hélène; Faye, Malick; Gueye, Ramatoulaye Diagne; Mbaye, Aminata Diack; Patassi, Akessiwe; Kotosso, Awèrou; Kariyare, Benjamin Goilibe; Gbadamassi, Gafarou; Komi, Agbo; Mensah-Zukong, Kankoé Edem; Pakpame, Pinuwe; Lawson-Evi, Annette Koko; Atakouma, Yawo; Takassi, Elom; Djeha, Améyo; Ephoévi-gah, Ayoko; Djibril, Sherifa El-Hadj; Dabis, François; Bissagnene, Emmanuel; Arrivé, Elise; Coffie, Patrick; Ekouevi, Didier; Jaquet, Antoine; Leroy, Valériane; Lewden, Charlotte; Sasco, Annie; Azani, Jean-Claude; Allou, Gérard; Balestre, Eric; Bohossou, Franck; Karcher, Sophie; Gonsan, Jules Mahan; Carrou, Jérôme Le; Lenaud, Séverin; Nchot, Célestin; Malateste, Karen; Yao, Amon Roseamonde; Siloué, Bertine; Clouet, Gwenaelle; Djetouan, Hugues; Doring, Alexandra; Kouakou, Adrienne; Rabourdin, Elodie; Rivenc, Jean; Anglaret, Xavier; Ba, Boubacar; Essanin, Jean Bosco; Ciaranello, Andrea; Datté, Sébastien; Desmonde, Sophie; Diby, Jean-Serge Elvis; Gottlieb, Geoffrey S.; Horo, Apollinaire Gninlgninrin; Kangah, Serge N'zoré; Malvy, Denis; Meless, David; Mounkaila-Harouna, Aida; Ndondoki, Camille; Shiboski, Caroline; Thiébaut, Rodolphe; PAC-CI; Abidjan
Background HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). Methods We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d’Ivoire, Mali, and Senegal, in the West Africa region. Results Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3–51.7) and 42.4 years, IQR (37.0–47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm3, IQR (83–247) among HIV-2 infected patients and 146 cells/mm3, IQR (55–249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm3 after 24 months on ART for HIV-2 patients and 169 cells/mm3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7–4.3). Conclusions This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population. PMID:23824279
In May 2015 the UK elected a new government. In election campaigns, health is one of the most important areas of debate and over the preceding 12 months, the state of child and adolescent mental health services (CAMHS) had held a particularly high profile in the media and in political debate. Many had suggested that the rate of mental illness starting in adolescence is increasing and that service provision is not of sufficient quality or scale to meet this need. A brief review of the sources for these statistics reveals that whilst this may be true, there is a dearth of accurate and up to date data on the scale of the need for CAMHS or the extent to which it is being met. Nonetheless, members of all parties claimed to support improvements in mental health service provision for children and adolescents through increases in funding. A key question for policy makers has therefore become, from where any additional funding might be derived. One suggestion has been that funding be transferred from spending on adult mental health services. The exact practical nature of such a policy is yet to be explored in detail by government or stakeholders. The primary purpose of the present discussion is therefore to consider the possible ethical implications of such a policy in principle. The discussion forms part of a wider and evolving political and professional discourse on society's and government's attitude towards mental illness, towards the balance of individual and societal needs and towards the balance between preventative and supportive interventions to improve health.
Wolff, Marcelo; Shepherd, Bryan E.; Cortés, Claudia; Rebeiro, Peter; Cesar, Carina; Cardoso, Sandra Wagner; Pape, Jean W.; Padgett, Denis; Sierra-Madero, Juan; Echevarria, Juan; McGowan, Catherine C.
Background HIV-infected persons in lower income countries may experience high rates of antiretroviral therapy (ART) change, particularly due to toxicity or other non-failure reasons. Few reports address patient outcomes after these modifications. Methods HIV-infected adults from 7 Caribbean, Central and South America network (CCASAnet) clinical cohorts who modified > or = 1 drug from first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. Results 5,565 ART-naïve HAART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 due to toxicity and 11% due to failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4% and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio[aHR]=1.5 vs. failure, 95% confidence interval[CI]=1.0–2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at start of ART-2, and starting ART-2 because of failure (aHR=2.1 vs. toxicity, 95% CI=1.5–2.8). Conclusions Among patients modifying first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success. PMID:26761273
T A Bicanic; Jarvis, J. N.; A. Loyse; Harrison, T.S.
Ever since the public sector rollout of antiretroviral therapy (ART) in 2004, the question of the optimal time to start ART following diagnosis of an opportunistic infection has aroused controversy among South African HIV clinicians and researchers.
Mondy, Kristin; Tebas, Pablo
The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.
Umemura, Tomo; Lacinová, Lenka; Macek, Petr; Kunnen, E. Saskia
Only a few studies have longitudinally explored to whom emerging adults prefer to turn to seek closeness, comfort, and security (called "attachment preferences"), and previous studies on attachment preferences in emerging adults have focused only on the beginning of romantic relationships but not on the end of relationships. Czech…
Reekie, J; Mocroft, A; Ledergerber, B
OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategies....... METHODS: A total of 1827 patients on cART starting at least one new antiretroviral from 1 January 2000 while maintaining a suppressed viral load were included in the analysis. Poisson regression analysis identified factors predictive of virological failure after baseline in addition to traditional...... demographic variables. Baseline was defined as the date of starting new antiretrovirals. RESULTS: Four hundred and fifty-one patients (24.7%) experienced virological failure, with an incidence rate (IR) of 7.3 per 100 person-years of follow-up (PYFU) [95% confidence interval (CI) 6.7-8.0]. After adjustment...
Meloni, Seema T.; Chang, Charlotte A.; Eisen, Geoffrey; Jolayemi, Toyin; Banigbe, Bolanle; Okonkwo, Prosper I.; Kanki, Phyllis J.
Background While there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria. Methods We conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted. Results Of 70,002 patients, 65.2% were female and median age was 35 (IQR: 29–41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mm3 (IQR: 78–220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients
Kume, Kodai; Ikeda, Kazuyo; Kamada, Masaki; Touge, Tetsuo; Deguchi, Kazushi; Masaki, Tsutomu
A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.
Vera Lúcia da Silveira
Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.
Judd, A; Lodwick, R; Noguera-Julian, A
OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS......: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged
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
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.
Opaas, Marianne; Varvin, Sverre
Adverse and potentially traumatic experiences (PTEs) in childhood were examined among 54 adult refugee patients with pre-flight PTEs of war and human rights violations (HRVs) and related to mental health and quality of life at treatment start. Extent of childhood PTEs was more strongly related to mental health and quality of life than the extent of war and HRV experiences. Childhood PTEs were significantly related to arousal and avoidance symptoms of posttraumatic stress disorder (PTSD) and to quality of life, whereas pre-flight war and HRV experiences were significantly related to reexperiencing symptoms of PTSD only. Within childhood adversities, experiences of family violence and external violence, but not of loss and illness, were significantly related to increased mental health symptoms and reduced quality of life. These results point to the importance of taking childhood adverse experiences into account in research and treatment planning for adult refugees with war and HRVs trauma.
Full Text Available BACKGROUND: The purpose of this study was to evaluate the efficacy and safety of three nevirapine-based antiretroviral treatments for adult antiretroviral-naïve Chinese patients with HIV-1 infection. METHODOLOGY: This was a prospective, multicenter study. 198 antiretroviral-naïve HIV-1 positive subjects with CD4 lymphocyte counts between 100/ul and 350/ul and plasma HIV-1 RNA levels more than 500 copies/ml were randomized to start three NVP-based antiretroviral treatments: group A, NVP+AZT+ddI; group B, NVP+3TC+d4T; group C, NVP+AZT+3TC. Viral responses, immunologic responses, adverse events and drug resistance were monitored at baseline and the end of week 4, 12, 24, 36, 52. Viralogical response and immunological response were also compared in different strata of baseline CD4 T lymphocyte counts and plasma HIV-1 RNA concentrations. At baseline, the plasma HIV-1 RNA was 4.44+/-0.68, 4.52+/-0.71 and 4.41+/-0.63 lg copies/ml in group A, B and C respectively (p = 0.628. At the end of the study, the plasma viral load reached 2.54+/-1.11, 1.89+/-0.46 and 1.92+/-0.58 lg copies/ml in group A, B and C respectively (p200/ul (subgroup H. But in subgroup L, viral response rate of three groups has no significant statistic difference. There were no statistically significant differences among three groups in immunological response within any of the CD4 or pVL strata. 3 out of 193 patients with available genotype at baseline showed primary drug resistant. Of 26 patients with virologic failure, 17 patients showed secondary drug resistant, 16 subjects in group A and 1 subject in group B. Logistic regression analysis indicated that presence of hepatotoxicity was associated with HCV-Ab positive (OR = 2.096, 95%CI: 1.106-3.973, P = 0.023 and higher CD4 baseline (CD4 count >250/ul (OR = 2.096, 95%CI: 1.07-4.107, P = 0.031. CONCLUSION: Our findings strongly support the use of 3TC+d4T and 3TC+AZT as the nucleoside analogue combination in NVP-based antiretroviral
Full Text Available The Acquired Immune Deficiency Syndrome epidemic, caused by the Human Immunodeficiency Virus, is a global crisis which threatens development gains, economies, and societies. Within sub-Saharan Africa, where the epidemic began the earliest and the HIV prevalence is the highest, African countries have death rates not seen before. In South Africa the epidemic has a devastating impact which creates profound suffering on individuals and their families, and the impact on the socio-economic level is of great concern. The eradication of HIV/AIDS represents one of humanity’s greatest challenges, which requires co-operation and comprehensive collaboration between many different role players. In this endeavour clinical information plays a major role. To combat the effect of the disease, the Free State Department of Health started with the provisioning of antiretroviral therapy in the public health sector. The objective of this paper was to address the challenges they faced in order to develop and implement an information system to manage the rollout of antiretroviral treatment effectively. They started with a paper-based system to collect vital information. It was followed by a palm computer project that was initiated to electronically capture the data collected by the paper-based system. This system was then replaced by a comprehensive Hospital and Clinic Information System which was acquired and customised for the antiretroviral data collection process. Research partners developed a standalone antiretroviral data warehouse for collecting information associated with the monitoring and evaluation of the Free State antiretroviral and HIV/ AIDS treatment programme. The data warehouse successfully produced several management information reports to the antiretroviral management team. A need was identified to design a comprehensive antiretroviral data warehouse that will integrate data from several operational sources which are all associated with HIV/AIDS.
Kotzé, J E; McDonald, T
The Acquired Immune Deficiency Syndrome epidemic, caused by the Human Immunodeficiency Virus, is a global crisis which threatens development gains, economies, and societies. Within sub-Saharan Africa, where the epidemic began the earliest and the HIV prevalence is the highest, African countries have death rates not seen before. In South Africa the epidemic has a devastating impact which creates profound suffering on individuals and their families, and the impact on the socio-economic level is of great concern. The eradication of HIV/AIDS represents one of humanity's greatest challenges, which requires co-operation and comprehensive collaboration between many different role players. In this endeavour clinical information plays a major role. To combat the effect of the disease, the Free State Department of Health started with the provisioning of antiretroviral therapy in the public health sector. The objective of this paper was to address the challenges they faced in order to develop and implement an information system to manage the rollout of antiretroviral treatment effectively. They started with a paper-based system to collect vital information. It was followed by a palm computer project that was initiated to electronically capture the data collected by the paper-based system. This system was then replaced by a comprehensive Hospital and Clinic Information System which was acquired and customised for the antiretroviral data collection process. Research partners developed a standalone antiretroviral data warehouse for collecting information associated with the monitoring and evaluation of the Free State antiretroviral and HIV/ AIDS treatment programme. The data warehouse successfully produced several management information reports to the antiretroviral management team. A need was identified to design a comprehensive antiretroviral data warehouse that will integrate data from several operational sources which are all associated with HIV/AIDS.
... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...
Mocroft, Amanda; Sterne, Jonathan A C; Egger, Matthias
BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started...
Jacobson, Jeffrey M.; Kuritzkes, Daniel R.; Godofsky, Eliot; DeJesus, Edwin; Larson, Jeffrey A.; Weinheimer, Steven P.; Lewis, Stanley T.
Ibalizumab (formerly TNX-355) is a humanized monoclonal antibody that binds CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1), and inhibits the viral entry process. A phase lb multidose study of the safety, pharmacokinetics, and antiviral activity of ibalizumab was conducted with 22 HIV-1-infected patients. Nineteen patients were randomized to receive either 10 mg/kg of body weight weekly (arm A) or a 10-mg/kg loading dose followed by 6 mg/kg every 2 weeks (arm B) intravenously for 9 weeks. Three patients were assigned to receive 25 mg/kg every 2 weeks for five doses (arm C). During the study, the patients remained off other antiretrovirals or continued a stable failing regimen. Treatment with ibalizumab resulted in substantial reductions in HIV-1 RNA levels (0.5 to 1.7 log10) in 20 of 22 subjects. In most patients, HIV-1 RNA fell to nadir levels after 1 to 2 weeks of treatment and then returned to baseline despite continued treatment. Baseline viral isolates were susceptible to ibalizumab in vitro, regardless of coreceptor tropism. Emerging resistance to ibalizumab was manifested by reduced maximal percent inhibition in a single-cycle HIV infectivity assay. Resistant isolates remained CD4 dependent and were susceptible to enfuvirtide in vitro. Complete coating of CD4+ T-cell receptors was correlated with serum ibalizumab concentrations. There was no evidence of CD4+ T-cell depletion in ibalizumab-treated patients. Ibalizumab was not immunogenic, and no serious drug-related adverse effects occurred. In conclusion, ibalizumab administered either weekly or biweekly was safe and well tolerated and demonstrated antiviral activity. Further studies with ibalizumab in combination with standard antiretroviral treatments are warranted. PMID:19015347
Bärnighausen Till W
Full Text Available Abstract Background KwaZulu-Natal is the South African province worst affected by HIV and the focus of early modeling studies investigating strategies of antiretroviral treatment (ART delivery. The reality of antiretroviral roll-out through primary care has differed from that anticipated and real world data are needed to inform the planning of further scaling up of services. We investigated the factors associated with uptake of antiretroviral treatment through a primary healthcare system in rural South Africa. Methods Detailed demographic, HIV surveillance and geographic information system (GIS data were used to estimate the proportion of HIV positive adults accessing antiretroviral treatment within northern KwaZulu-Natal, South Africa in the period from initiation of antiretroviral roll-out until the end of 2008. Demographic, spatial and socioeconomic factors influencing the likelihood of individuals accessing antiretroviral treatment were explored using multivariable analysis. Results Mean uptake of ART among HIV positive resident adults was 21.0% (95%CI 20.1-21.9. Uptake among HIV positive men (19.2% was slightly lower than women (21.8%, P = 0.011. An individual's likelihood of accessing ART was not associated with level of education, household assets or urban/rural locale. ART uptake was strongly negatively associated with distance from the nearest primary healthcare facility (aOR = 0.728 per square-root transformed km, 95%CI 0.658-0.963, P = 0.002. Conclusions Despite concerns about the equitable nature of antiretroviral treatment rollout, we find very few differences in ART uptake across a range of socio-demographic variables in a rural South African population. However, even when socio-demographic factors were taken into account, individuals living further away from primary healthcare clinics were still significantly less likely to be accessing ART
Riedel, H-P; Ellger-Rüttgardt, S; Karbe, H; Niehaus, M; Rauch, A; Schian, H-M; Schmidt, C; Schott, T; Schröder, H; Spijkers, W; Wittwer, U
Established by the Federal Ministry of Labour and Social Affairs (BMAS) in October 2007, the Scientific Expert Group RehaFutur had been commissioned to elaborate cornerstones for the medium- and long-term development of vocational rehabilitation of adults with disabilities (re-integration). Initial questions inter alia were as follows: Which function should vocational rehabilitation have in a service- and knowledge-oriented working world that will increasingly be affected by demographic change? How can disabled persons' right to occupational participation by way of vocational rehabilitation, a right stipulated both under the German constitution and in German law, be realized as needed also in the future? Various fields of action have been derived on the basis, for one, of an investigation of the factors, social law, social and education policy as well as European, influencing vocational rehabilitation and, for the other, of an evaluation of current labour market and demographic developments. Dealt with in the fields of action outlined are the aspects: equitable opportunities of access, developmental and needs orientation, closeness to the real occupational and working world, as well as the role of self-determination and self-responsibility. The fields of action are to be understood as framework concept for shaping a cross-actor innovation process. Sustainable vocational rehabilitation is characterized in particular by the fact that it is specifically targeted at promoting disabled persons' self-determination and self-responsibility actively using these in the process and that it strengthens an independent lifestyle, ensures social participation by inclusive structures; also, it facilitates continued participation in working life by ongoing education involving holistic development of professional and personal competencies oriented towards the individual's resources and potentials, safeguarding it by systematic networking with companies. The concept presented for
Full Text Available Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents 15.1-19 years (adolescents, 19.1-24 years (young adults and 24.1-29.9 years (older adults. Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008. Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35. Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52. This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults.
Lodi, Sara; Sharma, Shweta; Lundgren, Jens D;
OBJECTIVE: The START trial found a lower risk of a composite clinical outcome in HIV-positive individuals assigned to immediate initiation of antiretroviral therapy (ART) compared with those assigned to deferred initiation. However, 30% of those assigned to deferred initiation started ART earlier...
Hartman, K.; Verweel, G.; Groot, R. de; Hartwig, N.G.
BACKGROUND: Highly active antiretroviral therapy has been associated with lipodystrophy in adults. Much is unknown about its characteristics, especially in children. OBJECTIVE: To obtain an objective case definition of the lipodystrophy syndrome. METHODS: This was a cross-sectional study. One invest
Kinabo, G.; Sprengers, M.; Msuya, L.J.; Shayo, A.M.; Asten, H.A.G.H. van; Dolmans, W.M.V.; Ven, A.J.A.M. van der; Warris, A.
OBJECTIVE: : Highly active antiretroviral therapy (HAART) has been associated with lipodystrophy (LD) in adults but data are more limited for children. The purpose of this study was to determine the prevalence of and risk factors for LD in Tanzanian children receiving HAART by clinical assessment an
LUO Ling; LI Tai-sheng
As the severity of the HIV epidemic in China grew, National Free Antiretroviral Treatment (ART) Program was announced since 2003. Even though there still were many difficulties, China had obtained great achievements in fighting against HIV.Over 52 000 adult patients had received first-line HAART thus far and the mortality of AIDS in China decreased significantly. This paper presents an overview of the HIV/AIDS epidemic in China; the status of national free ART program,the difficulties suffered and the achievements made since the initiation of program and the challenges ahead for continued progress for China. This paper also provides suggestions to overcome these challenges.
Tengiz Tsertsvadze; Nikoloz Chkhartishvili; Lali Sharvadze; Natia Dvali; Otar Chokoshvili; Pati Gabunia; Akaki Abutidze; Kenrad Nelson; Jack DeHovitz; Carlos del Rio
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 (...
Effects of highly active antiretroviral therapy including tenofovir disoproxil fumarate on renal function among antiretroviral-na(i)ve HIV-infected adult patients%含TDF的HAART方案对抗逆转录病毒药物初治成年HIV感染患者肾功能的影响研究
段兴钧; 章银娣; 杨宏; 谢金沛; 曹东冬; 排云珍; 白洁; 王国见; 高卓
目的 探索含替诺福韦酯(tenofovir disoproxil fumarate,TDF)的高效抗逆转录病毒疗法(highly active antiretroviral therapy,HAART)对抗逆转录病毒药物初治HIV感染患者肾功能的影响.方法 本研究回顾性分析TDF治疗组和非TDF治疗组、依非韦伦(efavirenz,EFV)治疗组(即采用TDF+ lamivudine (3TC)+EFV方案治疗)和克力芝(lopinavir/ritonavir,LPV/RTV)治疗组(即采用TDF+ 3TC+ LPV/RTV方案治疗)在CD4细胞计数和内生肌酐清除率(rate of creatinine clearance,CrCl)上的差异.结果 TDF治疗组和非TDF治疗组患者的CD4细胞计数开始明显升高的时间分别为12周和48周.TDF治疗组患者在第24、48、60、72、84、96周时,CrCl比其基线时降低,差异具有统计学意义(均有P ＜0.05),而非TDF治疗组患者治疗后,CrCl未出现明显降低,无有统计学意义(均有P＞0.05).EFV治疗组和LPV/RTV治疗组患者均从第12周起,CD4细胞计数升高,差异均有统计学意义(均有P＜0.05).EFV治疗组患者和LPV/RTV治疗组患者的CrCl开始比其基线时降低的时间分别是72周和12周.结论 在患者各项危险因素可控的情况下,推荐TDF+ 3TC+ EFV为初治HIV患者的首选治疗方案.
Full Text Available The World Health Organization (WHO currently recommends that HIV-positive adults start antiretroviral therapy (ART at CD4 counts <350 cells/μl. Several countries have changed their guidelines to recommend ART irrespective of CD4 count or at a threshold of 500 CD4 cells/μl. Consequently, WHO is currently revising its treatment guidelines and considering recommending ART initiation at CD4 counts <500 cells/μl. Such decisions are critically important, as WHO guidelines inform healthcare policies in developing countries and are used by activists in their advocacy work. Changing the CD4 initiation point from 350 to 500 cells/μl would, however, be premature and have profound cost implications on Global Fund, President’s Emergency Plan for AIDS Relief (PEPFAR and developing country health budgets. We should be willing to campaign for such a change in guidelines despite cost implications, if supported by evidence. However, the evidence remains outstanding. S Afr J HIV Med 2013;14(1:6-7. DOI:10.7196/SAJHIVMED.906
Mocroft, A; Phillips, A; Ledergerber, B;
BACKGROUND: It is unknown if the CD4 cell count response differs according to antiretroviral drugs used in combination antiretroviral therapy (cART) in patients with maximal virological suppression [viral load (VL) < 50 copies/ml]. OBJECTIVES: To compare the change in CD4 cell count over consecut......BACKGROUND: It is unknown if the CD4 cell count response differs according to antiretroviral drugs used in combination antiretroviral therapy (cART) in patients with maximal virological suppression [viral load (VL) ... consecutive measurements with VL patients, were used to compare CD4 cell count changes after adjustment for antiretrovirals, time...... from starting cART, age, CD4 at first VL patients. The mean annual change in CD4 cell count was +45.5/microl [95% confidence interval (CI...
Petersen, TS; Andersen, SE; Gerstoft, Jan
WHAT IS ALREADY KNOW ABOUT THIS SUBJECT • National guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients are available in many Western world countries. However the impact of the guidelines on clinical practice is poorly documented. WHAT THIS STUDY ADDS...... HAART as a part of a clinical trial from 1998 to 2000. AIM To determine the adherence to the national guidelines for start of highly active antiretroviral treatment (HAART) in HIV infected patients. METHODS We used a Danish nationwide cohort of HIV infected patients to calculate the fraction of patients...... guidelines for start of HAART can be high. We suggest that simplicity of the guidelines, centralization of treatment and involvement of local clinicians in the development of guidelines are of major importance for high adherence to treatment guidelines....
Yiannoutsos Constantin T
Full Text Available Abstract Background Mortality of HIV-infected patients initiating antiretroviral therapy in the developing world is very high immediately after the start of ART therapy and drops sharply thereafter. It is necessary to use models of survival time that reflect this change. Methods In this endeavor, parametric models with changepoints such as Weibull models can be useful in order to explicitly model the underlying failure process, even in the case where abrupt changes in the mortality rate are present. Estimation of the temporal location of possible mortality changepoints has important implications on the effective management of these patients. We briefly describe these models and apply them to the case of estimating survival among HIV-infected patients who are initiating antiretroviral therapy in a care and treatment programme in sub-Saharan Africa. Results As a first reported data-driven estimate of the existence and location of early mortality changepoints after antiretroviral therapy initiation, we show that there is an early change in risk of death at three months, followed by an intermediate risk period lasting up to 10 months after therapy. Conclusion By explicitly modelling the underlying abrupt changes in mortality risk after initiation of antiretroviral therapy we are able to estimate their number and location in a rigorous, data-driven manner. The existence of a high early risk of death after initiation of antiretroviral therapy and the determination of its duration has direct implications for the optimal management of patients initiating therapy in this setting.
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...... entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients...... per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)....
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.
Anoje, Chukwuemeka; Agu, Kenneth Anene; Oladele, Edward A; Badru, Titilope; Adedokun, Oluwasanmi; Oqua, Dorothy; Khamofu, Hadiza; Adebayo, Olufunso; Torpey, Kwasi; Chabikuli, Otto Nzapfurundi
Medication adherence is a major determinant of antiretroviral treatment (ART) success. Promptness in medication refill pick-ups may give an indication of medication adherence. This study determined medication refill adherence among HIV positive patients on ART and its association with treatment outcomes in HIV treatment centers in Nigeria. This retrospective multi-center cohort study involved a review of ART refill records for 3534 HIV-positive patients aged 18-60 years who initiated first-line ART between January 2008 and December 2009 and were on therapy for ≥18 months after ART initiation. Drug refill records of these patients for 10 consecutive refill visits after ART initiation were analyzed. The first ten consecutive refill appointment-keeping rates after ART initiation ranged from 64.3 % to 76.1 % which decreased with successive visits. Altogether, 743 (21.1 %) patients were deemed adherent, meaning they picked up their drugs within 7 days of the drug refill appointment date on at least nine out of ten refill visits. The adherent group of patients had a mean CD4 cells increase of 206 ± 6.1 cells/dl after 12 months of ART compared to 186 ± 7.1 cells/dl reported among the nonadherent group (p = 0.0145). The proportion of patients in the adherent category who showed no OIs after 12 months on ART (81 %) was significantly higher when compared to the proportion in the non-adherent category (23.5 %), (p = 0.008). The multivariate analysis showed that the odds of being adherent was 2-3 times more in patients who had a baseline CD4 count of less than 200 cells/dl compared to those with a baseline CD4 of >350 cells/dl. (AOR 2.43, 95 % CI 1.62-3.66). In addition, for patients with baseline CD4 cell count of 201-350 cells/dl, the odds of being adherent was found to be 1.9 compared to those with baseline CD4 of greater than 350 cells/dl (AOR 1.93, 95 % CI 1.27-2.94). Pharmacy refill data can serve as an adherence measure. Adherence to on-time drug
Impact of HIV subtype on response and resistance in antiretroviral-naïve adults comparing treatment with once daily versus twice daily ritonavir boosted fosamprenavir in combination with Abacavir/Lamivudine
Lisa L. Ross
Full Text Available The impact of HIV-1 subtype on resistance mutation selection and on virologic response to fosamprenavir in combination with once-daily (QD versus twice-daily (BID dosing of ritonavir was examined in a prospective, open label, randomized study in antiretroviral-naïve, HIV-1 infected subjects. We studied APV109141 compared QD fosamprenavir/ritonavir (1400mg/100mg to BID fosamprenavir/ritonavir (700mg/100mg, administered in combination with a QD fixed-dose abacavir/lamivudine (600 mg/300 mg combination tablet through 48 weeks in ART-naïve subjects. HIV genotypes were obtained from all subjects at screen. Subjects with virologic failure (VF were also genotyped at baseline and VF. HIV subtypes observed in the ITT (n=214 population were A or AE or AG circulating recombinant forms (CRFs 19%; B 62%; BF or BG CRFs 2%; C or CPX CRFs 7%; D 2%; F1 7%; G <1%. By TLOVR (ITT-exposed, 86/106 (81% of subjects on QD study arm and 87/106 (82% in the BID arm achieved plasma HIV-RNA<400 copies/mL at Week 48. Three subjects met VF criteria, 2 receiving QD fosamprenavir/ritonavir; 1 receiving BID fosamprenavir/ritonavir; (HIV subtype B, F1 A1, respectively. Baseline drug resistance was detected in 2/3 VFs: Subject 1-RT: K103K/N, T215C; major PI: V82A, L90M; and Subject 2-RT: M41L, L74V. Only virus from one subject with VF selected for any treatment-emergent mutation (Subject 1; M184V. Post-VF, Subject 3 (subtypeA1 suppressed HIV-RNA >400 copies/mL through 48 weeks. Subtype appeared to have no preferential impact on virologic response or selection for specific resistance mutations in subjects receiving fosamprenavir/ritonavir. Virologic failure rate was rare (3 subjects; each from different subtypes. At VF, virus from only one subject selected any HIV NRTI mutation (M184V; none selected major protease mutations.
Nanda, Kavita; Stuart, Gretchen S.; Robinson, Jennifer; Gray, Andrew L.; Tepper, Naomi K.; Gaffield, Mary E.
Objective: To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals. Design: Systematic review of the published literature. Methods: We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses. Results: Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives. Conclusion: Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices. PMID:28060009
Jensen, Brigid K; Monnerie, Hubert; Mannell, Maggie V; Gannon, Patrick J; Espinoza, Cagla Akay; Erickson, Michelle A; Bruce-Keller, Annadora J; Gelman, Benjamin B; Briand, Lisa A; Pierce, R Christopher; Jordan-Sciutto, Kelly L; Grinspan, Judith B
Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors ritonavir or lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed after drug removal. Conversely, nucleoside reverse transcriptase inhibitor zidovudine had no effect. Furthermore, in vivo ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity and have implications for myelination in juvenile HIV patients and myelin maintenance in adults on lifelong therapy.
赵德才; 范吉祥; 刘学真; 宫伟彦; 刘中夫; 汪宁; 马烨; 张福杰; 孙定勇; 刘伟; 李惠琴; 彭国平; 刘爱文; 原琛利
Objective To investigate the situation of drug resistance among HIV-infected patients receiving long term first-line combination antiretroviral treatment (cART) and to assess the interrelated risk factors. Methods A prospective cohort study was established in 8 provinces in China since 2007. Baseline information was collected in a cross-sectional survey through multi-stage random sampling. Totall of 688 HIV-infected patients who had received first-line cART and achieved virologic suppression in 2009 were enrolled into the cohort. HIV-infected patients with viral load higher than 1000 copies/ml in 2010 were detected by ViroSeqM HIV-1 genotyping system. Life table analysis was applied to calculate the incidence of drug resistance. A sensitivity analysis was applied to evaluate the effect of second-line regimens. Based on the bivariable results, the risk factors were included into the Multivariable Logistic Regression model. Results Total of 688 HIV-infected patients receiving cART and achieving virologic suppression were eligible to this study. Among those cases, 10 cases died and 8 cases switched to second-line regimens after 12 months of follow-up. There were 29 cases with a viral load higher than 1000 copies/ml among whom, 22 patients were resistant to at least one antiretroviral drug based on genotypic assay. The incidence among drug resistance was (3.4-4.6)/100 person-years. All 22 patients were resistant to non-nucleoside reverse transcriptase inhibitor (NNRT1) and 16 patients were resistant to nucleoside reverse transcriptase inhibitor (NRTIs). No case was resistant to protease inhibitor (PI) or the combination of 3TC and TDF. Compared with patients who received cART in county level clinics or above and treated successfully, those who received cART in the village level clinic (95%CI: 2.1-19.6) and experienced virologic treatment failure (95%CI: 2.2-13.0) were most likely to occur drug resistance. Conclusions The incidence of drug resistance remained low among
@@ Xinjiang Dushanzi petroleum refining and chemical integrated project,is the largest one so far in China, with a capacity of ten-million-ton petroleum refinery and onemillion-ton ethylene complex, directly under PetroChina Company Limited (PetroChina), was started construction along with laying a foundation on August 22, 2005.
Ouedraogo, Denis; Artavia-Mora, Luis; Bedi, Arjun; Thiombiano, Boundia Alexandre
Background Retention in care and adherence to antiretroviral therapy (ART) among people living with human immunodeficiency virus (PLHIV) is a critical challenge in many African countries including Burkina Faso. Delivering text messaging (short message service, SMS) interventions through mobile phones may help facilitate health service delivery and improve patient health. Despite this potential, no evaluations have been delivered for national scale settings to demonstrate the impact of mobile health (mHealth) for PLHIV. Objectives This study aims to test the impact of SMS text messaging reminders for PLHIV in Burkina Faso, who are under ART. The evaluation identifies whether patients who receive SMS text messages are more likely to (1) retain in care (measured as a dichotomous variable), (2) adhere to antiretroviral regimens (measured as the number of doses missed in the past 7 days), and (3) experience slower disease progression (measured with T-lymphocytes cells). The second objective is to assess its effects on the frequency of health center visits, physical and psychosocial health, nutrition and whether the type of message (text vs image) and frequency (weekly vs semiweekly) have differential impacts including the possibility of message fatigue over time. Methods This 24-month, wide-scale intervention implements a randomized controlled trial (RCT) to evaluate the impact of four variants of a mHealth intervention versus a control group. Our sample comprises adult patients (>15 years of age) undergoing antiretroviral therapy with access to mobile phone services. Multivariate regression analysis will be used to analyze the effect of the intervention on the study population. Data collection is done at baseline and three follow-up waves 6, 12, and 24 months after the intervention starts. Results The targeted 3800 patients were recruited between February 2015 and May 2015. But political uncertainty delayed the launch of the intervention until October 2015. Data
Borges, Álvaro H; Neuhaus, Jacqueline; Babiker, Abdel G;
BACKGROUND: In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts...... and human immunodeficiency virus (HIV) RNA between the study arms. METHODS: Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline...... covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART. RESULTS: There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23...
Full Text Available Cryptococcosis is the most common cause of meningitis in Africa due to the high burden of HIV. Immune reconstitution inflammatory syndrome (IRIS is a frequent and deadly complication of cryptococcal meningitis. We report a fatal case of cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral therapy (unmasking IRIS and markedly worsened postpartum after delivery (paradoxical IRIS.
Lundgren, Jens Dilling; Mocroft, Amanda; Gatell, Jose M;
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...
The number of patients receiving antiretroviral therapy (ART) has increased from around half a million in 2003 to almost 10 million in only 10 years, and will continue to increase in the coming years. Over 16 million more are eligible to start ART according to the last World Health Organization (WHO) guidelines. The demand is also switching from the less expensive antiretrovirals (ARVs) that allowed such scale-up to newer more expensive ones with fewer side effects or those that can be used by people who have developed resistance to first-line treatment. However, patents on these new drugs can delay robust generic competition and, consequently, price reduction made possible by economies of scale. Various ways to address this issue have been envisaged or implemented, including the use of the flexibilities available under the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), systematic widespread voluntary licensing, of which the Medicines Patent Pool (MPP) is an example, and the application of different prices in different countries, called tiered pricing. This paper helps explain the impact of patents on market competition for ARVs and analyses various approaches available today to minimize this impact.
Bailey Kerry A
Full Text Available Abstract Background Antiretroviral treatment services delivered in hospital settings in Africa increasingly lack capacity to meet demand and are difficult to access by patients. We evaluate the effectiveness of nurse led primary care based antiretroviral treatment by comparison with usual hospital care in a typical rural sub Saharan African setting. Methods We undertook a prospective, controlled evaluation of planned service change in Lubombo, Swaziland. Clinically stable adults with a CD4 count > 100 and on antiretroviral treatment for at least four weeks at the district hospital were assigned to either nurse led primary care based antiretroviral treatment care or usual hospital care. Assignment depended on the location of the nearest primary care clinic. The main outcome measures were clinic attendance and patient experience. Results Those receiving primary care based treatment were less likely to miss an appointment compared with those continuing to receive hospital care (RR 0·37, p p = 0·001. Those receiving primary care based, nurse led care were more likely to be satisfied in the ability of staff to manage their condition (RR 1·23, p = 0·003. There was no significant difference in loss to follow-up or other health related outcomes in modified intention to treat analysis. Multilevel, multivariable regression identified little inter-cluster variation. Conclusions Clinic attendance and patient experience are better with nurse led primary care based antiretroviral treatment care than with hospital care; health related outcomes appear equally good. This evidence supports efforts of the WHO to scale-up universal access to antiretroviral treatment in sub Saharan Africa.
CCL3L1- CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1- infected individuals. Nat Med 2008, 14:413...Riley ED, Bangsberg DR: Food insecurity is associated with incomplete HIV RNA suppression among homeless and marginally housed HIV- infected ...increases in HIV- infected adults experiencing 4 years of viral suppression on antiretroviral therapy. Aids 2003, 17:1907-1915. 48. Kaufmann GR, Furrer
Milke-García, María Del Pilar
Adulthood starts after youth and is characterized by the completion of growth and the achievement of organic and psychological maturity. Obesity and other preventable diseases related to lifestyle are common at this age. A complete, balanced and sufficient diet, together with exercise are important in order to prevent and treat these diseases. Several studies have brought about the mechanisms by which the incorporation of milk and dairy products to diet is beneficial in order to prevent and treat these diseases. Milk also contributes to the improvement of dental, bone and intestinal health, theoretically helps in body weight control, has a definite role on the muscular and bone mass maintenance and is an option for hydration during exercise, this being as important as diet for overweight, obesity, diabetes, dislipidemias and hypertension control.
Lawn, Stephen D; Wilkinson, Robert J; Lipman, Marc C. I.; Wood, Robin
Tuberculosis (TB) is the most common opportunistic disease in HIV-infected patients during the initial months of antiretroviral therapy (ART) and presents a great challenge to ART programs in resource-limited settings. The mechanisms underlying development of TB in this period are complex. Some cases may represent progression of undiagnosed subclinical disease present before starting ART, emphasizing the importance of careful screening strategies for TB. It has been suggested that progression...
Zetterberg, Eva; Neuhaus, Jacqueline; Baker, Jason V
To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow...
Full Text Available Global commitments aim to provide antiretroviral therapy (ART to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings.
Parrott, F.R.; Mwafulirwa, C.; Ngwira, B.; Nkhwazi, S.; Floyd, S.; Houben, R.M.G.J.; Glynn, J.R.; Crampin, A.C.; French, N.
Background Treatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa. Objective To better understand antiretroviral treatment (ART) seeking behaviour in HIV-infected adults in rural M
T A Bicanic
Full Text Available Ever since the public sector rollout of antiretroviral therapy (ART in 2004, the question of the optimal time to start ART following diagnosis of an opportunistic infection has aroused controversy among South African HIV clinicians and researchers.
Krentz, Hartmut B; Gill, M John
Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy.
Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier
While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) - with a cost of 47,139.91 € - would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets.
Rasmussen, Erik Stavnsager; Tanev, Stoyan
The risk of launching new products and starting new firms is known to be extremely high. The Lean Start-up approach is a way of reducing these risks and enhancing the chances for success by validating the products and services in the market with customers before launching it in full scale. The main...
Peet, Julia; Selyutina, Anastasia; Bredihhin, Aleksei
The antiretroviral activity of azulene derivatives was detected for the first time. A series of eighteen diversely substituted azulenes was synthesized and tested in vitro using HIV-1 based virus-like particles (VLPs) and infectious HIV-1 virus in U2OS and TZM-bl cell lines. Among the compounds tested, the 2-hydroxyazulenes demonstrated the most significant activity by inhibiting HIV-1 replication with IC50 of 2-10 and 8-20 μM for the VLPs and the infectious virus, respectively. These results indicate that azulene derivatives may be potentially useful candidates for the development of antiretroviral agents.
Fox, Zoe V; Cozzi-Lepri, Alessandro; D'Arminio Monforte, Antonella;
Background: Guidelines suggest that patients on continuous antiretroviral therapy for >4 months with current viral load (VL)>1,000 copies/ml should be tested for resistance. There are limited data showing the frequency of resistance testing in routine clinical practice following these recommendat......Background: Guidelines suggest that patients on continuous antiretroviral therapy for >4 months with current viral load (VL)>1,000 copies/ml should be tested for resistance. There are limited data showing the frequency of resistance testing in routine clinical practice following...... these recommendations. Methods: In EuroSIDA, virological failure (VF) was defined as confirmed VL>1,000 copies/ml after =4 months continuous use of any antiretroviral in a =3-drug regimen started during or after 2002. We assessed whether a resistance test was performed around VF (from 4 months before to 1 year after VF...
U.S. Department of Health & Human Services — Longitudinal information from an evaluation where children were randomly assigned to Early Head Start or community services as usual;direct assessments and...
U.S. Department of Health & Human Services — Nationally representative, longitudinal information from an evaluation where children were randomly assigned to Head Start or community services as usual;direct...
Minnesota Department of Natural Resources — This table contains information about station starting locations. These locations indicate the reference point that was used as the origin for distance measurements...
Getting Started with Unity is written in an easy-to-follow tutorial format.""Getting Started with Unity"" is for[ 3D game developers[/color] who would like to learn how to use Unity3D and become familiar with its core features. This book is also suitable for intermediate users who would like to improve their skills. No prior knowledge of Unity3D is required.
Salmanton-García, Jon; Herrador, Zaida; Ruiz-Seco, Pilar; Nzang-Esono, Jesús; Bendomo, Veronica; Bashmakovic, Emma; Nseng-Nchama, Gloria; Benito, Agustín; Aparicio, Pilar
The human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) represent a serious public health problem in Equatorial Guinea, with a prevalence of 6.2% among adults. the high-activity antiretroviral treatment (HAART) coverage data is 10 points below the overall estimate for Sub-Saharan Africa, and only 61% patients continue with HAART 12 months after it started. This study aims to assess HAART adherence and related factors in Litoral Province of Equatorial Guinea. In this cross-sectional study, socio-demographic and clinical data were collected at Regional Hospital of Bata, during June-July 2014. Adherence to treatment was assessed by using the Spanish version of CEAT-VIH. Bivariate and linear regression analyses were employed to assess HAART adherence-related factors. We interviewed 50 men (35.5%) and 91 women (64.5%), with a mean age of 47.7 ± 8.9 and 36.2 ± 11.2, respectively (p VIH score varied by ethnic group (p = .005). There was a positive correlation between CEAT-VIH score and current CD4 T-cells count (p = .013). The Cronbach's α value was 0.52. To our knowledge, this is the first study to assess HAART adherence in Equatorial Guinea. Internal reliability for CEAT-VIH was low, nonetheless the positive correlation between the CEAT-VIH score and the immunological status of patients add value to our findings. Our results serve as baseline for future research and will also assist stakeholders in planning and undertaking contextual and evidence-based policy initiatives.
... More... Home Getting Started National Resource Center on Psychiatric Advance Directives - Getting Started Getting Started Psychiatric advance directives (PADs) are relatively new legal instruments ...
Full Text Available Àngels Andreu-Crespo,1,* Josep M Llibre,2,3,* Glòria Cardona-Peitx,1 Ferran Sala-Piñol,1 Bonaventura Clotet,2,4 Xavier Bonafont-Pujol1 1Pharmacy Department, 2HIV Unit and “Lluita contra la SIDA” Foundation, University Hospital Germans Trias i Pujol, Badalona, 3Universitat Autònoma de Barcelona, 4Universitat de Vic-Universitat Central de Catalunya (UVIC-UCC, Vic, Barcelona, Spain *These authors contributed equally to the work Abstract: While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals – with a cost of 47,139.91€ – would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar, should minimize the treatment expenditures paid by national health budgets. Keywords: antiretroviral treatment, cost efficacy, drug packaging, treatment change
Bazin, Gabriela Ricordi; Gaspar, Mariza Curto Saavedra; Silva, Nicole Carvalho Xavier Micheloni da; Mendes, Carolina da Costa; Oliveira, Cora Pichler de; Bastos, Leonardo Soares; Cardoso, Claudete Aparecida Araújo
This study aims to evaluate antiretroviral therapy in children and adolescents with AIDS. We selected 247 abstracts published from 1983 to 2013, collected from the PubMed and LILACS databases. Sixty-nine articles were selected. Attention to research in the pediatric age bracket in 30 years of the epidemic is explained by the age group's immunological characteristics, since AIDS progresses faster in children than in adults. Recent studies focus on the initiation of highly active antiretroviral therapy before the onset of symptoms. Early introduction of combination antiretroviral therapy has been implemented effectively and safely in populations with limited resources, leading to significantly improved survival. The current challenge is to manage a chronic disease with acute complications. New studies should focus on population specificities and identify the individual needs of pediatric patients.
Full Text Available BACKGROUND: Antiretroviral therapy (ART has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART. METHODOLOGY: Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885 was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103 testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis. FINDINGS: Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1% and individuals testing on their own initiative (53.5% the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period. CONCLUSION: Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.
Lopes, Carmen Andréa F; Soares, Marcelo A; Falci, Diego R; Sprinz, Eduardo
HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1%) and K130N (40.6%). Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%). There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option.
Carmen Andréa F. Lopes
Full Text Available HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1% and K130N (40.6%. Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%. There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option.
Bannister, WP; Ruiz, L; Loveday, C;
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......, observational cohort with 11,928 HIV-1-infected patients. METHODS: Response to cART was analysed in patients with subtypes determined pre-cART, via multivariable logistic regression on the first measurements 6–12 months after starting cART. A virological response was defined as a viral load ...-B-infected patients (P=0.334). After adjustment, there was no significant difference in odds of an immunological response (OR: 1.17, 95% CI: 0.73–1.87, P=0.524). CONCLUSIONS: There was no evidence of significant differences in virological or immunological response to cART between patients infected with HIV-1 B...
Full Text Available Background: Access to second-line antiretroviral therapy (ART for HIV-positive patients remains limited in sub-Saharan Africa. Furthermore, outcomes of second-line ART may be compromised by mortality and loss to follow-up (LTFU. Objective: To determine retention in care among patients receiving second-line ART in a public hospital in Ethiopia, and to investigate factors associated with LTFU among adults and adolescents. Design: HIV-positive persons with documented change of first-line ART to a second-line regimen were retrospectively identified from hospital registers, and data were collected at the time of treatment change and subsequent clinic visits. Baseline variables for adults and adolescents were analyzed using multivariate Cox proportional hazards models comparing subjects remaining in care and those LTFU (defined as a missed appointment of ≥90 days. Results: A total of 383 persons had started second-line ART (330 adults/adolescents; 53 children and were followed for a median of 22.2 months (the total follow-up time was 906 person years. At the end of study follow-up, 80.5% of patients remained in care (adults and adolescents 79.8%; children 85.7%. In multivariate analysis, LTFU among adults and adolescents was associated with a baseline CD4 cell count <100 cells/mm3 and a first-line regimen failure that was not confirmed by HIV RNA testing. Conclusions: Although retention in care during second-line ART in this cohort was satisfactory, and similar to that reported from first-line ART programs in Ethiopia, our findings suggest the benefit of earlier recognition of patients with first-line ART failure and confirmation of suspected treatment failure by viral load testing.
Desmonde, Sophie; Eboua, François T; Malateste, Karen;
BACKGROUND: We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa. METHODS: We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric IeDEA clin...... rare and switches after an immunological failure were insufficient. These gaps reveal that it is crucial to advocate for both sustainable access to first-line and alternative regimens to provide adequate roll-out of paediatric ART programmes....
Arneaud, J.M.; Langman, R.A. [Tasmania Univ., Hobart, TAS (Australia)
Large errors may occur if leakage path saturation is neglected when reduced-voltage test results are used to predict the direct-on-line starting current of induction motors. The results of applying three existing and two new methods for starting current prediction are compared with test data from 52 motors. A quantitative assessment is made of the probable reduction in error that would be achieved by increasing the number of available sets of reduced-voltage, locked rotor test results or by including slot design data. Guidelines are given for selecting an appropriate predictive method. (author). 4 tabs., 1 fig., 6 refs.
Healy, Justin; Hope, Rebecca; Bhabha, Jacqueline; Eyal, Nir
With the expansion of antiretroviral treatment programmes, many children and adolescents with HIV in sub-Saharan Africa could expect to live healthy lives. Yet adolescents have the highest levels of poor antiretroviral adherence and of loss to follow-up compared with other age groups. This can lead to increased morbidity and mortality, to the development of drug-resistant strains, and to high societal costs. While financial incentives have been extensively used to promote medication adherence among adults, their use among adolescents remains rare. And while there is a large body of ethical literature exploring financial incentives among adults, little philosophical thought has gone into their use among adolescents. This paper explores three oft-mentioned ethical worries about financial incentives for health behaviours and it asks whether these concerns are more serious in the context of incentives for improving adolescent adherence. The three worries are that such incentives would unduly coerce adolescents' decision-making, would compromise distributive justice and would crowd out intrinsic motivations and non-monetary values. Our tentative conclusion is that more empirical investigation of these concerns is necessary, and that at this point they are not compelling enough to rule out trials in which adolescents are incentivised for antiretroviral adherence.
Goodwill to the Islamic world and willingness to mend ties highlight Barack Obama’s new Middle East policy u.S. President Barack Obama started to implement his new Middle East policy soon after he assumed office. He paid a
If you are an Android developer who wants to learn how to use UDOO to build Android applications that are capable of interacting with their surrounding environment, then this book is ideal for you. Learning UDOO is the next great step to start building your first real-world prototypes powered by the Android operating system.
The first large active detector component was lowered into the ATLAS cavern on 1 March. It consisted of the 8 modules forming the lower part of the central barrel of the tile hadronic calorimeter. The work of assembling the barrel, which comprises 64 modules, started the following day.
May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D'Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan A C
The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70,000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org).
Shafer, Robert W.; Jonathan M Schapiro
As more drugs for treating HIV have become available, drug resistance profiles within antiretroviral drug classes have become increasingly important for researchers developing new drugs and for clinicians integrating new drugs into their clinical practice. In vitro passage experiments and comprehensive phenotypic susceptibility testing are used for the pre-clinical evaluation of drug resistance. Clinical studies are required, however, to delineate the full spectrum of mutations responsible fo...
Antiretroviral medications are known inhibitors and inducers of cytochrome p450 enzymes and can affect levels of non-HIV medications. Finasteride 1 mg (Propecia), which prevents the conversion of testosterone (T) to dihydrotestosterone (DHT) is commonly prescribed for prevention of hair loss. This medication is a substrate of p450 3A4. Its efficacy may therefore be affected by HIV medications which induce or inhibit this enzyme. Levels of DHT to prevent hair loss are not well established, but...
Written as a step-by-step guide, Getting Started with Hazelcast will teach you all you need to know to make your application data scalable.This book is a great introduction for Java developers, software architects, or developers looking to enable scalable and agile data within their applications. You should have programming knowledge of Java and a general familiarity with concepts like data caching and clustering.
This practical and easy-to-understand learning tutorial is one big exciting exercise for students and engineers that are always short on their schedules and want to regain some lost time with the help of Simulink.This book is aimed at students and engineers who need a quick start with Simulink. Though it's not required in order to understand how Simulink works, knowledge of physics will help the reader to understand the exercises described.
his book is a fast-paced, practical guide full of step-by-step examples which are easy to follow and implement.This book is for programmers with a basic grasp of C++. The examples start at a basic level, making few assumptions beyond fundamental C++ concepts. Those without any experience with C++ should be able to follow and construct the examples, although you may need further support to understand the fundamental concepts.
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.
Full Text Available BACKGROUND: Adolescents have been identified as a high-risk group for poor adherence to and defaulting from combination antiretroviral therapy (cART care. However, data on outcomes for adolescents on cART in resource-limited settings remain scarce. METHODS: We developed an observational study of patients who started cART at The AIDS Service Organization (TASO in Uganda between 2004 and 2009. Age was stratified into three groups: children (≤10 years, adolescents (11-19 years, and adults (≥20 years. Kaplan-Meier survival curves were generated to describe time to mortality and loss to follow-up, and Cox regression used to model associations between age and mortality and loss to follow-up. To address loss to follow up, we applied a weighted analysis that assumes 50% of lost patients had died. FINDINGS: A total of 23,367 patients were included in this analysis, including 810 (3.5% children, 575 (2.5% adolescents, and 21 982 (94.0% adults. A lower percentage of children (5.4% died during their cART treatment compared to adolescents (8.5% and adults (10%. After adjusting for confounding, other features predicted mortality than age alone. Mortality was higher among males (p<0.001, patients with a low initial CD4 cell count (p<0.001, patients with advanced WHO clinical disease stage (p<0.001, and shorter duration of time receiving cART (p<0.001. The crude mortality rate was lower for children (22.8 per 1000 person-years; 95% CI: 16.1, 29.5, than adolescents (36.5 per 1000 person-years; 95% CI: 26.3, 46.8 and adults (37.5 per 1000 person-years; 95% CI: 35.9, 39.1. INTERPRETATION: This study is the largest assessment of adolescents receiving cART in Africa. Adolescents did not have cART mortality outcomes different from adults or children.
Full Text Available High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit.RapIT (Rapid Initiation of Treatment was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC and a hospital-based HIV clinic. Adult (≥18 y old, non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study ("rapid arm" received a point-of-care (POC CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV dispensing. Patients in the standard-initiation arm of the study ("standard arm" followed standard clinic procedures (three to five additional clinic visits over 2-4 wk prior to ARV dispensing. Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition
Lewis, Joseph M; Volny-Anne, Alain; Waitt, Catriona; Boffito, Marta; Khoo, Saye
International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones.
Nakagawa, Fumiyo; Lodwick, Rebecca; Costagliola, Dominique;
Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF...
Mocroft, Amanda; Sterne, Jonathan A C; Egger, Matthias; May, Margaret; Grabar, Sophie; Furrer, Hansjakob; Sabin, Caroline; Fatkenheuer, Gerd; Justice, Amy; Reiss, Peter; d'Arminio Monforte, Antonella; Gill, John; Hogg, Robert; Bonnet, Fabrice; Kitahata, Mari; Staszewski, Schlomo; Casabona, Jordi; Harris, Ross; Saag, Michael; Niesters, Bert
BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started co
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 ana...
Kowalska, Justyna D; Mocroft, Amanda; Blaxhult, Anders;
The role of hemoglobin levels as an independent prognostic marker of progression to AIDS and/or death in HIV-infected patients starting combination antiretroviral therapy (cART) was investigated. A total of 2,579 patients from the EuroSIDA cohort with hemoglobin, CD4 cell count, and HIV RNA viral...
Full Text Available Introduction: Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. Methods: HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet sites were compared to Latino patients (based on country of origin or ethnic identity starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. Results: The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years, more likely to be female (27% vs. 20% and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all. In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR 1.61; 95% confidence interval (CI: 1.32 to 1.96, particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50, change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62 and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57. Conclusions: HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.
Cesar, Carina; Koethe, John R; Giganti, Mark J; Rebeiro, Peter; Althoff, Keri N; Napravnik, Sonia; Mayor, Angel; Grinsztejn, Beatriz; Wolff, Marcelo; Padgett, Denis; Sierra-Madero, Juan; Gotuzzo, Eduardo; Sterling, Timothy R; Willig, James; Levison, Julie; Kitahata, Mari; Rodriguez-Barradas, Maria C; Moore, Richard D; McGowan, Catherine; Shepherd, Bryan E; Cahn, Pedro
Introduction Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. Methods HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. Results The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). Conclusions HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation. PMID:26996992
Spring Roo goes a step beyond the Spring Framework by bringing true Rapid Application Development to Java-just as Grails has done with Groovy. This concise introduction shows you how to build applications with Roo, using the framework's shell as an intelligent and timesaving code-completion tool. It's an ideal RAD tool because Roo does much of the tedious code maintenance. You'll get started by building a simple customer relationship management application, complete with step-by-step instructions and code examples. Learn how to control any part of the application with Roo's opt-in feature, w
Learn computer programming the easy way with Processing, a simple language that lets you use code to create drawings, animation, and interactive graphics. Programming courses usually start with theory, but this book lets you jump right into creative and fun projects. It's ideal for anyone who wants to learn basic programming, and serves as a simple introduction to graphics for people with some programming skills. Written by the founders of Processing, this book takes you through the learning process one step at a time to help you grasp core programming concepts. You'll learn how to sketch wi
Sievertsen, Hans Henrik
I Danmark er det muligt at afvige fra reglen om, at barnet skal starte i skole det kalenderår, hvor barnet fylder 6 år. Det gør 10-15 procent af en årgang, mens 80-90 procent af børnene følger normen, og 2-3 procent starter i skole et år tidligere end normen, viser en analyse baseret på børn født i...
Arduino is the open-source electronics prototyping platform that's taken the design and hobbyist world by storm. This thorough introduction, updated for Arduino 1.0, gives you lots of ideas for projects and helps you work with them right away. From getting organized to putting the final touches on your prototype, all the information you need is here! Inside, you'll learn about: Interaction design and physical computingThe Arduino hardware and software development environmentBasics of electricity and electronicsPrototyping on a solderless breadboardDrawing a schematic diagram Getting started
Start building electronics projects with Netduino, the popular open source hardware platform that's captured the imagination of makers and hobbyists worldwide. This easy-to-follow book provides the step-by-step guidance you need to experiment with Netduino and the .NET Micro Framework. Through a set of simple projects, you'll learn how to create electronic gadgets-including networked devices that communicate over TCP/IP. Along the way, hobbyists will pick up the basics of .NET programming, and programmers will discover how to work with electronics and microcontrollers. Follow the projects in
Allison L Agwu
Full Text Available Three decades into the HIV/AIDS epidemic there is a growing cohort of perinatally HIV-infected adolescents globally. Their survival into adolescence and beyond represent one of the major successes in the battle against the disease that has claimed the lives of millions of children. This population is diverse and there are unique issues related to antiretroviral treatment and management. Drawing from the literature and experience, this paper discusses several broad areas related to antiretroviral management, including: 1 diverse presentation of HIV, (2 use of combination antiretroviral therapy including in the setting of co-morbidities and rapid growth and development, (3 challenges of cART, including nonadherence, resistance, and management of the highly treatment-experienced adolescent patient, (4 additional unique concerns and management issues related to PHIV-infected adolescents, including the consequences of longterm inflammation, risk of transmission, and transitions to adult care. In each section, the experience in both resource-rich and limited settings are discussed with the aim of highlighting the differences and importantly the similarities, to share lessons learnt and provide insight into the multi-faceted approaches that may be needed to address the challenges faced by this unique and resilient population.
Agwu, Allison L; Fairlie, Lee
Three decades into the HIV/AIDS epidemic there is a growing cohort of perinatally HIV-infected adolescents globally. Their survival into adolescence and beyond represent one of the major successes in the battle against the disease that has claimed the lives of millions of children. This population is diverse and there are unique issues related to antiretroviral treatment and management. Drawing from the literature and experience, this paper discusses several broad areas related to antiretroviral management, including: 1) diverse presentation of HIV, (2) use of combination antiretroviral therapy including in the setting of co-morbidities and rapid growth and development, (3) challenges of cART, including nonadherence, resistance, and management of the highly treatment-experienced adolescent patient, (4) additional unique concerns and management issues related to PHIV-infected adolescents, including the consequences of longterm inflammation, risk of transmission, and transitions to adult care. In each section, the experience in both resource-rich and limited settings are discussed with the aim of highlighting the differences and importantly the similarities, to share lessons learnt and provide insight into the multi-faceted approaches that may be needed to address the challenges faced by this unique and resilient population.
Full Text Available It remains controversial whether and, if so, the extent to which antiretroviral therapy (ART results in net benefit if used by HIV-positive persons with a high CD4 count, particularly those with early HIV infection. This controversy is primarily reflecting lack of solid evidence from randomized controlled trials. Currently published trials have compared early ART with initiation of ART below currently globally accepted thresholds for initiation (i.e. CD4 count at 350 cells/µL and, hence, are unable to inform this discussion. Analyses on large observational studies that have attempted to address this question have shown inconsistent results; therefore, those results are considered low-quality evidence, as per the GRADE criteria used by, for example, WHO when formulating guidelines. In resource-constrained regions, not even observational data are available to inform this question. The START study is underway to answer this question. Data remain blinded, but START may show net harm from early use of ART; such a result would severely undermine use of ART as prevention in early HIV infection. Prescription of any type of medicine is guided by the principle of “do no harm” – that is, “the doctor should not prescribe medications unless s/he knows that the treatment is unlikely to be harmful.” Hence, the balance of risk/benefit to individuals versus prevention benefit is important to accurately determine, and current guidelines of generally initiating ART once the patient develops HIV-related symptoms or the CD4 count drops to levels around 350 cells/µL should be adhered to until further evidence has emerged.
Calmy, A; Carey, D; Mallon, P W G
BACKGROUND: No biological marker has been identified that predicts the development of lipodystrophy (LD). We investigated whether metabolic and body composition parameters could predict the development of LD over 2 years in adults initiating antiretroviral therapy (ART). METHODS: We used stored p...
Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate
Mocroft, Amanda; Lundgren, Jens D; Ross, Michael
of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR). METHODS: In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D...
Center for Law and Social Policy, Inc. (CLASP), 2012
Missouri's Early Head Start/Child Care Partnership Project expands access to Early Head Start (EHS) services for children birth to age 3 by developing partnerships between federal Head Start, EHS contractors, and child care providers. Head Start and EHS contractors that participate in the initiative provide services through community child care…
Full Text Available Antiretroviral medications are known inhibitors and inducers of cytochrome p450 enzymes and can affect levels of non-HIV medications. Finasteride 1 mg (Propecia, which prevents the conversion of testosterone (T to dihydrotestosterone (DHT is commonly prescribed for prevention of hair loss. This medication is a substrate of p450 3A4. Its efficacy may therefore be affected by HIV medications which induce or inhibit this enzyme. Levels of DHT to prevent hair loss are not well established, but likely need to be<15–20 ng/dl, or a DHT/T ratio of<0.02. Observational analysis in a private practice, measuring DHT and T levels in patients on finasteride and various antiretrovirals 21 patients were identified. 7 patients were taking protease inhibitors and had DHT levels<12 ng/dL; DHT/T<0.20. Three of these patients decreased their finasteride dose to 1 mg every-other-day and still have DHT <10. 8 patients were taking potent p450 inducers (efavirenz or etravirine and had DHT levels between >20; DHT/T>0.025. Two of these patients increased the dose of finasteride to 2 mg/day and subsequently decreased DHT to 14 and 17. Two additional patients on efavirenz, however, had DHT levels of<15 without dose adjustment. Four patients taking nevirapine, a less potent inducer of p450 had DHT levels of<15, as did one patient on raltegravir, which does not affect CYP450. Antiretrovirals that affect CYP 3A4 may interact with finasteride. While it is unlikely that this interaction is dangerous, it may affect its efficacy of the finasteride. Evaluation of DHT/T levels, and/or dose adjustment of finasteride may be appropriate in men being treated for HIV.
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.
Full Text Available BACKGROUND: Although the importance of concurrent treatment for multidrug-resistant tuberculosis (MDR-TB and HIV co-infection has been increasingly recognized, there have been few studies reporting outcomes of MDR-TB and HIV co-treatment. We report final outcomes of comprehensive, integrated MDR-TB and HIV treatment in Lesotho and examine factors associated with death or treatment failure. METHODS: We reviewed clinical charts of all adult patients who initiated MDR-TB treatment in Lesotho between January 2008 and September 2009. We calculated hazard ratios (HR and used multivariable Cox proportional hazards regression to identify predictors of poor outcomes. RESULTS: Of 134 confirmed MDR-TB patients, 83 (62% were cured or completed treatment, 46 (34% died, 3 (2% transferred, 1 (1% defaulted, and 1 (1% failed treatment. Treatment outcomes did not differ significantly by HIV status. Among the 94 (70% patients with HIV co-infection, 53% were already on antiretroviral therapy (ART before MDR-TB treatment initiation, and 43% started ART a median of 16 days after the start of the MDR-TB regimen. Among HIV co-infected patients who died, those who had not started ART before MDR-TB treatment had a shorter median time to death (80 days vs. 138 days, p=0.065. In multivariable analysis, predictors of increased hazard of failure or death were low and severely low body mass index (HR 2.75, 95% confidence interval [CI] 1.27-5.93; HR 5.50, 95% CI 2.38-12.69, and a history of working in South Africa (HR 2.37, 95% CI 1.24-4.52. CONCLUSIONS: Favorable outcomes can be achieved in co-infected patients using a community-based treatment model when both MDR-TB and HIV disease are treated concurrently and treatment is initiated promptly.
Since the end of November, various teams have been getting stuck into dismantling the LEP accelerator and its four experiments. After making the installations safe, the dismantling and removal of 40,000 tonnes of equipment is underway. Down in the tunnel, it is a solemn moment. It is 10 o'clock on 13 December and Daniel Regin, one of those heading the dismantling work, moves in on a magnet, armed with a hydraulic machine. Surrounded by teams gathered there for a course in dismantling, he makes the first cut into LEP. The great deconstruction has begun. In little over than a year, the accelerator will have been cleared away to make room for its successor, the LHC. The start of the operation goes back to 27 November. Because before setting about the machine with hydraulic shears and monkey wrenches, LEP had first to be made safe - it was important to make sure the machine could be taken apart without risk. All the SPS beam injection systems to LEP were cut off. The fluids used for cooling the magnets and superc...
This has been an excellent week for the LHC, with a succession of fills rapidly increasing the number of proton bunches to 194 per beam. This has allowed the experiments to reach a peak luminosity of 2.5 × 1032 cm-2s-1, thereby surpassing the record for 2010 where we reached 2.0 × 1032 cm-2s-1. At the time of writing, the integrated luminosity delivered by the LHC in 2011 is around 28 inverse picobarns, which is already more than half of the total 2010 dataset. These are impressive numbers, but what impresses me most is how quickly the LHC operators are now able to turn the machine around between fills, and how well LHC running has been incorporated into the overall operation of CERN’s accelerator complex. The flexibility of the LHC was illustrated on Thursday when we started a short phase of running at 1.38 TeV per beam, equivalent to the energy-per-nucleon of a lead-ion run. This lower energy data will be used by the experiments, in particular by ALICE, to compare...
Della Mussia, S
The first large active detector component was lowered into the ATLAS cavern on 1st March. It consisted of the 8 modules forming the lower part of the central barrel of the tile hadronic calorimeter. The work of assembling the barrel, which comprises 64 modules, started the following day. Two road trailers each with 64 wheels, positioned side by side. This was the solution chosen to transport the lower part of the central barrel of ATLAS' tile hadronic calorimeter from Building 185 to the PX16 shaft at Point 1 (see Figure 1). The transportation, and then the installation of the component in the experimental cavern, which took place over three days were, to say the least, rather spectacular. On 25 February, the component, consisting of eight 6-metre modules, was loaded on to the trailers. The segment of the barrel was transported on a steel support so that it wouldn't move an inch during the journey. On 26 February, once all the necessary safety checks had been carried out, the convoy was able to leave Buildi...
From a Cartesian perspective of rational analysis, the electric potential difference across the cell membrane is one of the fundamental concepts for the study of physiology. Unfortunately, undergraduate students often struggle to understand the genesis of this energy gradient, which makes the teaching activity a hard task for the instructor. The topic of bioelectrogenesis encompasses multidisciplinary concepts, involves several mechanisms, and is a dynamic process, i.e., it never turns off during the lifetime of the cell. Therefore, to improve the transmission and acquisition of knowledge in this field, I present an alternative didactic model. The design of the model assumes that it is possible to build, in a series of sequential steps, an assembly of proteins within the membrane of an isolated cell in a simulated electrophysiology experiment. Initially, no proteins are inserted in the membrane and the cell is at a baseline energy state; the extracellular and intracellular fluids are at thermodynamic equilibrium. Students are guided through a sequence of four steps that add key membrane transport proteins to the model cell. The model is simple at the start and becomes progressively more complex, finally producing transmembrane chemical and electrical gradients. I believe that this didactic approach helps instructors with a more efficient tool for the teaching of the mechanisms of resting membrane potential while helping students avoid common difficulties that may be encountered when learning this topic.
Lodwick, Rebecca; Costagliola, Dominique; Reiss, Peter;
the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI...... to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF. CONCLUSIONS: The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over...
姚仕堂; 何纳; 段松; 时允; 李品银; 许元武; 杨文芹; 张银娣; 尹春英; 寸柳青; 翟志坚
目的：了解云南省德宏州成年艾滋病患者抗病毒治疗（ART）脱失比例及其原因。方法对德宏州截至2014年9月30日的参加ART的8367名成年艾滋病患者脱失情况进行调查。结果德宏州累计接受ART的成年艾滋病患者中脱失比例为14.4%（1202/8367）。单因素logistic回归分析，ART脱失与患者所在县（市）、性别、年龄、婚姻状况、感染途径、基线CD4＋T淋巴细胞计数和初始治疗方案有关。多因素logistic回归分析，ART脱失与患者所在县（市）、婚姻状况、感染途径、基线CD4＋T淋巴细胞计数和初始治疗方案有关。芒市、梁河县、盈江县、已婚或同居、性传播、基线CD4＋T淋巴细胞计数≤200 cells/mm3、初始治疗方案含齐多夫定（AZT）者脱失比例低；瑞丽市、未婚、注射吸毒、基线CD4＋T淋巴细胞计数＞200 cells/mm3、初始治疗方案不含AZT者脱失比例高。ART患者随着治疗时间的延长，其脱失比例下降。调查发现1202例脱失治疗的患者中，失访704例（58.6%）、依从性困难303例（25.2%）、外出74例（6.2%）、缅甸籍回国64例（5.3%）、医嘱停药29例（2.4%）、羁押18例（1.5%）、其他原因10例（0.8%）。不同特征患者其脱失原因不同。结论德宏州不同特征的艾滋病患者ART脱失比例不同，需采取针对性的措施以减少脱失，重点是减少失访和提高治疗依从性。%Objective To examine the proportion and reasons of drop-out from antiretroviral therapy(ART)among 8 367 adult HIV-infected individuals in Dehong prefecture,Yunnan province. Methods All adult HIV-infected patients receiving ART before September 30 of 2014 were examined for the situation of drop-out from ART. Results The proportion of drop-out from ART among adult HIV-infected patients in Dehong prefecture was 14.4%(1 202/8 367). Results from the univariate logistic regression analyses indicated that drop-out from ART
Borges, Álvaro H
PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer...
Margaret (Maggie Williams
Full Text Available Despite efforts to scale up access to antiretroviral therapy (ART, particularly at primary health care (PHC facilities, antiretroviral therapy (ART continues to be out of reach for many human immunodeficiency virus (HIV-positive children in sub-Saharan Africa. In resource limited settings decentralisation of ART is required to scale up access to essential medication. Traditionally, paediatric HIV care has been provided in tertiary care facilities which have better human and material resources, but limited accessibility in terms of distance for caregivers of HIV-positive children. The focus of this article is on the experiences of caregivers whilst accessing ART for HIV-positive children at PHC (decentralised care facilities in Nelson Mandela Bay (NMB in the Eastern Cape, South Africa. A qualitative, explorative, descriptive and contextual research design was used. The target population comprised caregivers of HIV-positive children. Data were collected by means of in-depth individual interviews, which were thematically analysed. Guba's model was used to ensure trustworthiness. Barriers to accessing ART at PHC clinics for HIV-positive children included personal issues, negative experiences, lack of support and finance, stigma and discrimination. The researchers recommend standardised programmes be developed and implemented in PHC clinics to assist in providing treatment, care and support for HIV-positive children.
Full Text Available The management of multidrug-resistant human immunodeficiency virus (MDR HIV infections in children is particularly challenging due to the lack of experience with new drugs. Dolutegravir, combined with an optimized antiretroviral background therapy, is promising for the treatment of MDR HIV and has been approved recently for adults and adolescents. Data for children are extremely limited. We describe the efficacy, safety and plasmatic levels of a dolutegravir-based, complex active antiretroviral treatment regimen in a severely overweight 11-year-old child infected with an MDR HIV strain.
Hermanides, H S; Holman, R; Gras, L; Winkel, C N; Gerstenbluth, I; de Wolf, F; Duits, A J
Retention in care is one of the major challenges to scaling up and maximizing the effectiveness of combination antiretroviral therapy (cART). High attrition rates have been reported in the Caribbean region, varying from 6% to 23%. We studied the incidence of and risk factors for intermittent care in a cohort of adult HIV-1-positive patients, who entered into care in Curaçao between January 2005 and July 2009. A total of 214 therapy-naïve HIV-1-infected patients aged 15 years or older, entered HIV care between January 2005 and July 2009. Intermittent care was defined as at least one period of 365 days or longer in which there was no HIV care contact in Curaçao. Cox regression models were used to identify characteristics associated with time to intermittent care. In all, 203 (95%) patients could be classified as having intermittent or continuous care. The incidence of intermittent care before starting cART was 25.4 per 100 person years observation (PYO), whilst it was 6.1 per 100 PYO after starting cART. Being born outside Curaçao was associated with intermittent care before and after starting cART. Time from diagnosis to entry into care was an independent predictor for intermittent care before starting cART. Younger age was independently associated with intermittent care after starting cART. Half of the patients returned to care after intermitting care. Upon returning to care, median CD4 count was 264 cells/mm(3) (IQR, 189-401) for those who intermitted care before starting cART, and 146 cells/mm(3) (IQR, 73-436) in those who intermitted care after starting cART. In conclusion, the incidence of intermitting care is high in Curaçao, especially before starting cART, and intermitting care before starting cART is an independent predictor for starting cART late.
Estelle M. Mclean
Full Text Available Objective: Verbal autopsies (VAs are interviews with a relative or friend of the deceased; VAs are a technique used in surveillance sites in many countries with incomplete death certification. The goal of this study was to assess the accuracy and validity of data on HIV status and antiretroviral therapy (ART usage reported in VAs and their influence on physician attribution of cause of death. Design: This was a prospective cohort study. Methods: The Karonga Health and Demographic Surveillance Site monitors demographic events in a population in a rural area of northern Malawi; a VA is attempted on all deaths reported. VAs are reviewed by clinicians, who, with additional HIV test information collected pre-mortem, assign a cause of death. We linked HIV/ART information reported by respondents during adult VAs to database information on HIV testing and ART use and analysed agreement using chi-square and kappa statistics. We used multivariable logistic regression to analyse factors associated with agreement. Results: From 2003 to 2014, out of a total of 1,952 VAs, 80% of respondents reported the HIV status of the deceased. In 2013–2014, this figure was 99%. Of those with an HIV status known to the study, there was 89% agreement on HIV status between the VA and pre-mortem data, higher for HIV-negative people (92% than HIV-positive people (83%. There was 84% agreement on whether the deceased had started ART, and 72% of ART initiation dates matched within 1 year. Conclusions: In this population, HIV/ART information was often disclosed during a VA and matched well with other data sources. Reported HIV/ART status appears to be a reliable source of information to help classification of cause of death.
Full Text Available Abstract Background Our intention was to analyze demographic and contextual factors associated with sexual risk taking among HIV-infected patients on antiretroviral treatment (ART in Africa's largest informal urban settlement, Kibera in Nairobi, Kenya. Methods We used a cross-sectional survey in a resource-poor, urban informal settlement in Nairobi; 515 consecutive adult patients on ART attending the African Medical and Research Foundation clinic in Kibera in Nairobi were included in the study. Interviewers used structured questionnaires covering socio-demographic characteristics, time on ART, number of sexual partners during the previous six months and consistency of condom use. Results Twenty-eight percent of patients reported inconsistent condom use. Female patients were significantly more likely than men to report inconsistent condom use (aOR 3.03; 95% CI 1.60-5.72. Shorter time on ART was significantly associated with inconsistent condom use. Multiple sexual partners were more common among married men than among married women (adjusted OR 4.38; 95% CI 1.82-10.51. Conclusions Inconsistent condom use was especially common among women and patients who had recently started ART, i.e., when the risk of HIV transmission is higher. Having multiple partners was quite common, especially among married men, with the potential of creating sexual networks and an increased risk of HIV transmission. ART needs to be accompanied by other preventive interventions to reduce the risk of new HIV infections among sero-discordant couples and to increase overall community effectiveness.
Krishnan, S; Schouten, JT; Atkinson, B; Brown, T; Wohl, D; McComsey, GA; Glesby, MJ; Shikuma, C; Haubrich, R; Tebas, P; Campbell, TB; Jacobson, DL
Background Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease and diabetes, many of which are associated with HIV and antiretroviral therapy (ART). We examined prevalence and incidence of MetS, and risk factors for MetS in ART-naïve HIV-infected individuals starting ART. Methods MetS, defined by the Adult Treatment Panel III criteria, was assessed at and after ART initiation in HIV-infected individuals who enrolled in selected AIDS Clinical Trials Group (ACTG) trials and were followed long-term after these trials as part of the ACTG Longitudinal Linked Randomized Trials cohort. Cox proportional hazards models were used to examine risk factors of incident MetS. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) are reported. Results At ART initiation, the prevalence of MetS was 20%. After ART initiation, the incidence of MetS was 8.5 per 100 person-years. After adjusting for demographics and body mass index, the risk of MetS was decreased for CD4+ T-cell counts>50 cells/mm3 (aHR = 0.62, 95% CI=0.43 to 0.90 for CD4>500), and the risk was increased for HIV-1 RNA >400 copies/mL (aHR=1.55 (95% CI=1.25 to 1.92) and use of a protease-inhibitor (PI) based regimen (relative to no PI use, aHR=1.25 (95% CI=1.04 to 1.51) for any PI use). Conclusion In HIV-infected individuals on ART, virologic suppression and maintenance of high CD4+ T-cell counts may be potentially modifiable factors that can reduce the risk of MetS. The effect of MetS on the risk of cardiovascular disease and diabetes needs to be evaluated. PMID:22828718
Jan A C Hontelez
Full Text Available BACKGROUND: Expanded access to antiretroviral therapy (ART using universal test and treat (UTT has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study's finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV. METHODS AND FINDINGS: We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ≤350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study's major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled. CONCLUSIONS: Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic
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.
Cesar, Carina; Jenkins, Cathy A.; Shepherd, Bryan E.; Padgett, Denis; Mejía, Fernando; Ribeiro, Sayonara Rocha; Cortes, Claudia P.; Pape, Jean W.; Madero, Juan Sierra; Fink, Valeria; Sued, Omar; McGowan, Catherine; Cahn, Pedro
Background Access to combination antiretroviral therapy (cART) is expanding in Latin America and the Caribbean (LAC). There is little information in this region regarding incidence of and factors associated with regimen failure and regimen change. Methods Antiretroviral-naïve adults starting cART from 2000-2014 at sites in seven countries throughout LAC were included. Cumulative incidence of virologic failure and major regimen change were estimated with death considered a competing event. Findings 14,027 cART initiators (60% male, median age 37 years, median CD4 156 cells/mm3, median HIV-RNA 5·0 log10 copies/mL, and 28% with clinical AIDS) were followed for a median of 3·9 years. 1,719 patients presented virologic failure and 1,955 had a major regimen change. Excluding GHESKIO-Haiti (which did not regularly measure HIV-RNA), cumulative incidence of virologic failure was 7·8%, 19·2%, and 25·8% at one, three, and five years after cART initiation, respectively; cumulative incidence of major regimen change was 5·9%, 12·7%, and 18·2%. Incidence of major regimen change at GHESKIO-Haiti at five years was 10·7%. Virologic failure was associated with younger age (adjusted hazard ratio[aHR]=2·03 for 20 vs. 40 years; 95% confidence interval[CI] 1·68-2·44), infection through injection-drug use (IDU) (aHR=1·60; 95%CI 1·02-2·52), initiation in earlier calendar years (aHR=1·28 for 2002 vs. 2006; 95%CI 1·13-1·46), and starting with a boosted protease inhibitor (aHR=1·17 vs. non-nucleoside reverse transcriptase inhibitor; 95%CI 1·00-1·64). Interpretation Incidence of virologic failure was generally lower than in North America/Europe. Our results suggest the need to design strategies to reduce failure and major regimen change among younger patients and those with a history of IDU. Funding US National Institutes of Health: U01 AI069923. PMID:26520929
Full Text Available Mohammed Biset Ayalew,1 Dawit Kumilachew,2 Assefa Belay,3 Samson Getu,4 Derso Teju,4 Desalegn Endale,4 Yemisirach Tsegaye,4 Zebiba Wale4 1Department of Clinical Pharmacy, 2Department of Pharmaceutics, 3Department of Pharmacology, 4School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Background: Antiretroviral therapy (ART restores immune function and reduces HIV-related adverse outcomes. But treatment failure erodes this advantage and leads to an increased morbidity and compromised quality of life in HIV patients. The aim of this study was to determine the prevalence and factors associated with first-line ART failure in HIV patients at the University of Gondar Teaching Hospital.Patients and methods: A retrospective study was conducted on 340 adults who had started ART during the period of September 2011 to May 2015. Data regarding patients’ sociodemographics, baseline characteristics, and treatment-related information were collected through review of their medical charts. Data were analyzed using SPSS version 21. Descriptive statistics, cross-tabs, and binary and multiple logistic regressions were utilized. P<0.05 was used to declare association.Results: Among the 340 patients enrolled, 205 were females (60.3%. The mean age at ART initiation was 34.4 years. A total of 14 (4.1% patients were found to have treatment failure. The median duration of treatment failure from initiation of treatment was 17.5 months (8–36 months. Poor adherence to treatment and low baseline CD4 cell count were found to be significant predictors of treatment failure.Conclusion: The prevalence of first-line ART failure was 4.1%. Treatment failure was most likely to occur for the patients who had poor drug adherence and those who were delayed to start ART till their CD4 cell count became very low (<100 cells/mm3. Keywords: treatment failure, antiretroviral drugs, risk factor, adherence
Full Text Available The purpose of this review is to examine the literature for reports of clinically significant interactions noted amongst HIV antiretroviral medications when coadministered with posaconazole. A literature search was conducted to identify studies addressing drug interactions between posaconazole and HIV antiretroviral medications. Two pharmacokinetic studies and three clinical trials involving the administration of posaconazole to HIV-infected patients were identified. The pharmacokinetic studies involved concomitant administration of either a protease inhibitor (PI or non-nucleoside reverse transcriptase inhibitor (NNRTI. Both studies showed alterations in systemic concentrations of either posaconazole or the HIV antiretroviral when administered together. Of the three clinical trials, all patients were on HIV antiretrovirals. However, their potential interaction with posaconazole was not explored. To date, there is no published literature regarding the interaction between maraviroc or elvitegravir and posaconazole. Dose adjustments for each are recommended when coadministered with strong CYP 3A4 inhibitors or inducers. Currently available literature points to the potential for clinically significant drug interactions when posaconazole is coadministered with HIV antiretrovirals, specifically NNRTIs and PIs. More studies are needed involving a wider range of HIV antiretrovirals to determine the significance of the interaction. Clinicians should be aware of this potentially significant interaction and avoid concomitant administration when possible. When available, consideration should be given to therapeutic drug monitoring of antiretroviral serum concentrations in select patients.
Phelps Benjamin R
Full Text Available Abstract Background Lack of adherence to antiretroviral medications is one of the key challenges for paediatric HIV care and treatment programmes. There are few hands-on opportunities for healthcare workers to gain awareness of the psychosocial and logistic challenges that caregivers face when administering daily antiretroviral therapy to children. This article describes an educational activity that allows healthcare workers to simulate this caregiver role. Methods Paediatric formulations of several antiretroviral medications were dispensed to a convenience sample of staff at the Baylor College of Medicine-Bristol-Myers Squibb Children's Clinical Center of Excellence in Mbabane, Swaziland. The amounts of the medications remaining were collected and measured one week later. Adherence rates were calculated. Following the exercise, a brief questionnaire was administered to all staff participants. Results The 27 clinic staff involved in the exercise had varying and low adherence rates over the week during which the exercise was conducted. Leading perceived barriers to adherence included: "family friends don't help me remember/tell me I shouldn't take it" and "forgot". Participants reported that the exercise was useful as it allowed them to better address the challenges faced by paediatric patients and caregivers. Conclusions Promoting good adherence practices among caregivers of children on antiretrovirals is challenging but essential in the treatment of paediatric HIV. Participants in this exercise achieved poor adherence rates, but identified with many of the barriers commonly reported by caregivers. Simulations such as this have the potential to promote awareness of paediatric ARV adherence issues among healthcare staff and ultimately improve adherence support and patient outcomes.
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.
ZHAO De-cai; ZHANG Fu-jie; WEN Yi; MA Ye; ZHAO Yan; ZHANG Yao; WU Ya-song; LIU Xia; Elizabeth Au; LIU Zhong-fu
Background In 2003,China's National Free Antiretroviral Treatment Program (NFATP) was initiated as a pilot,which covered only 100 HIV/AIDS patients.By 2011,the pilot had evolved into a nationwide program and had provided free treatment for over 150 000 patients.The objective of this study was to report and evaluate the progress of China's free antiretroviral treatment program.Methods The NFATP Database was systematically reviewed and a total of 150 692 HIV/AIDS patients were included in this study.Program progress indicators including the number of treated HIV/AIDS patients,follow-up visit rate,CD4 test rate,and viral load test rate were summarized and examined over a calendar year to evaluate the progress of NFATP quantitatively and qualitatively.Results By the end of 2011,a total of 150 692 HIV/AIDS patients had been treated through the NFATP and 122 613 of them were still on treatment.Of all patients,about 72％ were enrolled during the past four years.The dominant transmission route was blood related in the early phase of the NFATP,but gradually changed to sexual contact.Besides quantitative improvements,progress indicators also demonstrated significant qualitative improvements that the program had made during the past 9 years.Conclusions Great achievement has been made by China's NFATP.China's experience indicates the importance of a comprehensive response to the success of its treatment program.However,to ensure the quality and sustainability of treatment in the long term,more attention and resources should be paid towards program management.Chin Med J 2012; 125(19):3514-3521
Nyasha Bakare; Ivor Ralph Edwards; Andy Stergachis; Shanthi Pal; Holmes, Charles B; Marie Lindquist; Chris Duncombe; Alex Dodoo; Joel Novendstern; Jude Nwokike; Ricardo Kuchenbecker; Aberg, Judith A.; Veronica Miller; Jur Strobos
Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings.
Full Text Available Abstract Objective To evaluate the feasibility of a large immediate versus deferred antiretroviral therapy (ART study in children. Methods We conducted an open-label pilot randomized clinical trial study in 43 Thai children with CD4 15 to 24% of starting generic AZT/3TC/NVP immediately (Arm 1 or deferring until CD4 Results Recruitment took 15 months. Twenty-six of 69 (37.7% were not eligible due mainly to low CD4%. Twenty four and 19 were randomized to arms 1 and 2 respectively. All accepted the randomized arm; however, 3 in arm 1 stopped ART and 1 in arm 2 refused to start ART. Ten/19 (53% in arm 2 started ART. At baseline, median age was 4.8 yrs, CDC A:B were 36:7, median CD4 was 19% and viral load was 4.8 log. All in arm 1 and 17/19 in arm 2 completed the study (median of 134 weeks. No one had AIDS or death. Four in immediate arm had tuberculosis. Once started on ART, deferred arm children achieved similar CD4 and viral load response as the immediate arm. Adverse events were similar between arms. The deferred arm had a 26% ART saving. Conclusion Almost 40% of children were not eligible due mainly to low CD4% but adherence to randomized treatment and retention in trial were excellent. A larger study to evaluate when to start ART is feasible.
Cattaneo, Dario; Baldelli, Sara; Castoldi, Simone; Charbe, Nitin; Cozzi, Valeria; Fucile, Serena; Clementi, Emilio
We document our experience with therapeutic drug monitoring (TDM) of antiretroviral agents (1807 determinations) carried out as day-by-day clinical practice for the optimization of drug dosing in HIV-infected patients. A significant proportion of patients had lopinavir, atazanavir and nevirapine trough concentrations exceeding the upper therapeutic threshold. Further studies are needed to identify good candidates/drugs for TDM, eventually allowing the selection of patients who may benefit from TDM-driven adjustments in antiretrovirals dosage.
Full Text Available Abstract Background Data on combination antiretroviral therapy (cART in remote rural African regions is increasing. Methods We assessed prospectively initial cART in HIV-infected adults treated from 2005 to 2008 at St. Francis Designated District Hospital, Ifakara, Tanzania. Adherence was assisted by personal adherence supporters. We estimated risk factors of death or loss to follow-up by Cox regression during the first 12 months of cART. Results Overall, 1,463 individuals initiated cART, which was nevirapine-based in 84.6%. The median age was 40 years (IQR 34-47, 35.4% were males, 7.6% had proven tuberculosis. Median CD4 cell count was 131 cells/μl and 24.8% had WHO stage 4. Median CD4 cell count increased by 61 and 130 cells/μl after 6 and 12 months, respectively. 215 (14.7% patients modified their treatment, mostly due to toxicity (56%, in particular polyneuropathy and anemia. Overall, 129 patients died (8.8% and 189 (12.9% were lost to follow-up. In a multivariate analysis, low CD4 cells at starting cART were associated with poorer survival and loss to follow-up (HR 1.77, 95% CI 1.15-2.75, p = 0.009; for CD4 100 cells/μl. Higher weight was strongly associated with better survival (HR 0.63, 95% CI 0.51-0.76, p Conclusions cART initiation at higher CD4 cell counts and better general health condition reduces HIV related mortality in a rural African setting. Efforts must be made to promote earlier HIV diagnosis to start cART timely. More research is needed to evaluate effective strategies to follow cART at a peripheral level with limited technical possibilities.
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
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.
This diploma thesis is dedicated to marketing of start-ups and the most frequent mistakes they make in this field. The goal of this thesis is to propose recommendations for start-up founders which could help them avoid mistakes while building their business. The thesis is divided into three parts. The first part defines the concept of start-ups, explores their history and introduces the main issues start-ups have to deal with in the field of marketing. The second part contains interviews with...
Full Text Available Giorgio L Colombo,1,2 Antonella Castagna,3 Sergio Di Matteo,2 Laura Galli,3 Giacomo Bruno,2 Andrea Poli,3 Stefania Salpietro,3 Alessia Carbone,3 Adriano Lazzarin3,41Department of Drug Sciences, School of Pharmacy, University of Pavia, Italy; 2Studi Analisi Valutazioni Economiche (S.A.V.E., Milan, 3Infectious Diseases Department, San Raffaele Hospital, Milan, 4Vita-Salute San Raffaele University, Milan, ItalyObjective: In the study reported here, single-tablet regimen (STR versus (vs multi-tablet regimen (MTR strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART. Adult human immunodeficiency virus (HIV 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis.Methods: The most frequently used first-line HAART regimens (>10% were grouped into two classes: 1 STR of tenofovir disoproxil fumarate (TDF + emtricitabine (FTC + efavirenz (EFV and 2 MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r, TDF + FTC + darunavir/ritonavir (DRV/r, and TDF + FTC + lopinavir/ritoavir (LPV/r. Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR were examined using chi-square or Fisher's exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens.Results: A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log10 copies/mL, and cluster of
Full Text Available Study of plasma and intracellular concentrations of atazanavir, lopinavir, nevirapine, and efavirenz was conducted on 48 patients under short cycles of antiretroviral therapy. Intracellular concentrations (IC were still measurable for all drugs after 85 h or 110 h drug intake despite the absence of drug in plasma for atazanavir and lopinavir. A linear relationship between plasma and intracellular efavirenz was observed. Further studies to fully understand the impact of IC in the intermittent antiviral treatment are required.
Antonieta Medina Lara
Full Text Available BACKGROUND: Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART have rarely been evaluated. METHODS: Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779. Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM or laboratory and clinical monitoring (LCM; individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial. RESULTS: 3316 (1660LCM;1656CDM symptomatic, immunosuppressed ART-naive adults (median (IQR age 37 (32,42; CD4 86 (31,139 cells/mm(3 were followed for median 4.9 years. LCM had a mean 0.112 year (41 days survival benefit at an additional mean cost of $765 [95%CI:685,845], translating into an adjusted incremental cost of $7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below $3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks. CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term. CONCLUSIONS: There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low
Landersø, Rasmus; Nielsen, Helena Skyt; Simonsen, Marianne
This paper investigates the effects of school starting age on crime while relying on variation in school starting age induced by administrative rules; we exploit that Danish children typically start first grade in the calendar year they turn seven, which gives rise to a discontinuity in children......’s school starting age. Analyses are carried out using register-based Danish data. We find that higher age at school start lowers the propensity to commit crime, but that this reduction is caused by incapacitation while human capital accumulation is unaffected. Importantly, we also find that the individuals...... who benefit most from being old-for-grade are those with high latent abilities whereas those with low latent ability seem to be unaffected by being old-for-grade in school....
GABA transporter 1(GAT1)takes important roles in multiple physiological processes through the uptake and release of GABA,but the regulation of GAT1 gene expression in different tissues is rarely known.To address the question,first,5' Rapid amplification of cDNA end(RACE)was used to determine GAT1 transcriptional starting sites in neonatal mouse cerebral cortex and intestine,adult mouse brain and adult rat testis.The products of 5'RACE were confirmed by DNA sequencing.We found that the transcript of GAT1 in neonatal mouse cerebral cortex and adult mouse brain starts at the same site(inside of exon 1),while in mouse intestine,GAT1 starts transcription in intron 1,and in rat testis,the transcript of GAT1 has an additional untranslation exon to the 5' direction.
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.
González, Ramón E. R.; Coutinho, Sérgio; Zorzenon dos Santos, Rita Maria; de Figueirêdo, Pedro Hugo
The dynamics of human immunodeficiency virus infection under antiretroviral therapy is investigated using a cellular automata model where the effectiveness of each drug is self-adjusted by the concentration of CD4+ T infected cells present at each time step. The effectiveness of the drugs and the infected cell concentration at the beginning of treatment are the control parameters of the cell population’s dynamics during therapy. The model allows describing processes of mono and combined therapies. The dynamics that emerges from this model when considering combined antiretroviral therapies reproduces with fair qualitative agreement the phases and different time scales of the process. As observed in clinical data, the results reproduce the significant decrease in the population of infected cells and a concomitant increase of the population of healthy cells in a short timescale (weeks) after the initiation of treatment. Over long time scales, early treatment with potent drugs may lead to undetectable levels of infection. For late treatment or treatments starting with a low density of CD4+ T healthy cells it was observed that the treatment may lead to a steady state in which the T cell counts are above the threshold associated with the onset of AIDS. The results obtained are validated through comparison to available clinical trial data.
Sandeep D Patel
Full Text Available BACKGROUND: In South Africa in 2010, about 340,000 children under the age of 15 were infected with HIV. We describe the increase in the treatment of South African pediatric HIV-infected patients assisted by the President's Emergency Plan for AIDS Relief (PEPFAR from 2004 to 2010. METHODS: We reviewed routine program data from PEPFAR-funded implementing partners among persons receiving antiretroviral treatment age 15 years old and less. Data quality was assessed during the reporting period by program officials through routine analysis of trends and logic checks. Based on UNAIDS estimated mortality rates of untreated HIV-infected children, we calculated the number of deaths averted and life-years gained in children under five receiving PEPFAR-assisted antiretroviral treatment. RESULTS: From October 2004 through September 2010, the number of children newly initiated on antiretroviral treatment in PEPFAR-assisted programs increased from 154 to 2,641 per month resulting in an increase from 2,412 children on antiretroviral treatment in September 2005 to 79,416 children in September 2010. Of those children who initiated antiretroviral treatment before September 2009, 0-4 year olds were 1.4 (95% CI: 1.3-1.5 times as likely to transfer out of the program or die as 5-14 year olds; males were 1.3 (95% CI: 1.0-1.7 times as likely to stop treatment as females. Approximately 27,548 years of life were added to children under-five years old from PEPFAR-assisted antiretroviral treatment. CONCLUSIONS: Pediatric antiretroviral treatment in South Africa has increased substantially. However, additional case-finding and a further acceleration in the implementation of pediatric care and treatment services is required to meet the current treatment need.
Ripin, David J; Jamieson, David; Meyers, Amy; Warty, Umesh; Dain, Mary; Khamsi, Cyril
Procurement, the country-level process of ordering antiretrovirals (ARVs), and supply chain management, the mechanism by which they are delivered to health-care facilities, are critical processes required to move ARVs from manufacturers to patients. To provide a glimpse into the ARV procurement and supply chain, the following pages provide an overview of the primary stakeholders, principal operating models, and policies and regulations involved in ARV procurement. Also presented are key challenges that need to be addressed to ensure that the supply chain is not a barrier to the goal of universal coverage. This article will cover the steps necessary to order and distribute ARVs, including different models of delivery, key stakeholders involved, strategic considerations that vary depending on context and policies affecting them. The single drug examples given illustrate the complications inherent in fragmented supply and demand-driven models of procurement and supply chain management, and suggest tools for navigating these hurdles that will ultimately result in more secure and reliable ARV provision. Understanding the dynamics of ARV supply chain is important for the global health community, both to ensure full and efficient treatment of persons living with HIV as well as to inform the supply chain decisions for other public health products.
Full Text Available Abstract Background Studies indicate that there is high early mortality among patients starting antiretroviral treatment in sub-Saharan Africa. However, there is paucity of evidence on long term survival of patients on anti-retroviral treatment in the region. The objective of this study is to examine mortality and its predictors among a cohort of HIV infected patients on anti-retroviral treatment retrospectively followed for five years. Methods A retrospective cohort study was conducted among HIV infected patients on ART in eastern Ethiopia. Cox regression and Kaplan-Meier analyses were performed to investigate factors that influence time to death and survival over time. Result A total of 1540 study participants were included in the study. From the registered patients in the cohort, the outcome of patients as active, deceased, lost to follow up and transfer out was 1005 (67.2%, 86 (5.9%, 210 (14.0% and 192 (12.8% respectively. The overall mortality rate provides an incidence density of 2.03 deaths per 100 person years (95% CI 1.64 - 2.50. Out of a total of 86 deaths over 60 month period; 63 (73.3% died during the first 12 months, 10 (11.6% during the second year, and 10 (11.6% in the third year of follow up. In multivariate analysis, the independent predictors for mortality were loss of more 10% weight loss, bedridden functional status at baseline, ≤ 200 CD4 cell count/ml, and advanced WHO stage patients. Conclusion A lower level of mortality was detected among the cohort of patients on antiretroviral treatment in eastern Ethiopia. Previous history of weight loss, bedridden functional status at baseline, low CD4 cell count and advanced WHO status patients had a higher risk of death. Early initiation of ART, provision of nutritional support and strengthening of the food by prescription initiative, and counseling of patients for early presentation to treatment is recommended.
Resino, Salvador; Alvaro-Meca, Alejandro; de José, Maria Isabel; Martin-Fontelos, Pablo; Gutiérrez, Maria Dolores Gurbindo; Léon, Juan Antonio; Ramos, José Tomás; Ciria, Luis; Muñoz-Fernández, Maria Angeles
We conducted a retrospective study to analyze the CD4 recovery of naive vertically human immunodeficiency virus-infected children with severe immunodeficiency who were followed up during at least 4 years of receiving highly active antiretroviral therapy (HAART). Children with baseline CD4 of or =25% after the 4th year on HAART. We conclude that starting HAART after severe immunosuppression of naive HIV-infected children may not be effective for recovery of normal %CD4.
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.
Full Text Available Abstract Background Antiretroviral scale-up is increasing in resource-constrained settings. To date, few studies have explored the barriers and facilitators of adherence to ART in these settings. Facilitators and barriers of antiretroviral adherence in Peru are not completely understood. Methods At two clinics that serve a large number of HIV-positive individuals in Lima, Peru, 31 in-depth interviews were carried out in 2006 with adult HIV-positive individuals receiving ART. Purposive sampling was used to recruit the participants. Interviews were transcribed and coded using two Spanish-speaking researchers and a content analysis approach to identify themes in the data. Results Among the participants, 28/31 (90% were male, 25/31 (81% were self-identified as mestizo, and 19/31 (61% had an education above high school. The most frequently discussed barriers to adherence included side effects, simply forgetting, inconvenience, dietary requirements, being away from home, and fear of disclosure/stigma. The most frequently discussed facilitators to adherence included having a fixed routine, understanding the need for compliance, seeing positive results, treatment knowledge, and faith in treatment. Conclusions Overall, these findings were similar to the facilitators and challenges experienced by individuals on ART in other resource constrained settings. Further treatment support tools and networks should be developed to decrease the challenges of ART adherence for HIV-positive individuals in Lima, Peru.
Nyanzi-Wakholi, Barbara; Lara, Antonieta Medina; Munderi, Paula; Gilks, Charles
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 improved physical health, restored self-esteem, acceptance in the community and hope for a longer and healthier life and reduced fear of HIV/AIDS-related death. Barriers to adherence included a high pill burden, ART side effects and socio-economic constraints, including lack of food and safe water for taking the pills. Visible ART side effects and involvement in an exclusively HIV/AIDS clinic could expose their HIV status, thus exacerbating stigma. Gender and socio-economic differences were found in the variety of strategies employed to ensure adherence. ART was perceived as improving the overall quality of life of recipients; however, it is crucial for ART programmes to be gender and socio-economic cognizant in order to enhance adherence to a lifelong therapy.
Cozzi-Lepri, Alessandro; Phillips, Andrew N; Clotet, Bonaventura;
OBJECTIVE(S): To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death. DESIGN: Virological failure was defined as experiencing two consecutive viral loads of more than 400......-up. We observed 829 AIDS events and 571 deaths during 38,814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis...
Ricketts, Kenneth E.
Describes how Lawndale District, near Los Angeles, developed a system of accountability starting with the superintendent. Describes the subgoals and objectives developed by the superintendent in cooperation with the Board of Trustees and members of the community. (JF)
Clifford, Alcillia; Kahn, David
Discusses the use of the Montessori method in Head Start programs, focusing on educational environment, teacher training, parent involvement, and funding. Outlines the phased implementation of a Montessori program and provides a list of Montessori publications and organizations. (MDM)
Dickinson, Laura; Khoo, Saye; Back, David
Current antiretroviral treatment has allowed HIV infection to become a chronic manageable condition with many HIV patients living longer. However, available antiretrovirals are not without limitations, for example the development of resistance and adverse effects. Consequently, new drugs in existing and novel classes are urgently required to provide viable treatment options to patients with few remaining choices. Darunavir, etravirine, maraviroc and raltegravir have been recently approved for treatment-experienced patients and other agents such as rilpivirine, vicriviroc and elvitegravir are currently under phase III study. Clinical studies are necessary to optimise potential treatment combinations and to manage drug-drug interactions to help avoid toxicity or therapy failure. This review aims to summarise the pharmacokinetics and key drug-drug interaction studies for newly available antiretrovirals and those in development. Further information regarding drug-drug interactions of well established antiretrovirals and those recently approved are readily available online at sites such as http://www.hiv-druginteractions.org, http://www.clinicaloptions.com/hiv, http://hivinsite.ucsf.edu. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.
Ballif, Marie; Renner, Lorna; Claude Dusingize, Jean;
BACKGROUND: The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. METHODS: We describe TB diagnosis...... and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries...... participated in the study. RESULTS: Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART...
Campos, Lorenza Nogueira; Guimarães, Mark Drew Crosland; Remien, Robert H
Depression and anxiety are common among HIV-infected people and rank among the strongest predictors of non-adherence to antiretroviral therapy (ART). This longitudinal study aimed to assess whether symptoms of anxiety and depression are predictors of non-adherence among patients initiating ART at two public referral centers (n = 293) in Belo Horizonte, Brazil. Prevalence of severe anxiety and depression symptoms before starting ART was 12.6% and 5.8%, respectively. Severe anxiety was a predictor of non-adherence to ART during follow-up period (RH = 1.87; 95% CI = 1.14-3.06) adjusted for low education, unemployment, alcohol use in the last month and symptoms of AIDS; while a history of injection drug use had borderline statistical significance with non-adherence. These findings suggest that using a brief screening procedure to assess anxiety and depression symptoms before initiating ART help identify individuals for interventions to improve adherence and quality of life.
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...
Elenga, Narcisse; Hanf, Matthieu; Nacher, Mathieu
French Guiana is the French territory where the HIV epidemic is most preoccupying. In Cayenne, the mother to child HIV transmission rate was 6% in 2006-2008. Despite free testing and treatment, HIV pregnant women often have delayed or insufficient access to care. The aim of this study was to identify predictive factors of antiretroviral treatmentFrench Guiana) and then to describe their attitudes, practices, and beliefs regarding HIV/AIDS. A case control study was conducted including all deliveries in Cayenne from 2003 to 2010. For each case, a standardized questionnaire including epidemiological, clinical, and biological data was administered. The analysis first described the summary statistics and then bivariate analysis studied the relation of each variable with the outcome. Multivariate analysis adjusted for the confounding factors. Thirty-three women in the first group and 96 in the control group were included in the study. Women born in French Guiana (OR = 5, IC95% = 1.22-20.86, p=0.027) had a high risk of treatment<4 weeks. The other factors associated with treatment<4 weeks in our study were benefiting from food parcels (OR = 12.72, IC95% = 2.07-78.14, p=0.006), consulting a traditional healer when sick (OR = 9.86, IC95% = 2.57-37.88, p= < 0.001), and drug use (OR = 6.27, IC95% = 1.26-31.13, p=0.025). These predictive factors should be considered in prevention programs against mother to child transmission of HIV.
[CLINICAL AND PHARMACOECONOMIC RESULTS OF THE USAGE OF VARIOUS HIV REVERSE TRANSCRIPTASE INHIBITORS IN THE SCHEMES OF ANTIRETROVIRAL THERAPY OF PATIENT RECEIVING THERAPY FOR THE CHRONIC HEPATITIS C VIRUS].
Moshkovich, G F; Minaeva, S V; Varlova, L W; Goryaeva, M P; Gulyaeva, S S; Tichonova, E V
Efficacy, safety, and economical aspects of treatment with abacavir, zidovudine, stavudine, and phosphazide in the schemes of antiretroviral therapy of the HIV-infected patients receiving therapy for hepatitis C virus were tested. Clinical, immunological, and virologic efficacy of treatment and dynamics of hemoglobin, thrombocytes, and alanine aminotransferase as markers of common adverse events recorded at the start of the antiviral therapy of chronic hepatitis C and after 4, 8, 12, 24, 48 weeks of the treatment were evaluated. The usage of these drugs in the schemes of antiretroviral therapy exhibited efficacy, high tolerability and safety for all HIV reverse transcriptase inhibitors.
Dillingham, Rebecca A.; Pinkerton, Relana; Leger, Paul; Severe, Patrice; Guerrant, Richard L.; Pape, J. William; Fitzgerald, Daniel W
This case-control study examines whether chronic diarrhea at initiation of antiretroviral therapy (ART) affects survival of human immunodefiency virus–infected patients. Cases (288) were treatment-naive, non-pregnant, adults with self report of frequent loose stool for > 3 weeks at the time ART was initiated. One-third of patients had an enteric pathogen identified including Cryptosporidium spp., Giardia spp., Isospora belli, Cyclospora cayetanensis, and Entamoeba histolytica. Control patient...
Michael N. Neely
Full Text Available Large populations of HIV-infected and exposed infants, children and adolescents are increasingly exposed to antiretroviral therapy throughout dramatic changes of the body composition and maturation process in utero, perinatally and during the later growth and development throughout childhood and puberty. The majority of HIV-infected children live in the resource-limited setting where the presence of other significant co-morbidities such as malnutrition, tuberculosis and malaria complicates the selection of the most effective, safe and least toxic combination of antiretroviral drug therapy. This review focuses on the role of the pharmacokinetic factors including clinically important drug-drug interactions on the therapeutic targets of antiretroviral therapy throughout childhood and adolescence. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research
Superior adherence to HIV-1 antiretroviral therapy is a mainstay of successful HIV management. Studies performed in the early era of highly active antiretroviral therapy demonstrated the need for > or =95% adherence in order to achieve and sustain viral suppression. High rates of viral suppression have been observed at more moderate levels of adherence with newer antiretroviral regimens. The term 'forgiveness' is being used to describe the ability of a regimen to achieve and sustain viral suppression, despite suboptimal adherence. A variety of pharmacological, viral and host properties determine the level of forgiveness of any specific regimen. As the choice of treatment options continues to expand, forgiveness of non-adherence is likely to emerge as an increasingly important factor in therapeutic decision-making.
Nattrass, Nicoli J
Despite unprecedented international mobilisation to support universal provision of highly active antiretroviral therapy (HAART), national governments continue to play the key role in determining access to treatment. Whereas some AIDS-affected countries have performed as well as or better than expected given their level of development, institutional characteristics and demographic challenges (e.g. Thailand and Brazil), others (notably South Africa) have not. This article argues that the 'economics' of antiretroviral drug delivery is at heart a political-economy of access to treatment. It depends on commitment on the part of national governments to negotiate with pharmaceutical companies over patented antiretroviral drug prices, on their policy towards compulsory licensing, and on the approach they adopt to delivering HAART. Civil society has an important role to play in encouraging governments to become, and remain, committed to taking action to ensure sustainable and widespread access to HAART.
Full Text Available HIV management is currently in an era of effective, potent antiretroviral therapy. Modern drug discovery and development have transformed HIV-1 disease into a treatable, chronic infectious disease. Complete suppression of viral replication is critical for long-term durability of antiretroviral therapy. Partial suppression, even at very low levels, is likely to lead to virologic failure and ultimately to the appearance of drug resistance. The relationship between adherence and resistance to HIV antiretroviral therapy is more complex than to state ′non-adherence increases the risk of drug resistance.′ In many patients who fail to respond to initial therapy, the primary reason for failure is their inability to take the prescribed drug regimen or nonadherence.
Rasmussen, Dlama; da Silva Te, David; Rodkjær, Lotte Ørneborg;
Adherence is a decisive factor in achieving a successful response to antiretroviral therapy (ART) for HIV infection. No previous studies have been conducted regarding HIV treatment adherence in Guinea-Bissau. In this study we assessed barriers and facilitators to patient ART adherence. Semi......-structured interviews were conducted with 20 adult, HIV infected individuals receiving ART at a HIV treatment centre in Bissau, Guinea-Bissau. The grounded theory method was used to gather and analyse data. Results indicated that HIV-related knowledge was a determining factor for optimal adherence. The facilitators...
Full Text Available 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 failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR: 57.28–99.89 and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L of serum selenium, we observed increased hazards (adjusted hazards ratio (HR: 3.50; 95% confidence intervals (CI: 1.30–9.42 of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium.
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.
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.
Tymejczyk, Olga; Hoffman, Susie; Kulkarni, Sarah Gorrell; Gadisa, Tsigereda; Lahuerta, Maria; Remien, Robert H; Elul, Batya; El-Sadr, Wafaa; Melaku, Zenebe; Nash, Denis
To better understand patient beliefs, which may influence adherence to HIV care and treatment, we examined three dimensions of beliefs among Ethiopian adults (n = 1177) initiating antiretroviral therapy (ART). Beliefs about benefits of ART/HIV clinical care were largely accurate, but few patients believed in the ability of ART to prevent sexual transmission and many thought Holy Water could cure HIV. Factors associated with lower odds of accurate beliefs included advanced HIV, lack of formal education, and Muslim religion (benefits of ART/clinical care); secondary or university education and more clinic visits (ART to prevent sexual transmission); and pregnancy and Orthodox Christian religion (Holy Water). Assessment of patient beliefs may help providers identify areas needing reinforcement. In this setting, counselors also need to stress the benefits of ART as prevention and that Holy Water should not be used to the exclusion of HIV care and ART.
Ian R Grubb
Full Text Available Introduction: Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART, and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion: Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions: Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including
Hudson, Hank; Grigson, Susan [Ortloff Engineers Ltd. (United States)
The authors discuss an Ortloff sulfur plant design concept using the Claus reaction that differs from accepted 'industry practice': cold reactor bed start-up. The process is designed to eliminate catalyst sulfation, heat damage and furnace overheating in sulfur recovery units. (UK)
@@ As of July, scientists at the CAS Center for Space Science and Applied Research (CSSAR) have been busy modulating and testing the payloads that will be onboard a space exploration satellite, marking the start of the countdown for China's Double Star Project.
Full Text Available Introduction: Combination antiretroviral therapy (ART significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment. Methods: Participants from the Canadian Observational Cohort (CANOC, a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec were included. Late initiation was defined as a CD4 count <200 cells/mm3 or an AIDS-defining illness before ART initiation (baseline. Temporal trends were assessed using the Cochran–Armitage test, and independent correlates of late initiation were identified using logistic regression. Results: In total, 8942 participants (18% female of median age 40 years (Q1–Q3 33–47 were included. The median baseline CD4 count increased from 190 cells/mm3 (Q1–Q3 80–320 in 2000 to 360 cells/mm3 (Q1–Q3 220–490 in 2012 (p<0.001. Overall, 4274 participants (48% initiated ART with a CD4 count <200 cells/mm3 or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec, persons with injection drug use (IDU history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012 predictors using an updated CD4 criterion (<350 cells/mm3, IDU and residence in BC (vs. Québec were no longer significant correlates of late initiation. Conclusions: This analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.
Full Text Available Abstract Background The HIV and AIDS epidemic in Malawi poses multiple challenges from an equity perspective. It is estimated that 12% of Malawians are living with HIV or AIDS among the 15-49 age group. This paper synthesises available information to bring an equity lens on Counselling and Testing (CT and Antiretroviral Therapy (ART policy, practice and provision in Malawi. Methods A synthesis of a wide range of published and unpublished reports and studies using a variety of methodological approaches was undertaken. The analysis and recommendations were developed, through consultation with key stakeholders in Malawi. Findings At the policy level Malawi is unique in having an equity in access to ART policy, and equity considerations are also included in key CT documents. The number of people accessing CT has increased considerably from 149,540 in 2002 to 482,364 in 2005. There is urban bias in provision of CT and more women than men access CT. ART has been provided free since June 2004 and scale up of ART provision is gathering pace. By end December 2006, there were 85,168 patients who had ever started on ART in both the public and private health sector, 39% of the patients were male while 61% were female. The majority of patients were adults, and 7% were children, aged 14 years or below. Despite free ART services, patients, especially poor rural patients face significant barriers in access and adherence to services. There are missed opportunities in strengthening integration between CT and ART and TB, Sexually Transmitted Infections (STI and maternal health services. Conclusion To promote equitable access for CT and ART in Malawi there is need to further invest in human resources for health, and seize opportunities to integrate CT and ART services with tuberculosis, sexually transmitted infections and maternal health services. This should not only promote access to services but also ensure that resources available for CT and ART strengthen
Full Text Available Purpose: To study the various changes in the course of cytomegalovirus (CMV retinitis following combination antiretroviral treatment. Methods: Combination antiretroviral treatment was given to 12 patients with active CMV retinitis following which all anti-CMV medications were discontinued once the CD4 cell counts were> 100/mm3 for 3 months. Results: The median CD4 cell count increased from 36.5/mm3 (range, 3-74/mm3 at baseline to 175.5/mm3 (range, 97-410/mm3 at 3 months. No patient had reactivation of CMV retinitis or developed extraocular CMV infection during median follow-up of 16.7 months. In one patient with peripheral active CMV retinitis, the retinitis resolved completely and remained so throughout the follow-up period without specific anti-CMV treatment. Five (41.7% patients had immune recovery vitritis. Conclusion: Patients receiving combination antiretroviral treatment following treatment for CMV retinitis have better control of CMV retinitis but immune recovery vitritis is a common sequelae. Reactivation of CMV retinitis is common in patients who discontinue combination antiretroviral treatment
Lohse, N.; Ladefoged, K.; Obel, N.
Analyses from the Danish HIV Cohort Study showed that, despite comparable economic means and general education of healthcare personnel, antiretroviral treatment of HIV in Greenland began later and has been implemented at a slower pace with lower therapeutic effectiveness than in Denmark. However...
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; Scasso, A; Vincenti, A; Abbadesse, V.; Mancuso, S; Alberici, F; Ruggieri, A; Arlotti, M; Ortolani, P; De Lalla, F; Tositti, G; Piersantelli, N; Piscopo, R; Raise, E; Pasquinucci, S; Soscia, F; Tacconi, L; Tirelli, U; Nasti, G; Santoro, D; Pusterla, L; Carosi, G; Castelli, F; Cadeo, G; Vangi, D; Carnevale, G; Galloni, D; Filice, G; Bruno, R; Sinicco, A; Sciandra, M; Caramello, P; Gennero, L; Soranzo, ML; Bonasso, M; Rizzardini, G; Migliorino, G; Chiodo, F; Colangeli, V.; Magnani, G; Ursitti, M; Menichetti, F; Martinelli, C; Esposito, R; Mussini, C; Ghinelli, F; Sighinolfi, L; Coronado, O; Zauli, T; Ballardini, G; Montroni, M; Zoli, A; Petrelli, E; Cioppi, A; Ortona, L; De Luca, A; Petrosillo, N; Noto, P; Narciso, P; Salcuni, P; Antinori, A; De Longis, P; Vullo, V.; Lichtner, M; Pastore, G; Minafra, G; Chiriann, A; Loiacono, L; Piazza, M; Nappa, S; Abrescia, N; De Marco, M; Colomba, A; Prestileo, T; De Stefano, C; La Gala, A; Ferraro, T; Scerbo, A; Grima, P; Tundo, P; Pizzigallo, E; D'Alessandro, M; Grisorio, B; Ferrara, S; Pradier, C; Fontas, E; Caissotti, C; Dellamonica, P; Bentz, L; Bernard, E; Chaillou, S; De Salvador-Guillouet, F; Durant, J; Guttman, R; Heripret, L; Mondain-Miton, V.; Perbost, I.; Prouvost-Keller, B; Pugliese, P; Rahelinirina, V.; Roger, PM; Vandenbos, F; Bernasconi, E; Bucher, H; Burgisser, P; Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Ten Napel, C.
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
P.L.A. Fraaij (Pieter); J.J.A. van Kampen (Jeroen); D.M. Burger (David); R. de Groot (Ronald)
textabstractThe initiation of antiretroviral therapy has resulted in an impressive reduction in the rate of disease progression in AIDS and HIV-1-related deaths in children; however, there are still several major challenges to be faced in order to improve therapy. A major topic that needs to be deal
Yazdanpanah, Y; Schwarzinger, M
The cost of HIV care in European countries is high. Direct medical costs, in France, have been estimated at 500,000 Euros per patient's lifetime (20,000 Euros/year/patient). Overall, 73% of these costs are related to antiretroviral treatments. In the current financial crisis context, some European countries are beginning to make economic decisions on the drugs to be used. These approaches are likely to become more frequent. It is obviously essential to prescribe the most effective, appropriate, best tolerated, and easy-to-use antiretroviral treatments to patients. However, while taking the above into consideration, and if various treatment options or combinations are available, cost should also be considered in the treatment choice. One may thus reflect on the use of generic antiretroviral agents as they have just been launched in France. We aimed to review the cost and cost-effectiveness of generic antiretroviral drugs and to review treatment strategies other than generic drugs that could help reduce HIV-related costs. HIV clinicians should consider treatment costs to avoid any future coercive measures.
Koosha Paydary; Parisa Khaghani; Sahra Emamzadeh-Fard; SeyedAhmad SeyedAlinaghi; Kazem Baesi
After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world;however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint.
Manisha V Ghate
Full Text Available Background: Retention in HIV care ensures delivery of services like secondary prevention, timely initiation of treatment, support, and care on a regular basis. The data on retention in pre antiretroviral therapy (ART care in India is scanty. Materials and Methods: Antiretroviral naοve HIV-infected adult patients registered between January 2011 and March 2012 in HIV care (pre-ART were included in the study. The follow-up procedures were done as per the national guidelines. Patients who did not report to the clinic for 1 year were considered as pre-ART lost to follow-up (pre-ART LFU. They were contacted either telephonically or by home visits. Logistic regression analysis was done to find out factors associated with pre-ART loss to follow-up. Results: A total of 689 antiretroviral naοve adult patients were registered in the HIV care. Fourteen (2% patients died and 76 (11% were LFU till March 2013. The multivariate analysis showed that baseline CD4 count >350 cells/mm 3 (P < 0.01 and illiteracy (P = 0.044 were significantly associated with LFU. Of the total pre-ART LFUs, 35 (46.1% informed that they would visit the clinic at their convenient time. NGOs that referred 16 female sex workers (FSWs who were LFU (21.1% informed that they would make efforts to refer them to the clinic. Conclusion: Higher CD4 count and illiteracy were significantly associated with lower retention in pre-ART care. Developing effective "retention package" for patients and strengthening linkage strategies between key sub-population such as FSWs and ART programming will help to plug the leaky cascade in HIV care.
Tittle, Victoria; Bull, Lauren; Boffito, Marta; Nwokolo, Nneka
More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women
Lessells Richard J
Full Text Available Abstract Background There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods (i Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ≤ 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR of significantly impaired renal function (combining severe and moderate impairment. Co-variates for analysis were age, sex and CD4 count at initiation. Results (i There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8 whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5 with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/μl. In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1, male gender (aOR 1.89, 95% C.I. 1.39–2.56 and CD4 Conclusion In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited.
Harland, M J; Steele, J R
Many variables have been studied pertaining to the block sprint start. Research suggests that the adoption of a medium block spacing is preferred, with front and rear knee angles in the set position approximating 90 and 130 degrees, respectively, with the hips held moderately high. The sprinter must be capable of developing a high force rate combined with a high maximum force, especially in the horizontal direction. This ability to create high force underlies other important indicators of starting performance such as minimum block clearance time, maximum block leaving velocity and maximum block leaving acceleration. Once the sprinter has projected him/herself from the blocks at a low angle (40 to 45 degrees) relative to the ground, the following 2 post-block steps should occur with the total body centre of gravity ahead of the contacting foot at foot strike to minimise potential horizontal braking forces.
A simple yet concise step-by-step tutorial that starts from scratch and builds up your knowledge with focused examples that will enable you to set up and run an e-commerce website.This book is for beginners and will take you through the installation and configuration of Drupal Commerce from scratch, but some familiarity with Drupal 7 will be an advantage. All examples are based on development on a local computer - you do not need a hosted Drupal environment.
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 wh...
Baker, Jason V; Neuhaus, Jacqueline; Duprez, Daniel;
HIV infection is associated with premature development of cardiovascular disease. Understanding the effects of HIV replication on endothelial dysfunction and platelet activation may identify treatment targets to reduce cardiovascular disease risk.......HIV infection is associated with premature development of cardiovascular disease. Understanding the effects of HIV replication on endothelial dysfunction and platelet activation may identify treatment targets to reduce cardiovascular disease risk....
Gagnon, M P; Godin, G
The aim of this study was to evaluate possible changes in predisposing factors in sexual preventive behaviors that could result from the availability of an efficient new antiretroviral therapy. A total of 136 young adults were randomly assigned a vignette to read describing AIDS as a lethal or chronic disease. After reading the vignette, the participants completed a self-administered questionnaire assessing the psychosocial determinants of intention to use a condom with a new sexual partner. The variables were measured according to Ajzen's (1985, 1988, 1991) theory of planned behavior and Triandis's (1977) theory of interpersonal behavior. The experimental manipulation was more successful when the disease was described as lethal (66 of the 68 subjects) rather than chronic (30 of the 68 subjects). For the 96 participants who correctly identified the expected outcome of the disease presented in the vignette, a significant difference in intention was found between the two experimental situations (p intention to use condoms on the psychosocial variables yielded an adjusted R2 of .62. Perceived behavioral control, social norms, personal normative belief and anticipated affective reaction were the significant variables explaining this intention. The results suggest that intention to use condoms with a new sexual partner is likely to be modified by the expected outcome of the disease, that is, whether lethal or chronic. Thus, it is suggested that interventions aimed at young adults take into account the impacts the new antiretroviral treatments are likely to have on preventive behaviors.
Reneé de Waal
Full Text Available BACKGROUND: Lipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART. Both are assumed to be antiretroviral adverse drug reactions. METHODS: We conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals. RESULTS: Twenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs showed more limb fat loss (or less fat gain with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs; efavirenz (versus protease inhibitors (PIs; and NRTI-containing (versus NRTI-sparing. RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens. CONCLUSIONS: There is clear evidence of a causal relationship between NRTIs (especially thymidine analogues and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching.
Ernesto Antonio Figueiró Filho
írus da imunodeficiência humana.PURPOSE: to evaluate experimentally the effects of antiretroviral drugs used alone and in association upon the fertility of pregnant Wistar rats and the perinatal effects on the offspring. METHODS: adult female pregnant Wistar rats weighing 200-230 g were used. The antiretroviral drugs zidovudine (AZT, lamivudine (3TC and nelfinavir (NFV were used alone and in association at daily doses of ten times the dose normally used in pregnant women, proportionally to the animal's body weight. Seven groups were studied, including the control one. The experiment started on day 0 and the pregnant animals were sacrificed on day 21. The alive and dead fetuses, the total implantation sites and the total numbers of corporea lutea were used to calculate the fertility values. The statistical analysis was performed by Student's t test and by the Mann-Whitney test. RESULTS: there were no significant statistical differences regarding preimplantation loss and implantation efficiency values of the rats treated with isolated and associated antiretroviral drugs. There was a significant increase in the postimplantation loss values (control group: 7.6%; drug groups variation: 20.2-26.7%, a decrease in the fetal viability values (control group: 92.4%, drug groups variation: 73.3-79.8%, and a decreasing number of fetuses per animal (control group: 14.7; drug groups variation: 11.1-12.7. There was a significant weight reduction of the female rats and of the offspring of animals treated with 3TC, AZT + 3TC and AZT + 3TC + NFV. CONCLUSION: with the administration of high antiretroviral doses, important fertility effects could be observed, which showed that less histotoxic antiretroviral drugs must be studied in order to warrant the safety of using these medicines in pregnant HIV-1 - infected women.
Török, M. Estee; Yen, Nguyen Thi Bich; Chau, Tran Thi Hong; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Mai, Pham Phuong; Dung, Nguyen Thi; Van Vinh Chau, Nguyen; Bang, Nguyen Duc; Tien, Nguyen Anh; Minh, N. H.; Hien, Nguyen Quang; Thai, Phan Vuong Khac; Dong, Doan The; Anh, Do Thi Tuong; Thoa, Nguyen Thi Cam; Hai, Nguyen Ngoc; Lan, Nguyen Ngoc; Lan, Nguyen Thi Ngoc; Quy, Hoang Thi; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Simmons, Cameron Paul; de Jong, Menno; Wolbers, Marcel; Farrar, Jeremy James
Background The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–associated tuberculous meningitis is unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses. Results A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81–1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87–1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration ISRCTN63659091. PMID:21596680
... Year-Old Formula Feeding FAQs: Starting Solids and Milk KidsHealth > For Parents > Formula Feeding FAQs: Starting Solids ... When can I start giving my baby cow's milk? Before their first birthday, babies still need the ...
Full Text Available Abstract Background Successful antiretroviral treatment is dependent on sustaining high rates of adherence. In the southern African context, only a handful of studies (both quantitative and qualitative have looked at the determinants including a health behaviour theory of adherence to antiretroviral therapy. The aim of this study is to assess factors including the information, motivation and behavioural skills model (IMB contributing to antiretroviral (ARV adherence six months after commencing ARVs at three public hospitals in KwaZulu-Natal, South Africa. Methods Using systematic sampling, 735 HIV-positive patients were selected prior to commencing on ART from outpatient departments from three hospitals and followed-up at six months and interviewed with a questionnaire. Results A good proportion of patients were found to be adherent using both adherence instruments (visual analog scale = VAS 82.9%; Adult AIDS Clinical Trials Group = AATCG 70.8%. After adjusting for significant socio-economic variables, both the VAS and the dose, schedule and food adherence indicator found levels of adherence amongst urban residents to be almost 3 times greater than that of rural residents. After adjusting for health-related variables, for both indicators better adherence was associated with low depression and poorer adherence was associated with poor environmental factors. Adjusted odds ratios for adherence when taking into account different behavioural variables were for both adherence indicators, discrimination experiences were associated with lower adherence, and higher scores in adherence information and behavioural skills were associated with higher adherence. For the VAS adherence indicator, higher social support scores were associated with higher adherence. For the dose, schedule and food adherence indicator, using herbal medicines for HIV was associated with lower adherence. Conclusion For the patients in this study, particularly those not living in
Fortuin-de Smidt, Melony; de Waal, Reneé; Cohen, Karen; Technau, Karl-Günter; Stinson, Kathryn; Maartens, Gary; Boulle, Andrew; Igumbor, Ehimario U.; Davies, Mary-Ann
Introduction There are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART) durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010. Methods We included children (<16 years at ART initiation) who initiated ≥3 antiretrovirals between 2004–2014 with ≥1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity. Results We included 3579 children with median follow-up duration of 41 months (IQR 14–72). At ART initiation, median age was 44 months (IQR 13–89) and median CD4 percent was 15% (IQR 9–21%). At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%), treatment failure (18%), treatment simplification (5%), drug interactions (3%), and other or unspecified reasons (18%). The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2–55.4), 1.6 (0.5–4.8), 2.0 (1.2–3.3), and 1.3 (0.6–2.8) per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively. Conclusions While stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health
Mugavero, M.J.; May, M.; Harris, R.; Saag, M.S.; Costagliola, D.; Egger, M.; Phillips, A.; Gunthard, H.F.; Dabis, F.; Hogg, R.; Wolf, F. de; Fatkenheuer, G.; Gill, M.J.; Justice, A.; Monforte, A. D'Arminio; Lampe, F.; Miro, J.M.; Staszewski, S.; Sterne, J.A.
OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naive patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between Jan
NN, NN; Mugavero, Michael J; May, Margaret
OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between ...
Getting Started With Amazon Redshift is a step-by-step, practical guide to the world of Redshift. Learn to load, manage, and query data on Redshift.This book is for CIOs, enterprise architects, developers, and anyone else who needs to get familiar with RedShift. The CIO will gain an understanding of what their technical staff is working on; the technical implementation personnel will get an in-depth view of the technology, and what it will take to implement their own solutions.
Hibernate has clearly arrived. Are you ready to benefit from its simple way of working with relational databases as Java objects? This PDF updates the introductory material from the award-winning Hibernate: A Developer's Notebook to teach you how to jump right in and get productive with the current release of Hibernate. You'll be walked through the ins and outs of setting up Hibernate and some related tools that make it easier to use--and that may give you new ideas about how to store information in your Java programs. In short, this PDF gives you exactly the information you need to start u
Daniel Arbenz was bom and educated in Switzerland. In 1978, he entered the hotel indastry as a chef and worked his way up through all segments of the business. After graduating from the famous Swiss Hotel Management School in Luceme and obtaining management exposure in the finest hotels in Switzerland, he moved to Hong Kong in 1989, starting his career in Asia. Arbenz moved to Singapore, then to Bali, for Resort Hotels and has been with the Intercontinental Hotels Group for almost 10 years in general man...
Full Text Available A problem of highly active antiretroviral therapy (HAART in HIV patients is their adherence to treatment. The aim of this study was to compare the schemes adopted in the initial therapy of these treatments with their adherence, changes in HAART schemes and treatment costs. The study included patients over 16 years old, HIV positive, in treatment for more than 30 days. Adherence to HAART was calculated based on the withdrawal of the drug, which was related to the total treatment time. We evaluated how many patients changed HAART. The costs of each regimen were also estimated and related to the benefit of each treatment. 142 patients who were between 38 and 1,150 days of treatment were included (57.7% women. The schemes with lower costs, highest adherence and greater benefit were efavirenz with biovir and efavirenz with lamivudine and tenofovir. This study suggested the advantageous therapeutic regimens to start of treatment, both from the point of view of patients and the health system. This information can serve as a subsidy to clinicians in the decision of starting HAART.
Full Text Available Background: Healthcare workers are often reluctant to start combination antiretroviral therapy (ART in patients receiving tuberculosis (TB treatment because of the fear of high pill burden, immune reconstitution inflammatory syndrome, and side-effects.Object: To quantify changes in adherence to tuberculosis treatment following ART initiation.Design: A prospective observational cohort study of ART-naïve individuals with baseline CD4 count between 50 cells/mm3 and 350 cells/mm3 at start of TB treatment at a primary care clinic in Johannesburg, South Africa. Adherence to TB treatment was measured by pill count,self-report, and electronic Medication Event Monitoring System (eMEMS before and after initiation of ART.Results: ART tended to negatively affect adherence to TB treatment, with an 8% – 10% decrease in the proportion of patients adherent according to pill count and an 18% – 22% decrease in the proportion of patients adherent according to eMEMS in the first month following ART initiation, independent of the cut-off used to define adherence (90%, 95% or 100%. Reasons for non-adherence were multi factorial, and employment was the only predictor for optimal adherence (adjusted odds ratio 4.11, 95% confidence interval 1.06–16.0.Conclusion: Adherence support in the period immediately following ART initiation could optimise treatment outcomes for people living with TB and HIV.
Munir, Kerim; Kanabkaew, Cheeraya; Le Coeur, Sophie
Background Existing studies have suggested decreased adherence and rebound in mortality in perinatally HIV-infected adolescents receiving antiretroviral therapy (ART) as compared to adults and young children. Methods We used both quantitative and qualitative approaches to identify factors influencing adherence among perinatally infected adolescents in Thailand. We analyzed data from 568 pairs of perinatally infected adolescents (aged 12–19) and their primary caregivers in the Teens Living With Antiretrovirals (TEEWA) study, a cross-sectional survey conducted in 2010–2012. We also conducted 12 in-depth interviews in 2014 with infected adolescents or their primary caregivers to elicit experiences of living with long-term ART. Results From the quantitative analysis, a total of 275 (48.4%) adolescents had evidence of suboptimal adherence based on this composite outcome: adolescents self-reported missing doses in the past 7 days, caregiver rating of overall adherence as suboptimal, or latest HIV-RNA viral load ≥1000 copies/ml. In multivariate logistic regression analysis, younger age, having grandparents or extended family members as the primary caregiver, caregiver-assessed poor intellectual ability, having a boy/girlfriend, frequent online chatting, self-reported unhappiness and easiness in asking doctors questions were significantly associated with suboptimal adherence. From the in-depth interviews, tensed relationships with caregivers, forgetfulness due to busy schedules, and fear of disclosing HIV status to others, especially boy/girlfriends, were important contributors to suboptimal adherence. Social and emotional support and counseling from peer group was consistently reported as a strong adherence-promoting factor. Conclusion Our findings highlight unique barriers of ART adherence among the perinatally infected adolescents. Future interventions should be targeted at helping adolescents to improve interpersonal relationships and build adaptive skills in
Zhao, Yan; Sun, Xin; He, Yun; Tang, Zhirong; Peng, Guoping; Liu, Aiwen; Qiao, Xiaochun; Li, Huiqin; Chen, Zhiqiang; Dou, Zhihui; Ma, Ye; Liu, Zhongfu; Zhang, Fujie
In 2003, the Chinese Government initiated a free antiretroviral therapy (ART) program focusing on adult AIDS patients. Pediatric antiretroviral (ARV) formulations were yet unavailable. It was not until July 2005, with the initiation of a two-stage program implemented by the Chinese Ministry of Health, that pediatric formulations became accessible in China. Initially, the pediatric ART program was piloted in six provinces with the highest incidences of pediatric HIV/AIDS. The pilot stage allowed the Chinese Center for Disease Control and Prevention (CCDC) to finalize entry criteria, treatment regimen, and patient monitoring and follow-up procedures. The second stage commenced at the end of 2006 when the program was scaled-up nationally. In order to guarantee treatment of pediatric patients, extensive training in the selection of appropriate ARV drug regimen and dosage was provided to doctors, often through on-site collaboration with domestic and international experts. The CCDC simultaneously established a pediatric ARV management system and a pediatric ART information system. CD4 count and other laboratory tests are being routinely performed on these pediatric patients. By the end of June 2009, 1529 pediatric patients had received ARV under the national program. However, challenges remain. Firstly, many children infected with HIV/AIDS live in rural areas where the treatment quality is hindered by the limited number of medical facilities and skilled medical workers. Secondly, much of the pediatric ARV drug supply depends on donation. An effort needs to be made by the Chinese Government to establish China's own drug procurement and supply system.
The first major particle physics summer conference has just started this week in Grenoble. After the Quark-Matter conference, the Europhysics Conference on High-Energy Physics marks the start of a promising harvest for the LHC experiments. For the first time, the collaborations will be presenting their latest results based on all luminosity taken until end of June, which will provide more precise measurements in many areas. Thanks to the excellent performance of the LHC, the experiments have already accumulated a substantial quantity of data allowing them to push back the known limits and refine measurements in many fields ranging from b physics to the search for the Higgs boson and for dark matter. At the time of writing, the LHC collaborations are about to present these new results in an energy range which has never previously been explored. I have congratulated all the teams involved in getting the LHC into operation in record time with great efficiency. Today I would like to acknowledge the...
BACKGROUND: We have previously demonstrated an association between combination antiretroviral therapy and the risk of myocardial infarction. It is not clear whether this association differs according to the class of antiretroviral drugs. We conducted a study to investigate the association...... to the other drug class and established cardiovascular risk factors (excluding lipid levels), the relative rate of myocardial infarction per year of protease-inhibitor exposure was 1.16 (95% confidence interval [CI], 1.10 to 1.23), whereas the relative rate per year of exposure to nonnucleoside reverse......-transcriptase inhibitors was 1.05 (95% CI, 0.98 to 1.13). Adjustment for serum lipid levels further reduced the effect of exposure to each drug class to 1.10 (95% CI, 1.04 to 1.18) and 1.00 (95% CI, 0.93 to 1.09), respectively. CONCLUSIONS: Increased exposure to protease inhibitors is associated with an increased risk...
Campero, Lourdes; Herrera, Cristina; Kendall, Tamil; Caballero, Marta
The goal in this article is to examine social problems associated with highly active antiretroviral therapy (HAART) adherence in Mexico and the related challenges for Mexican persons living with HIV/AIDS (PLWHAs). The study was conducted from the perspective of infected and affected individuals. The authors completed 64 in-depth interviews with heterosexual male and female PLWHAs, as well as with some key individuals from their social network. Following the principles of grounded theory, they carried out inductive analysis to create codes and organize central themes. The authors identified problems related to accessing HAART and found that conditions for implementing recommendations made in the international literature to improve adherence are poor. The findings highlight the importance of social factors, such as health care system irregularities, ineffective physician-patient communication, and availability of family and other sources of social support such as self-help groups for PLWHAs' access and adherence to antiretroviral therapy in Mexico.
Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C.; France, Charles P.; Dillon, Glenn H.; Forster, Michael J; Schetz, John A.
Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indola...
Broyles, Lauren Matukaitis; Gordon, Adam J; Sereika, Susan M.; Ryan, Christopher M.; Erlen, Judith A.
Alcohol use negatively affects adherence to antiretroviral therapy (ART), thus HIV/AIDS providers need accurate, efficient assessments of alcohol use. Using existing data from an efficacy trial of two cognitive-behavioral ART adherence interventions, we sought to determine if results on two common alcohol screening tests (Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) and its binge-related question (AUDIT-3)) predict ART nonadherence. Twenty seven percent of the sample (n=308...
Calcagno, Andrea; Di Perri, Giovanni; Bonora, Stefano
HIV-positive patients may be effectively treated with highly active antiretroviral therapy and such a strategy is associated with striking immune recovery and viral load reduction to very low levels. Despite undeniable results, the central nervous system (CNS) is commonly affected during the course of HIV infection, with neurocognitive disorders being as prevalent as 20-50 % of treated subjects. This review discusses the pathophysiology of CNS infection by HIV and the barriers to efficacious control of such a mechanism, including the available data on compartmental drug penetration and on pharmacokinetic/pharmacodynamic relationships. In the reviewed articles, a high variability in drug transfer to the CNS is highlighted with several mechanisms as well as methodological issues potentially influencing the observed results. Nevirapine and zidovudine showed the highest cerebrospinal fluid (CSF) to plasma ratios, although target concentrations are currently unknown for the CNS. The use of the composite CSF concentration effectiveness score has been associated with better virological outcomes (lower HIV RNA) but has been inconsistently associated with neurocognitive outcomes. These findings support the CNS effectiveness of commonly used highly antiretroviral therapies. The use of antiretroviral drugs with increased CSF penetration and/or effectiveness in treating or preventing neurocognitive disorders however needs to be assessed in well-designed prospective studies.
Full Text Available Shantanu Balkundi1, Ari S Nowacek1, Ram S Veerubhotla1, Han Chen2, Andrea Martinez-Skinner1, Upal Roy1, R Lee Mosley1,3, Georgette Kanmogne1, Xinming Liu1,3,4, Alexander V Kabanov3,4, Tatiana Bronich3,4, JoEllyn McMillan1, Howard E Gendelman1,31Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA; 2Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA; 3Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE, USA; 4Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility.Keywords: human immunodeficiency virus type one, nanotoxicology, monocyte-derived macrophage, nanoformulated antiretroviral therapy, manufacturing techniques
Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H
The advent of combination antiretroviral drug regimens has transformed HIV infection from a fatal illness into a manageable chronic condition. All patients with HIV infection should be considered for antiretroviral therapy, regardless of CD4 count or HIV viral load, for individual benefit and to prevent HIV transmission. Antiretroviral drugs affect HIV in several ways: entry inhibitors block HIV entry into CD4 T cells; nucleotide and nucleoside reverse transcriptase inhibitors prevent reverse transcription from RNA to DNA via chain-terminating proteins; nonnucleoside reverse transcriptase inhibitors prevent reverse transcription through enzymatic inhibition; integrase strand transfer inhibitors block integration of viral DNA into cellular DNA; protease inhibitors block maturation and production of the virus. Current guidelines recommend six combination regimens for initial therapy. Five are based on tenofovir and emtricitabine; the other uses abacavir and lamivudine. Five include integrase strand transfer inhibitors. HIV specialists should assist with treating patients with complicated HIV infection, including patients with treatment-resistant HIV infection, coinfection with hepatitis B or C virus, pregnancy, childhood infections, severe opportunistic infections, complex drug interactions, significant drug toxicity, or comorbidities. Family physicians can treat most patients with HIV infection effectively by choosing appropriate treatment regimens, monitoring patients closely, and retaining patients in care.
Lorna A Renner
Full Text Available Introduction: There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART containing zidovudine (ZDV recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Methods: Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ≥18 months followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7g/dL per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. Results: As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was−2.7; and 1772 (60.4% had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p≤0.01: the prevalence of severe anaemia was 3.0% (n=38 in the ZDV group versus 10.2% (n=89 in those without (p<0. 01. Over the first-line follow-up, 58.9% of the children had ≥1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45. Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p≤0.01. Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ≤−3 was a strong predictor associated with a 5.59 times risk of
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González-Baeza, A; Carvajal, F; Bayón, C; Pérez-Valero, I; Montes-Ramírez, M; Arribas, J R
The emotional processing in human immunodeficiency virus-seropositive individuals (HIV+) has been scarcely studied. We included HIV+ individuals (n = 107) on antiretroviral therapy (≥2 years) who completed 6 facial processing tasks and neurocognitive testing. We compared HIV+ and healthy adult (HA) participants (n = 40) in overall performance of each facial processing task. Multiple logistic regressions were conducted to explore predictors of poorer accuracy in those measures in which HIV+ individuals performed poorer than HA participants. We separately explored the impact of neurocognitive status, antiretroviral regimen, and hepatitis C virus (HCV) coinfection on the tasks performance. We found similar performance in overall facial emotion discrimination, recognition, and recall between HIV+ and HA participants. The HIV+ group had poorer recognition of particular negative emotions. Lower WAIS-III Vocabulary scores and active HCV predicted poorer accuracy in recognition of particular emotions. Our results suggest that permanent damage of emotion-related brain systems might persist despite long-term effective antiretroviral therapy.
Full Text Available BACKGROUND: The provision of antiretroviral therapy (ART to migrant populations raises particular challenges with respect to ensuring adequate treatment support, adherence, and retention in care. We assessed rates of loss to follow-up for migrant workers compared with non-migrant workers in a routine treatment programme in Morjia, Lesotho. DESIGN: All adult patients (≥18 years initiating ART between January 1, 2008, and December 31, 2008, and followed up until the end of 2009, were included in the study. We described rates of loss to follow-up according to migrant status by Kaplan-Meier estimates, and used Poisson regression to model associations between migrant status and loss to follow-up controlling for potential confounders identified a priori. RESULTS: Our cohort comprised 1185 people, among whom 12% (148 were migrant workers. Among the migrant workers, median age was 36.1 (29.6-45.9 and the majority (55% were male. We found no statistically significant differences between baseline characteristics and migrant status. Rates of lost to follow up were similar between migrants and non-migrants in the first 3 months but differences increased thereafter. Between 3 and 6 months after initiating antiretroviral therapy, migrants had a 2.78-fold increased rate of defaulting (95%CI 1.15-6.73; between 6 and 12 months the rate was 2.36 times greater (95%CI 1.18-4.73, whereas after 1 year the rate was 6.69 times greater (95%CI 3.18-14.09. CONCLUSIONS: Our study highlights the need for programme implementers to take into account the specific challenges that may influence continuity of antiretroviral treatment and care for migrant populations.
Full Text Available A cross-sectional study was conducted on HIV-infected adults being treated with antiretroviral drugs at a reference service in Southern Brazil. Participants answered a sociodemographic questionnaire and were tested by scales assessing sociocognitive variables. Adherence to treatment was assessed by a self-report inventory developed for the study. Clinical information was obtained from the patients' records. Significance tests were conducted using univariate logistic regressions followed by multivariate logistic regression analysis. A total of 195 patients participated in the study and 56.9% of them reported > or = 95% adherence on the previous two days. In univariate analysis, the odds of adherence increased with self-efficacy (a person's conviction that he/she can successfully execute the behavior required to produce a certain desired outcome in taking medications as prescribed (OR = 3.50, 95% CI 1.90-6.55, and decreased with perception of negative affect and physical concerns (OR = 0.71, 95% CI 0.53-0.95. The odds were lower for taking antiretroviral medications >4 times a day (OR = 0.44, 95% CI 0.20-0.94 and higher for patients with 8 years of schooling (OR = 2.28, 95% CI 1.12-4.66. In the multivariate analysis, self-efficacy (OR = 3.33, 95% CI 1.69-6.56 and taking medication >4 times a day (OR = 0.34, 95% CI 0.14-0.80 were independently associated with adherence. Self-efficacy was the most important predictor of adherence, followed by number of times antiretroviral medication was taken per day. Among sociodemographic and clinical variables, only the number of years of schooling was associated with adherence. Motivational interventions based on self-efficacy may be useful for increasing treatment adherence.
El-Sadr, W M; Grund, B; Neuhaus, J;
BACKGROUND: Episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. OBJECTIVE: To determine whether reinitiating continuous antiretroviral therapy in patients who received episodic treatment reduces excess risk for opportunistic disease ...
Full Text Available Introduction: Whether early antiretroviral therapy (ART initiation could impact sexual risk behaviours remains to be documented. We aimed to investigate changes in sexual behaviours within the 24 months following an early versus standard ART initiation in HIV-positive adults with high CD4 counts. Methods: We used data from a prospective behavioural study nested in a randomized controlled trial of early ART (Temprano-ANRS12136. Time trends in sexual behaviours from enrolment in the trial (M0 to 12-month (M12 and 24-month (M24 visits were measured and compared, using Generalized Estimating Equations models, between participants randomly assigned either to initiate ART immediately (early ART or to defer ART initiation until on-going WHO starting criteria are met (standard ART. Indicators of sexual behaviours included 1 sexual activity in the past year, 2 multiple partnership in the past year, 3 unprotected sex at last intercourse and 4 risky sex (i.e. unprotected sex with a partner of HIV negative/unknown status at last intercourse. Results: Analyses included 1952 participants (975 with early ART and 977 with standard ART; overall median baseline CD4 count: 469/mm3. Among participants with early ART, significant decreases were found between M0 and M24 in sexual activity (Odds Ratio [OR] 0.72, 95% Confidence Interval [95% CI] 0.57–0.92, multiple partnership (OR 0.57, 95% CI 0.41–0.79, unprotected sex (OR 0.59, 95% CI 0.47–0.75 and risky sex (OR 0.58, 95% CI 0.45–0.76. Among participants with standard ART, sexual behaviours showed similar trends over time. These decreases mostly occurred within the 12 months following enrolment in the trial in both groups and prior to ART initiation in participants with standard ART. For unprotected sex and risky sex, decreases were or tended to be more pronounced among patients reporting that their last sexual partner was non-cohabiting. Conclusions: In these sub-Saharan adults with high CD4 counts, entry
Peluso, Michael J; Spudich, Serena
The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.
Marcelo E. Corti
Full Text Available La tuberculosis y otras micobacteriosis constituyen asociaciones o coinfecciones frecuentes en pacientes con sida y se asocian con una elevada mortalidad. En esta revisión se actualizan los tratamientos de las principales enfermedades micobacterianas asociadas al sida (tuberculosis y micobacteriosis por Mycobacterium avium, con especial énfasis en las interacciones farmacológicas entre antimicobacterianos, principalmente rifampicina y claritromicina, y fármacos antirretrovirales. Se analizan los esquemas de tratamiento, su duración, la quimioprofilaxis primaria y secundaria y el momento óptimo de iniciación del tratamiento antirretroviral. Finalmente se describe el síndrome inflamatorio de reconstitución inmune y su tratamiento.Tuberculosis and other mycobacterial diseases are frequent coinfections in AIDS patients with an increased related mortality. In this review we have updated the treatment of the main mycobacterial diseases (tuberculosis and Mycobacterium avium disease, under the scope of pharmacological interactions between antimycobacterial drugs, specially rifampicin and clarithromycin, and anti-retroviral drugs. Antimycobacterial treatment schemes, their duration, primary and secondary chemoprophylaxis and the optimal time to start the anti-retroviral therapy are analized. Finally, the immnune reconstitution inflammatory syndrome and its treatment are discussed.
Alfred C Banda
Full Text Available BACKGROUND: HIV/AIDS affects all sectors of the population and the defence forces are not exempt. A national survey was conducted in all public and private sectors in Malawi that provide antiretroviral therapy (ART to determine the uptake of ART by army personnel, their outcomes while on treatment, and the impact of ART on mortality in the Malawi Defence Force. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort analysis was carried out, collecting data on access and retention on treatment from all 103 public and 38 private sector ART clinics in Malawi, using standardised patient master cards and clinic registers. Observations were censored on December 31(st 2006. Independent data on mortality trends in army personnel from all causes between 2002 and 2006 were available from army records. By December 31(st 2006, there were 85,168 patients ever started on ART in both public and private sectors, of whom 547 (0.7% were army personnel. Of these, 22% started ART in WHO clinical stage 1 or 2 with a CD4-lymphocyte count of
Jordan, M R; Obeng-Aduasare, Y; Sheehan, H; Hong, S Y; Terrin, N; Duong, D V; Trung, N V; Wanke, C; Kinh, N V; Tang, A M
The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9 ± 4.9 years. The median duration on antiretroviral therapy was 16.2 ± 12.7 months; 83% reported 'very good' or 'perfect' adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30-3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14-1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases.
AIDS-associated diarrhea and wasting in northeast Brazil is associated with subtherapeutic plasma levels of antiretroviral medications and with both bovine and human subtypes of Cryptosporidium parvum
Richard K. Brantley
Full Text Available Advanced HIV infection is frequently complicated by diarrhea, disruption of bowel structure and function, and malnutrition. Resulting malabsorption of or pharmacokinetic changes in antiretroviral agents might lead to subtherapeutic drug dosing and treatment failure in individual patients, and could require dose adjustment and/or dietary supplements during periods of diarrheal illness. We determined the plasma levels of antiretroviral medications in patients that had already been started on medication by their physicians in an urban infectious diseases hospital in northeast Brazil. We also obtained blood samples from patients hospitalized for diarrhea or AIDS-associated wasting, and we found reduced stavudine and didanosine levels in comparison with outpatients without diarrhea or wasting who had been treated at the same hospital clinic. There was a predominance of the protozoal pathogens Cryptosporidium and Isospora belli, typical opportunistic pathogens of AIDS-infected humans, in the stool samples of inpatients with diarrhea. We conclude that severe diarrhea and wasting in this population is associated with both protozoal pathogens and subtherapeutic levels of antiretroviral medications.
Meehan, Merrill L.
The Monongalia County (West Virginia) Even Start Program is a comprehensive, rural, home-based family literacy program that provides families with adult literacy education, parenting education, and early childhood education. Although all Even Start programs conduct some home visits, the Monongalia County program is unique in that home visits are…
Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia
SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy.
Full Text Available Josep M Llibre,1,2 Gloria Cardona,3 José R Santos,2 Angels Andreu,3 Josep O Estrada,4 Jordi Ara,4 Xavier Bonafont,3 Bonaventura Clotet1,21HIV Unit, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 2Lluita contra la SIDA Foundation, Badalona, Barcelona, Spain; 3Hospital Pharmacy, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 4Hospital Management, University Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainBackground: The current economic recession in European countries has forced governments to design emergency measures to reduce spending on drugs, including antiretroviral therapy (ART. Switching antiretroviral drugs for others that have the same efficacy and safety profile at a lower cost (cost-reduction measures, CRM could prove to be a valid means of generating savings.Methods: Descriptive study of prospective consensus-based CRM undertaken in 2011 in a Catalonian hospital HIV unit among patients with prolonged plasma HIV-1 RNA <50 copies/mL.Results: During the study period, we made 673 switches (87.5% more than the previous year, of which 378 (56.2% were CRM (16% of all patients treated, leading to a savings of €87,410/month. Switching tenofovir/emtricitabine for abacavir/lamivudine was the most common CRM (129, 31.3%, followed by simplification to boosted protease inhibitor monotherapy (bPImono, 102, 26%. The CRM that generated the greatest saving were switching to bPImono (38%, withdrawal or replacement of raltegravir (24%, switching tenofovir/emtricitabine for abacavir/lamivudine (13%, and switching to nevirapine (5%. Cost savings with CRM were slightly higher than those achieved with medication paid for by clinical trial sponsors (€80,333/month or through discount arrangements (€76,389/month.Conclusion: Proactively switching antiretroviral therapy in selected treated patients with sustained virological suppression can generate significant cost savings in pharmacy spending in
Full Text Available Background. Regular clinic attendance for antiretroviral (ARV drug refills is important for successful clinical outcomes in HIV management. Methods. Clinic attendance for ARV drug refills and medication adherence using a clinic-based pill count in 392 adult patients receiving antiretroviral therapy (ART in a district hospital in Uganda were prospectively monitored over a 28-week period. Results. Of the 2267 total scheduled clinic visits, 40 (1.8% were missed visits. Among the 392 clients, 361 (92% attended all appointments for their refills (regular attendance. Clinic attendance for refills was statistically significantly associated with medication adherence with regular attendant clients having about fourfold greater odds of achieving optimal (≥95% medication adherence [odds ratio (OR=3.89, 95% CI: 1.48 to 10.25, exact P=.013]. In multivariate analysis, clients in age category 35 years and below were less likely to achieve regular clinic attendance. Conclusion. Monitoring of clinic attendance may be an objective and effective measure and could be a useful adjunct to an adherence measure such as pill counting in resource-constrained settings. Where human resource constraints do not allow pill counts or other time-consuming measures, then monitoring clinic attendance and acting on missed appointments may be an effective proxy measure.
Liotta, Giuseppe; Chimbwandira, Frank; Wouters, Kristien; Nielsen-Saines, Karin; Jere, Haswell; Mancinelli, Sandro; Ceffa, Susanna; Erba, Fulvio; Palombi, Leonardo; Marazzi, Maria Cristina
Combination antiretroviral therapy has been shown to reduce HIV transmission and incident infections. In recent years, Malawi has significantly increased the number of individuals on combination antiretroviral drugs through more inclusive treatment policies. Using a retrospective observational cohort design, records with HIV test results were reviewed for pregnant women attending a referral hospital in Malawi over a 5-year period, with viral load measurements recorded. HIV prevalence over time was determined, and results correlated with population viral load. A total of 11 052 women were included in this analysis, with 440 (4.1%) HIV infections identified. HIV prevalence rates in pregnant women in Malawi halved from 6.4% to 3.0% over 5 years. Mean viral loads of adult patients decreased from 120 000 copies/mL to less than 20 000 copies/mL. Results suggest that community viral load has an effect on HIV incidence rates in the population, which in turn correlates with reduced HIV prevalence rates in pregnant women.
Fantauzzi, Alessandra; Digiulio, Maria Anna; Cavallari, Eugenio Nelson; d'Ettorre, Gabriella; Vullo, Vincenzo; Mezzaroma, Ivano
HIV-1-associated Guillan-Barre syndrome (hGBS) is an ascendant progressive polyradiculoneuropathy described throughout the course of the viral disease, mainly associated with the acute retroviral syndrome. HGBS is occasionally described in severely immunocompromised subjects in the context of the immune reconstitution inflammatory syndrome. The case described occurred soon after the start of a combined antiretroviral treatment in an HIV-1 infected patient with ulcerative colitis in the absence of severe immunosuppression. This manifestation may be interpreted as an uncommon appearance of an immune reconstitution syndrome in the presence of a predisposing autoimmune pathology.
Full Text Available Abstract Background Adequate antiretroviral drug potency is essential for obtaining therapeutic benefit, however, the behavioral aspects of proper adherence and readiness to medication, often determine therapeutic outcome. Therefore, this study aimed to assess the level and determinants of nonadherence and nonreadiness to highly active antiretroviral therapy (HAART among people living with HIV/AIDS (PLWHA at Gondar University Teaching Hospital and Felege Hiwot Hospital in Northwest Ethiopia. Methods A cross-sectional study was conducted between July and September 2008 using structured interviewer-administered questionnaire. All consecutive adult outpatients who were receiving antiretroviral treatment for at least three months, seen at both hospitals during the study period and able to give informed consent were included in the study. Multivariate logistic regression was used to determine factors associated with nonadherence and nonreadiness. Results A total of 504 study subjects were included in this study. The prevalence rates of nonadherence and nonreadiness to HAART were 87 (17.3% and 70 (13.9% respectively. Multivariate logistic regression analysis revealed that medication adverse effects, nonreadiness to HAART, contact with psychiatric care service and having no goal had statistically significant association with nonadherence. Moreover, unwillingness to disclose HIV status was significantly associated with nonreadiness to HAART. Conclusions In this study the level of nonadherence and nonreadiness to HAART seems to be encouraging. Several factors associated with nonadherance and nonreadiness to HAART were identified. Efforts to minimize nonadherence and nonreadiness to HAART should be integrated in to regular clinical follow up of patients.
Full Text Available Abstract Introduction The global scale-up of antiretroviral therapy (ART for HIV patients has led to concerns regarding inequities in utilization of ART services in resource-limited contexts. In this paper, we describe regional and sex differentials in the distribution of ART among adult HIV patients in Ghana. We highlight the need for interventions to address the gender-based and geographic inequities related to the utilization of ART services in Ghana. Methods We reviewed National AIDS/STIs Control Program’s ART service provision records from January 2003 through December 2010, extracting data on adults aged 15+ who initiated ART in Ghana over a period of eight years. Data on the number of patients on treatment, year of enrollment, sex, and region were obtained and compared. Results The number of HIV patients receiving ART in Ghana increased more than 200-fold from 197 in 2003, to over 45,000 in 2010. However, for each of six continuous years (2005-2010 males comprised approximately one-third of adults newly enrolled on ART. As ART coverage has expanded in Ghana, the proportion of males receiving ART declined from 41.7% in 2004 to 30.1% in 2008 and to 27.6% in 2010. Also, there is disproportionate regional ART utilization across the country. Some regions report ART enrollment lower than their percent share of number of HIV infected persons in the country. Conclusions Attention to the comparatively fewer males initiating ART, as well as disproportionate regional ART utilization is urgently needed. All forms of gender-based inequities in relation to HIV care must be addressed in order for Ghana to realize successful outcomes at the population level. Policy makers in Ghana and elsewhere need to understand how gender-based health inequities in relation to HIV care affect both men and women and begin to design appropriate interventions.
Akanbi, Maxwell O; Achenbach, Chad J; Feinglass, Joe; Taiwo, Babafemi; Onu, Adamu; Pho, Mai T; Agbaji, Oche; Kanki, Phyllis; Murphy, Robert L
Our objective was to determine tuberculosis (TB) incidence and evaluate TB risk in adults after one or more years of use of combination antiretroviral therapy (cART) through a retrospective cohort study in Jos, Nigeria. We studied a cohort of HIV-infected adults treated with ART for at least 1 year. Based on immunologic and virologic responses to ART, patients were categorized into four groups: CD4 T cell count ≥350 cells/mm(3) and HIV-1 RNA level ≤400 copies/ml (group 1), CD4 T cell count ≥350 cells/mm(3) and HIV-1 RNA level >400 copies/ml (group 2), CD4 T cell count 400 copies/ml (group 4). Time to incident TB for the four groups was analyzed using the Kaplan-Meier method. Cox regression models were used to evaluate predictors of incident TB. In this cohort of 5,093 HIV-infected adults, of which 68.4% were female, with a mean age 35.1 years (standard deviation 9.1 years), we observed 98 cases of incident TB during 4 years and 3 months of follow-up. The overall TB incidence rate was 8.7 cases/1,000 patient-years of follow-up. Adjusted hazards for incident TB were 2.11 (95% CI 0.97-4.61), 2.05 (95% CI 1.10-3.79), and 3.65 (95% CI 1.15-5.06) in group 2, 3, and 4 patients, respectively, compared to group 1. Tuberculosis incidence in patients on ART is driven by poor immunologic and/or virologic response. Optimization of HIV treatment should be prioritized to reduce the burden of TB in this high-risk population.
Maciel, B. A. P. C.; Neto, R. P.; Hartmann, R. P.; Melo, M. O.; Gonçalves, M.; Marques, G.; Rocha, F. L.; Silveira, G. M.
Unlike other natural hazards, earthquakes strike suddenly and without warning. Consequently, prevention is the best we can do to ensure safety. In spite of the large and medium earthquakes, some of them tsunamigenic, that affected Portugal in the past, the Portuguese society is little aware of the seismic risk and has not developed an adequate culture of prevention. This is most probably due to the long time interval between destructive earthquakes. Earthquakes can be a real danger to societies, damaging human-made structures and endangering human lives. Earthquakes can trigger additional emergencies, and individuals should also be prepared to contend with it. By planning and practicing what to do if an earthquake strikes, children and their family can learn to react correctly and automatically when the shaking begins. Risks can then be dramatically lessened if the population is educated on how to react before, during and after an earthquake. Children's knowledge is ever growing. They have a fundamental role in changing societies. By educating the children of today we are forming better adults of tomorrow. We are simultaneously passing this knowledge to their caregivers and families. Through demonstrating how fundamental it is to be conscious of those issues, not only will the children will be informed, but also their relatives will be aware of such risks. We use this approach to explain children how to assess risk in a broader sense. We teach them other preventive measures, namely those related with electricity, gas and the danger on non-potable water, essential topics on "what to do before an earthquake" but also on the daily routines. This presentation will highlight the importance of encouraging a culture of prevention. This project funded by the Portuguese "Ciência Viva" program, and is conducted by science high-school students, teachers and the parents association. Scientific support is given by the seismology research group at Instituto Dom Luíz.
NSGIC GIS Inventory (aka Ramona) — A label (point) feature class of Head Start / Early Head Start/ Delegate Agencies/ Child Care Partnership & Family Day Care Homes Programs location in Miami-Dade...
Tingzikou key water control project on Jialing River, one of 18 newly started key projects in 2009 for China's western part development program, formally started construction at the end of November last year.
Niklaus Daniel Labhardt
Full Text Available Introduction: Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs to scale up the provision of antiretroviral therapy (ART. We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. Methods: The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. Results: Of 3747 patients, 2042 (54.5% started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81 and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001. These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR: 0.89, 95% confidence interval (CI: 0.73–1.09 and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20–1.96. The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51–0.93. Conclusions: In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities
Mills, Edward J.; Nachega, Jean B.; Nsanzimana, Sabin; Penazzato, Martina; Appolo, Tsitsi; Ford, Nathan
Background Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities. Methods and Findings We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%–45.4%; adolescents 63.1%, 95% CI 46.3%–80.0%; children/caregivers 29.2%, 95% CI 20.1%–38.4%), being away from home (adults 30.4%, 95% CI 25.5%–35.2%; adolescents 40.7%, 95% CI 25.7%–55.6%; children/caregivers 18.5%, 95% CI 10.3%–26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%–35.0%; adolescents 32.4%, 95% CI 0%–75.0%; children/caregivers 26.3%, 95% CI 15.3%–37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%–18.3%; adolescents 25.7%, 95% CI 17.7%–33.6%; children 15.1%, 95% CI 3.9%–26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%–16.1%) and adolescents (28.8%, 95% CI 11.8%–45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%–15.3%; children/caregivers 22.3%, 95% CI 10.2%–34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%–18.8%) was a more commonly cited barrier to
Vazquez-Guillen, Jose Manuel; Palacios-Saucedo, Gerardo C.; Rivera-Morales, Lydia G.; Garcia-Campos, Jorge; Ortiz-Lopez, Rocio; Noguera-Julian, Marc; Paredes, Roger; Vielma-Ramirez, Herlinda J.; Ramirez, Teresa J.; Chavez-Garcia, Marcelino; Lopez-Guillen, Paulo; Briones-Lara, Evangelina; Sanchez-Sanchez, Luz M.; Vazquez-Martinez, Carlos A.; Rodriguez-Padilla, Cristina
Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM’s) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM’s in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM’s during STI. PMID:26807922
Jose Manuel Vazquez-Guillen
Full Text Available Although Structured Treatment Interruptions (STI are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM's at levels under limit of detection of conventional genotyping (<20% of quasispecies could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM's in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM's during STI.
Jones, Deborah; Zulu, Isaac; Mumbi, Miriam; Chitalu, Ndashi; Vamos, Szonja; Gomez, Jacqueline; Weiss, Stephen M.
This study sought to identify strategies for living with the challenges of HIV and antiretroviral (ARV) use among new medication users in urban Zambia. Participants (n = 160) were recruited from urban Lusaka, Zambia. Qualitative Data was drawn from monthly ARV treatment education intervention groups addressing HIV and antiretroviral use. Themes…
Beukel, C. van den; Koopmans, P.P.; Ven, A.J.A.M. van der; Smet, P.A.G.M. de; Burger, D.M.
Herbal medicines are widely used by HIV patients. Several herbal medicines have been shown to interact with antiretroviral drugs, which might lead to drug failure. We have aimed to provide an overview of the modulating effects of Western and African herbal medicines on antiretroviral drug-metabolizi
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...
Bannister, WP; Ruiz, L; Loveday, C;
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...
Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L;
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)....
Wormser, Gary P; Lappas, Thomas
The high cost of antiretroviral drugs has limited access to treatment for some HIV-infected patients in the United States and strained public resources. With the introduction of much cheaper generic versions of some of these agents, and with more to come in the next few years, the need increases to define the role of generic antiretroviral drugs in patient management.
Regina Flávia de Castro Almeida
Full Text Available Lack of information on antiretroviral drugs or the misunderstanding of available information can facilitate incorrect use of such drugs. This can result in non-adherence to the prescribed regimen, leading to a great possibility of a therapeutic failure. The aim of this study was to know which information HIV/AIDS patients, who receive their medicines at the pharmacy of a reference hospital in the northeast Brazil, have on the drugs they use, the source of this information and whether there is a need for additional information. A total of 195 HIV/AIDS patients, who were using either zidovudina + lamivudina 300+150mg (AZT+3TC, efavirenz 600mg (EFZ or lopinavir/ritonavir 133.33/33mg (LPV/r, were interviewed. The mean age was 41 years (SD = 9.55 and 70.8% were males. Of the total, 55.4% didn't know the effect of the drug in the organism; 35.9% were unaware of the necessity of taking antiretroviral drugs for the rest of their lives; only 14.4% knew how to proceed when a dosage was missed; 22.1% said they could die and the same number of individuals believed in aggravation of the disease in case of treatment interruption. The majority, 68.2%, considered it very necessary to receive drug information. The results show that there is an apparent lack of general information among users of antiretroviral drugs, and at the same time a need for it. It is necessary that all professionals involved in the health care of the patients agree that an efficient supply of information on prescribed drugs is an ethical component of the treatment that favors and fosters its adherence.
Full Text Available Abstract Background Combination antiretroviral (AR therapy continues to be the mainstay for HIV treatment. However, antiretroviral drug nonadherence can lead to the development of resistance and treatment failure. We have designed nanoparticles (NP that contain three AR drugs and characterized the size, shape, and surface charge. Additionally, we investigated the in vitro release of the AR drugs from the NP using peripheral blood mononuclear cells (PBMCs. Methods Poly-(lactic-co-glycolic acid (PLGA nanoparticles (NPs containing ritonavir (RTV, lopinavir (LPV, and efavirenz (EFV were fabricated using multiple emulsion-solvent evaporation procedure. The nanoparticles were characterized by electron microscopy and zeta potential for size, shape, and charge. The intracellular concentration of AR drugs was determined over 28 days from NPs incubated with PBMCs. Macrophages were imaged by fluorescent microscopy and flow cytometry after incubation with fluorescent NPs. Finally, macrophage cytotoxicity was determined by MTT assay. Results Nanoparticle size averaged 262 ± 83.9 nm and zeta potential -11.4 ± 2.4. AR loading averaged 4% (w/v. Antiretroviral drug levels were determined in PBMCs after 100 μg of NP in 75 μL PBS was added to media. Intracellular peak AR levels from NPs (day 4 were RTV 2.5 ± 1.1; LPV 4.1 ± 2.0; and EFV 10.6 ± 2.7 μg and continued until day 28 (all AR ≥ 0.9 μg. Free drugs (25 μg of each drug in 25 μL ethanol added to PBMCs served as control were eliminated by 2 days. Fluorescence microscopy and flow cytometry demonstrated phagocytosis of NP into monocytes-derived macrophages (MDMs. Cellular MTT assay performed on MDMs demonstrated that NPs are not significantly cytotoxic. Conclusion These results demonstrated AR NPs could be fabricated containing three antiretroviral drugs (RTV, LPV, EFV. Sustained release of AR from PLGA NP show high drug levels in PBMCs until day 28 without cytotoxicity.
Full Text Available Abstract Background Rhodococcus equi (R.equi is an acid fast, GRAM + coccobacillus, which is widespread in the soil and causes pulmonary and extrapulmonary infections in immunocompromised people. In the context of HIV infection, R.equi infection (rhodococcosis is regarded as an opportunistic disease, and its outcome is influenced by highly active antiretroviral therapy (HAART. Case presentation We report two cases of HIV-related rhodococcosis that disseminated despite suppressive HAART and anti-rhodococcal treatment; in both cases there was no immunological recovery, with CD4+ cells count below 200/μL. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years. Conclusions Our report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection.
Ntusi, N B A; Taylor, D; Naidoo, N G; Mendelson, M
Cardiovascular abnormalities were appreciated early in the epidemic of the acquired immunodeficiency syndrome (AIDS), even before the aetiological agent, human immunodeficiency virus (HIV) was isolated and characterised. The aetiology and pathogenesis of cardiovascular disease in HIV infection is still the subject of intense speculation, and is likely multi-factorial. HIV affects every aspect of the cardiac axis, causing pericarditis, myocarditis, cardiomyopathy, coronary artery disease and microvascular dysfunction, valvular heart disease, pulmonary vascular disease and pulmonary hypertension, stroke and peripheral vascular disease. HIV-associated vasculopathy is an increasingly recognised clinical entity, causing high morbidity and increasing mortality in southern Africa, particularly from stroke and cardiovascular disease. HIV causes disease of the vascular tree, either by a direct effect on vascular or perivascular tissue, or indirectly via immune complex-mediated mechanisms, associated opportunistic infections and malignancies. As a result, highly active antiretroviral therapy (HAART) may have an important role in controlling disease progression. We report a case of histologically defined primary HIV vasculopathy in which the chance to start HAART was initially missed and in which the patient progressed to require bilateral amputations, but obtained disease quiescence upon commencement of HAART.
Mujugira, Andrew; Celum, Connie; Coombs, Robert W.; Campbell, James D.; Ndase, Patrick; Ronald, Allan; Were, Edwin; Bukusi, Elizabeth A.; Mugo, Nelly; Kiarie, James; Baeten, Jared M.
Objective Combination antiretroviral therapy (ART) decreases the risk of sexual HIV transmission by suppressing blood and genital HIV RNA concentrations. We sought to determine HIV transmission risk prior to achieving complete viral suppression. Design Prospective cohort study. Methods Using data from the Partners PrEP Study, a prospective study of 4747 heterosexual HIV-serodiscordant couples in Kenya and Uganda, we examined multiple markers of HIV transmission risk during the first months after ART initiation: time to viral suppression in blood, persistence of HIV RNA in genital specimens, sexual risk behavior, pregnancy incidence, and HIV transmission using survival analysis and GEE logistic regression. Results The cumulative probabilities of achieving blood viral suppression (6 months of ART (0 infections; 167 person-years). Conclusions Residual HIV transmission risk persists during the first 6-months of ART, with incomplete viral suppression in blood and genital compartments. For HIV-serodiscordant couples in which the infected partner starts ART, other prevention options are needed, such as pre-exposure prophylaxis, until viral suppression is achieved. PMID:27070123
Bohlius, Julia; Schmidlin, Kurt; Boué, François;
The risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4⁺ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1-infected...... lost 98 CD4 cells (95% CI, -159 to -36 cells), whereas controls gained 35 cells (95% CI, 24-46 cells; P HIV-1 replication on cART may harbor HL....
Weijsenfeld, Annouschka M.; Smit, Colette; Cohen, Sophie; Wit, Ferdinand W N M; Mutschelknauss, Michelle; Van Der Knaap, Linda C.; Van Zonneveld, Laura M.; Zomer, Bert J.; Nauta, Nike; Patist, Joke C.; Kuipers-Jansen, Marien H J; Smit, Esther P.; Blokhuis, Charlotte; Pajkrt, Dasja; Weijsenfeld, A. M.; Cohen, S.; Blokhuis, C.; Van Der Plas, A.; Scherpbier, H. J.; Mutschelknauss, M.; Nellen, F. J B; Prins, J. M.; Pajkrt, D.; Smit, C.; Wit, F. W N M; Reiss, P.; Van Der Knaap, L.; Visser, E.; Van Zonneveld, L. M.; Vriesde, M. E.; Bassant, N. Y.; Van Der Ende, M. E.; Van Rossum, A. M C; Driessen, G. J A; Fraaij, P. L A; Smit, J. V.; Smit, E. P.; Kastelijns, M. P W; Den Hollander, J. G.; Pogány, K.; Moons, C.; Kroon, F. P.; Oude Geerdink, E.; Van Der Meche, I. B.; Schouten, W. E M; Brinkman, K.; Ter Beest, G.; Gisolf, E. H.; Richter, C.; Zomer, B. J.; Strik-Albers, R.; Van Der Flier, M.; Henriet, S. S.; Koopmans, P. P.; Patist, J. C.; Nauta, N.; Geelen, S. P M; Wolfs, T. F W; Hoepelman, I. M.; Mudrikova, T.; Van Der Meulen, P. A.; De Jonge, H.; Scholvink, E. H.; Bierman, W. F W; Van Den Berg, J. F.; Bouwhuis, J. W.; Faber, S.; Van Vonderen, M.; Schippers, J. A.; Lowe, S. H.; Kuipers-Jansen, M. H J; Van Kasteren, M. E E; Brouwer, A. E.; Pronk, D. C.; Kortmann, W.
Background. As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to tr
In this paper, with the starting velocity experiments of natural cohesive sedimentation, the author proposes an assumption concerning the starting mechanism of cohesive sedimentation and gives a formula to determine the starting velocity of compact clay. It is pointed out that the fluctuating function of flow is a main factor for the starting of sedimentation. And the component and the structure of cohesive sedimentation are also the affecting factors for the starting. Consequently, the study shows that modern results of soil mechanics, clay mineralogy and fluid mechanics are helpful in the investigation of this kind of engineering problem.
Conclusions: Evidence of HBV infection was detected in 26.8% of HIV patients with HBsAg-negative infection, with viraemia detected in 15.1% of the patients. All HIV-infected patients should be screened carefully for HBV infection with HBsAg and anti-HBc IgG antibodies prior to starting antiretroviral therapy.
Chileshe, Muatale; Bond, Virginia Anne
The vulnerabilities that underlie barriers faced by the rural poor whilst trying to access and adhere to "free" antiretroviral treatment (ART) demand more attention. This paper highlights barriers that poor rural Zambians co-infected with tuberculosis (TB) and HIV and their households faced in accessing ART between September 2006 and July 2007, and accounts for patient outcomes by the end of TB treatment and (more sporadically) beyond October 2009. The analysis draws on findings from wider anthropological fieldwork on the converging impact of TB, HIV and food insecurity, focusing for the purpose of this paper on ethnographic case-studies of seven newly diagnosed TB patients co-infected with HIV and their six households (one household had two TB patients). Economic barriers included being pushed into deeper poverty by managing TB, rural location, absence of any external assistance, and mustering time and extended funds for transport and "special food" during and beyond the end of TB. In the case of death, funeral costs were astronomical. Social barriers included translocation, broken marriages, a sub-ordinate household position, gender relations, denial, TB/HIV stigma and the difficulty of disclosure. Health facility barriers involved understaffing, many steps, lengthy procedures and inefficiencies (lost blood samples, electricity cuts). By the end of TB treatment, outcomes were mixed; two co-infected patients had died, three had started ART and two had yet to start ART. The three on ART underwent a striking transformation in the short term. By October 2009, two more had died and three were doing well. The study advocates nutritional support and other material support (especially transport funds) for co-infected TB patients until ART is accessed and livelihood regained. More prompt diagnosis of TB and reducing steps and increasing the reach of the ART programme in rural areas are also recommended.
Rizzardi, G. Paolo; Harari, Alexandre; Capiluppi, Brunella; Tambussi, Giuseppe; Ellefsen, Kim; Ciuffreda, Donatella; Champagne, Patrick; Bart, Pierre-Alexandre; Chave, Jean-Philippe; Lazzarin, Adriano; Pantaleo, Giuseppe
Primary HIV-1 infection causes extensive immune activation, during which CD4+ T cell activation supports massive HIV-1 production. We tested the safety and the immune-modulating effects of combining cyclosporin A (CsA) treatment with highly active antiretroviral therapy (HAART) during primary HIV-1 infection. Nine adults with primary HIV-1 infection were treated with CsA along with HAART. At week 8, all patients discontinued CsA but maintained HAART. Viral replication was suppressed to a comparable extent in the CsA + HAART cohort and in 29 control patients whose primary infection was treated with HAART alone. CsA restored normal CD4+ T cell levels, both in terms of percentage and absolute numbers. The increase in CD4+ T cells was apparent within a week and persisted throughout the study period. CsA was not detrimental to virus-specific CD8+ or CD4+ T cell responses. At week 48, the proportion of IFN-γ–secreting CD4+ and CD4+CCR7– T cells was significantly higher in the CsA + HAART cohort than in the HAART-alone cohort. In conclusion, rapid shutdown of T cell activation in the early phases of primary HIV-1 infection can have long-term beneficial effects and establish a more favorable immunologic set-point. Appropriate, immune-based therapeutic interventions may represent a valuable complement to HAART for treating HIV infection. PMID:11877476
Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin Cs; Peter, Aniekan I; Azu, Onyemaechi O
Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A-D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.
Full Text Available Abstract Background In resource limited settings, many People Living with HIV/AIDS (PLWHA lack access to sufficient quantities of nutritious foods, which poses additional challenges to the success of antiretroviral therapy (ART. Maintaining adequate food consumption and nutrient intake levels and meeting the special nutritional needs to cope up with the disease and the ART are critical for PLWHA to achieve the full benefit of such a treatment. Objective To determine the prevalence and correlates of food insecurity among HIV-infected individuals receiving highly active antiretroviral therapy in resource-limited settings. Methods A cross sectional study was carried out from January 1, 2009 to March 3, 2009 at ART clinic at Jimma University specialized hospital (JUSH in Ethiopia. We used multivariable logistic regression model to compare independent risk factors by food insecurity status among 319 adult PLWHA (≥18 years attending ART Clinic. Results A total of 319 adult PLWHA participated in the study giving a response rate of 100%. Out of 319 PLWHA the largest numbers of participants, 46.4% were in the age group of 25-34 years. The overall 201(63.0% PLWHA were food insecure. Educational status of elementary or lower [OR = 3.10 (95%CI; (1.68-5.71], average family monthly income Conclusion Food insecurity is a significant problem among PLWHA on HAART. Lower educational status and low family income were the predictors of food insecurity. Food security interventions should be an integral component of HIV/AIDS care and support programs. Special attention need to be given to patients who have lower educational status and are members of households with low income.
Full Text Available Sclerosing colangitis (SC due to cytomegalovirus (CMV is very rare. It has been described mainly in immunocompromised patients. Currently, in HIV infected patients it is exceptional. The most of cases belong to pre-highly active antiretroviral therapy (pre-HAART and those cases were in stage AIDS with less than 100 CD4/μl. The most frequently involved pathogen in pre-HAART period was Cryptosporidium parvum (30-57% and CMV (10-30%; in late HAART period this information are unaware. CMV has been implicated as a possible etiological agent in primary SC partly because of the ability to cause liver damage and its relationship with smooth muscle antibodies. The most effective treatment for SC was the combination of antiretroviral therapy and endoscopic retrograde cholangiopancreatography with sphincterotomy and stent placement. Following, we present the first case of late HAART period which describes a SC extrahepatic without papillary stenosis with CMV as the only cause and clinical presentation of HIV infection in a woman with 177 CD4/μl.
Staltari, Orietta; Leporini, Christian; Caroleo, Benedetto; Russo, Emilio; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca
With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrates of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reversetranscriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but show several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs.
Camacho, Ángela; Rivero, Antonio
Lopinavir/ritonavir (LPV/r) was approved for use in the treatment of human immunodeficiency virus (HIV) infection in 2001 and is the protease inhibitor that has been most widely studied in clinical trials. Despite the time interval since its approval, all the evidence accumulated in the last 14 years indicates that LPV/r continues to occupy an important position among antiretroviral drugs. Firstly, LPV/r plus 2 nucleoside/nucleotide analogs is still considered a good option for initial antiretroviral therapy (ART). Secondly, numerous studies have evaluated the efficacy and safety of new initial ART strategies based on LPV/r in dual therapy. The results obtained suggest that LPV/r plus lamivudine (3TC) or raltegravir can be as effective in initial ART as standard triple therapy and justify their consideration as alternative regimens in this scenario. Thirdly, LPV/r is a pioneer drug, as well as being the agent with the largest amount of evidence from clinical trials on simplification to monotherapy (LPV/r) or dual therapy (LPV/r + 3TC). Lastly, LPV/r is highly useful is special situations. It has a low risk of liver toxicity in patients with chronic liver disease, its use is preferred in the treatment of patients with HIV-2, and it is safe and effective in preventing vertical HIV transmission.
Linnemayr, Sebastian; Ryan, Gery W; Karir, Veena; Liu, Jenny; Palar, Kartika
Antiretroviral treatment has transformed HIV from a death sentence to a chronic condition, allowing people with HIV to live longer and healthier lives. However, they face significant barriers to accessing and affording life-saving-but expensive-antiretroviral (ARV) medications. These barriers are particularly severe for low-income patients, and they disproportionately affect racial and ethnic minorities. High ARV prices create pressure for government insurers to contain costs either by rationing care or by restricting eligibility for public programs. Limited funding, coupled with a growing demand for HIV care and treatment, is likely to make programmatic decisions about who is covered become more difficult over time. Therefore, it is important to identify options for reducing the cost of providing ARVs to allow more people to receive treatment. This study examines a variety of options for negotiating lower ARV procurement costs in U.S. markets. A case-study approach is used to assess options that different stakeholders could use in negotiating ARV price discounts with drug manufacturers given the regulatory and market constraints that exist in the United States.
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.
Full Text Available The provision of antiretroviral therapy (ART in low and middle-income countries is a chronic disease intervention of unprecedented magnitude and is the dominant health systems challenge for high-burden countries, many of which rank among the poorest in the world. Substantial external investment, together with the requirement for service evolution to adapt to changing needs, including the constant shift to earlier ART initiation, makes outcome monitoring and reporting particularly important. However, there is growing concern at the inability of many high-burden countries to report on the outcomes of patients who have been in care for various durations, or even the number of patients in care at a particular point in time. In many instances, countries can only report on the number of patients ever started on ART. Despite paper register systems coming under increasing strain, the evolution from paper directly to complex electronic medical record solutions is not viable in many contexts. Implementing a bridging solution, such as a simple offline electronic version of the paper register, can be a pragmatic alternative. This paper describes and recommends a three-tiered monitoring approach in low- and middle-income countries based on the experience implementing such a system in the Western Cape province of South Africa. A three-tier approach allows Ministries of Health to strategically implement one of the tiers in each facility offering ART services. Each tier produces the same nationally required monthly enrolment and quarterly cohort reports so that outputs from the three tiers can be aggregated into a single database at any level of the health system. The choice of tier is based on context and resources at the time of implementation. As resources and infrastructure improve, more facilities will transition to the next highest and more technologically sophisticated tier. Implementing a three-tier monitoring system at country level for pre-antiretroviral
Dhamija, P; Bansal, D; Medhi, B
The prospects for expanded access to antiretroviral therapy (ART) in resource-poor settings have greatly improved as a result of global and national efforts to reduce the cost of antiretroviral drugs (ARV), growing availability of cheaper generics, and increased financing available from the Global Funds like Medicines Sans Frontieres. Indian health set-up provides drugs free-of-cost to HIV infected patients through government network and also through open-market to those who intend to have personalized care. Post-2005, implementation of WTO agreement on TRIPS is expected to have a significant impact on pricing and availability of generic ARV. The study has been planned to explore the trends and gaps in availability & accessibility of ARV in India. The trends in per-patient-per-year (PPPY) cost of individual ARV and treatment regimes were also explored. The epidemiological data demonstrated stabilization of the epidemic in India. Most ARV are available in India by the generic manufacturers with a median drug lag period of 2.05 years (Range 0.75-6.51 years). There is a significant price difference in drugs available from generic and originator companies. Prices for patented and generic ARV in India reflect price negotiations that have taken place since the introduction of drugs in the country, still most of the ARVs are available at a much higher cost in the market [median 2.6 times (range 1-7)]. The per-patient per year (PPPY) cost of providing first-line regime in 2008 has decreased 2.75 times from that in 2003. The analysis shows the stabilization of prices of all drugs after 2006. HIV spending in India has seen a growth of 26 percent and 28 percent in 2005-06 and 2006-07 respectively. Still, the expected expenditure to cover the whole patient population needing therapy is considerably higher than the actual expenditure incurred for providing ARV. Despite the price reductions and availability of ARV at a lower cost through agencies like MSF, there is a large gap
Full Text Available Abstract Background Several lines of evidence suggest that retinoids (retinol-ROL or vitamin A, and its active metabolites, retinoic acids-RAs play important pathogenic roles in HIV infection and combination antiretroviral therapy (cART-related events. We previously reported that antiretrovirals alter RAs synthesis in vitro. We hypothesised that in vivo serum retinoid concentrations are affected by both cART and HIV infection. This might explain several clinical and laboratory abnormalities reported in HIV-infected patients receiving cART. Methods The effects of optimal cART and chronic HIV on serum retinoids were firstly assessed longitudinally in 10 HIV-infected adults (group1 = G1: twice while on optimal cART (first, during long-term and second, during short term cART and twice during 2 cART interruptions when HIV viral load (VL was detectable. Retinoid concentrations during optimal long term cART in G1 were compared with cross-sectional results from 12 patients (G2 with suboptimal cART (detectable VL and from 28 healthy adults (G3. Serum retinoids were measured by HPLC with ultraviolet detection. Retinoid concentrations were correlated with VL, CD4+ T- cell count and percentages, CD8+38+ fluorescence, triglycerides, cholesterol and C-peptide serum levels. Results During optimal cART, G1 participants had drastically reduced RAs (0.5 ± 0.3 μg/dL; P + T- cell count, CD8+38+ fluorescence, VL. ROL correlated with triglycerides and cholesterol in G1 (rs = 0.8; P = 0.01. Conclusions Serum RAs levels are significantly diminished by cART, whereas ROL concentrations significantly decreased during uncontrolled HIV infection but augmented with optimal cART. These alterations in retinoid concentrations may affect the expression of retinoid-responsive genes involved in metabolic, hormonal and immune processes and be responsible for some adverse events observed in HIV-infected persons treated with antiretrovirals. Further studies should assess
Full Text Available Theory of attachment primarily described early relationships between a child and his caretakers. In the last twenty years there is a growing interest in adult attachment research. Theories and research findings of adult attachment stem from two different methodological approaches. The first approach measures adult attachment through Adult Attachment Interview (AAI; Main, 1991 where the attachment is assessed through the narratives of adult people of their early child experiences with their primary caretakers. The second approach measures adult attachment with the help of self-evaluative questionnaires, developed by (a Hazan and Shaver (1987 who started this approach in the field of personality and social psychology, and (b Bartholomew and Horowitz (1991. Research shows that there is significant correlation between early and adult attachment style. Attachment styles are passed from generation to generation. Basic adult attachment styles are: securely attached, preoccupied, fearful-avoidant, dismissing-avoidant and disorganized. Previous research using Barholomew and Horowitz (1991 Relationship Questionnaire on 176 Slovenian students showed that 48% students are securely attached, 29% are fearful-avoidant, 10% are dismissing-avoidant, and 13% have preoccupied attachment style. Theory of attachment is very useful for understanding the behavior and subjective experiences of children and adults. It is applicable to different contexts (psychotherapy, counseling, education .... The paper proposes further research focused on integration of adult attachment styles and types of object relations measured by Test of object relations (Žvelc, 1998 and Pictorial test of Separation and Individuation (Žvelc, 2003.
Full Text Available Introduction: There is little information on adherence to antiretroviral therapy (ART in the Eastern European region. This prospective study evaluated multiple measures of adherence and their association with viral suppression among HIV patients in Georgia. Methods: A prospective cohort study enrolled 100 consecutive antiretroviral-naïve adult (age ≥18 years patients, who were followed for three months. Adherence was assessed by medication refill and three self-report measures (an AIDS Clinical Trial Group [ACTG] tool for four-day adherence, a visual analogue scale [VAS] and a rating task for 30-day adherence. The VAS represented a line anchored by 0 and 100% corresponding to the percentage of prescribed doses taken. The rating task asked patients to rate their ability to take all medications as prescribed, with responses categorized into six levels of adherence: very poor (0%, poor (20%, fair (40%, good (60%, very good (80% and excellent (100%. Patients with adherence of ≥95% by medication refill, ACTG and VAS, and ≥80% by rating task, were defined as adherent. Results: Of 100 patients enrolled, eight had missing data and were excluded from analysis. Among the remaining 92 patients, the median age was 39 years, and 70% were men. Major modes of HIV acquisition were injection drug use (IDU; 47.3% and heterosexual contact (44.1%. The proportions of adherent patients were as follows: 68% by medication refill, 90% by ACTG questionnaire, 38% by VAS and 42% by rating task. On average, four months after commencing ART, 52 (56.5% patients had a viral load <400 copies/ml and 26 (28.3% patients had a viral load <50 copies/ml. Of 43 persons with a history of IDU, 22 (51.2% reached a viral load of <400 copies/ml. In multivariate analysis, only refill adherence was a statistically significant predictor of viral suppression of <400 copies/ml: the risk ratio was 1.7 (95% CI: 1.1–2.8. Refill adherence, VAS and rating task were associated with viral
Katherine T Steele
Full Text Available BACKGROUND: Adverse outcomes occurring early after antiretroviral therapy (ART initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana. METHODS: This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%. RESULTS: Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1-4.8 and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4-4.7. However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively. CONCLUSIONS: Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on
... Federal Transit Administration Capital Investment Program--New Starts and Small Starts Program Funds... appropriated for the Capital Investments Grant Account, which includes the New Starts and Small Starts programs... Transportation's (DOT) Federal Transit Administration (FTA) announces the apportionment of the FY 2011...
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.
Full Text Available Background CD4 and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or negatively affect the risk of disease this would not be identified prior to licensing. The aims of this study were to investigate the CD4 and viral load specific rates of fatal and non-fatal AIDS and non-AIDS events according to current antiretrovirals. Methods Poisson regression was used to compare overall events (fatal or non-fatal AIDS, non-AIDS or death, AIDS events (fatal and non-fatal or non-AIDS events (fatal or non-fatal for specific nucleoside pairs and third drugs used with>1000 person-years of follow-up (PYFU after January 1st 2001. Results 9801 patients were included. The median baseline date was January 2004 (interquartile range [IQR] January 2001–February 2007, age was 40.4 (IQR 34.6–47.3 years, and time since starting cART was 3.3 (IQR 0.9–5.1 years. At baseline, the median nadir CD4 was 162 (IQR 71–257/mm3, baseline CD4 was 390 (IQR 249–571/mm3, viral load was 1.9 (IQR 1.7–3.3 log10copies/ml and 2961 (30.2% had a prior AIDS diagnosis and 6.4 years prior to baseline. During 42372.5 PYFU, 1203 (437 AIDS and 766 non-AIDS events occurred. The overall event rate was 2.8 per 100 PYFU (95% confidence interval [CI] 2.7–3.0, of AIDS events was 1.0 (95% CI 0.9–1.1 and of non-AIDS events was 1.8 (95% CI 1.7–1.9. Of the AIDS events, 53 (12.1%were fatal as were 239 (31.2% of the non-AIDS events. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global p-value=0.084, and third drugs (global p-value=0.031. Compared to zidovudine/lamivudine, patients taking abacavir/lamivudine (adjusted incidence rate ratio [aIRR] 1.22; 95% CI 0.99–1.49 and abacavir plus one other nucleoside (aIRR 1.51; 95% CI 1.14–2.02 had an increased incidence of overall events. Comparing the third drugs
Full Text Available This Paper Presents The Starting Time Calculation For A Squirrel Cage Induction Motor. The Importance Of Starting Time Lies In Determining The Duration Of Large Current, Which Flows During The Starting Of An Induction Motor. Normally, The Starting Current Of An Induction Motor Is Six To Eight Time Of Full Load Current. Plenty Of Methods Have Been Discovered To Start Motor In A Quick Time, But Due To Un-Economic Nature, Use Are Limited. Hence, For Large Motors Direct Online Starting Is Most Popular Amongst All Due To Its Economic And Feasible Nature. But Large Current With Dol Starting Results In A Heavy Potential Drop In The Power System. Thus, Special Care And Attention Is Required In Order To Design A Healthy System. A Very Simple Method To Calculate The Starting Time Of Motor Is Proposed In This Paper. Respective Simulation Study Has Been Carried Out Using Matlab 7.8.0 Environment, Which Demonstrates The Effectiveness Of The Starting Time Calculation.
Jha, Arun Kumar; Uppal, Beena; Chadha, Sanjim; Aggarwal, Prabhav; Ghosh, Roumi; Dewan, Richa
Intestinal infection causing diarrheal disease is a dominant contributor to high morbidity and mortality in developing countries. This intervention study aimed to assess the response of specific anti-microbial and anti-retroviral therapy (ART) on enteropathogens identified in HIV/AIDS adult subjects from northern India. Seventy five ART naive (group 1) and seventy five ART adherent (group 2) HIV/AIDS adult subjects with diarrhea were enrolled. Stool samples from all subjects were examined for enteropathogens by wet mount, staining methods, culture and ELISA. Subjects with enteropathogens were started on specific therapy as per National AIDS Control Organisation, Government of India's guidelines. Follow-up stool samples were examined after 2-4 weeks of completion of therapy for persistence/clearing of enteropathogens. CD4+ T lymphocyte count was done for all subjects. At enrollment, group 1 had 26.13% bacterial, 57.66% parasitic & 16.22% fungal pathogens while group 2 had 11.9%, 69.05% & 19.05% pathogens, respectively. Parasitic diarrhea was more common than bacterial diarrhea. The coccidian parasites (Cryptosporidium spp. & Isospora belli) were the common parasites identified. Clearance of enteric pathogens was significant after specific anti-microbial therapy (p = 0.0001). Persistence of enteropathogens was seen primarily for coccidian parasites. Clearance of enteropathogens after specific therapy and the diagnostic yield of stool specimens were influenced by the CD4+ counts. Immune competence coupled with specific anti-microbial therapy displays the best response against enteric pathogens.
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......-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 years...
Gert U Van Zyl
Full Text Available South Africa's national antiretroviral (ARV treatment program expanded in 2010 to include the nucleoside reverse transcriptase (RT inhibitors (NRTI tenofovir (TDF for adults and abacavir (ABC for children. We investigated the associated changes in genotypic drug resistance patterns in patients with first-line ARV treatment failure since the introduction of these drugs, and protease inhibitor (PI resistance patterns in patients who received ritonavir-boosted lopinavir (LPV/r-containing therapy.We analysed ARV treatment histories and HIV-1 RT and protease mutations in plasma samples submitted to the Tygerberg Academic Hospital National Health Service Laboratory.Between 2006 and 2012, 1,667 plasma samples from 1,416 ARV-treated patients, including 588 children and infants, were submitted for genotypic resistance testing. Compared with 720 recipients of a d4T or AZT-containing first-line regimen, the 153 recipients of a TDF-containing first-line regimen were more likely to have the RT mutations K65R (46% vs 4.0%; p<0.001, Y115F (10% vs. 0.6%; p<0.001, L74VI (8.5% vs. 1.8%; p<0.001, and K70EGQ (7.8% vs. 0.4% and recipients of an ABC-containing first-line regimen were more likely to have K65R (17% vs 4.0%; p<0.001, Y115F (30% vs 0.6%; p<0.001, and L74VI (56% vs 1.8%; p<0.001. Among the 490 LPV/r recipients, 55 (11% had ≥1 LPV-resistance mutations including 45 (9.6% with intermediate or high-level LPV resistance. Low (20 patients and intermediate (3 patients darunavir (DRV cross resistance was present in 23 (4.6% patients.Among patients experiencing virological failure on a first-line regimen containing two NRTI plus one NNRTI, the use of TDF in adults and ABC in children was associated with an increase in four major non- thymidine analogue mutations. In a minority of patients, LPV/r-use was associated with intermediate or high-level LPV resistance with predominantly low-level DRV cross-resistance.
Kallen, Alexander; Woloshin, Steven; Shu, Jennifer; Juhl, Ellen; Schwartz, Lisa
Direct-to-consumer (DTC) prescription drug advertisements for HIV anti-retrovirals are controversial and have been criticized in the past for including deceptive images and underplaying HIV drug limitations. We sought to describe the state of recent DTC ads for HIV antiretrovirals in popular magazines by performing a content analysis of all complete DTC ads for antiretroviral medications appearing in eight national magazines during a one-year period. Current ads appear to have addressed previous concerns, but important problems still exist, such as failing to specify the medication's role in current treatment, to quantify drug efficacy, or to highlight life-threatening side effects.
Full Text Available Distal sensory polyneuropathy, which occur commonly in human immunodeficiency virus (HIV patients can occur as a consequence of the disease itself or the antiretroviral treatment the patient is receiving. Among the antiretroviral agents, nucleoside analogues are commonly associated with neuropathy and the main underlying mechanism is thought to be the mitochondrial toxicity exhibited by these agents. Clinical presentation of antiretroviral induced neuropathy is similar to that associated with the HIV infection and in many patients they may overlap. Treatment is primarily symptomatic and certain pathogenesis-based approaches have shown promising results.
Griffith, M J; Baloff, N
The complex start-up effect on utilization of health care services is too often overlooked or underestimated by marketing planners, leading to a range of negative consequences for both the users of services and the provider organization. Start-up analysis allows accurate estimation of these utilization effects for coordinated strategic planning among marketing finance, and operations.
A practical and fast-paced guide, Getting Started with SBT for Scala walks you through the setup of Scala projects in SBT with sample code for common as well as critical scenarios.Getting Started with SBT for Scala is for developers working on Scala projects who are interested in learning and utilizing Simple Build Tool to manage the build process.
A study of four European countries (France, United Kingdom, Italy, and Spain) was conducted to gather data on the business start-up process and its impact on the generation of jobs, small business start-up support programs, training and counseling programs, and characteristics of successful business starters. (The original aim of the study was to…
Elias KRAMBOVITIS; Filippos PORICHIS; Demetrios A SPANDIDOS
AIDS is presently treatable, and patients can have a good prognosis due to the success of highly active antiretroviral therapy (HAART), but it is still not curable or preventable. High toxicity of HAART, and the emergence of drug resistance add to the imperative to continue research into new strategies and interventions.Considerable progress in the understanding of HIV attachment and entry into host cells has suggested new possibilities for rationally designing agents that interfere with this process. The approval and introduction of the fusion inhibitor enfuvirtide (Fuzeon) for clinical use signals a new era in AIDS therapeutics. Here we review the crucial steps the virus uses to achieve cell entry, which merit attention as potential targets, and the compounds at pre-clinical and clinical development stages, reported to effectively inhibit cell entry.
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.
Kimberly N. Capers
Full Text Available Guillain-Barré syndrome (GBS has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome.
do Lago, Regina Ferro; Costa, Nilson do Rosário
This paper addresses institutional constraints that have affected Brazilian politics regarding provision of anti-retroviral treatment (ART) to HIV/Aids patients. We analyzed the normative conflict resulting from international agreements on intellectual property rights, especially patent protection, and the constitutional rights of Brazilian patients to universal and free access to ART. These constraints have not substantially changed the Brazilian public policy yet, but they may impact the future sustainability of this policy. As the main barrier to the production of patented drugs is not technological but institutional, Brazilian government faces a dilemma. It may either abide by existing monopolistic restrictions or it may incite competitiveness of domestic industries and developing countries in the pharmaceutical market.
Globally, 240,000 infants are newly infected with HIV-1 each year and 3.2 million children are living with the infection. Combination antiretroviral therapy (cART) has reduced HIV-1-related disease and mortality in children but is not curative owing to the early generation of a latent reservoir of long-lived memory CD4(+) T cells bearing replication-competent HIV-1 provirus integrated into cellular DNA. This review focuses on recent advances in our understanding of the establishment of HIV-1 persistence in children and how early initiation of cART in the setting of the developing infant immune system limits the formation of the long-lived latent CD4(+) cell reservoir that remains a barrier to remission or cure.
Lodi, Sara; Dray-Spira, Rosemary; Touloumi, Giota;
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...... included individuals diagnosed with HIV between 1996 and 2011, aged at least 16 years, with known educational level and at least one CD4 cell count within 6 months of HIV diagnosis. We examined trends by education level in presentation with advanced HIV disease (AHD) (CD4 ... count at cART initiation was lower with poorer educational level. CONCLUSIONS: Socioeconomic inequalities in delayed HIV diagnosis and initiation of cART are present in European countries with universal healthcare systems and individuals with lower educational level do not equally benefit from timely c...
Jacinta Nwamaka Nwogu
Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.
Maggi, Paolo; Montinaro, Vincenzo; Mussini, Cristina; Di Biagio, Antonio; Bellagamba, Rita; Bonfanti, Paolo; Calza, Leonardo; Cherubini, Chiara; Corsi, Paola; Gargiulo, Miriam; Montella, Francesco; Rusconi, Stefano
Chronic kidney disease is a major comorbidity in patients affected by HIV infection. In addition, the introduction of new antiretroviral agents that interact with creatinine transporters is raising some concerns. In this review we analyze the currently available data about three new antiretroviral drugs and one new pharmacokinetic enhancer. Three of them (rilpivirine, cobicistat, dolutegravir) have shown some interactions with renal function, while tenofovir alafenamide fumarate reduces the plasmatic concentration of the parent drug. The future use of tenofovir alafenamide seems to be encouraging in order to reduce the renal interaction of tenofovir. Rilpivirine, cobicistat, and dolutegravir reduce the tubular secretion of creatinine, inducing a decrease of estimated glomerular filtration rate according to creatinine. Rilpivirine and dolutegravir block the uptake of creatinine from the blood, inhibiting organic cation transporter 2, and cobicistat interacts with the efflux inhibiting multidrug and toxin extrusion protein 1. This effect can then be considered a "reset" of the estimated glomerular filtration rate according to creatinine. However, clinicians should carefully monitor renal function in order to identify possible alterations suggestive of a true renal functional impairment. Owing to the interference of these drugs with creatinine secretion, an alternative way of estimation of glomerular filtration rate would be desirable. However, at the moment, other methods of direct glomerular filtration rate measurement have a high impact on the patient, are not readily available, or are not reliable in HIV patients. Consequently, use of classic formulas to estimate glomerular filtration rate is still recommended. Also, tubular function needs to be carefully monitored with simple tests such as proteinuria, phosphatemia, urinary excretion of phosphate, normoglycemic glycosuria, and excretion of uric acid.
Ferrari, Luiz F; Levine, Jon D
A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKCε-independent, and alcohol-induced painful neuropathy was PKCε-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKCε-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction.
Luni, Faraz Khan; Khan, Abdur Rahman; Prashar, Rohini; Vetteth, Sandeep; Duggan, Joan M
Antiretroviral medications such as tenofovir have been associated with Fanconi syndrome (FS) usually identified within the first 1-29 months after exposure to the medication. We present a case of life-threatening FS which developed in a 37-year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later, and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3 years before admission for FS. She developed nausea, vomiting, diarrhea, and generalized weakness over a 2-week time period and presented to the hospital. In the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12 mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95 mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by antiretroviral therapy (ART) was suspected and the ART was discontinued with resolution of the renal abnormalities within 7 days. A non-tenofovir-containing ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over the next 8 months, the patient was without recurrence of the FS. This case report demonstrates the acute development of FS after prolonged exposure to tenofovir without exposure to additional nephrotoxins such as nonsteroidal medications or aminoglycosides. Tenofovir can cause FS at any time and should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure.
Ruíz-López, Patricia; Moreno-Coutiño, Gabriela; Fernández-Martínez, Ramón; Espinoza-Hernández, Jessica; Rodríguez-Zulueta, Patricia; Reyes-Terán, Gustavo
Onychomycosis in HIV-infected patients has a prevalence of 20-44% and is more frequently seen with CD4(+) T cell counts ≤450 cel μl(-1). There are case reports of improvement in onychomycosis after initiation of combined antiretroviral therapy (cART), but there are no prospective studies that prove the existence and frequency of this phenomenon. The aim of this study was to evaluate if HIV-infected patients with onychomycosis who begin cART improve and/or cure without antifungal treatment. We included HIV-infected patients with onychomycosis who had not started cART and nor received antifungal therapy during 6 months prior to the study. We evaluated affected the nails with the Onychomycosis Severity Index (OSI); nail scrapings were collected and direct microscopy with potassium hydroxide (KOH) as well as mycological culture were performed. We repeated these procedures at 3 and 6 months to assess changes. CD4 T cell counts and HIV viral load were obtained. A total of 16 patients were included, with male gender predominance (68.7%); distal and lateral subungual onychomycosis (DLSO) was the most common form (31.3%). Trichophyton rubrum was the most frequently isolated microorganism. OSI decreased 21.5% at 3 months and 40% at 6 months after initiation of antiretrovirals (P = 0.05). We found a non-significant tendency towards improvement with higher CD4(+) T cell counts and with viral loads <100 000 copies ml(-1). This could be due to the increase in CD4(+) T cells, decreased percentage of Treg (CD4(+)CD25(+)) among CD4(+) Tcells and/or a decreased viral load; further studies are necessary to prove these hypothesis.
Rasmussen, Line D; Kronborg, Gitte; Larsen, Carsten S
no injection drug abuse or hepatitis C infection. Population controls were identified from The Danish Civil Registration System and matched on age and gender (5:1). We analyzed the proportion of individuals who redeemed 0-1, 2-4, 5-9, or 10 or more non-antiretroviral drugs. Data were analyzed according......AIM: We investigated the use of non-antiretroviral drugs in the HIV-infected compared to the general population. METHODS: From the Danish HIV Cohort Study, we identified all HIV-infected individuals older than 18 years at HIV diagnosis who received care in Denmark through 1995-2013 and reported...... to calendar time, age, time from initiation of combination antiretroviral therapy (cART) and stratified by gender, geographical origin and route of HIV transmission. We further analyzed the use of the 25 most used non-antiretroviral drug classes. RESULTS: We identified 4,928 HIV-infected individuals (median...
Hansen, Birgitte R; Haugaard, Steen B; Iversen, Johan;
Following the introduction of highly active antiretroviral therapy (HAART), metabolic and morphological complications known as HIV associated lipodystrophy syndrome (HALS) have been increasingly common. The approaches to target these complications span from resistance exercise, diet and use...
Full Text Available Abstract As sub-Saharan African countries continue to scale up antiretroviral treatment, there has been an increasing emphasis on moving provision of services from hospital level to the primary health care clinic level. Delivery of antiretroviral treatment at the clinic level increases the number of entry points to care, while the greater proximity of services encourages retention in care. In Tete City, Mozambique, patients on antiretrovirals were rapidly down referred from a provincial hospital to four urban clinics in large numbers without careful planning, resulting in a number of patients being lost to follow-up. We outline some key lessons learned to support down referral, including the need to improve process management, clinic infrastructure, monitoring systems, and patient preparation. Down referral can be avoided by initiating patients' antiretroviral treatment at clinic level from the outset.
At their summit meeting in the spring of 1990, Presidents Bush and Gorbachev issued a joint statement expressing their intentions to continue the process of strategic arms control beyond the Strategic Arms Reduction Treaty (START), which was eventually signed in July 1991, toward agreement on further reductions. They set general goals for negotiation of a follow-on treaty to START, which has been called START II. President Bush's historic speech on September 27, 1991, reinforced those goals and specified several actions the US would take. It is the purpose of this report to examine possible provisions of START II and the implications of those provisions for achievement of the goals set at the 1990 summit, for verifiability, and for US force planning. This look ahead will contribute to advance planning of appropriate negotiating positions, verification research and development (R D), and force modernization and restructuring. This report describes the goals for a START II treaty and possible means for achieving them. It postulates one set of provisions for such a treaty, while it examines force structures for the US that could result from adoption of a treaty with these provisions. The adequacy of methods for verifying START II are examined and the implications of a START II treaty are postulated.
Do, Thi Nhan; Nguyen, Thi Minh Thu; Do, Mai Hoa; Masaya, Kato; Dang, Thi Bich; Pham, Thuy Linh; Yoshikawa, Kayoko; Cao, Thi Than Thuy; Nguyen, Thi Thuy Van; Bui, Duc Duong; Nguyen, Van Kinh; Nguyen, Thanh Long; Fujita, Masami
Antiretroviral therapy (ART) retention and 5 early-warning indicators (EWIs) of HIV drug resistance (HIVDR) were abstracted at 27 adult and 4 pediatric clinics in Vietnam in 2009. Of 4531 adults and 313 children, 81.2% and 84.4% respectively were still on ART at 12 months. More than 90% of the clinics monitored achieved the World Health Organization (WHO) targets for lost-to-follow-up (LTFU), ART prescribing practices, and ARV supply continuity. Only 83.9% of the clinics met the target for first-line ART retention and 79.3% met the target for clinic appointment-keeping. Clinic factors (i.e. number of patients, administrative level, and geographical region) were associated with ART retention and LFTU. Data were useful in guiding public health action to optimize ART services.
Vance, David E.; Humphrey, Shameka C.; Nicholson, William C.; Jablonski-Jaudon, Rita
Despite advances in combination Antiretroviral Therapy (cART), adults with HIV continue to experience cognitive impairments. In addition to these cognitive impairments, research suggests as many as 40% and 20% of adults with HIV are diagnosed with depression and anxiety, respectively. The impact of these cognitive and emotional deficits increases caregiver burden, impairs occupational and driving performance, contributes to poor emotional processing, increases cognitive complaints, and reduce...
Nowacek, Ari S; McMillan, JoEllyn; Miller, Reagan; Anderson, Alec; Rabinow, Barrett; Gendelman, Howard E
We posit that improvements in pharmacokinetics and biodistributions of antiretroviral therapies (ART) for human immunodeficiency virus type one-infected people can be achieved through nanoformulationed drug delivery systems. To this end, we manufactured nanoparticles of atazanavir, efavirenz, and ritonavir (termed nanoART) and treated human monocyte-derived macrophages (MDM) in combination therapies to assess antiretroviral responses. This resulted in improved drug uptake, release, and antiretroviral efficacy over monotherapy. MDM rapidly, within minutes, ingested nanoART combinations, at equal or similar rates, as individual formulations. Combination nanoART ingested by MDM facilitated individual drug release from 15 to >20 days. These findings are noteworthy as a nanoART cell-mediated drug delivery provides a means to deliver therapeutics to viral sanctuaries, such as the central nervous system during progressive human immunodeficiency virus type one infection. The work brings us yet another step closer to realizing the utility of nanoART for virus-infected people.
Harries, Anthony D; Ford, Nathan; Jahn, Andreas; Schouten, Erik J; Libamba, Edwin; Chimbwandira, Frank; Maher, Dermot
The scale-up of antiretroviral therapy (ART) in Malawi was based on a public health approach adapted to its resource-poor setting, with principles and practices borrowed from the successful tuberculosis control framework. From 2004 to 2015, the number of new patients started on ART increased from about 3000 to over 820,000. Despite being a small country, Malawi has made a significant contribution to the 15 million people globally on ART and has also contributed policy and service delivery innovations that have supported international guidelines and scale up in other countries. The first set of global guidelines for scaling up ART released by the World Health Organization (WHO) in 2002 focused on providing clinical guidance. In Malawi, the ART guidelines adopted from the outset a more operational and programmatic approach with recommendations on health systems and services that were needed to deliver HIV treatment to affected populations. Seven years after the start of national scale-up, Malawi launched a new strategy offering all HIV-infected pregnant women lifelong ART regardless of the CD4-cell count, named Option B+. This strategy was subsequently incorporated into a WHO programmatic guide in 2012 and WHO ART guidelines in 2013, and has since then been adopted by the majority of countries worldwide. In conclusion, the Malawi experience of ART scale-up has become a blueprint for a public health response to HIV and has informed international efforts to end the AIDS epidemic by 2030.
Maina, E K; Bonney, E Y; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K
The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART.
Full Text Available Abstract Background Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir. Methods Consecutive patients initiating antiretroviral therapy (ART with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP, interleukin-6 (IL-6, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1 and plasminogen activator inhibitor-1 (PAI-1 were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status. Results 50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir (+225%, p Conclusion Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs.
Cole, Steven W.
Voltage regulator bypassed to supply starting current. Starting or "pullup" circuit supplies large inrush of current required by erasable programmable logic device (EPLD) while being turned on. Operates only during such intervals of high demand for current and has little effect any other time. Performs needed bypass, acting as current-dependent shunt connecting battery or other source of power more nearly directly to EPLD. Input capacitor of regulator removed when starting circuit installed, reducing probability of damage to transistor in event of short circuit in or across load.
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.
Abstract The number of people receiving antiretroviral treatment (ART) has increased considerably in recent years and is expected to continue to grow in the coming years. A major challenge is to maintain uninterrupted supplies of antiretroviral (ARV) drugs and prevent stock outs. This article discusses issues around the management of ARVs and prevention of stock outs in Malawi, a low-income country with a high HIV/AIDS burden, and a weak procurement and supply chain management system. This sy...
Jiménez-Montero, Beatriz; Beceiro, José; de José-Gómez, M Isabel; González-Tomé, M Isabel; Gurbindo-Gutierrez, Dolores; Martínez-Pérez, Jorge; Mellado-Peña, M José; Navarro-Gómez, M Luisa; Roa-Francia, Miguel A; Rojo-Conejo, Pablo; Saavedra-Lozano, Jesús; Jiménez de Ory, Santiago; Ramos-Amador, José T
We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.
U.S. Department of Health & Human Services — Office of Head Start (OHS) web based search tool for finding Head Start program office contact information. Searchable by location, grant number or center type....
Full Text Available Abstract Introduction Many countries ravaged by conflict have substantial morbidity and mortality attributed to HIV/AIDS yet HIV treatment is uncommonly available. Universal access to HIV care cannot be achieved unless the needs of populations in conflict-affected areas are addressed. Methods From 2003 Médecins Sans Frontières introduced HIV care, including antiretroviral therapy, into 24 programmes in conflict or post-conflict settings, mainly in sub-Saharan Africa. HIV care and treatment activities were usually integrated within other medical activities. Project data collected in the Fuchia software system were analysed and outcomes compared with ART-LINC data. Programme reports and other relevant documents and interviews with local and headquarters staff were used to develop lessons learned. Results In the 22 programmes where ART was initiated, more than 10,500 people were diagnosed with HIV and received medical care, and 4555 commenced antiretroviral therapy, including 348 children. Complete data were available for adults in 20 programmes (n = 4145. At analysis, 2645 (64% remained on ART, 422 (10% had died, 466 (11% lost to follow-up, 417 (10% transferred to another programme, and 195 (5% had an unclear outcome. Median 12-month mortality and loss to follow-up were 9% and 11% respectively, and median 6-month CD4 gain was 129 cells/mm 3. Patient outcomes on treatment were comparable to those in stable resource-limited settings, and individuals and communities obtained significant benefits from access to HIV treatment. Programme disruption through instability was uncommon with only one program experiencing interruption to services, and programs were adapted to allow for disruption and population movements. Integration of HIV activities strengthened other health activities contributing to health benefits for all victims of conflict and increasing the potential sustainability for implemented activities. Conclusions With commitment, simplified
HABERLEN, Sabina A.; NAKIGOZI, Gertrude; GRAY, Ronald H.; BRAHMBHATT, Heena; SSEKASANVU, Joseph; SERWADDA, David; NALUGODA, Fred; KAGAAYI, Joseph; WAWER, Maria. J.
Background A decade after the rollout of antiretroviral therapy (ART) in sub-Saharan Africa, the effects of this structural change on social aspects of HIV such as rates of HIV disclosure to partners remain largely unmeasured. We evaluated whether the introduction of ART was associated with disclosure of HIV diagnosis to spouses in Rakai, Uganda, using longitudinal, population-based data. Methods We identified individuals in marital/cohabitating unions who were newly diagnosed with HIV in Rakai Community Cohort Study (RCCS) surveys between 2000 and 2008, where antiretroviral therapy (ART) was introduced in mid-2004. Using discrete-time survival analysis, we assessed the hazard of self-reported HIV disclosure to spouse after diagnosis pre- and post-ART rollout, adjusting for individual and union characteristics. Disclosure in the ART period was further stratified by ART initiation. Results The analysis included 557 married adults, 264 of whom were diagnosed with HIV before ART was available (2000-2004) and 293 diagnosed after ART was introduced (2005-2008). The cumulative incidence of self-reported disclosure was 75.2% in the post-ART period, compared to 58.3% before ART availability (p<0.001, adjusted hazard 1.46 [95% CI 1.16, 1.83]). In the post-ART period, observed disclosure rates were 39% (72/184) among those not in HIV care, 65% (82/126) among those in pre-ART care, and 85% (64/75) among persons on ART (p<0.001). Conclusions Treatment availability and use, especially ART initiation, was associated with increased self-disclosure of HIV diagnosis to partners. ART access may facilitate the prevention of transmission to uninfected partners and linkage to treatment for infected couples. PMID:26009833