Search

The primary human immunodeficiency virus (HIV) reservoir is composed of resting memory CD4.sup.+ T cells, which often express the immune checkpoint receptors programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4), which limit T cell activation via synergistic mechanisms. Using simian immunodeficiency virus (SIV)-infected, long-term antiretroviral therapy (ART)-treated rhesus macaques, we demonstrate that PD-1, CTLA-4 and dual CTLA-4/PD-1 immune checkpoint blockade using monoclonal antibodies is well tolerated, with evidence of bioactivity in blood and lymph nodes. Dual blockade was remarkably more effective than PD-1 blockade alone in enhancing T cell cycling and differentiation, expanding effector-memory T cells and inducing robust viral reactivation in plasma and peripheral blood mononuclear cells. In lymph nodes, dual CTLA-4/PD-1 blockade, but not PD-1 alone, decreased the total and intact SIV-DNA in CD4.sup.+ T cells, and SIV-DNA and SIV-RNA in B cell follicles, a major site of viral persistence during ART. None of the tested interventions enhanced SIV-specific CD8.sup.+ T cell responses during ART or viral control after ART interruption. Thus, despite CTLA-4/PD-1 blockade inducing robust latency reversal and reducing total levels of integrated virus, the degree of reservoir clearance was still insufficient to achieve viral control. These results suggest that immune checkpoint blockade regimens targeting PD-1 and/or CTLA-4, if performed in people living with HIV with sustained aviremia, are unlikely to induce HIV remission in the absence of additional interventions. Immune checkpoint blockade has been proposed as a potentially curative strategy to reduce the HIV reservoir. Studies in monkeys now show that this approach alone is ineffective at enabling viral control after antiretroviral treatment interruption., Author(s): Justin Harper [sup.1] , Shari Gordon [sup.2] [sup.3] , Chi Ngai Chan [sup.4] , Hong Wang [sup.1] , Emily Lindemuth [sup.5] , Cristin Galardi [sup.3] [sup.6] , Shane D. [...]

We administered Ad26, modified vaccinia Ankara vectors containing mosaic HIV-1 antigens or placebo in 26 individuals who initiated antiretroviral therapy during acute human immunodeficiency virus infection as an exploratory study to determine the safety and duration of viremic control after treatment interruption. The vaccine was safe and generated robust immune responses, but delayed time to viral rebound compared to that in placebo recipients by only several days and did not lead to viremic control after treatment interruption (clinical trial NCT02919306). Test of therapeutic mosaic vaccines in HIV-infected individuals shows no control of virus after treatment interruption., Author(s): Donn J. Colby [sup.1] , Michal Sarnecki [sup.2] , Dan H. Barouch [sup.3] , Somporn Tipsuk [sup.1] , Daniel J. Stieh [sup.4] , Eugène Kroon [sup.1] , Alexandra Schuetz [...]

: Background: HIV and tuberculosis are frequently diagnosed concurrently. In March 2021, World Health Organization recommended that antiretroviral therapy (ART) should be started within two weeks of tuberculosis treatment start, at any CD4 count. We assessed whether earlier ART improved outcomes in people with newly diagnosed HIV and tuberculosis. Methods: We did a systematic review by searching nine databases for trials that compared earlier ART to later ART initiation in people with HIV and tuberculosis. We included studies published from database inception to 12 March 2021. We compared ART within four weeks versus ART more than four weeks after TB treatment, and ART within two weeks versus ART between two and eight weeks, and stratified analysis by CD4 count. The main outcome was death; secondary outcomes included IRIS and AIDS‐defining events. We pooled effect estimates using random effects meta‐analysis. Results and discussion: We screened 2468 abstracts, and identified nine trials. Among people with all CD4 counts, there was no difference in mortality by earlier ART (≤4 week) versus later ART (>4 week) (risk difference [RD] 0%, 95% confidence interval [CI] −2% to +1%). Among people with CD4 count ≤50 cells/mm[sup.3], earlier ART (≤4 weeks) reduced risk of death (RD −6%, −10% to −1%). Among people with all CD4 counts earlier ART (≤4 weeks) increased the risk of IRIS (RD +6%, 95% CI +2% to +10%) and reduced the incidence of AIDS‐defining events (RD −2%, 95% CI −4% to 0%). Results were similar when trials were restricted to the four trials which permitted comparison of ART within two weeks to ART between two and eight weeks. Trials were conducted between 2004 and 2014, before recommendations to treat HIV at any CD4 count or to rapidly start ART in people without TB. No trials included children or pregnant women. No trials included integrase inhibitors in ART regimens. Discussion: Earlier ART did not alter risk of death overall among people living with HIV who had TB disease. For logistical and patient preference reasons, earlier ART initiation for everyone with TB and HIV may be preferred to later ART., Introduction Tuberculosis (TB) is the most important cause of morbidity and mortality among people living with HIV (PLHIV) globally [1,2]. All people with TB should be offered testing for HIV [...]

: Introduction: We aimed to assess the effectiveness and tolerability of dolutegravir (DTG), abacavir (ABC) and lamivudine (3TC) administered as branded STR (DTG/ABC/3TC) or as two separate pills (DTG and either branded ABC/3TC [DTG+(ABC/3TC)b] or generic ABC/3TC [DTG+(ABC/3TC)g]). Methods: We included individuals from the multicentre cohort of the Spanish HIV/AIDS Research Network (CoRIS) who received DTG/ABC/3TC, DTG+(ABC/3TC)b or DTG+(ABC/3TC)g during 2015 to 2018. We used multivariable logistic regression to compare the proportion of antiretroviral‐naïve individuals who achieved viral suppression (VS) (viral load ≤50 copies/mL) at 24 weeks of initiating with DTG+(ABC/3TC)b or DTG+(ABC/3TC)g versus DTG/ABC/3TC. We also calculated the proportion of virologically suppressed individuals who maintained VS at 24 weeks after switching from DTG/ABC/3TC to DTG+(ABC/3TC)g. Results: During the study period, 829, 68 and 47 treatment‐naïve individuals started treatment with DTG/ABC/3TC, DTG+(ABC/3TC)b or DTG+(ABC/3TC)g respectively. The proportions of individuals who changed their regimens due to side effects during the first 24 weeks were 3.7%, 4.4% and 6.4% respectively (p = 0.646). We did not find significant differences in VS at 24 weeks among individuals starting with DTG+(ABC/3TC)b or DTG+(ABC/3TC)g compared to those initiating with DTG/ABC/3TC. Among 177 virologically suppressed individuals who switched from DTG/ABC/3TC to DTG+(ABC/3TC)g, 170 (96.0%) maintained VS at 24 weeks. Conclusions: In naïve individuals, the effectiveness and tolerability at 24 weeks of DTG plus ABC/3TC administered as two separate pills, either as branded or generic ABC/3TC, was similar to the STR DTG/ABC/3TC. Switching the STR DTG/ABC/3TC to its separate components DTG+(ABC/3TC)g in virologically suppressed individuals did not seem to impair its effectiveness., INTRODUCTION Highly active antiretroviral therapy (ART) has substantially increased the life expectancy of people living with HIV [1,2]. People living with HIV (PLHIV) have a life expectancy that can reach [...]

Author(s): Daniel I. S. Rosenbloom [1]; Alison L. Hill [2]; Sarah B. Laskey [3]; Robert F. Siliciano (corresponding author) [3, 4] ARISING FROM R. Lorenzo-Redondo et al . Nature 530, [...]

Background Dolutegravir (DTG)-based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL'HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART. Methods and findings SIMPL'HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with Conclusions In this study, DTG + FTC as maintenance therapy was non-inferior to cART in terms of efficacy, with a similar safety profile and a greater improvement in quality of life, thus expanding the offer of 2-drug simplification options among virologically suppressed individuals. Trial registration ClinicalTrials.gov NCT03160105., Author(s): Delphine Sculier 1,2,*, Gilles Wandeler 3,4, Sabine Yerly 5, Annalisa Marinosci 1, Marcel Stoeckle 6, Enos Bernasconi 7, Dominique L. Braun 8,9, Pietro Vernazza 10, Matthias Cavassini 11, Marta [...]

: Introduction: Up to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/mm[sup.3] despite plasma viral suppression. We investigated the frequency and associations of suboptimal CD4 recovery after ART started during acute HIV infection (AHI). Methods: Participants who started ART in Fiebig I to V AHI with ≥48 weeks of continuous documented HIV‐RNA < 50 copies/mL were stratified by CD4 count at latest study visit to suboptimal immune recovery (SIR; CD4 < 350 cells/mm[sup.3]), intermediate immune recovery (IIR; 350 ≤ CD4 < 500) and complete immune recovery (CIR; CD4 ≥ 500). Clinical and laboratory parameters were assessed at pre‐ART baseline and latest study visit. Additional inflammatory and neurobehavioral endpoints were examined at baseline and 96 weeks. Results: Of 304 participants (96% male, median 26 years old) evaluated after median 144 (range 60 to 420) weeks of ART initiated at median 19 days (range 1 to 62) post‐exposure, 3.6% (n = 11) had SIR and 14.5% (n = 44) had IIR. Pre‐ART CD4 count in SIR compared to CIR participants was 265 versus 411 cells/mm[sup.3] (p = 0.002). Individuals with SIR or IIR had a slower CD4 rate of recovery compared to those with CIR. Timing of ART initiation by Fiebig stage did not affect CD4 count during treatment. Following ART, the CD8[sup.+]T cell count (p = 0.001) and CD4/CD8 ratio (p = 0.047) were lower in SIR compared to CIR participants. Compared to the CIR group at week 96, the combined SIR and IIR groups had higher sCD14 (p = 0.008) and lower IL‐6 (p = 0.04) in plasma, without differences in neuropsychological or psychiatric indices. Conclusions: Despite immediate and sustained treatment in AHI, suboptimal CD4 recovery occurs uncommonly and is associated with low pre‐ART CD4 count as well as persistent low CD8 count and CD4/CD8 ratio during treatment., Introduction In the era of potent antiretroviral therapy (ART), ongoing HIV replication is adequately suppressed to undetectable levels in appropriately treated individuals. However, up to 30% of ART‐treated individuals fail [...]

: Introduction: The World Health Organisation recommends to Treat All people with HIV, irrespective of CD4 count. However, people with CD4 counts >500 cells/µL may be asymptomatic and therefore less motivated to adhere to antiretroviral therapy (ART). We aimed to assess whether people initiated with CD4 counts >500 cells/µL had worse treatment outcomes compared to those initiated at lower CD4 counts. Methods: We performed a retrospective cohort study among non‐pregnant adults initiating ART at eight public clinics in South Africa between September 2016, when Treat All was implemented, and August 2017. We assessed whether initiation CD4 count >500 cells/µL was associated with the outcomes of attrition (death, lost to follow‐up or treatment interruption >180 days), and viraemia >1000 copies/mL, by twelve months using Cox proportional hazards and Poisson regression models. Results and discussion: Among 4952 patients initiating ART, the median age was 32.4 years (interquartile range (IQR) 27.2 to 39.7), 58.9% were women and 30.3% had an initiation CD4 count >500 cells/µL. After twelve months, 3382 (68.3%) were retained in care, 303 (6.1%) had transferred to another clinic, 1010 (20.4%) were lost to follow‐up, 232 (4.7%) had a treatment interruption >180 days and 25 (0.5%) were known to have died. Overall, 1267 experienced attrition at a median time of 91 days (IQR 23 to 213), with 302 of these (23.8%) experiencing attrition immediately after their ART initiation visit. Among those in care at twelve months with viral load results, 4.6% had viraemia. In multivariable analysis, the hazard of attrition was similar between patients newly eligible for ART with CD4 counts >500 cells/µL compared to those with CD4 ≤500 cells/µL (adjusted hazard ratio 1.03, 95% confidence interval (CI) 0.90 to 1.17). The risk of viraemia was lower among patients with CD4 counts >500 cells/µL compared to those with CD4 ≤500 cells/µL (adjusted risk ratio 0.58, 95% CI 0.37 to 0.92). Conclusions: After implementation of Treat All in South African public clinics, we found that patients newly eligible for ART with initiation CD4 counts >500 cells/µL had comparable or better outcomes compared to those with lower CD4 counts. These finding support ongoing implementation of Treat All in our setting., Introduction In 2015 the World Health Organization (WHO) introduced its Treat All guidelines, which recommend antiretroviral therapy (ART) for all people living with HIV (PLHIV), including those with CD4 counts [...]

Background: CUSTOMIZE examined implementation strategies for provider-administered long-acting (LA) injectable ART in diverse US healthcare settings. Findings from staff and patients after 12 months of cabotegravir+rilpivirine (CAB+RPV) LA implementation are [...]

: Introduction: Multiple comorbidities among HIV‐positive individuals may increase the potential for polypharmacy causing drug‐to‐drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age‐associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age‐associated comorbidities on therapeutic outcomes of cART in HIV‐positive adults in Asian countries. Methods: Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those Results: The incidence of virologic failure was 7.72/100 person‐years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged Conclusions: In our Asia regional cohort, age‐associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients, Introduction Combination antiretroviral therapy (cART) has dramatically improved the survival and quality of life for people living with HIV. A growing proportion of patients are over the age of 50 [...]

Background: Approaches to deplete persistent HIV infection are needed. We investigated the combined impact of the latency reversing agent vorinostat (VOR) and VRC-07-523-LS, a broadly-neutralizing HIV antibody with prolonged half-life, [...]

Background: In Nigeria, adolescents (10 to 19 years) account for about 23% of the total population, and 7% of people living with HIV (PLHIV); treatment outcomes for adolescents and youth [...]

Background: In vitro studies suggest that reducing cholesterol inhibits HIV replication. However, this effect may not hold in vivo, where other factors, such as cholesterol's immunomodulatory properties, may interact. Methods: Fasting blood samples were obtained on 165 people living with HIV at baseline and after 24 weeks on highly active antiretroviral therapy (HAART). Participants were classified as hypocholesterolemic (HypoCHL; 150 mg/dl) and were compared on viro‐immune outcomes. Results: At baseline, participants with HypoCHL (40%) exhibited lower CD4 (197 ± 181 vs. 295 ± 191 cells/mm3, p = 0.02) and CD8 (823 ± 448 vs. 1194 ± 598 cells/mm[sup.3], p = 0.001) counts and were more likely to have detectable viral loads (OR = 3.5, p = 0.01) than non‐HypoCHL controls. After HAART, participants with HypoCHL were twice as likely to experience a virological failure >400 copies (95% CI 1‐2.6, p = 0.05) and to exhibit Conclusions: The study implicates, for the first time, HypoCHL with impaired HAART effectiveness, including limited CD4 repletion by the thymus and suboptimal viral clearance., Background During the course of HIV disease, disturbances of lipid metabolism have been observed long before the introduction of highly active antiretroviral therapy (HAART) and included hypocholesterolemia (HypoCHL; Conversely, the [...]

Introduction: The overlapping drug toxicity profiles, drug‐drug interactions and complications of management of both HIV and tuberculosis (TB) in patients with advanced HIV have not been fully delineated. Methods: We conducted a retrospective chart review of the outcomes of tuberculosis treatment among 69 HIV‐infected patients with TB, who were hospitalized in Masih Daneshvari Hospital in Tehran, Iran between 2002 and 2006, and who received standard category 1 (CAT‐1) regimens. Group I (N = 47) included those treated from 2002 to 2005 with highly active antiretroviral therapy (HAART) initiated after eight weeks of TB treatment for those whose CD4 count was Results: There were no differences between Groups I and II with regard to: adverse drug reactions [four (8.5%) versus two (9%), p = ns]; IRIS [six (12.7%) versus three (10.7%), p = ns]; and new opportunistic infections [eight (17.0%) versus two (9.1%), p = ns]. Death, however, occurred more frequently in Group I than in Group II [13 (27.7%) versus (4.5%), p = 0.03], where HAART was initiated earlier. Injection of drugs was the most common route of HIV transmission in both groups (72.3% in Group I and 77.3% in Group II). Conclusion: This manuscript shows that in a retrospective review of HIV/TB patients hospitalized in Tehran, improved survival was associated with earlier initiation of antiretroviral therapy in HIV/TB patients with CD4 counts of below 100 cells/mm[sup.3]., Findings Multiple complications in the co‐management of HIV and TB have been documented or suggested, including: overlapping medication toxicity profiles; pharmacokinetic drug interactions; premature death from non‐tuberculosis causes; development of [...]

Objective: To study the effectiveness and tolerance of an antiretroviral therapy (ART) regimen composed of the antiretroviral agents (ARVs) stavudine (d4T) plus didanosine (ddI) plus efavirenz (EFV) in patients with advanced HIV infection in Senegal. Design and methods: This was an open‐label, single‐arm, 18‐month trial in treatment‐naive patients. The primary virologic end point was the percentage of patients with plasma HIV RNA < 500 copies/mL at months 6 (M6), 12 (M12) and 18 (M18). The primary analysis was done as intent‐to‐treat. Results: The staging of HIV disease, performed using the definitions of the US Centers for Disease Control and Prevention (CDC), was CDC stage B or C for all 40 recruited patients. At baseline, the mean CD4+ cell count was 133 ± 92/mcL (± standard deviation [SD]; range 1–346), and 23% of patients had CD4+ cell counts below 50/mcL. The mean baseline plasma HIV RNA level was 5.5 ± 0.4 log[sub.10] copies/mL (± SD; range 4.6–5.9). The proportion of patients with plasma HIV‐1 RNA below 500 copies/mL fell during the study from 73% (95% CI [56; 85]) at M6 to 56% (95% CI [41; 73]) at M12 and 43% (95% CI [27; 59]) at M18. Plasma HIV‐RNA was below 50 copies/mL in 50% of study subjects (95% CI [31; 66]) at M6, 43% (95% CI [27; 59]) at M12, and 33% (95% CI [19; 49]) at M18. The mean increase in the CD4+ cell count was 105 ± 125/mcL (n = 38) at M3 and 186 ± 122/mcL (n = 21) at M18. Eight patients died, including 6 because of infectious complications. The last viral load (VL) value before death was < 500 copies/mL in all these patients except 1 nonadherent patient. Fifteen patients (37.5%) had peripheral neuropathy that was severe enough in 5 patients (12.5%) to require ddI and d4T discontinuation. Conclusion: Virologic efficacy combination therapy with d4T, ddI, and EFV was measured by the percentage of patients with plasma HIV RNA values below 500 copies/mL and 50 copies/mL; for both parameters, virologic efficacy decreased during the study period. This is explained by the high mortality rate (20%) and treatment modifications due to adverse events (13%). These data strengthen the recently revised World Health Organization (WHO) guidelines advocating initiation of highly active antiretroviral therapy (HAART) before profound CD4 lymphocyte depletion occurs and avoiding HAART regimens containing d4T and ddI because of treatment‐limiting side effects., Introduction The efficacy of antiretroviral treatments in sub‐Saharan Africa has been demonstrated in cohort studies and pilot trials.[1‐3] The treatment regimens tested in these studies were derived from those used [...]

Introduction: Antiretroviral therapy (ART) prevents HIV transmission within HIV serodiscordant couples (SDCs), but slow implementation and low uptake has limited its impact on population‐level HIV incidence. Home HIV testing and counselling (HTC) campaigns could increase ART uptake among SDCs by incorporating couples’ testing and ART referral. We estimated the reduction in adult HIV incidence achieved by incorporating universal ART for SDCs into home HTC campaigns in KwaZulu‐Natal (KZN), South Africa, and southwestern (SW) Uganda. Methods: We constructed dynamic, stochastic, agent‐based network models for each region. We compared adult HIV incidence after 10 years under three scenarios: (1) “Current Practice,” (2) “Home HTC” with linkage to ART for eligible persons (CD4 Results: ART for SDCs reduced HIV incidence by 38% versus Home HTC: from 1.12 (95% CI: 0.98–1.26) to 0.68 (0.54–0.82) cases per 100 person‐years (py) in KZN, and from 0.56 (0.50–0.62) to 0.35 (0.30–0.39) cases per 100 py in SW Uganda. A quarter of incident HIV infections were averted over 10 years, and the proportion of virally suppressed HIV‐positive persons increased approximately 15%. Conclusions: Using home HTC to identify SDCs and deliver universal ART could avert substantially more new HIV infections than home HTC alone, with a smaller number needed to treat to prevent new HIV infections. Scale‐up of home HTC will not diminish the effectiveness of targeting SDCs for treatment. Increasing rates of couples’ testing, disclosure, and linkage to care is an efficient way to increase the impact of home HTC interventions on HIV incidence., Introduction A key challenge for HIV prevention is delivering effective and efficient interventions to populations at highest risk of HIV acquisition, such as HIV‐negative persons in stable, ongoing relationships with [...]

Introduction: T cell immunoglobulin and mucin domain (Tim) 3 and programmed death 1 (PD‐1) are co‐inhibitory receptors involved in the so‐called T cell exhaustion, and in vivo blockade of these molecules restores T cell dysfunction. High expression of Tim‐3 and PD‐1 is induced after chronic antigen‐specific stimulation of T cells during HIV infection. We have previously demonstrated that the interaction of Tim‐3 with its ligand galectin‐9 induces macrophage activation and killing of Mycobacterium tuberculosis. Our aim in this study was to analyze the Tim‐3 expression profile before and after six months of antiretroviral therapy and the impact of Tim‐3 and PD‐1 blocking on immunity against M. tuberculosis. Materials and methods: HIV+ patients naïve to anti‐retroviral therapy (ART) were followed up for six months. Peripheral immune‐cell phenotype (CD38/HLA‐DR/galectin‐9/Tim‐3 and PD‐1) was assessed by flow cytometry. Supernatants were analyzed with a multiplex cytokine detection system (human Th1/Th2 cytokine Cytometric Bead Array) by flow cytometry. Control of bacterial growth was evaluated by using an in vitro experimental model in which virulent M. tuberculosis‐infected macrophages were cultured with T cells in the presence or absence of Tim‐3 and PD‐1 blocking antibodies. Interleukin‐1 beta treatment of infected macrophages was evaluated by enumerating colony‐forming units. Results: We showed that HIV+ patients had an increased expression of Tim‐3 in T cells and were able to control bacterial growth before ART administration. By blocking Tim‐3 and PD‐1, macrophages and T cells recovered their functionality and had a higher ability to control bacterial growth; this result was partially dependent on the restitution of cytokine production. Conclusions: In this study, we demonstrated that increased Tim‐3 expression can limit the ability of the immune system to control the infection of intracellular bacteria such as M. tuberculosis. The use of ART and the in vitro manipulation of the Tim‐3 and PD‐1 molecules restored the functionality of T cells and macrophages to restrict bacterial growth. Our results provide a novel immune strategy that may be implemented in the near future in order to improve the immune responses in HIV+ patients., Introduction Pulmonary tuberculosis (TB) is one of the most important causes of death from infectious disease around the world. It is the leading cause of opportunistic infection and mortality among [...]

Introduction: Switch to Stribild (STB) was non‐inferior to continuation of a non‐nucleoside reverse transcriptase inhibitor (NNRTI) with emtricitabine and tenofovir DF (FTC/TDF) at week 48 in virologically suppressed HIV adults [1]. We report the Week 48 efficacy and safety of STB versus nevirapine (NVP) or rilpivirine (RPV) with FTC/TDF in suppressed subjects. Materials and Methods: Virologically suppressed subjects on an NNRTI with FTC/TDF regimens for ≥6 months were randomized (2:1) to switch to STB versus continue their NNRTI regimen. Eligibility criteria included no documented resistance to FTC and TDF, no history of virologic failure and eGFR ≥70 mL/min. The primary endpoint was the proportion of subjects in the modified ITT population who maintained HIV‐1 RNA Results: The mITT population included 433 subjects who were randomized and treated. In the non‐EFV NNRTI subgroup, 59 switched to STB; 37 continued a non‐EFV NNRTI (27 NVP, 10 RPV) with FTC/TDF. At week 48, 97% STB versus 95% non‐EFV NNRTI maintained HIV‐1 RNA Conclusions: In this small group of virologically suppressed subjects, switch to STB vs continuation of NVP or RPV with FTC/TDF was safe, well‐tolerated, and associated with a high rate of virologic suppression at week 48. There was more treatment ease with STB use., Reference Pozniak A, Markowitz M, Mills A, Stellbrink HJ, Antela A, Domingo P, et al. Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non‐nucleoside reverse transcriptase inhibitor [...]

Introduction: First antiretroviral therapy (ART) is often switched to simpler, more potent or better tolerated regimens [1, 2]. Although discontinuation rates are frequently studied, the durability of regimens is rarely approached. Materials and Methods: Retrospective study with the following objectives: analyze first ART schemes and their durability in naive patients with chronic HIV‐1 and 2 infections, evaluate factors influencing ART change, second‐line ART and consequent virologic and immunologic responses. Patients had follow‐ups in a Central University Hospital, started ART between January 2007 and December 2012 and changed first regimens. Clinical data was obtained from medical records and analyzed using the Statistical Package for the Social Sciences (version 20). Results: Of the 652 naive patients who started ART, 164 changed regimens. The majority had HIV‐1 infection (n=158). The mean age was 43.9 years (standard deviation±14.3), with a male predominance of 57.9%. Regimens with efavirenz were the most common amongst HIV‐1 patients (50%) followed by lopinavir/r (22%). In HIV‐2 patients, lopinavir/r (n=3) regimens were most prevalent. First ART regimens had a mean duration of 12.1 months. There was no difference between NNRTI (59.8%) and protease inhibitor (40.2%) schemes regarding durability. Adverse reactions were the major cause of ART switching (55.5%) followed by therapy resistance (12.1%). Age was inversely related to durability (p=0.007 Mann‐Whitney, Phi coefficient −0.161) and associated with the appearance of adverse reactions (p=0.04, Chi‐square). Younger patients had a reduced risk of adverse reactions by 27%. Adverse reactions increased the risk of inferior durability by 40%. Psychiatric symptoms (28.4%) were the most prevalent, all attributed to efavirenz. The year of ART initiation was associated with different durability rates (p=0.005, Mann‐Whitney). Patients started on ART before the year 2010 reduced the probability of inferior ART duration by 25.8%. After second‐line ART regimens, TCD4+ counts>500 cell/µL were increased by 38% and favourable virologic outcome achieved in 84%. Conclusions: Adverse reactions were the main cause for ART switching, supporting a cautious approach when initiating regimens, particularly in older patients. All ART naive patients who changed initial therapy had favourable immunological and virologic responses., References Haering M, Hordt A, Meyer‐Hermannn M, Hernandez‐Vargas EA. Computational study to determine when to initiate alternate therapy in HIV infection. Germany: BioMed Research International; 2014. Lee FJ, Amin J, [...]

Introduction: The long‐term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short‐term four‐drugs induction regimen in patients with high baseline viral load. Methods: Naive patients with HIV‐RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab‐initio with TDF+FTC+EFV (E) or TDF+FTC+RAL (R) were used. Results: 19 patients with a mean age of 38 years and mean baseline CD4 count of 334 (SD 216) cells/mcL and HIV‐RNA of 5.47 log (SD 0.32) copies/mL were enrolled. No baseline significant difference was observed among groups. Early HIV‐RNA reduction was significantly higher in ER compared to the other groups from week 1 to week 4 (P from 0.026 to 0.003) (figure 1), thereafter HIV‐RNA values were comparable among the groups. At week 96, all patients had an HIV‐RNA < 50 copies/mL, however only patients in the ER group had in all cases an HIV‐RNA level < 3 copies/mL with a statistically significant difference compared to E (60%; P=0.038) and R (50%; P=0.020). At 96 weeks, CD4 cell median counts were 765 cells/mcL for ER, 600 cells/mcL for E and 771 for R (P=0.16), however patients in the ER group presented a lower proportion of activated CD4+CD38+HLADR+ cells (1.9% versus 3.9 and 3.8%) and CD8+CD38+HLADR+ cells (10.3% versus 16.8 and 16.5%) and a significantly better CD4/CD8 ratio (0.98 versus 0.53 and 0.61; P=0.03). Conclusions: A four‐drug regimen in naive patients with high pre‐therapy viral load improves early virologic response. A quick drop of HIV‐RNA seems to correlate with a sustained virologic response. Although limited in time (four months), the four‐drug regimens correlates with an improved immunological response as measured by the CD4/CD8 ratio or the percentage of activated CD4+ and CD8+ cells. The reasons why this happens deserve further studies. This study highlights the importance of a personalised therapy especially in high risk patients., Figure 1: HIV‐RNA reduction among the three groups. [Figure omitted] Reference Maggiolo F, Masini G, Astuti N, Di Filippo E, Benatti S, Valenti D, et al. Division of Infectious Diseases; [...]

Introduction: The optimal timing and modality of therapeutic intervention during early phases of HIV infection is still debated; in our prospective observational study we evaluated immunological and virological outcome in HIV+ patients treated during acute or recent HIV infection. Materials and Methods: A total of 25 naïve patients with acute (detectable HIV‐RNA, immature Western Blot) or recent (documented infection within six months) HIV infection were recruited at the Infectious Diseases Units of the University of Milan and Turin from 2009 to 2014. Patients received treatment with two NRTIs+one NNRTI/bPI, with or without an induction phase with an additional fourth drug (raltegravir or maraviroc) until HIV‐RNA undetectability maintained for six months. Blood samples for HIV‐RNA, lymphocyte subsets and tropism assessment were obtained at the beginning of the treatment (BL). Patients underwent subsequent six‐monthly follow up for clinical outcome, CD4 cell count and HIV‐RNA up to 18 months. Results: Median increase in CD4 cells from 0 to 12 months was greater in patients treated during acute (n=18) versus recent (n=7) infection [284/µL, IQR (227–456) versus 176/µL, IQR (70–235); Mann‐Whitney test, p=0.046]. This higher value was maintained through 18 months, although failing to reach statistical significance. Patients with acute or recent infection did not significantly differ in virological success (83.3% versus 85.7% at 12 months). We considered CD4 cells gains at six months (multivariate analysis, ANCOVA; Figure 1) and detected an inverse correlation with CD4 levels at BL (r=−0.517; p=0.008) and a direct correlation with the status of acute infection (r=0.234, p NS). This last correlation reached statistical significance at 12 months (r=0.418, p=0.035), whereas the inverse correlation with CD4 levels at BL was still present without a statistical significance (r=−0.350; p=0.072). Patients treated with three or four drugs did not show any significant difference in immunological nor virological response (Mann‐Whitney and χ[sup.2] test). Modification or interruption of therapy for tolerability took place in 4 out of 25 patients, all while receiving four drugs; two patients underwent STI between 12 and 18 months following virological success. Conclusions: Treatment of primary infection appeared to be effective in preserving the pool of CD4 cells in acute more than recent infection. There was no evidence of a different outcome through the addition of a fourth drug to the standard treatment., Figure 1: CD4/CL recovery among BL and months 6 and 12. [Figure omitted] DOI: [...]

Introduction: Assessing virological response of four‐drugs antiretroviral regimen that include raltegravir (RAL) in naïve patients with high viral load (>500,000 copies/mL) selected from a multicentre Italian database. Methods: Naïve patients with HIV RNA>500,000 copies/mL, who began standard antiretroviral regimens either based on non‐nucleoside reverse transcriptase inhibitors (NNRTI) or boosted‐PI (PI/r), or a standard regimen plus RAL between 2008 and 2013 were analyzed. Observation was censored at 12 months and the percentage of patients who achieved a viral load below the limit of detection (BLD) was calculated. Virological failure was defined as two consecutive viral loads>40 copies/mL. Results: Overall, 179 patients were included (13% with primary HIV infection (PHI), and 42.5% with AIDS diagnosis). Of them, 156 started standard three‐drugs antiretroviral regimen (75.6% PI/r‐based, 24.4% NNRTI‐based. Among patients with PHI, 23 patients (12.8%), 6 (25%) started a four‐drugs antiretroviral regimen containing both RAL and PI/r. Patients’ characteristics were as follows: males 74%, median age 42 years (IQR 35–51), sexually transmission 75.1%, median CD4 count 156 cells/µL (IQR 47–368) and median HIV‐RNA 6.1 log10 copies/mL (IQR 5.8–6.4). 91 of 179 patients (50.8%) reached BLD viral load during the twelve months of observation. Three patients (1.7%) who began regimens PI/r‐based with three‐drugs had virological rebound after reaching BLD viral load. By use of survival analysis, we show that those patients who added RAL to the standard regimen have reached the primary end point faster (mean 8.4 months (95% CI 7.2–9.6) vs 11.4 (95% CI 11.0–11.8) in PI group and 10.3 (95% CI 9.4–11.1) in NNRTI group; p Conclusions: Only half of the naïve patients who began antiretroviral therapy having >500,000 copies/mL HIV‐RNA had virological success at 12 months. The success was reached faster using the RAL‐containing four‐drugs regimen, suggesting that strengthening the initial regimen could be an option in patients with very high viral load to improve virological response., Figure 1: Probability of HIV viral load below the limit of detection in naïve HIV‐1 patients with viral loads >500,000 copies/mL treated with a 4‐drugs regimen containing raltegravir versus standard [...]

Introduction: The persistence of immune activation and inflammation in HIV patients with HIV‐RNA (VL) undetectable causes many co‐morbidities [1–3]. The aim of this study is to correlate monocytes (m) and NK cell activation levels, soluble markers and oxidative stress with clinical, biochemical and metabolic data in HIV‐1 infected patients with VL≤50 copies (cp)/mL on antiretroviral therapy. Materials and Methods: Multicentre, cross‐sectional study in patients with VL≤50 cp/mL and on antiretroviral therapy by at least six months. We studied: activation/homing markers (CD38, HLA‐DR, CCR‐2, PDL‐1) on inflammatory, intermediate, proinflammatory m; activatory receptors NKp30, NKp46 and HLA‐DR on NK cells; soluble inflammatory (sCD14, adiponectina, MCP‐1) and stress oxidative markers (dRoms, antiRoms). Univariate analyses are performed with non‐parametric and Pearson tests. The significant correlations were adjusted for possible known confounding factors (smoking, Cytomegalovirus IgG serology, Raltegravir, Protease Inhibitor [PI] therapy and HCV‐RNA) with multivariate analysis. Results: In the 68 patients the positive correlation between age and antiRoms was significant also after adjustment for PI use (p=0.05). The% CD8+T was associated with% proinflammatory m (p=0.043) and with their expression of CCR2 mean fluorescence intensity (MFI) (p=0.012). The% NKp46+ was positively correlated with CD4+T count (p=0.001). The fibrinogen was positively associated with dRoms (p=0.052) and the positive correlation between triglycerides and antiRoms has been confirmed (p Conclusions: Patients with long history of HIV infection and stable immunological and virological status showed interactions between acquired and innate immunity activation; moreover, the levels of some metabolic and inflammatory parameters correlate with oxidative stress values and innate immunity activation. The age, BMI and smoking impact metabolic and immunological parameters. The correlations between antiretroviral drugs and clinical‐immunological parameters need further confirmations., Table 1: Patients' characteristics Age, years (median, IQR) 49 (46–54) Sex, n males (%) 46 (68) Prior AIDS events, n (%) 25 (37) Co‐infection HCV and/or HBV, n (%) 21 [...]

Introduction: The government of Lesotho introduced tenofovir disoproxil fumarate (TDF) for first‐line antiretroviral treatment (ART), as recommended by the World Health Organization (1), in 2008. The use of TDF has been associated with renal toxicity (2); furthermore, renal function outcomes following the use of TDF has not been studied at Roma Health Service Area (RHSA) in Lesotho. Lesotho is a small landlocked country surrounded by South Africa. The study used an analytical design to compare retrospective creatinine clearance (CrCl) data of 312 (64%) antiretroviral treatment naïve adults exposed to TDF and 173 (36%) unexposed patients. Methods: Impaired renal function was defined as CrCl less than 50 mL/min calculated using the Cockcroft‐Gault equation. The Ministry of Health and Social Welfare of Lesotho approved the study on 13 January 2012. The study included adult (excluding pregnant females) HIV patients enrolled on ART between December 2006 and December 2012 at St Joseph's Mission Hospital and at Nazareth Health Centre (RHSA). Patients at Nazareth Health Centre and at St Joseph's Mission Hospital made up 80% of the circa 4 116 HIV patients on ART. Only 485 patients met the set inclusion criteria. Results: In 56 patients (17.9%), TDF was found to be contraindicated. The use of TDF was marginally significant factor for renal toxicity (p=0.054) in univariate analysis, but was insignificant (p=0.122) in multivariate logistic analysis. Univariate (p60 (p=0.004) were significantly associated with CrCl Conclusions: In this study, TDF proofed to be a weak contributing factor of renal impairment. Routine baseline renal function screening should however be adopted to prevent patients with impaired renal function receiving TDF., References World Health Organisation. Antiretroviral therapy for HIV infection in adults and adolescents: Recommendations for a public health approach. Geneva, World Health Organization, 2010. 2010 version [cited 2013 Oct 20]. [...]

Introduction: The incomplete immune recovery upon effective long‐term highly active antiretroviral therapy (HAART) has been associated with increased morbidity and mortality in HIV infected patients [1]. Immune cellular activation, Tregs or very low‐level viraemia has been alternatively suspected, but never investigated simultaneously [2]. Materials and Methods: We performed a cross‐sectional study in 87 aviraemic patients (men=62, mean CD4+T cells=570/mm[sup.3], mean duration of HAART=12 years). Patients with at least 500 CD4+ T cells /mm[sup.3] were classified as complete immunological responders (cIR), whereas remaining patients were classified as inadequate immunological responder (iIR). Tregs were characterized based on CD4+CD25highFoxP3+phenotype using a one‐step intracellular staining. Effector Tregs and terminal effectors Tregs were respectively defined as CD4+CD25+FoxP3+CD45RA‐, and CD4+CD25+FoxP3+CD45RA‐HLADR+phenotypes as recently described [3]. Activated T cells were identified using (i) elevated HLA‐DR expression for CD4+T cells, and (ii) increased expressions of HLA‐DR, or CD38, or both (HLADR+CD38+cells) for CD8+T cells. Very low‐level viraemia was defined as detectable viraemia between 1 and 39 cp/mL. Univariate and multivariate analyses were performed to identify determinants of iIR. Results: Thirty‐nine patients were classified as iIR, and 48 as cIR. Patients from the iIR group were significantly older (55 vs 50 years, p=0.027), and had percentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs significantly higher (5.3 vs 4%, p=0.014; 9 vs 7.5%, p=0,022; 8 vs 6.3%, p=0.01 and 1.8 vs 1.3%, p=0,033 among CD4+T cells, respectively). Neither the percentage of activated CD8+T cell nor very low‐level viraemia were found to be associated with iIR. In the multivariate analysis, nadir of CD4+T cell count and percentage of Tregs were the only two parameters independently associated with iIR (OR=2.339, p=0.001, and OR=0.803, p=0.041, respectively). Conclusions: We present here the largest study investigating simultaneously immune response to long‐term HAART, immune activation of CD4+ and CD8+ T cells, Tregs percentages and very low‐level viraemia. Our results highlight the importance of Tregs in CD4 homeostasis. This aspect should now be prospectively explored in a large cohort of patients., References Rodger AJ, Lodwick R, Schechter M, Deeks S, Amin J, Gilson R, et al. Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and [...]

Introduction: Although hepatotoxicity related to antiretroviral treatment (ART) has become less frequent, hepatotoxic events, such as transaminase elevations (TE), are still a matter of concern. RPV/FTC/TDF (EPA) is a new single tablet regimen which is widely used in real life practice. Clinical trials showed an adequate profile of liver safety in the sub‐population of HIV/HCV‐coinfected patients receiving rilpivirine. However, the number of individuals included in these analyses is low [1]. The aim of this ongoing study is to evaluate the incidence of TE and total bilirubin elevations (TBE) during the first 48 weeks of EPA‐based therapy in a large population of HIV/HCV‐coinfected subjects outside of clinical trials. Patients and Methods: This is a retrospective analysis of HIV/HCV‐coinfected subjects who started EPA at the infectious diseases units of 14 centres throughout Spain, included as cases. Subjects who started an ART different to EPA during the study period at the same hospitals were selected as controls. The primary outcome variables were grade 3 or 4 TE and grade 4 TBE. Results: Of the 191 patients included, 31 (16.2%) subjects were naïve to ART. Eighty‐seven individuals started EPA and the remaining ones were controls. The most common NRTI backbone among the controls was TDF/FTC [59 (56.7%) patients] followed by NRTI‐sparing regimens [24 (23.1%) individuals] and ABC/3TC [17 (16.3%) subjects]. Among controls, 67 (64.4%) started a ritonavir‐boosted protease inhibitor, mainly DRV/r [41 (39.4%) patients] followed by ATV/r [16 (15.4%) subjects]. EFV, ETV and RAL were started in 16 (15.4%), 12 (11.5%) and 13 (12.5%) subjects, respectively. The median (Q1–Q3) follow‐up was 5.79 (3.65–8.61) months for the cases and 11.44 (5.8–12.88) months for the controls. TE was observed in two (2.3%) cases versus five (4.8%) controls (p=0.358), accounting for a density of incidence of 4.32/100 person‐years versus 5.51/100 person‐years [incidence rate difference (95% confidence interval): −1.88 (−9.95–6.2), p=0.354]. All TE were grade 3 and no patient discontinued ART due to TE. None of the cases developed TBE versus four (3.8%) controls, all of them receiving ATV/r. Conclusions: The frequency of grade 3–4 TE associated with EPA in HIV/HCV‐coinfected patients under real life conditions is very low. In addition, TE in HIV/HCV‐coinfected patients treated with EPA are usually mild and do not lead to treatment discontinuation. TBE was not seen in patients taking EPA. All these data confirm that EPA is safe in this particular subpopulation., Reference Nelson M, Amaya G, Clumeck N, et al. Efficacy and safety of rilpivirine in treatment‐naive, HIV‐1‐infected patients with hepatitis B virus/hepatitis C virus coinfection enrolled in the Phase III [...]

Introduction: Recent clinical trials have provided clear evidence to support early anti‐retroviral therapy (ART) in patients with HIV/TB co‐infection and low CD4 counts. We investigated how this has changed treatment and outcomes in Singapore. Materials and Methods: A retrospective review was performed with inpatient and outpatient records for all subjects diagnosed with HIV/TB co‐infection from 2006 to 2011 attending the Tuberculosis Control Unit, Tan Tock Seng Hospital, Singapore. Data for subjects with a presenting CD4 Results: One hundred thirty‐four out of 180 subjects in the database met the inclusion criteria for this study, 89 in the delayed group and 45 in the early. No statistically significant differences in baseline demographics between the two groups were identified. Both groups presented with markedly low CD4 counts, with overall 60% Conclusions: Significant improvements in HIV/TB infection outcomes correlate with the switch to earlier ART., Figure 1: Kaplan‐Meier survival curve, censored at first event per subject. Hazard ratio for death or opportunistic infection 8.36 in the delayed ART group (CI 95: 4.02–17.36). [Figure omitted] DOI: [...]

Introduction: Antiretroviral (ARV) treatment available in low‐middle income countries differs as suggested in international HIV‐treatment guidelines. Thus, we compared ARV regimens introduced as a first‐line therapy, time of initiation, frequency of making combination antiretroviral therapy (cART) switches, frequency of viral and immunological monitoring and treatment outcome in south east European (SEE) country (i.e. HIV Centre in Belgrade, Serbia, (HCB)) and west European country (i.e. Royal Free Centre for HIV Medicine at the Royal Free Hospital London, UK (RFH)). Materials and Methods: ARV naïve patients starting cART from 2003 to 2012 were included. Comparisons of the two cohorts were made using a chi‐square test or Fisher's exact test for categorical variables and a Mann‐Witney U test for continuous variables. Kaplan Meier survival curves were compared using the log rank test. Results: Of 597 patients from HCB, 361 (61%) initiated cART with prior AIDS diagnosed, while 337 (19%) of 1763 patients from RFH. Average baseline CD4+ T cell counts were significantly lower in Serbia than in UK (177 cells/mm[sup.3] vs 238 cells/mm[sup.3]). The total (mediana, IQR) CD4+ T cell count measurements in the first year of cART was 2 (1, 2) at the HCB, while it was statistically significant higher at the RFH 5 (3, 7), respectively (p Conclusions: In south European countries, as a consequence of low testing rate, ARV treatment is introduced at an advanced stage of disease, having a high mortality rate as a consequence. Switching within ARV drugs appears often due to lack of drug supplies and frequently drug‐related toxicity in south east Europe, while in the east European country due to patient's preferences and rarely due to drug‐related toxicity., Figure 1: Mortality in HCB and RFH after 3 years of introducing cART. [Figure omitted] DOI: [...]

Introduction: Several studies from resource-limited settings have demonstrated that clinical and immunologic criteria are poor predictors of virologic failure, confirming the need for viral load monitoring or at least an algorithm to target viral load testing. We used data from an electronic patient management system to develop an algorithm to identify patients at risk of viral failure using a combination of accessible and inexpensive markers. Methods: We analyzed data from HIV-positive adults initiated on antiretroviral therapy (ART) in Johannesburg, South Africa, between April 2004 and February 2010. Viral failure was defined as [greater than or equal to] 2 consecutive HIV-RNA viral loads >400 copies/ml following suppression ≤ 400 copies/ml. We used Cox- proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Weights for each predictor associated with virologic failure were created as the sum of the natural logarithm of the adjusted HR and dichotomized with the optimal cut-off at the point with the highest sensitivity and specificity (i.e. ≤ 4 vs. >4). We assessed the diagnostic accuracy of predictor scores cut-offs, with and without CD4 criteria (CD4 30% drop in CD4), by calculating the proportion with the outcome and the observed sensitivity, specificity, positive and negative predictive value of the predictor score compared to the gold standard of virologic failure. Results: We matched 919 patients with virologic failure (1:3) to 2756 patients without. Our predictor score included variables at ART initiation (i.e. gender, age, CD4 count < 100 cells/[mm.sup.3], WHO stage III/IV and albumin) and laboratory and clinical follow-up data (drop in haemoglobin, mean cell volume (MCV) Conclusions: Predictor scores or risk categories, with CD4 criteria, could be used to identify patients at risk of virologic failure in resource-limited settings so that these patients may be targeted for focused interventions to improve HIV treatment outcomes. Keywords: antiretroviral therapy; viral load; resource limited; monitoring; algorithm; HIV; CD4., Introduction In 2012, 9.7 million people in low- and middle-income countries received antiretroviral therapy (ART), representing 61% of all who were eligible under the 2010 WHO HIV treatment guidelines [1]. [...]

Byline: Kailash. Mohanty Introduction Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory reaction in HIV infected patients after initiation of antiretroviral therapy (ART) resulting from restored immunity to specific infectious [...]

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Purpose The clinical status of HIV‐1 infected patients initiated on modern anti‐retroviral (ARV) therapy is consistently improved as indicated by reduced viral load (VL) and increased CD4+ T‐cell count, however, [...]

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Purpose of the study To evaluate long‐term outcomes in pts maintaining a NVP‐based regimen Methods Retrospective cohort study. Pts received a NVP regimen for at least 5 years and continued [...]

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Purpose of the study Atazanavir is a good but expensive regimen in resource limited settings (RLS). A previous HIV‐NAT study showed that a low dose of ATV/r 200/100mg once daily [...]