Suchergebnisse

IntroductionIn many resource‐limited settings, combination antiretroviral therapy (cART) failure is diagnosed clinically or immunologically. As such, there is a high likelihood that patients may stay on a virologically failing regimen for a substantial period of time. Here, we compared the long‐term impact of initiating non‐nucleoside reverse transcriptase inhibitor (NNRTI)‐ versus boosted protease inhibitor (bPI)‐based cART in British Columbia (BC), Canada.MethodsWe followed prospectively 3925 ART‐naïve patients who started NNRTIs (N=1963, 50%) or bPIs (N=1962; 50%) from 1 January 2000 until 30 June 2013 in BC. At six months, we assessed whether patients virologically failed therapy (a plasma viral load (pVL) >50 copies/mL), and we stratified them based on the pVL at the time of failure ≤500 versus >500 copies/mL. We then followed these patients for another six months and calculated their probability of achieving subsequent viral suppression (pVL <50 copies/mL twice consecutively) and of developing drug resistance. These probabilities were adjusted for fixed and time‐varying factors, including cART adherence.ResultsAt six months, virologic failure rates were 9.5 and 14.3 cases per 100 person‐months for NNRTI and bPI initiators, respectively. NNRTI initiators who failed with a pVL ≤500 copies/mL had a 16% higher probability of achieving subsequent suppression at 12 months than bPI initiators (0.81 (25th–75th percentile 0.75–0.83) vs. 0.72 (0.61–0.75)). However, if failing NNRTI initiators had a pVL >500 copies/mL, they had a 20% lower probability of suppressing at 12 months than pVL‐matched bPI initiators (0.37 (0.29–0.45) vs. 0.46 (0.38–0.54)). In terms of evolving HIV drug resistance, those who failed on NNRTI performed worse than bPI in all scenarios, especially if they failed with a viral load >500 copies/mL.ConclusionsOur results show that patients who virologically failed at six months on NNRTI and continued on the same regimen had a lower probability of subsequently achieving viral suppression and a higher chance of evolving HIV drug resistance. These results suggest that improving access to regular virologic monitoring is critically important, especially if NNRTI‐based cART is to remain a preferred choice for first‐line therapy in resource‐limited settings.

IntroductionHIV‐1 plasma viral load during treatment can be highly variable. Thus, there is the need to find a measure of cumulative viremia that can be used to assess both the short‐ and long‐term efficacy of highly active antiretroviral therapy (HAART). Here, we validate a measure of cumulative viremia to evaluate HAART efficacy.MethodsWe accessed HAART efficacy using data from a randomized clinical trial conducted in Mexico. We compared the proportion of individuals achieving a viral load <50 and <400 copies/mL at week 48, against the cumulative plasma viral load, estimated as the area under the plasma viral load curve (AUVLC). High AUVLC indicates high cumulative viremia.Results and discussionThere was a strong and significant association between the proportion of individuals achieving a viral load <50 and <400 copies/mL at week 48, with individuals suppressed having significant lower cumulative viremia. The median area was 7513 (25th–75th percentile [Q1–Q3] 6634−8180) if viral load <50 copies/mL and 7679 (Q1–Q3 6899−9373) if viral load ≥50 copies/mL (p‐value 0.0284). When the analysis was stratified by study arm, individuals on efavirenz had lower cumulative viremia than those on boosted lopinavir.ConclusionsOur findings suggest that cumulative viremia should be explored further as a tool to simultaneously evaluate the individual and public health efficacy of HAART. This is particularly relevant to the implementation and evaluation of the Treatment 2.0 strategy recently proposed by UNAIDS and the WHO, as a means to maximize the individual and public health benefit of HAART.

AbstractIntroductionAntiretroviral therapy (ART) scale‐up is central to the global strategy to control the HIV/AIDS pandemic. To accelerate efforts towards ending the AIDS epidemic, the Joint United Nations Programme on HIV/AIDS released the 90‐90‐90 and 95‐95‐95 targets, which have recently been approved by the United Nations (UN). This study characterizes the province of British Columbia (BC)'s progress towards achieving the UN targets, predicts a trajectory up to 2030 according to each of the individual steps (i.e. %Diagnosed, %On ART and %Virologically Suppressed), and identifies the population sub‐groups at higher risk of not achieving these targets.MethodsThe analyses were based on linked individual‐level datasets of people living with HIV (PLWH) in BC, aged ≥18 months, from 2000 to 2013. Using past trends in HIV prevalence and of each individual UN targets, we forecasted these outcomes until 2030 via generalized additive models. We ran a second set of analyses to assess the associations between individual demographic and behavioural factors and each of the individual steps of the UN targets. Lastly, we performed sensitivity analyses to account for uncertainty associated with prevalence estimates and suppression definitions.ResultsAmong the estimated 10666 PLWH in BC in 2013, 82% were diagnosed, 76% of those diagnosed were on ART and 83% of those on ART were virologically suppressed. We identified that females, PLWH aged <30 years and those with unknown risk or who self‐identify as having a history of injection drug use were the population subgroups that experienced the most challenge in engaging on ART and achieving viral suppression. Our model projections suggest that BC will achieve 90%‐91%‐90% and 97%‐99%‐97% by 2020 and 2030 respectively.ConclusionsAs we approach 2020, BC is rapidly moving towards achieving the UN targets. However, region‐specific challenges persist. Identification of remaining regional challenges will be essential to achieving the proposed UN targets and therefore fulfilling the promise to end AIDS as a pandemic by 2030.

In recent years, evidence has accumulated regarding the ability of HAART to prevent HIV transmission. Early supportive evidence was derived from observational, ecological and population-based studies. More recently, a randomized clinical trial showed that immediate use of HAART led to a 96% decrease in HIV transmission events within HIV serodiscordant heterosexual couples. However, the generalizability of the effect of HAART, and the population-level impact on HIV transmission continues to generate substantial debate. We, therefore, conducted a review of the evidence regarding the preventive effect of HAART on HIV transmission within the context of the Bradford Hill criteria for causality. Taken together, we find the accumulated evidence supporting HIV treatment as prevention meets each of the Bradford Hill criteria for causality. We conclude that the opportunity cost of inaction while waiting for additional evidence on the generalizability of effect in other risk groups is too high. Efforts should be redoubled to mobilize the financial capital and political will to optimize implementation of HIV Treatment as Prevention strategies on a wide scale.

AbstractIntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio‐metabolic disease. We assessed relationships between ART drug class and weight change among treatment‐naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD).MethodsAdult, treatment‐naïve PWH in NA‐ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non‐nucleoside reverse‐transcriptase inhibitor (NNRTI)‐based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV‐1 RNA level and CD4+ cell count. Due to shorter follow‐up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI‐, 31% started PI‐ and 20% started INSTI‐based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI‐based regimens had mean estimated five‐year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two‐year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI‐based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI‐based regimens gained, on average, more weight compared to NNRTI‐based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.