Universal Test and Treat is not associated with sub-optimal antiretroviral therapy adherence in rural South Africa: the ANRS 12249 TasP trial

Introduction HIV treatment guidelines now recommend antiretroviral therapy (ART) initiation regardless of CD4 count to maximise benefit both for the individual and society. It is unknown whether the initiation of ART at higher CD4 counts would affect adherence levels. We investigated whether initiating ART at higher CD4 counts was associated with sub-optimal adherence (<95%) during the first 12 months of ART. Methods A prospective cohort study nested within a two-arm cluster-randomised trial of universal test and treat implemented March 2012 - June 2016 to measure impact of ART on HIV incidence in rural KwaZulu-Natal. ART was initiated regardless of CD4 count in the intervention arm and according to national guidelines in the control arm. ART adherence was measured monthly using a visual analogue scale (VAS) and pill counts (PC). HIV viral load was measured at ART initiation, 3 and 6 months, and six monthly thereafter. We pooled data from participants in both arms and used random-effects logistic regression models to examine the association between CD4 count at ART initiation and sub-optimal adherence, and assessed if adherence levels were associated with virological suppression. Results Among 900 individuals who initiated ART = 12 months before study end, median (IQR) CD4 at ART initiation was 350 cells/mm3 (234, 503); median age was 34.6 years (IQR 27.4-46.4) and 71.7% were female. Adherence was sub-optimal in 14.7% of visits as measured by VAS and 20.7% by PC. In both the crude analyses and after adjusting for potential confounders, adherence was not significantly associated with CD4 count at ART initiation (adjusted OR for linear trend in sub-optimal adherence with every 100 cells/mm3 increase in CD4 count: 1.00, 95% CI 0.95-1.05, for VAS, and 1.03, 95%CI 0.99-1.07, for PC). Virological suppression at 12 months was 97%. Optimal adherence by both measures was significantly associated with virological suppression (p<0.001 for VAS; p=0.006 for PC). Conclusions We found no evidence that higher CD4 counts at ART initiation were associated with sub-optimal ART adherence in the first 12 months. Our findings should alleviate concerns about adherence in individuals initiating ART at higher CD4 counts, however long-term outcomes are needed

HIV testing and diagnosis rates (per 100,000 population) for persons seeking testing April 2013– March 2014 in Kiev City, Ukraine.

<p>* Excluding 32 persons: 7 records were missing year of birth, sex or identification number, and 25 persons were already known to be HIV positive.</p><p>HIV testing and diagnosis rates (per 100,000 population) for persons seeking testing April 2013– March 2014 in Kiev City, Ukraine.</p

Distribution of all persons testing for HIV and persons newly diagnosed at any one of the four HIV testing sites between April 2013 –March 2014 in Kiev City, Ukraine.

<p>* Persons with more than one reported risk factor were classified by the following hierarchical order: PWID, MSM, then heterosexual contact. Persons with more than one reported reason for test were classified by the following hierarchical order: general Screening, clinical indication, then high risk population.</p><p>^<b>≠</b> Excluding 32 persons: 7 records were missing year of birth, sex or identification number, and 25 persons were already known to be HIV positive.</p><p>Distribution of all persons testing for HIV and persons newly diagnosed at any one of the four HIV testing sites between April 2013 –March 2014 in Kiev City, Ukraine.</p

Factors associated with repeat testing among persons attending for an HIV test April 2013– March 2014 in Kiev City, Ukraine.

<p>* Adjusted for all other factors in table.</p><p>Factors associated with repeat testing among persons attending for an HIV test April 2013– March 2014 in Kiev City, Ukraine.</p

Factors association with testing recent according to the LAg assay in Kiev City, Ukraine: April 2013 –March 2014

<p>Factors association with testing recent according to the LAg assay in Kiev City, Ukraine: April 2013 –March 2014</p

Incidence estimates for Kiev City, Ukraine, April 2013 –March 2014, by subpopulations.

Incidence estimates for Kiev City, Ukraine, April 2013 –March 2014, by subpopulations.</p

Impact of next-generation sequencing defined human immunodeficiency virus pretreatment drug resistance on virological outcomes in the ANRS 12249 treatment-as-prevention trial

Background Previous studies in human immunodeficiency virus (HIV)-positive individuals on thymidine analogue backbone antiretroviral therapy (ART) with either nevirapine or efavirenz have suggested poorer virological outcomes in the presence of pretreatment drug resistance (PDR). We assessed the impact of PDR on virological suppression (VS; 1000 copies/mL had next-generation sequencing (NGS) of the HIV pol gene with MiSeq technology. Results were obtained for 1148 individuals, and the presence of PDR was assessed at 5% and 20% detection thresholds. Virological outcome was assessed using Cox regression in 837 of 920 ART initiators with at least 1 follow-up VL after ART initiation. Results PDR prevalence was 9.5% (109/1148) and 12.8% (147/1148) at 20% and 5% thresholds, respectively. After a median of 1.36 years (interquartile range, 0.91–2.13), mostly on fixed-dose combination tenofovir/emtricitabine/efavirenz, presence of both nonnucleoside reverse transcriptase inhibitor (NNRTI)/nucleoside reverse transcriptase inhibitor PDR vs no PDR was associated with longer time to VS (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.12–0.86), while there was no difference between those with only NNRTI PDR vs no PDR (aHR, 1.05; 95% CI, 0.82–1.34) at the 5% threshold. Similar differences were observed for mutations detected at the 20% threshold, although without statistical significance. Conclusions NGS uncovered a high prevalence of PDR among participants enrolled in trial clinics in rural KwaZulu-Natal. Dual-class PDR to a mainly tenofovir/emtricitabine/efavirenz regimen was associated with poorer VS. However, there was no impact of NNRTI PDR alone

Characteristics of persons newly diagnosed with HIV and the proportion identified as recently infected using the LAg Avidity EIA, Kiev City, Ukraine: April 2013 –March 2014.

<p>Characteristics of persons newly diagnosed with HIV and the proportion identified as recently infected using the LAg Avidity EIA, Kiev City, Ukraine: April 2013 –March 2014.</p

art_primary_dryad

Dataset containing all ART data from those individuals included in the primary analysis investigating time from HIV seroconversion to HIV disease progression