Dataset Information

Better Virological Outcomes Among People Living With Human Immunodeficiency Virus (HIV) Initiating Early Antiretroviral Treatment (CD4 Counts ?500 Cells/µL) in the HIV Prevention Trials Network 071 (PopART) Trial in South Africa.

ABSTRACT:

Background

There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation.

Methods

This prospective cohort study included adults initiating ART at facilities providing universal ART since January 2014. VS (<400 copies/mL), confirmed virological failure (VF) (2 consecutive viral loads >1000 copies/mL), and viral rebound were compared between participants in strata of baseline CD4 cell count.

Results

The sample included 1901 participants. VS was ?94% among participants with baseline CD4 count ?500 cells/µL at all 6-month intervals to 30 months. The risk of an elevated viral load (?400 copies/mL) was independently lower among participants with baseline CD4 count ?500 cells/µL (3.3%) compared to those with CD4 count 200-499 cells/µL (9.2%) between months 18 and 30 (adjusted relative risk, 0.30 [95% confidence interval, .12-.74]; P = .010). The incidence rate of VF was 7.0, 2.0, and 0.5 per 100 person-years among participants with baseline CD4 count <200, 200-499, and ?500 cells/µL, respectively (P < .0001). VF was independently lower among participants with baseline CD4 count ?500 cells/µL (adjusted hazard ratio [aHR], 0.23; P = .045) and 3-fold higher among those with baseline CD4 count <200 cells/µL (aHR, 3.49; P < .0001).

Conclusions

Despite previous concerns, participants initiating ART with CD4 counts ?500 cells/µL had very good virological outcomes, being better than those with CD4 counts 200-499 cells/µL.

Clinical trials registration

NCT01900977.

SUBMITTER: Fatti G

PROVIDER: S-EPMC7768744 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Better Virological Outcomes Among People Living With Human Immunodeficiency Virus (HIV) Initiating Early Antiretroviral Treatment (CD4 Counts ≥500 Cells/µL) in the HIV Prevention Trials Network 071 (PopART) Trial in South Africa.

Fatti Geoffrey G Grimwood Ashraf A Nachega Jean B JB Nelson Jenna A JA LaSorda Kelsea K van Zyl Gert G Grobbelaar Nelis N Ayles Helen H Hayes Richard R Beyers Nulda N Fidler Sarah S Bock Peter P

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20200101 3

<h4>Background</h4>There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation.<h4>Methods</h4>This prospecti ...[more]

PMID: 30877753

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Project description:IntroductionWHO recommends antiretroviral treatment (ART) for all HIV-positive individuals. This study evaluated the association between baseline CD4 count and attrition in a cohort of HIV positive adults initiating ART at three department of health (DOH) clinics routinely providing ART at baseline CD4 counts >500cells/?L for the HPTN 071 (PopART) trial.MethodsAll clients attending the DOH clinics were managed according to standard care guidelines with the exception that those starting ART outside of pertinent local guidelines signed research informed consent. DOH data on all HIV-positive adult clients recorded as having initiated ART between January 2014 and November 2015 at the three study clinics was analysed. Attrition, included clients lost to follow up or died, and was defined as 'being three or more months late for an antiretroviral pharmacy pick-up appointment'. All clients were followed until attrition, transfer out or end May 2016.ResultsA total of 2423 clients with a median baseline CD4 count of 328 cells/?L (IQR 195-468) were included of whom 631 (26.0%) experienced attrition and 140 (5.8%) were TFO. Attrition was highest during the first six months of ART (IR 38.3/100 PY; 95% CI 34.8-42.1). Higher attrition was found amongst those with baseline CD4 counts > 500 cells/?L compared to those with baseline CD4 counts of 0-500 cells/?L (aHR 1.26, 95%CI 1.05 to 1.52) This finding was confirmed on subset analyses when restricted to individuals non-pregnant at baseline and when restricted to individuals with follow up of > 12months.ConclusionsAttrition in this study was high, particularly during the first six months of treatment. Attrition was highest amongst clients starting ART at baseline CD4 counts > 500 cells/?L. Strategies to improve retention amongst ART clients, particularly those starting ART at baseline CD4 counts >500cells/?L, need strengthening. Improved monitoring of clients moving in and out of ART care and between clinics will assist in better understanding attrition and ART coverage in high burden countries.

Project description:BackgroundA universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent.MethodsIn the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months.ResultsThe population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P = 0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P = 0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B.ConclusionsA combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977.).

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Project description: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.

Project description:IntroductionUniversal HIV testing and treatment (UTT) has individual and public health benefits. HPTN 071 (PopART), a community-randomized trial in Zambia and South Africa, demonstrated that UTT decreased HIV incidence. This endpoint was assessed in a cohort of >48,000 randomly selected adults in the study communities. We evaluated the impact of UTT on HIV drug resistance in this cohort and compared other resistance-related outcomes in participants with recent versus non-recent HIV infection.MethodsTwo years after the start of HPTN 071 (2016-2017), 6259 participants were HIV positive and 1902 were viremic (viral load >400 copies/ml). HIV genotyping and antiretroviral (ARV) drug testing were performed for viremic participants in three groups: seroconverters (infected <1 year), non-seroconverters (infected >1 year, random subset) and participants with unknown duration of infection (random subset). A two-stage cluster-based approach was used to assess the impact of the study intervention on drug resistance. Treatment failure was defined as being viremic with ARV drugs detected. Participants were classified as ARV naïve based on self-report and ARV drug testing.ResultsGenotyping results were obtained for 758 participants (143 seroconverters; 534 non-seroconverters; and 81 unknown duration of infection). The estimated prevalence of resistance in the study communities was 37% for all viremic persons and 11% for all HIV-positive persons. There was no association between UTT and drug resistance. Resistance was detected in 14.0% of seroconverters and 40.8% of non-seroconverters (non-nucleoside reverse transcriptase inhibitor resistance: 14.0% and 39.9%; nucleoside/nucleotide reverse transcriptase inhibitor resistance: 0.7% and 15.5%; protease inhibitor resistance: 0% and 1.9%; multi-class resistance: 0.7% and 16.1%, respectively). ARV drugs were detected in 2/139 (1.4%) of seroconverters and 94/534 (17.6%) of non-seroconverters tested. These participants were classified as failing ART; 88 (93.6%) of the non-seroconverters failing ART had resistance. Mutations used for surveillance of transmitted drug resistance were detected in 10.5% of seroconverters and 15.1% of non-seroconverters who were ARV naive.ConclusionsUTT was not associated with an increase in drug resistance in this cohort. Higher rates of drug resistance and multi-class resistance were observed in non-seroconverters compared to seroconverters.