HIV drug resistance in a community-randomized trial of universal testing and treatment: HPTN 071 (PopART)

被引:5
作者
Fogel, Jessica M. [1 ]
Wilson, Ethan A. [2 ]
Piwowar-Manning, Estelle [1 ]
Breaud, Autumn [1 ]
Clarke, William [1 ]
Petropoulos, Christos [3 ]
Moore, Ayana [4 ]
Fraser, Christophe [5 ,6 ]
Kosloff, Barry [7 ,8 ]
Shanaube, Kwame [7 ]
van Zyl, Gert [9 ]
Scheepers, Michelle [10 ]
Floyd, Sian [11 ]
Bock, Peter [10 ]
Ayles, Helen [7 ,8 ]
Fidler, Sarah [12 ]
Hayes, Richard [11 ]
Donnell, Deborah
Eshleman, Susan H. [1 ]
机构
[1] Johns Hopkins Univ, Dept Pathol, Sch Med, Ross Bldg,Room 646,720 Rutland Ave, Baltimore, MD 21205 USA
[2] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA
[3] Monogram Biosci, San Francisco, CA USA
[4] FHI 360, Durham, NC USA
[5] Univ Oxford, Big Data Inst, Oxford, England
[6] Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England
[7] Zambart, Lusaka, Zambia
[8] London Sch Hyg & Trop Med, Dept Clin Res, London, England
[9] Stellenbosch Univ, Div Med Virol, Cape Town, South Africa
[10] Stellenbosch Univ, Desmond Tutu TB Ctr, Dept Paediat & Child Hlth, Western Cape, South Africa
[11] London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London, England
[12] Imperial Coll London, Dept Infect Dis, HIV Clin Trials Unit, London, England
基金
比尔及梅琳达.盖茨基金会;
关键词
Africa; ARV; clinical trials; drug resistance; HIV prevention; transmitted drug resistance; PREVENTION; THERAPY;
D O I
10.1002/jia2.25941
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Introduction Universal 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. Methods Two 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 naive based on self-report and ARV drug testing. Results Genotyping 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. Conclusions UTT 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.
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页数:8
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