HPTN 071 (PopART): A Cluster-Randomized Trial of the Population Impact of an HIV Combination Prevention Intervention Including Universal Testing and Treatment: Mathematical Model

被引：84

作者：

Cori, Anne ^{[1
]}

Ayles, Helen ^{[2
,3
]}

Beyers, Nulda ^{[4
]}

Schaap, Ab ^{[2
,5
]}

Floyd, Sian ^{[5
]}

Sabapathy, Kalpana ^{[5
]}

Eaton, Jeffrey W. ^{[1
]}

Hauck, Katharina ^{[6
]}

Smith, Peter ^{[6
]}

Griffith, Sam ^{[7
]}

Moore, Ayana ^{[7
]}

Donnell, Deborah ^{[8
]}

Vermund, Sten H. ^{[9
,10
]}

Fidler, Sarah ^{[11
]}

Hayes, Richard ^{[5
]}

Fraser, Christophe ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, MRC Ctr Outbreak Anal & Modelling, London, England

[2] Univ Zambia, Sch Med, ZAMBART, Lusaka, Zambia

[3] London Sch Hyg & Trop Med, Dept Clin Res, London WC1, England

[4] Univ Stellenbosch, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, ZA-7600 Stellenbosch, South Africa

[5] London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London WC1, England

[6] Univ London Imperial Coll Sci Technol & Med, Sch Business, London, England

[7] FHI 360, Res Triangle Pk, NC USA

[8] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA

[9] Vanderbilt Univ, Vanderbilt Inst Global Hlth, Nashville, TN 37235 USA

[10] Vanderbilt Univ, Dept Pediat, Nashville, TN USA

[11] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England

来源：

PLOS ONE | 2014年 / 9卷 / 01期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

ACTIVE ANTIRETROVIRAL THERAPY; CD4 CELL COUNT; MALE CIRCUMCISION; SOUTH-AFRICA; FOLLOW-UP; INFECTION; MEN; TRANSMISSION; RISK; EPIDEMIC;

D O I：

10.1371/journal.pone.0084511

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence. Methods and Findings: The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative threeyear HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by.60% in arm A and.25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence. Conclusions: The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by.60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.

引用

页数：11

共 47 条

[41] Immunological markers after long-term treatment interruption in chronically HIV-1 infected patients with CD4 cell count above 400x106 cells/I [J].