Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART): A cluster-randomized trial of the impact of a combination prevention package on population-level HIV incidence in Zambia and South Africa
What is HPTN 071?
HPTN 071 - Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) examined the impact of a package of HIV prevention interventions on community-level HIV incidence. The prevention interventions included universal voluntary HIV counseling and testing provided at the household level, linkage of HIV infected individuals to care and early initiation of antiretroviral therapy (ART) for all those testing HIV-positive. The study was conducted in 21 communities in the Western Cape of South Africa, and in Zambia.
Who participated in the study?
Twenty-one (21) urban and peri-urban communities in Zambia and South Africa, with a total population of around 1 million, participated in this study. To measure the impact of the intervention, a research cohort called the Population Cohort, consisting of a sample of approximately 2,300 adults aged 18–44 years, were recruited from the general population in each of the 21 communities (an overall total of 48,302 across all communities) and was followed up once a year for three years to measure HIV incidence and other outcomes.
Why was the study conducted?
HIV incidence rates remain at very high levels in many parts of southern Africa. More effective prevention strategies are needed to steeply reduce the number of new HIV infections and to ensure that care can be provided for all people living with HIV. Findings from HPTN 071 (PopART) will help inform the scale-up of future HIV programs and identify cost-effective interventions.
What was the design of the study?
A total of 21 communities participated in the HPTN 071 (PopART) trial, 12 in Zambia and nine in South Africa. In Zambia, the 12 communities were divided into four matched “triplets” of three communities each. The triplets were composed of communities that had been matched so all three had similar estimated HIV prevalence, to minimize the variability in baseline HIV incidence within the triplet. Then the communities in each triplet were randomly assigned to the three study arms: A, B and C. The same process was repeated for the nine communities in South Africa. In both countries, Arm A received the full PopART HIV combination prevention package including the offer of universal ART, Arm B received the PopART package, but with ART only offered to those eligible according to in-country guidelines, and Arm C communities had no household intervention but could access HIV testing and treatment services according to in-country guidelines.
Three Arm Cluster Randomized Trial with 21 Communities (Original Study Design)
What were the study objectives?
The primary study outcome was HIV incidence between month 12 and month 36 among members of the Population Cohort who were HIV-negative at baseline, comparing HIV incidence between the intervention and standard of care arms, (A vs C, and B vs C). This allowed the effectiveness of the PopART intervention at population level to be measured. Data to investigate secondary objectives were drawn from Population Cohort data as well as data from Community HIV-care Providers (CHiPs), health centers and social science research. These objectives assess the effect of the intervention on several additional variables, including:
What was included in the PopART intervention in Arms A and B?
The PopART HIV combination prevention package in Arms A and B was delivered throughout each study community by Community HIV-care Providers (CHiPs). They were specially trained, lay counselors, who worked in pairs. Each pair was responsible for delivering services to a zone consisting of around 500 households. CHiPs were tasked with visiting every household at least once a year for the duration of the trial, and provided the following services:
- Household-based HIV counseling and testing offered annually
- Linking those with HIV to care at the local health center
- Follow-up visits to clients living with HIV to ensure they had linked to care and to support ART adherence
- Promoting voluntary medical male circumcision for men who tested HIV-negative
- Promoting services for the prevention of mother-to-child transmission (PMTCT) to pregnant women living with HIV
- Referrao to treatment of sexually transmitted infections
- Providing condoms in the community
- Screening and referral for tuberculosis (TB)
How did the study design evolve over time?
HIV care and ART were provided at the local government clinic serving that community. In Arm A, all clients living with HIV were offered ART irrespective of CD4 count or clinical stage. In Arm B, ART was initiated according to in-country guidelines. Initially, this was at a CD4 count of 350, then later this changed to 500, and in 2016, following a change in World Health Organization (WHO) recommendations, ART was offered to all clients living with HIV, as in Arm A.
Timeline of HPTN 071 (PopART) Intervention and Evaluation Including Changes to Treatment Guidelines
The dates shown for the start of universal ART (i.e., ART irrespective of a patient's CD4 cell count or WHO stage) refer to when this was implemented in study clinics in the respective countries. In Zambia, the first study clinic transitioned April 19, 2016, and the last May 9, 2016. This transition is represented by the dark purple band in the figure. In South Africa, the first study clinics transitioned October 10, 2016, and the last on November 21, 2016, a period represented by the dark purple band in the figure. Study personnel, clinic staff and implementing partners worked to ensure study clinics implemented the new policy as soon as in-country guidelines and logistics such as staff training would allow. Transition to universal ART in study clinics, therefore, often preceded transition in neighboring communities.
Updated Study Design Reflecting 2016 Guidelines Change
What were the key findings from the HPTN 071 (PopART) study?
Findings from HPTN 071 (PopART) show delivery of an HIV prevention strategy that includes offering HIV testing to everyone, with immediate referral to HIV care, and treatment for people living with HIV based on prevailing in-country guidelines, can substantially reduce new HIV infections. In the study arm where the PopART intervention included HIV treatment according to in-country guidelines (Arm B), HIV incidence declined by 30 percent compared to standard of care communities (Arm C), an improvement that was highly statistically significant. In both intervention arms (A and B), the first two of the UNAIDS 90-90-90 targets (regarding knowledge of HIV status and being on treatment) were reached and high rates of viral suppression were achieved. In the study arm where the PopART intervention included the offer of universal ART even before it was national policy (Arm A), incidence only declined by seven percent compared to the standard-of-care arm, and this was not statistically significant. The lack of a clear effect in Arm A was surprising, and not explained by observed rates of viral load suppression. Further analyses underway may help explain this finding. These results, clarified by further analysis and in conjunction with those from other universal test and treat trials, will help guide policymakers on how best to leverage community-based HIV testing and linkage to care to achieve HIV control. Separately, projections from mathematical modelling and cost-effectiveness analyses were presented at the 10th International AIDS Society Conference on HIV Science in Mexico City (IAS 2019). Researchers found a continuation of community-wide HIV testing and prompt initiation of treatment as delivered in the study could lead to substantial reductions in new HIV cases, be cost-effective, and help to achieve the UNAIDS 2030 targets.
How did HPTN 071 (PopART) differ from the other UTT trials?
HPTN071 (PopART) differed from the other trials in the following ways:
1. The PopART communities were large urban or peri-urban communities whereas the other trials were in smaller rural communities.
2. HIV incidence was measured in a separately recruited population cohort in PopART and Ya Tsie/BCPP, while in TasP and SEARCH incidence was measured through the intervention.
3. In PopART and Ya Tsie/BCPP, the control communities did not receive any additional intervention outside of current standard of care, while SEARCH and TasP control communities received enhanced community-wide HIV services, particularly for HIV testing and linkage to care, probably explaining the lack of observed difference between the intervention and control arms.
What additional HPTN 071 (PopART) study analyses are underway?
HPTN 071 (PopART) researchers are currently examining the effects of the interventions on other study outcomes including herpes simplex virus-2 incidence, tuberculosis and HIV-related stigma.
- HPTN 071 Brochure
- HPTN 071 Individual-based Model Analysis Plan
- HPTN 071 Cost Effectiveness Analysis Plan
- HPTN 071 Statistical Analysis Plan
HPTN 071 Version 3.0
- HPTN 071 Protocol V3.0 - 16 Nov. 2015
- HPTN 071 Summary of Changes from V2.0 to V3.0 - 16 November 2015
- HPTN 071 V3.0 LoA #5 - 17 April 2018
- HPTN 071 V3.0 LoA #4 - 27 Sept. 2017
- HPTN 071 V3.0 LoA #3 - 6 June 2017
- HPTN 071 V3.0 LoA #2 - 6 Dec. 2016
- HPTN 071 V3.0 LoA #1 - 23 Aug. 2016
HPTN 071 Version 2.0
HPTN 071 Version 1.0
- HPTN 071 Protocol V1.0 - 26 Oct. 2012
- HPTN 071 V1.0 CM #2 - 17 October 2013
- HPTN 071 V1.0 CM #1 - 21 August 2013
Ancillary and Sub-Studies
- HPTN 071 Phylogenetics Ancillary Protocol V2.0 - 6 July 2017
- HPTN 071 Phylogenetics Ancillary Protocol V1.0 - 15 January 2015
- HPTN 071 Stigma Substudy V1.0 - 6 January 2014
- IAS 2019 Symposia Session: Towards Zero New HIV Infections: Lessons Learnt From the HPTN 071 (PopART) Trial
- HPTN 071 (PopART) Trial: Impact of a UTT Intervention on HIV Incidence (Dr. Richard Hayes and Dr. Sarah Fidler)
- Model Projections of the Impact of the PopART Intervention (Dr. William Probert)
- Cost and Societal Value of the Household-Based Combination HIV Prevention Intervention Implemented in HPTN 071 (PopART) (Dr. Katharina Hauck)
- Community and Stakeholder Engagement in the HPTN 071 (PopART) Trial (Dr. Musonda Simwinga)
- HPTN 071 Key Outcomes Web Conference - 27 March 2019
- HPTN 071 at AIDS 2018
- HPTN 071 at IAS 2017
- HPTN 071 Satellite Session at IAS 2017 ("Cross-Disciplinary Approaches to Understand Successes and Challenges of Implementing a Community-Wide Universal Test and Treat Programme in Sub-Saharan Africa")
- HPTN 071 at CROI 2017
- HPTN 071 at AIDS 2016
- HPTN 071 at CROI 2016
- HPTN 071 - Key Findings As Study Nears Completion
- HPTN 071 - Key Findings After the Third Year of Intervention
- HPTN 071 - Key Findings After the Second Year of Intervention
- HPTN 071 - Key Findings After One Year of Intervention
- July 2019: Intensive Anti-HIV Efforts Meeting with Mixed Success in Africa (New York Times)
- July 2019: HPTN 071 Modelling and Economic Analyses Show Benefits of Community-wide HIV Testing and Treatment
- March 2019: HPTN 071 Demonstrates Community-Wide HIV Prevention Strategy Can Reduce New Infections
- July 2018: HPTN Responds to Results from SEARCH and BCPP Studies Presented at AIDS 2018
- July 2016: HPTN Responds to Results from ANRS 12249 TasP Study Presented at AIDS 2016
- May 2016: Immediate ART Available to All People Living With HIV in HPTN 071 (PopART) Zambia Communities