Population health impact, cost-effectiveness, and affordability of community-based HIV treatment and monitoring in South Africa: A health economics modelling study.

Community-based delivery and monitoring of antiretroviral therapy (ART) for HIV has the potential to increase viral suppression for individual- and population-level health benefits. However, the cost-effectiveness and budget impact are needed for public health policy. We used a mathematical model of HIV transmission in KwaZulu-Natal, South Africa, to estimate population prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 2020 to 2060 for two scenarios: 1) standard clinic-based HIV care and 2) five-yearly home testing campaigns with community ART for people not reached by clinic-based care. We parameterised model scenarios using observed community-based ART efficacy. Using a health system perspective, we evaluated incremental cost-effectiveness and net health benefits using a threshold of $750/DALY averted. In a sensitivity analysis, we varied the discount rate; time horizon; costs for clinic and community ART, hospitalisation, and testing; and the proportion of the population receiving community ART. Uncertainty ranges (URs) were estimated across 25 best-fitting parameter sets. By 2060, community ART following home testing averted 27.9% (UR: 24.3-31.5) of incident HIV infections, 27.8% (26.8-28.8) of HIV-related deaths, and 18.7% (17.9-19.7) of DALYs compared to standard of care. Adolescent girls and young women aged 15-24 years experienced the greatest reduction in incident HIV (30.7%, 27.1-34.7). In the first five years (2020-2024), community ART required an additional $44.9 million (35.8-50.1) annually, representing 14.3% (11.4-16.0) of the annual HIV budget. The cost per DALY averted was $102 (85-117) for community ART compared with standard of care. Providing six-monthly refills instead of quarterly refills further increased cost-effectiveness to $78.5 per DALY averted (62.9-92.8). Cost-effectiveness was robust to sensitivity analyses. In a high-prevalence setting, scale-up of decentralised ART dispensing and monitoring can provide large population health benefits and is cost-effective in preventing death and disability due to HIV.

Protocol: Implementation evaluation of a combination intervention for sustainable blood pressure control in rural KwaZulu-Natal, South Africa (IMPACT BP): A three-arm, unblinded, parallel group individually randomized clinical trial.

BACKGROUND: Hypertension is the primary risk factor for stroke and heart disease, which are leading causes of death in South Africa. Despite the availability of treatments, there is an implementation gap in how best to deliver hypertension care in this resource-limited region. METHODS: We describe a three-arm parallel group individually randomized control trial to evaluate the effectiveness and implementation of a technology-supported, community-based intervention to improve blood pressure control among people with hypertension in rural KwaZulu-Natal. The study will compare three strategies: 1) standard of care (SOC arm) clinic-based management, 2) home-based blood pressure management supported by community blood pressure monitors (CBPM arm) and a mobile health application to record blood pressure readings and enable clinic-based nurses to remotely manage care, and 3) an identical strategy to the CBPM arm, except that participants will use a cellular blood pressure cuff, which automatically transmits completed readings over cellular networks directly to clinic-based nurses (eCBPM+ arm). The primary effectiveness outcome is change in blood pressure from enrollment to 6 months. The secondary effectiveness outcome is the proportion of participants with blood pressure control at 6 months. Acceptability, fidelity, sustainability, and cost-effectiveness of the interventions will also be assessed. CONCLUSIONS: In this protocol, we report the development of interventions in partnership with the South Africa Department of Health, a description of the technology-enhanced interventions, and details of the study design so that our intervention and evaluation can inform similar efforts in rural, resource-limited settings. PROTOCOL: Version 3 November 9th, 2022. CLINICALTRIALS: gov Trial Registration: NCT05492955 SAHPRA Trial Number: N20211201. SANCTR Number: DOH-27-112,022-4895.

Secondary Distribution of HIV Self-Testing Kits to Social and Sexual Networks of PLWH in KwaZulu-Natal, South Africa. A Brief Report.

Background: To reach 95% of persons living with HIV (PLWH) knowing their HIV status, alternative testing approaches such as HIV self-testing (HIVST) and secondary HIVST kit distribution are needed. We investigated if secondary HIVST kit distribution from male and female PLWH in South Africa would successfully lead to their contacts testing for HIV and linking to care if positive. Methods: Male and female PLWH participating in an HIV treatment trial between July and November 2018 in KwaZulu-Natal, South Africa were offered participation as "HIVST kit distributors" in a pilot of secondary distribution of HIVST kits to give to sexual partners and social networks. Univariate descriptive statistics were used to describe the characteristics of volunteer distributors, proportion of HIVST recipients who reported their results, and linkage to care among those who tested positive using HIVST were assessed. Results: Sixty-three participant kit distributors accepted kits to disperse to contacts, of whom 52% were female, median age was 34 years (IQR 26-42.5), 84% reported 1 sexual partner and 76% did not know their partner's HIV status. HIVST kit distributors took 218 kits, with 13/218 (6%) of kits reported to be intended to be given to a sexual partner. A total of 143 HIVST recipients reported their HIVST results; 92% reported their results were negative, 11 recipients reported positive results and 1 HIVST-positive recipient was linked to HIV care. Conclusion: Secondary distribution of HIVST to social networks and sexual partners from South African PLWH is feasible, with two thirds of contacts reporting use of the HIVST kits. Additional support is necessary to facilitate linkage to care.

Implementation of HIV Self-Testing to Reach Men in Rural uMkhanyakude, KwaZulu-Natal, South Africa. a DO-ART Trial Sub Study.

Background: KwaZulu-Natal, South Africa has one of the highest HIV prevalence rates globally. Persons <35 years and men have lower rates of HIV testing. HIV self-testing (HIVST) may overcome many barriers of facility-based HIV testing in order to identify HIV positive young persons and men and link them to care. We investigated whether HIVST distribution was a feasible approach to reach men and assessed the proportion of participants who reported their HIVST results, tested positive and linked to care. Methods: Teams comprised of a nurse, clinic research assistant, and recruiters distributed HIVST kits in rural uMkhanyakude, KwaZulu-Natal from August-November 2018 with a focus on testing men. Workplaces (farms), social venues, taxi ranks, and homesteads were used as HIVST kit distribution points following community sensitisation through community advisory boards and community leaders. HIVST kits, demonstration of use, and small incentives to report testing outcomes were provided. The Department of Health provided confirmatory testing and HIV care at clinics. Results: Over 11 weeks in late 2018, we distributed 2,634 HIVST kits of which 2,113 (80%) were distributed to persons aged <35 years, 2,591 (98%) to men and 356 (14%) to first time testers. Of the HIVST distributed, 2,107 (80%) reported their results to the study team, and 157 (7%) tested positive. Of persons who tested positive, 107/130 (82%) reported having a confirmatory test of which 102/107 (95%) were positive and initiated on ART. No emergencies or social harms were reported. Conclusion: Large scale distribution of HIVST kits targeting men in rural KwaZulu-Natal is feasible and highly effective in reaching men, including those who had not previously tested for HIV. While two-thirds of persons who tested HIV positive initiated ART, additional linkage strategies are needed for those who do not link after HIVST. HIVST should be used as a tool to reach men in order to achieve 95% coverage in the UNAIDS testing and care cascade in KwaZulu-Natal.

Undisclosed Antiretroviral Therapy Use at Primary Health Care Clinics in Rural KwaZulu Natal South Africa: A DO-ART Trial Sub-study.

Accurate reporting of antiretroviral therapy (ART) uptake is crucial for measuring the success of epidemic control. Programs without linked electronic medical records are susceptible to duplicating ART initiation events. We assessed the prevalence of undisclosed ART use at the time of treatment initiation and explored its correlates among people presenting to public ambulatory clinics in South Africa. Data were analyzed from the community-based delivery of ART (DO ART) clinical trial, which recruited people living with HIV who presented for ART initiation at two clinics in rural South Africa. We collected data on socioeconomic factors, clinical factors, and collected blood as part of study screening procedures. We estimated the proportion of individuals presenting for ART initiation with viral load suppression (< 20 copies/mL) and fitted regression models to identify social and clinical correlates of non-disclosure of ART use. We also explored clinical and national databases to identify records of ART use. Finally, to confirm surreptitious ART use, we measured tenofovir (TDF) and emtricitabine (FTC) levels in dried blood spots. A total of 193 people were screened at the two clinics. Approximately 60% (n = 114) were female, 40% (n = 78) reported a prior HIV test, 23% (n = 44) had disclosed to a partner, and 31% (n = 61) had a partner with HIV. We found that 32% (n = 62) of individuals presenting for ART initiation or re-initiation had an undetectable viral load. In multivariable regression models, female sex (AOR 2.16, 95% CI 1.08-4.30), having a prior HIV test and having disclosed their HIV status (AOR 2.48, 95% CI 1.13-5.46), and having a partner with HIV (AOR 1.94, 95% CI 0.95-3.96) were associated with having an undetectable viral load. In records we reviewed, we found evidence of ART use from either clinical or laboratory databases in 68% (42/62) and detected either TDF or FTC in 60% (37/62) of individuals with an undetectable viral load. Undisclosed ART use was present in approximately one in three individuals presenting for ART initiation or re-initiation at ambulatory HIV clinics in South Africa. These results have important implications for ART resource use and planning in the region. A better understanding of reasons for non-disclosure of ART at primary health care clinics in such settings is needed.

Community-based antiretroviral therapy versus standard clinic-based services for HIV in South Africa and Uganda (DO ART): a randomised trial.

BACKGROUND: Community-based delivery of antiretroviral therapy (ART) for HIV, including ART initiation, clinical and laboratory monitoring, and refills, could reduce barriers to treatment and improve viral suppression, reducing the gap in access to care for individuals who have detectable HIV viral load, including men who are less likely than women to be virally suppressed. We aimed to test the effect of community-based ART delivery on viral suppression among people living with HIV not on ART. METHODS: We did a household-randomised, unblinded trial (DO ART) of delivery of ART in the community compared with the clinic in rural and peri-urban settings in KwaZulu-Natal, South Africa and the Sheema District, Uganda. After community-based HIV testing, people living with HIV were randomly assigned (1:1:1) with mobile phone software to community-based ART initiation with quarterly monitoring and ART refills through mobile vans; ART initiation at the clinic followed by mobile van monitoring and refills (hybrid approach); or standard clinic ART initiation and refills. The primary outcome was HIV viral suppression at 12 months. If the difference in viral suppression was not superior between study groups, an a-priori test for non-inferiority was done to test for a relative risk (RR) of more than 0·95. The cost per person virally suppressed was a co-primary outcome of the study. This study is registered with ClinicalTrials.gov, NCT02929992. FINDINGS: Between May 26, 2016, and March 28, 2019, of 2479 assessed for eligibility, 1315 people living with HIV and not on ART with detectable viral load at baseline were randomly assigned; 666 (51%) were men. Retention at the month 12 visit was 95% (n=1253). At 12 months, community-based ART increased viral suppression compared with the clinic group (306 [74%] vs 269 [63%], RR 1·18, 95% CI 1·07-1·29; psuperiority=0·0005) and the hybrid approach was non-inferior (282 [68%] vs 269 [63%], RR 1·08, 0·98-1·19; pnon-inferiority=0·0049). Community-based ART increased viral suppression among men (73%, RR 1·34, 95% CI 1·16-1·55; psuperiority<0·0001) as did the hybrid approach (66%, RR 1·19, 1·02-1·40; psuperiority=0·026), compared with clinic-based ART (54%). Viral suppression was similar for men (n=156 [73%]) and women (n=150 [75%]) in the community-based ART group. With efficient scale-up, community-based ART could cost US$275-452 per person reaching viral suppression. Community-based ART was considered safe, with few adverse events. INTERPRETATION: In high and medium HIV prevalence settings in South Africa and Uganda, community-based delivery of ART significantly increased viral suppression compared with clinic-based ART, particularly among men, eliminating disparities in viral suppression by gender. Community-based ART should be implemented and evaluated in different contexts for people with detectable viral load. FUNDING: The Bill & Melinda Gates Foundation; the University of Washington and Fred Hutch Center for AIDS Research; the Wellcome Trust; the University of Washington Royalty Research Fund; and the University of Washington King K Holmes Endowed Professorship in STDs and AIDS.

An implementation study of oral and blood-based HIV self-testing and linkage to care among men in rural and peri-urban KwaZulu-Natal, South Africa.

INTRODUCTION: In South Africa, HIV-infected men are less likely than women to test and know their status (the first UNAIDS "90-90-90" target), and men have worse outcomes across the HIV care cascade. HIV self-testing (HIVST) may address this testing disparity but questions remain over the most effective distribution strategy and linkage following a positive test result. We implemented a men-focused HIVST distribution programme to evaluate components contributing to participation and retention. METHODS: We conducted an implementation study of multi-venue HIVST kit distribution in rural and peri-urban KwaZulu-Natal (KZN), South Africa. We distributed HIVST kits at community points, workplaces and social venues for on site or take-home use. Clients could choose blood-based or oral-fluid-based HIVST kits and elect to watch an in-person or video demonstration. We provided a USD2 incentive to facilitate reporting test results by phone or SMS. Persons with reactive HIVST results were provided immediate confirmatory tests (if used HIVST on site) or were referred for confirmatory testing (if took HIVST off site) and linkage to care for ART initiation. We describe the testing and linkage cascade in this sample and describe predictors of reactive HIVST results and linkage. RESULTS: Between July and November 2018, we distributed 4496 HIVST kits in two regions of KZN (96% to men, median age 28 (IQR 23 to 35). Most participants (58%) chose blood-based HIVST and 42% chose oral-swab kits. 11% of men were testing for the first time. A total of 3902 (83%) of testers reported their test result to the study team, with 314 (8%) screening positive for HIV. Among 274 men with reactive HIVST results, 68% linked to ART; no significant predictors of linkage were identified. 10% of kit users reported they would prefer a different type (oral vs. blood) of kit for repeat testing than the type they used. CONCLUSIONS: HIVST is acceptable to men and rapid distribution with optional testing support is feasible in rural and peri-urban settings. HIVST kits successfully reached younger men and identified undetected infections. Both oral and blood-based HIVST were selected. Scaling up HIVST distribution and guidance may increase the number of first-time testers among men and help achieve the first UNAIDS "90" for men in South Africa.