Pragmatic economic evaluation of community-led delivery of HIV self-testing in Malawi.

INTRODUCTION: Community-based strategies can extend coverage of HIV testing and diagnose HIV at earlier stages of infection but can be costly to implement. We evaluated the costs and effects of community-led delivery of HIV self-testing (HIVST) in Mangochi District, Malawi. METHODS: This economic evaluation was based within a pragmatic cluster-randomised trial of 30 group village heads and their catchment areas comparing the community-led HIVST intervention in addition to the standard of care (SOC) versus the SOC alone. The intervention involved mobilising community health groups to lead 7-day HIVST campaigns including distribution of HIVST kits. The SOC included facility-based HIV testing services. Primary costings estimated economic costs of the intervention and SOC from the provider perspective, with costs annualised and measured in 2018 US$. A postintervention survey captured individual-level data on HIV testing events, which were combined with unit costs from primary costings, and outcomes. The incremental cost per person tested HIV-positive and associated uncertainty were estimated. RESULTS: Overall, the community-led HIVST intervention costed $138 624 or $5.70 per HIVST kit distributed, with test kits and personnel the main contributing costs. The SOC costed $263 400 or $4.57 per person tested. Individual-level provider costs were higher in the community-led HIVST arm than the SOC arm (adjusted mean difference $3.77, 95% CI $2.44 to $5.10; p<0.001), while the intervention effect on HIV positivity varied based on adjustment for previous diagnosis. The incremental cost per person tested HIV positive was $324 but increased to $1312 and $985 when adjusting for previously diagnosed self-testers or self-testers on treatment, respectively. Community-led HIVST demonstrated low probability of being cost-effective against plausible willingness-to-pay values, with HIV positivity a key determinant. CONCLUSION: Community-led HIVST can provide HIV testing at a low additional unit cost. However, adding community-led HIVST to the SOC was not likely to be cost-effective, especially in contexts with low prevalence of undiagnosed HIV. TRIAL REGISTRATION NUMBER: NCT03541382.

Partner-delivered HIV self-test kits with and without financial incentives in antenatal care and index patients with HIV in Malawi: a three-arm, cluster-randomised controlled trial.

BACKGROUND: Secondary distribution of HIV self-testing (HIVST) kits by patients attending clinic services to their partners could improve the rate of HIV diagnosis. We aimed to investigate whether secondary administration of HIVST kits, with or without an additional financial incentive, via women receiving antenatal care (ANC) or via people newly diagnosed with HIV (ie, index patients) could improve the proportion of male partners tested or the number of people newly diagnosed with HIV. METHODS: We did a three-arm, open-label, pragmatic, cluster-randomised trial of 27 health centres (clusters), eligible if they were a government primary health centre providing ANC, HIV testing, and ART services, across four districts of Malawi. We recruited women (aged ≥18 years) attending their first ANC visit and whose male partner was available, not already taking ART, and not already tested for HIV during this pregnancy (ANC cohort), and people (aged ≥18 years) with newly diagnosed HIV during routine clinic HIV testing who had at least one sexual contact not already known to be HIV-positive (index cohort). Centres were randomly assigned (1:1:1), using a public selection of computer-generated random allocations, to enhanced standard of care (including an invitation for partners to attend HIV testing services), HIVST only, or HIVST plus a US$10 financial incentive for retesting. The primary outcome for the ANC cohort was the proportion of male partners reportedly tested, as ascertained by interview with women in this cohort at day 28. The primary outcome for the index cohort was the geometric mean number of new HIV-positive people identified per facility within 28 days of enrolment, as measured by observed HIV test results. Cluster-level summaries compared intervention with standard of care by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03705611. FINDINGS: Between Sept 8, 2018, and May 2, 2019, nine clusters were assigned to each trial arm, resulting in 4544 eligible women in the ANC cohort (1447 [31·8%] in the standard care group, 1465 [32·2%] in the HIVST only group, and 1632 [35·9%] in HIVST plus financial incentive group) and 708 eligible patients in the index cohort (234 [33·1%] in the standard care group, 169 [23·9%] in the HIVST only group, and 305 [42·9%] in the HIVST plus financial incentive group). 4461 (98·2%) of 4544 eligible women in the ANC cohort and 645 (91·1%) of 708 eligible patients in the index cohort were recruited, of whom 3378 (75·7%) in the ANC cohort and 439 (68·1%) in the index cohort were interviewed after 28 days. In the ANC cohort, the mean proportion of reported partner testing per cluster was 35·0% (SD 10·0) in the standard care group, 73·0% in HIVST only group (13·1, adjusted risk ratio [RR] 1·71, 95% CI 1·48-1·98; p<0·0001), and 65·2% in the HIVST plus financial incentive group (11·6, adjusted RR 1·62, 1·45-1·81; p<0·0001). In the index cohort, the geometric mean number of new HIV-positive sexual partners per cluster was 1·35 (SD 1·62) for the standard care group, 1·91 (1·78) for the HIVST only group (incidence rate ratio adjusted for number eligible as an offset in the negative binomial model 1·65, 95% CI 0·49-5·55; p=0·3370), and 3·20 (3·81) for the HIVST plus financial incentive group (3·11, 0·99-9·77; p=0·0440). Four self-resolving, temporary marital separations occurred due to disagreement in couples regarding HIV self-test kits. INTERPRETATION: Although administration of HIVST kits in the ANC cohort, even when offered alongside a financial incentive, did not identify significantly more male patients with HIV than did standard care, out-of-clinic options for HIV testing appear more acceptable to many male partners of women with HIV, increasing test uptake. Viewed in the current context, this approach might allow continuation of services despite COVID-19-related lockdowns. FUNDING: Unitaid, through the Self-Testing Africa Initiative.

Effect of community-led delivery of HIV self-testing on HIV testing and antiretroviral therapy initiation in Malawi: A cluster-randomised trial.

BACKGROUND: Undiagnosed HIV infection remains substantial in key population subgroups including adolescents, older adults, and men, driving ongoing transmission in sub-Saharan Africa. We evaluated the impact, safety, and costs of community-led delivery of HIV self-testing (HIVST), aiming to increase HIV testing in underserved subgroups and stimulate demand for antiretroviral therapy (ART). METHODS AND FINDINGS: This cluster-randomised trial, conducted between October 2018 and July 2019, used restricted randomisation (1:1) to allocate 30 group village head clusters in Mangochi district, Malawi to the community-led HIVST intervention in addition to the standard of care (SOC) or the SOC alone. The intervention involved mobilising community health groups to lead the design and implementation of 7-day HIVST campaigns, with cluster residents (≥15 years) eligible for HIVST. The primary outcome compared lifetime HIV testing among adolescents (15 to 19 years) between arms. Secondary outcomes compared: recent HIV testing (in the last 3 months) among older adults (≥40 years) and men; cumulative 6-month incidence of ART initiation per 100,000 population; knowledge of the preventive benefits of HIV treatment; and HIV testing stigma. Outcomes were measured through a post-intervention survey and at neighboring health facilities. Analysis used intention-to-treat for cluster-level outcomes. Community health groups delivered 24,316 oral fluid-based HIVST kits. The survey included 90.2% (3,960/4,388) of listed participants in the 15 community-led HIVST clusters and 89.2% (3,920/4,394) of listed participants in the 15 SOC clusters. Overall, the proportion of men was 39.0% (3,072/7,880). Most participants obtained primary-level education or below, were married, and reported a sexual partner. Lifetime HIV testing among adolescents was higher in the community-led HIVST arm (84.6%, 770/910) than the SOC arm (67.1%, 582/867; adjusted risk difference [RD] 15.2%, 95% CI 7.5% to 22.9%; p < 0.001), especially among 15 to 17 year olds and boys. Recent testing among older adults was also higher in the community-led HIVST arm (74.5%, 869/1,166) than the SOC arm (31.5%, 350/1,111; adjusted RD 42.1%, 95% CI 34.9% to 49.4%; p < 0.001). Similarly, the proportions of recently tested men were 74.6% (1,177/1,577) and 33.9% (507/1,495) in the community-led HIVST and SOC arms, respectively (adjusted RD 40.2%, 95% CI 32.9% to 47.4%; p < 0.001). Knowledge of HIV treatment benefits and HIV testing stigma showed no differences between arms. Cumulative incidence of ART initiation was respectively 305.3 and 226.1 per 100,000 population in the community-led HIVST and SOC arms (RD 72.3, 95% CI -36.2 to 180.8; p = 0.18). In post hoc analysis, ART initiations in the 3-month post-intervention period were higher in the community-led HIVST arm than the SOC arm (RD 97.7, 95% CI 33.4 to 162.1; p = 0.004). HIVST uptake was 74.7% (2,956/3,960), with few adverse events (0.6%, 18/2,955) and at US$5.70 per HIVST kit distributed. The main limitations include the use of self-reported HIV testing outcomes and lack of baseline measurement for the primary outcome. CONCLUSIONS: In this study, we found that community-led HIVST was effective, safe, and affordable, with population impact and coverage rapidly realised at low cost. This approach could enable community HIV testing in high HIV prevalence settings and demonstrates potential for economies of scale and scope. TRIAL REGISTRATION: Clinicaltrials.gov NCT03541382.

Community-led delivery of HIV self-testing to improve HIV testing, ART initiation and broader social outcomes in rural Malawi: study protocol for a cluster-randomised trial.

BACKGROUND: Prevention of new HIV infections is a critical public health issue. The highest HIV testing gaps are in men, adolescents 15-19 years old, and adults 40 years and older. Community-based HIV testing services (HTS) can contribute to increased testing coverage and early HIV diagnosis, with HIV self-testing (HIVST) strategies showing promise. Community-based strategies, however, are resource intensive, costly and not widely implemented. A community-led approach to health interventions involves supporting communities to plan and implement solutions to improve their health. This trial aims to determine if community-led delivery of HIVST can improve HIV testing uptake, ART initiation, and broader social outcomes in rural Malawi. METHODS: The trial uses a parallel arm, cluster-randomised design with group village heads (GVH) and their defined catchment areas randomised (1:1) to community-led HIVST or continue with the standard of the care (SOC). As part of the intervention, informal community health cadres are supported to plan and implement a seven-day HIVST campaign linked to HIV treatment and prevention. Approximately 12 months after the initial campaign, intervention GVHs are randomised to lead a repeat HIVST campaign. The primary outcome includes the proportion of adolescents 15-19 years old who have tested for HIV in their lifetime. Secondary outcomes include recent testing in adults 40 years and older and men; ART initiation; knowledge of HIV prevention; and HIV testing stigma. Outcomes will be measured through cross-sectional surveys and clinic registers. Economic evaluation will determine the cost per person tested, cost per person diagnosed, and incremental cost effectiveness ratio. DISCUSSION: To the best of our knowledge, this is the first trial to assess the effectiveness of community-led HTS, which has only recently been enabled by the introduction of HIVST. Community-led delivery of HIVST is a promising new strategy for providing periodic HIV testing to support HIV prevention in rural communities. Further, introduction of HIVST through a community-led framework seems particularly apt, with control over healthcare concurrently devolved to individuals and communities. TRIAL REGISTRATION: Clinicaltrials.gov registry ( NCT03541382 ) registered 30 May 2018.

Economic cost analysis of door-to-door community-based distribution of HIV self-test kits in Malawi, Zambia and Zimbabwe.

INTRODUCTION: HIV self-testing (HIVST) is recommended by the World Health Organization in addition to other testing modalities to increase uptake of HIV testing, particularly among harder-to-reach populations. This study provides the first empirical evidence of the costs of door-to-door community-based HIVST distribution in Malawi, Zambia and Zimbabwe. METHODS: HIVST kits were distributed door-to-door in 71 sites across Malawi, Zambia and Zimbabwe from June 2016 to May 2017. Programme expenditures, supplemented by on-site observation and monitoring and evaluation data were used to estimate total economic and unit costs of HIVST distribution, by input and site. Inputs were categorized into start-up, capital and recurrent costs. Sensitivity and scenario analyses were performed to assess the impact of key parameters on unit costs. RESULTS: In total, 152,671, 103,589 and 93,459 HIVST kits were distributed in Malawi, Zambia and Zimbabwe over 12, 11 and 10 months respectively. Across these countries, 43% to 51% of HIVST kits were distributed to men. The average cost per HIVST kit distributed was US$8.15, US$16.42 and US$13.84 in Malawi, Zambia and Zimbabwe, respectively, with pronounced intersite variation within countries driven largely by site-level fixed costs. Site-level recurrent costs were 70% to 92% of full costs and 20% to 62% higher than routine HIV testing services (HTS) costs. Personnel costs contributed from 26% to 52% of total costs across countries reflecting differences in remuneration approaches and country GDP. CONCLUSIONS: These early door-to-door community HIVST distribution programmes show large potential, both for reaching untested populations and for substantial economies of scale as HIVST programmes scale-up and mature. From a societal perspective, the costs of HIVST appear similar to conventional HTS, with the higher providers' costs substantially offsetting user costs. Future approaches to minimizing cost and/or maximize testing coverage could include unpaid door-to-door community-led distribution to reach end-users and integrating HIVST into routine clinical services via direct or secondary distribution strategies with lower fixed costs.

Exploring social harms during distribution of HIV self-testing kits using mixed-methods approaches in Malawi.

INTRODUCTION: HIV self-testing (HIVST) provides couples and individuals with a discreet, convenient and empowering testing option. As with all HIV testing, potential harms must be anticipated and mitigated to optimize individual and public health benefits. Here, we describe social harms (SHs) reported during HIVST implementation in Malawi, and propose a framework for grading and responding to harms, according to their severity. METHODS: We report findings from six HIVST implementation studies in Malawi (2011 to 2017) that included substudies investigating SH reports. Qualitative methods included focus group discussions, in-depth interviews and critical incident interviews. Earlier studies used intensive quantitative methods (post-test questionnaires for intimate partner violence, household surveys, investigation of all deaths in HIVST communities). Later studies used post-marketing reporting with/without community engagement. Pharmacovigilance methodology (whereby potentially life-threatening/changing events are defined as "serious") was used to grade SH severity, assuming more complete passive reporting for serious events. RESULTS: During distribution of 175,683 HIVST kits, predominantly under passive SH reporting, 25 serious SHs were reported from 19 (0.011%) self-testers, including 15 partners in eight couples with newly identified HIV discordancy, and one perinatally infected adolescent. There were no deaths or suicides. Marriage break-up was the most commonly reported serious SH (sixteen individuals; eight couples), particularly among serodiscordant couples. Among new concordant HIV-positive couples, blame and frustration was common but rarely (one episode) led to serious SHs. Among concordant HIV-negative couples, increased trust and stronger relationships were reported. Coercion to test or disclose was generally considered "well-intentioned" within established couples. Women felt empowered and were assertive when offering HIVST test kits to their partners. Some women who persuaded their partner to test, however, did report SHs, including verbal or physical abuse and economic hardship. CONCLUSIONS: After more than six years of large-scale HIVST implementation and in-depth investigation of SHs in Malawi, we identified approximately one serious reported SH per 10,000 HIVST kits distributed, predominantly break-up of married serodiscordant couples. Both "active" and "passive" reporting systems identified serious SH events, although with more complete capture by "active" systems. As HIVST is scaled-up, efforts to support and further optimize community-led SH monitoring should be prioritized alongside HIVST distribution.

The effectiveness and cost-effectiveness of community-based lay distribution of HIV self-tests in increasing uptake of HIV testing among adults in rural Malawi and rural and peri-urban Zambia: protocol for STAR (self-testing for Africa) cluster randomized evaluations.

BACKGROUND: Knowledge of HIV status remains below target in sub-Saharan Africa, especially among men and adolescents. HIV self-testing (HIVST) is a novel approach that enables unique distribution strategies, with potential to be highly decentralised and to provide complementary coverage to facility-based testing approaches. However, substantial gaps in evidence remain on the effectiveness and cost-effectiveness of HIVST, particularly in rural settings, and on approaches to facilitate linkage to confirmatory HIV testing, prevention, and treatment services. This protocol describes two cluster-randomized trials (CRT) included within the UNITAID/PSI HIV Self-Testing Africa (STAR) project. METHODS: Two independent CRTs were designed around existing reproductive health programmes in rural Malawi and rural/peri-urban Zambia. Common features include use of constrained randomisation to allocate health clinic catchment areas to either standard HIV testing (SOC) or SOC plus community-based distribution of OraQuick HIV Self Tests (Bethlehem, PA USA, assembled in Thailand) by trained lay distributors selected by the community. Community-based distribution agents will be trained (3-day curriculum) to provide brief demonstration of kit use and interpretation, information and encouragement to access follow up services, and management of social harm. The primary outcome of both CRTs is the proportion of the population aged 16 years and older who tested for HIV within the 12-month intervention period. Secondary outcomes in both trials include lifetime HIV testing, antiretroviral therapy (ART) initiation and ART use. Circumcision status among males will be a secondary outcome in Zambia and clinic-level demand for ART will be a secondary outcome in Malawi. Outcomes will be measured using cross-sectional household surveys, and routine data extraction from participating clinics. Costing studies will be used to evaluate the cost-effectiveness of the intervention arm. Qualitative research will be used to guide distribution and explore reasons for testing and linkage to onward care. DISCUSSION: The STAR-Malawi and STAR-Zambia trials will provide rigorous evidence of whether community-based lay HIVST distribution is an effective and cost-effective approach to increasing coverage of HIV testing and demand for follow-on HIV services in rural and peri-urban communities in sub-Saharan Africa. TRIAL REGISTRATION: Clinicaltrials.gov, Malawi: NCT02718274 , 18 March 2016; Zambia: NCT02793804 , 3 June 2016. Protocol date: 21 February 2018.