Effect of peer-distributed HIV self-test kits on demand for biomedical HIV prevention in rural KwaZulu-Natal, South Africa: a three-armed cluster-randomised trial comparing social networks versus direct delivery.

STUDY OBJECTIVE: We investigated two peer distribution models of HIV self-testing (HIVST) in HIV prevention demand creation compared with trained young community members (peer navigators). METHODS: We used restricted randomisation to allocate 24 peer navigator pairs (clusters) in KwaZulu-Natal 1:1:1: (1) standard of care (SOC): peer navigators distributed clinic referrals, pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) information to 18-30 year olds. (2) peer navigator direct distribution (PND): Peer navigators distributed HIVST packs (SOC plus two OraQuick HIVST kits) (3) incentivised peer networks (IPN): peer navigators recruited young community members (seeds) to distribute up to five HIVST packs to 18-30 year olds within their social networks. Seeds received 20 Rand (US$1.5) for each recipient who distributed further packs. The primary outcome was PrEP/ART linkage, defined as screening for PrEP/ART eligibility within 90 days of pack distribution per peer navigator month (pnm) of outreach, in women aged 18-24 (a priority for HIV prevention). Investigators and statisticians were blinded to allocation. Analysis was intention to treat. Total and unit costs were collected prospectively. RESULTS: Between March and December 2019, 4163 packs (1098 SOC, 1480 PND, 1585 IPN) were distributed across 24 clusters. During 144 pnm, 272 18-30 year olds linked to PrEP/ART (1.9/pnm). Linkage rates for 18-24-year-old women were lower for IPN (n=26, 0.54/pnm) than PND (n=45, 0.80/pnm; SOC n=49, 0.85/pnm). Rate ratios were 0.68 (95% CI 0.28 to 1.66) for IPN versus PND, 0.64 (95% CI 0.26 to 1.62) for IPN versus SOC and 0.95 (95% CI 0.38 to 2.36) for PND versus SOC. In 18-30 year olds, PND had significantly more linkages than IPN (2.11 vs 0.88/pnm, RR 0.42, 95% CI 0.18 to 0.98). Cost per pack distributed was cheapest for IPN (US$36) c.f. SOC (US$64). Cost per person linked to PrEP/ART was cheaper in both peer navigator arms compared with IPN. DISCUSSION: HIVST did not increase demand for PrEP/ART. Incentivised social network distribution reached large numbers with HIVST but resulted in fewer linkages compared with PrEP/ART promotion by peer navigators. TRIAL REGISTRATION NUMBER: NCT03751826.

Does community-based distribution of HIV self-tests increase uptake of HIV testing? Results of pair-matched cluster randomised trial in Zambia.

OBJECTIVES: Ending HIV by 2030 is a global priority. Achieving this requires alternative HIV testing strategies, such as HIV self-testing (HIVST) to reach all individuals with HIV testing services (HTS). We present the results of a trial evaluating the impact of community-based distribution of HIVST in community and facility settings on the uptake of HTS in rural and urban Zambia. DESIGN: Pair-matched cluster randomised trial. METHODS: In catchment areas of government health facilities, OraQuick HIVST kits were distributed by community-based distributors (CBDs) over 12 months in 2016-2017. Within matched pairs, clusters were randomised to receive the HIVST intervention or standard of care (SOC). Individuals aged ≥16 years were eligible for HIVST. Within communities, CBDs offered HIVST in high traffic areas, door to door and at healthcare facilities. The primary outcome was self-reported recent testing within the previous 12 months measured using a population-based survey. RESULTS: In six intervention clusters (population 148 541), 60 CBDs distributed 65 585 HIVST kits. A recent test was reported by 66% (1622/2465) in the intervention arm compared with 60% (1456/2429) in SOC arm (adjusted risk ratio 1.08, 95% CI 0.94 to 1.24; p=0.15). Uptake of the HIVST intervention was low: 24% of respondents in the intervention arm (585/2493) used an HIVST kit in the previous 12 months. No social harms were identified during implementation. CONCLUSION: Despite distributing a large number of HIVST kits, we found no evidence that this community-based HIVST distribution intervention increased HTS uptake. Other models of HIVST distribution, including secondary distribution and community-designed distribution models, provide alternative strategies to reach target populations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02793804).

ART initiations following community-based distribution of HIV self-tests: meta-analysis and meta-regression of STAR Initiative data.

INTRODUCTION: Measuring linkage after community-based testing, particularly HIV self-testing (HIVST), is challenging. Here, we use data from studies of community-based HIVST distribution, conducted within the STAR Initiative, to assess initiation of antiretroviral therapy (ART) and factors driving differences in linkage rates. METHODS: Five STAR studies evaluated HIVST implementation in Malawi, Zambia and Zimbabwe. New ART initiations during the months of intervention at clinics in HIVST and comparison areas were presented graphically, and study effects combined using meta-analysis. Meta-regression was used to estimate associations between the impact of community-based HIVST distribution and indicators of implementation context, intensity and reach. Effect size estimates used (1) prespecified trial definitions of ART timing and comparator facilities and (2) exploratory definitions accounting for unexpected diffusion of HIVST into comparison areas and periods with less distribution of HIVST than was expected. RESULTS: Compared with arms with standard testing only, ART initiations were higher in clinics in HIVST distribution areas in 4/5 studies. The prespecified meta-analysis found positive but variable effects of HIVST on facility ART initiations (RR: 1.14, 95% CI 0.93 to 1.40; p=0.21). The exploratory meta-analysis found a stronger impact of HIVST distribution on ART initiations (RR: 1.29, 95% CI 1.08 to 1.55, p=0.02).ART initiations were higher in studies with greater self-reported population-level intensity of HIVST use (RR: 1.12; 95% CI 1.04 to 1.21; p=0.02.), but did not differ by national-level indicators of ART use among people living with HIV, number of HIVST kits distributed per 1000 population, or self-reported knowledge of how to link to care after a reactive HIVST. CONCLUSION: Community-based HIVST distribution has variable effect on ART initiations compared with standard testing service alone. Optimising both support for and approach to measurement of effective and timely linkage or relinkage to HIV care and prevention following HIVST is needed to maximise impact and guide implementation strategies.

Comparison of community-led distribution of HIV self-tests kits with distribution by paid distributors: a cluster randomised trial in rural Zimbabwean communities.

BACKGROUND: We compared community-led versus an established community-based HIV self-testing (HIVST) model in rural Zimbabwe using a cluster-randomised trial. METHODS: Forty village groups were randomised 1:1 using restricted randomisation to community-led HIVST, where communities planned and implemented HIVST distribution for 4 weeks, or paid distribution (PD), where distributors were paid US$50 to distribute kits door-to-door over 4 weeks. Individual level primary outcomes compared household survey responses by arm 4 months post-intervention for: (1) newly diagnosed HIV during/within 4 months following HIVST distribution, (2) linkage to confirmatory testing, pre-exposure prophylaxis or voluntary medical male circumcision during/within 4 months following HIVST distribution. Participants were not masked to allocation; analysis used masked data. Trial analysis used random-effects logistic regression.Distribution costs compared: (1) community-led HIVST, (2) PD HIVST and (3) PD costs when first implemented in 2016/2017. RESULTS: From October 2018 to August 2019, 27 812 and 36 699 HIVST kits were distributed in community-led and PD communities, respectively. We surveyed 11 150 participants and 5683 were in community-led arm. New HIV diagnosis was reported by 211 (3.7%) community-led versus 197 (3.6%) PD arm participants, adjusted OR (aOR) 1.1 (95% CI 0.72 to 1.56); 318 (25.9%) community-led arm participants linked to post-test services versus 361 (23.9%) in PD arm, aOR 1.1 (95% CI 0.75 to 1.49.Cost per HIVST kit distributed was US$6.29 and US$10.25 for PD and community-led HIVST, both lower than 2016/2017 costs for newly implemented PD (US$14.52). No social harms were reported. CONCLUSIONS: Community-led HIVST can perform as well as paid distribution, with lower costs in the first year. These costs may reduce with programme maturity/learning. TRIAL REGISTRATION NUMBER: PACTR201811849455568.

Costs of integrating HIV self-testing in public health facilities in Malawi, South Africa, Zambia and Zimbabwe.

INTRODUCTION: As countries approach the UNAIDS 95-95-95 targets, there is a need for innovative and cost-saving HIV testing approaches that can increase testing coverage in hard-to-reach populations. The HIV Self-Testing Africa-Initiative distributed HIV self-test (HIVST) kits using unincentivised HIV testing counsellors across 31 public facilities in Malawi, South Africa, Zambia and Zimbabwe. HIVST was distributed either through secondary (partner's use) distribution alone or primary (own use) and secondary distribution approaches. METHODS: We evaluated the costs of adding HIVST to existing HIV testing from the providers' perspective in the 31 public health facilities across the four countries between 2018 and 2019. We combined expenditure analysis and bottom-up costing approaches. We also carried out time-and-motion studies on the counsellors to estimate the human resource costs of introducing and demonstrating how to use HIVST for primary and secondary use. RESULTS: A total of 41 720 kits were distributed during the analysis period, ranging from 1254 in Zimbabwe to 27 678 in Zambia. The cost per kit distributed through the primary distribution approach was $4.27 in Zambia and $9.24 in Zimbabwe. The cost per kit distributed through the secondary distribution approach ranged from $6.46 in Zambia to $13.42 in South Africa, with a wider variation in the average cost at facility-level. From the time-and-motion observations, the counsellors spent between 20% and 44% of the observed workday on HIVST. Overall, personnel and test kit costs were the main cost drivers. CONCLUSION: The average costs of distributing HIVST kits were comparable across the four countries in our analysis despite wide cost variability within countries. We recommend context-specific exploration of potential efficiency gains from these facility-level cost variations and demand creation activities to ensure continued affordability at scale.

Modelling costs of community-based HIV self-testing programmes in Southern Africa at scale: an econometric cost function analysis across five countries.

BACKGROUND: Following success demonstrated with the HIV Self-Testing AfRica Initiative, HIV self-testing (HIVST) is being added to national HIV testing strategies in Southern Africa. An analysis of the costs of scaling up HIVST is needed to inform national plans, but there is a dearth of evidence on methods for forecasting costs at scale from pilot projects. Econometric cost functions (ECFs) apply statistical inference to predict costs; however, we often do not have the luxury of collecting large amounts of location-specific data. We fit an ECF to identify key drivers of costs, then use a simpler model to guide cost projections at scale. METHODS: We estimated the full economic costs of community-based HIVST distribution in 92 locales across Malawi, Zambia, Zimbabwe, South Africa and Lesotho between June 2016 and June 2019. We fitted a cost function with determinants related to scale, locales organisational and environmental characteristics, target populations, and per capita Growth Domestic Product (GDP). We used models differing in data intensity to predict costs at scale. We compared predicted estimates with scale-up costs in Lesotho observed over a 2-year period. RESULTS: The scale of distribution, type of community-based intervention, percentage of kits distributed to men, distance from implementer's warehouse and per capita GDP predicted average costs per HIVST kit distributed. Our model simplification approach showed that a parsimonious model could predict costs without losing accuracy. Overall, ECF showed a good predictive capacity, that is, forecast costs were close to observed costs. However, at larger scale, variations of programme efficiency over time (number of kits distributed per agent monthly) could potentially influence cost predictions. DISCUSSION: Our empirical cost function can inform community-based HIVST scale-up in Southern African countries. Our findings suggest that a parsimonious ECF can be used to forecast costs at scale in the context of financial planning and budgeting.

Missing men with tuberculosis: the need to address structural influences and implement targeted and multidimensional interventions.

Tuberculosis (TB) is treatable but is the leading infectious cause of death worldwide, with men over-represented in some key aspects of the disease burden. Men's TB epidemiological scenario occurs within a wider public health and historical context, including their prior sidelining in health discussions. Differences are however noticeable in how some Western countries and high TB and HIV burden low and middle-income countries (LMIC) including in Africa have approached the subject(s) of men and health. The former have a comparatively long history of scholarship, and lately are implementing actions targeting men's health and wellness, both increasingly addressing multilevel social and structural determinants. In contrast, in the latter men have received attention primarily for their sexual practices and role in HIV and AIDS and gender-based violence; moreover, interventions, guided by the public health approach, have stressed short-term, measurable and medical goals. Debates and the limited available empirical literature on men's engagement with TB-related healthcare are nevertheless indicating need for a shift, within TB work with men in high burden LMICs towards, structural and multicomponent interventions.

Post-test adverse psychological effects and coping mechanisms amongst HIV self-tested individuals living in couples in urban Blantyre, Malawi.

INTRODUCTION: Mandatory face-to-face counselling is necessary during HIV testing but difficult to implement within the context of HIV self-testing. We investigated adverse psychological effects and coping mechanisms following HIV-positive and HIV-discordant test results amongst self-tested individuals living in couples in urban Blantyre, Malawi. METHODS: Qualitative data from 35 in-depth interviews with self-tested individuals living in couples for more than 3 months were collected and analysed using thematic content analysis. RESULTS: Adverse psychological effects seemed to mostly occur among individuals learning for the first-time that they were HIV-positive or living in HIV-discordant relationship. Irrespective of test outcomes, women living in couples expressed difficulty making important decisions about the future of their relationships while men seemed to shoulder the emotional burden associated with feeling or being seen as responsible for introducing HIV into the relationship. Post-test psychosocial support and ascertained positive behaviour change of the perceived index partner allowed some couples to overcome adverse psychological effects linked to test results. CONCLUSION: Self-tested individuals living in couples may lack collective coping capability to collaboratively manage post-test adverse events after new HIV-positive or HIV-discordant results. Psychosocial support seemed to enable couples to foster both an individual and a collective ability to manage adverse psychological effects within the context of a couple. More research is needed to ascertain the magnitude of the deficiency of collective coping competency in couples following an HIV test.

The effect of demand-side financial incentives for increasing linkage into HIV treatment and voluntary medical male circumcision: A systematic review and meta-analysis of randomised controlled trials in low- and middle-income countries.

INTRODUCTION: Linkage to HIV treatment is a vital step in the cascade of HIV services and is critical to slowing down HIV transmission in countries with high HIV prevalence. Equally, linkage to voluntary medical male circumcision (VMMC) has been shown to decrease HIV transmission by 60% and increasing numbers of men receiving VMMC has a substantial impact on HIV incidence. However, only 48% of newly diagnosed HIV positive people link to HIV treatment let alone access HIV prevention methods such as VMMC globally. METHODS: A systematic review investigating the effect of demand-side financial incentives (DSFIs) on linkage into HIV treatment or VMMC for studies conducted in low- and middle-income countries. We searched the title, abstract and keywords in eight bibliographic databases: MEDLINE, EMBASE, Web of Science, Econlit, Cochrane, SCOPUS, IAS Conference database of abstracts, and CROI Conference database of abstracts. Searches were done in December 2016 with no time restriction. We fitted random effects (RE) models and used forest plots to display risk ratios (RR) and 95% CIs separately for the linkage to VMMC outcome. The RE model was also used to assess heterogeneity for the linkage to HIV treatment outcome. RESULTS: Of the 1205 citations identified from searches, 48 full text articles were reviewed culminating in nine articles in the final analysis. Five trials investigated the effect of DSFIs on linkage to HIV treatment while four trials investigated linkage to VMMC. Financial incentives improved linkage to HIV treatment in three of the five trials that investigated this outcome. Significant improvements were observed among postpartum women RR 1.26 (95% CI: 1.08; 1.48), among people who inject drugs RR 1.42 (95% CI: 1.09; 1.96), and among people testing at the clinic RR 1.10 (95% CI: 1.07; 1.14). One of the two trials that did not find significant improvement in linkage to ART was among people testing HIV positive in clinics RR 0.96 (95% CI: 0.81; 1.16) while the other was among new HIV positive individuals identified through a community testing study RR 0.82 (95% CI: 0.56; 1.22). We estimate an average 4-fold increase in the uptake of circumcision among HIV negative uncircumcised men from our fitted RE model with overall RR 4.00 (95% CI: 2.17; 7.37). There was negligible heterogeneity in the estimates from the different studies with I-squared = 0.0%; p = 0.923. CONCLUSIONS: Overall, DSFIs appeared to improve linkage for both HIV treatment and VMMC with greater effect for VMMC. Demand-side financial incentives could improve linkage to HIV treatment or VMMC in low- and middle-income countries although uptake by policy makers remains a challenge.

Discordance, Disclosure and Normative Gender Roles: Barriers to Couple Testing Within a Community-Level HIV Self-Testing Intervention in Urban Blantyre, Malawi.

A community-based HIV self-testing study in Blantyre, Malawi demonstrated that not all individuals living in couples tested with their partner. We describe factors dissuading individuals in couples from self-testing with their partner. Data were drawn from qualitative study exploring consequences of HIV self-testing within couples. In-depth interviews were conducted with 33 individuals living in couples who tested alone. Participants expressed fear of dealing with HIV-discordant relationships. Failure to self-test with a partner was correlated with gender, with more men than women overtly declining or unconsciously unable to have joint HIV self-test. Men feared exposure of infidelity and were often not available at home for economic reasons. Barriers to uptake of couple HIV self-testing seemed to be shaped by gendered dichotomies of social-relationships. To help achieve the first 90% of the UNAIDS 90:90:90 goals, it is important to overcome structural barriers to realise the full potential of HIV self-testing.

Acceptability of woman-delivered HIV self-testing to the male partner, and additional interventions: a qualitative study of antenatal care participants in Malawi.

INTRODUCTION: In the era of ambitious HIV targets, novel HIV testing models are required for hard-to-reach groups such as men, who remain underserved by existing services. Pregnancy presents a unique opportunity for partners to test for HIV, as many pregnant women will attend antenatal care (ANC). We describe the views of pregnant women and their male partners on HIV self-test kits that are woman-delivered, alone or with an additional intervention. METHODS: A formative qualitative study to inform the design of a multi-arm multi-stage cluster-randomized trial, comprised of six focus group discussions and 20 in-depth interviews, was conducted. ANC attendees were purposively sampled on the day of initial clinic visit, while men were recruited after obtaining their contact information from their female partners. Data were analysed using content analysis, and our interpretation is hypothetical as participants were not offered self-test kits. RESULTS: Providing HIV self-test kits to pregnant women to deliver to their male partners was highly acceptable to both women and men. Men preferred this approach compared with standard facility-based testing, as self-testing fits into their lifestyles which were characterized by extreme day-to-day economic pressures, including the need to raise money for food for their household daily. Men and women emphasized the need for careful communication before and after collection of the self-test kits in order to minimize the potential for intimate partner violence although physical violence was perceived as less likely to occur. Most men stated a preference to first self-test alone, followed by testing as a couple. Regarding interventions for optimizing linkage following self-testing, both men and women felt that a fixed financial incentive of approximately USD$2 would increase linkage. However, there were concerns that financial incentives of greater value may lead to multiple pregnancies and lack of child spacing. In this low-income setting, a lottery incentive was considered overly disappointing for those who receive nothing. Phone call reminders were preferred to short messaging service. CONCLUSIONS: Woman-delivered HIV self-testing through ANC was acceptable to pregnant women and their male partners. Feedback on additional linkage enablers will be used to alter pre-planned trial arms.