Accuracy of and preferences for blood-based versus oral-fluid-based HIV self-testing in Malawi: a cross-sectional study.

BACKGROUND: HIV self-testing (HIVST) can use either oral-fluid or blood-based tests. Studies have shown strong preferences for self-testing compared to facility-based services. Despite availability of low-cost blood-based HIVST options, to date, HIVST implementation in sub-Saharan Africa has largely been oral-fluid-based. We investigated whether users preferred blood-based (i.e. using blood sample derived from a finger prick) or oral fluid-based HIVST in rural and urban Malawi. METHODS: At clinics providing HIV testing services (n = 2 urban; n = 2 rural), participants completed a semi-structured questionnaire capturing sociodemographic data before choosing to test using oral-fluid-based HVST, blood-based HIVST or provider-delivered testing. They also completed a self-administered questionnaire afterwards, followed by a confirmatory test using the national algorithm then appropriate referral. We used simple and multivariable logistic regression to identify factors associated with preference for oral-fluid or blood-based HIVST. RESULTS: July to October 2018, N = 691 participants enrolled in this study. Given the choice, 98.4% (680/691) selected HIVST over provider-delivered testing. Of 680 opting for HIVST, 416 (61.2%) chose oral-fluid-based HIVST, 264 (38.8%) chose blood-based HIVST and 99.1% (674/680) reported their results appropriately. Self-testers who opted for blood-based HIVST were more likely to be male (50.3% men vs. 29.6% women, p < 0.001), attending an urban facility (43% urban vs. 34.6% rural, p = 0.025) and regular salary-earners (49.5% regular vs. 36.8% non-regular, p = 0.012). After adjustment, only sex was found to be associated with choice of self-test (adjusted OR 0.43 (95%CI: 0.3-0.61); p-value < 0.001). Among 264 reporting blood-based HIVST results, 11 (4.2%) were HIV-positive. Blood-based HIVST had sensitivity of 100% (95% CI: 71.5-100%) and specificity of 99.6% (95% CI: 97.6-100%), with 20 (7.6%) invalid results. Among 416 reporting oral-fluid-based HIVST results 18 (4.3%) were HIV-positive. Oral-fluid-based HIVST had sensitivity of 88.9% (95% CI: 65.3-98.6%) and specificity of 98.7% (95% CI: 97.1-99.6%), with no invalid results. CONCLUSIONS: Offering both blood-based and oral-fluid-based HIVST resulted in high uptake when compared directly with provider-delivered testing. Both types of self-testing achieved high accuracy among users provided with a pre-test demonstration beforehand. Policymakers and donors need to adequately plan and budget for the sensitisation and support needed to optimise the introduction of new quality-assured blood-based HIVST products.

Lessons learned from implementation of four HIV self-testing (HIVST) distribution models in Zambia: applying the Consolidated Framework for Implementation Research to understand impact of contextual factors on implementation.

BACKGROUND: Although Zambia has integrated HIV-self-testing (HIVST) into its Human Immunodeficiency Virus (HIV) regulatory frameworks, few best practices to optimize the use of HIV self-testing to increase testing coverage have been documented. We conducted a prospective case study to understand contextual factors guiding implementation of four HIVST distribution models to inform scale-up in Zambia. METHODS: We used the qualitative case study method to explore user and provider experiences with four HIVST distribution models (two secondary distribution models in Antenatal Care (ANC) and Antiretroviral Therapy (ART) clinics, community-led, and workplace) to understand factors influencing HIVST distribution. Participants were purposefully selected based on their participation in HIVST and on their ability to provide rich contextual experience of the distribution models. Data were collected using observations (n = 31), group discussions (n = 10), and in-depth interviews (n = 77). Data were analyzed using the thematic approach and aligned to the four Consolidated Framework for Implementation Research (CFIR) domains. RESULTS: Implementation of the four distribution models was influenced by an interplay of outer and inner setting factors. Inadequate compensation and incentives for distributors may have contributed to distributor attrition in the community-led and workplace HIVST models. Stockouts, experienced at the start of implementation in the secondary-distribution and community-led distribution models often disrupted distribution. The existence of policy and practices aided integration of HIVST in the workplace. External factors complimented internal factors for successful implementation. For instance, despite distributor attrition leading to excessive workload, distributors often multi-tasked to keep up with demand for kits, even though distribution points were geographically widespread in the workplace, and to a less extent in the community-led models. Use of existing communication platforms such as lunchtime and safety meetings to promote and distribute kits, peers to support distributors, reduction in trips by distributors to replenish stocks, increase in monetary incentives and reorganisation of stakeholder roles proved to be good adaptations. CONCLUSION: HIVST distribution was influenced by a combination of contextual factors in variable ways. Understanding how the factors interacted in real world settings informed adaptations to implementation devised to minimize disruptions to distribution.

Experience of social harms among female sex workers following HIV self-test distribution in Malawi: results of a cohort study.

BACKGROUND: In Malawi, female sex workers (FSW) have high HIV incidence and regular testing is suggested. HIV self-testing (HIVST) is a safe and acceptable alternative to standard testing services. This study assessed; whether social harms were more likely to be reported after HIVST distribution to FSW by peer distributors than after facility-based HIV testing and whether FSW regretted HIVST use or experienced associated relationship problems. METHODS: Peer HIVST distributors, who were FSW, were recruited in Blantyre district, Malawi between February and July 2017. Among HIVST recipients a prospective cohort was recruited. Interviews were conducted at baseline and at end-line, 3 months later. Participants completed daily sexual activity diaries. End-line data were analysed using logistic regression to assess whether regret or relationship problems were associated with HIVST use. Sexual activity data were analysed using Generalised Estimating Equations to assess whether HIVST use was temporally associated with an increase in social harms. RESULTS: Of 265 FSW recruited and offered HIVST, 131 completed both interviews. Of these, 31/131(23.7%) reported initial regret after HIVST use, this reduced to 23/131(17.6%) at the 3-month follow-up. Relationship problems were reported by 12/131(9.2%). Regret about HIVST use was less commonly reported in those aged 26-35 years compared to those aged 16-25 years (OR immediate regret-0.40 95% CI 0.16-1.01) (OR current regret-0.22 95% CI 0.07 - 0.71) and was not associated with the HIVST result. There was limited evidence that reports of verbal abuse perpetrated by clients in the week following HIVST use were greater than when there was no testing in the preceding week. There was no evidence for increases in any other social harms. There was some evidence of coercion to test, most commonly initiated by the peer distributor. CONCLUSIONS: Little evidence was found that the peer distribution model was associated with increased levels of social harms, however programmes aimed at reaching FSW need to carefully consider possible unintended consequences of their service delivery approaches, including the potential for peer distributors to coerce individuals to test or disclose their test results and alternative distribution models may need to be considered.

Costs of distributing HIV self-testing kits in Eswatini through community and workplace models.

BACKGROUND: This study evaluates the implementation and running costs of an HIV self-testing (HIVST) distribution program in Eswatini. HIVST kits were delivered through community-based and workplace models using primary and secondary distribution. Primary clients could self-test onsite or offsite. This study presents total running economic costs of kit distribution per model between April 2019 and March 2020, and estimates average cost per HIVST kit distributed, per client self-tested, per client self-tested reactive, per client confirmed positive, and per client initiating antiretroviral therapy (ART). METHODS: Distribution data and follow-up phone interviews were analysed to estimate implementation outcomes. Results were presented for each step of the care cascade using best-case and worst-case scenarios. A top-down incremental cost-analysis was conducted from the provider perspective using project expenditures. Sensitivity and scenario analyses explored effects of economic and epidemiological parameters on average costs. RESULTS: Nineteen thousand one hundred fifty-five HIVST kits were distributed to 13,031 individuals over a 12-month period, averaging 1.5 kits per recipient. 83% and 17% of kits were distributed via the community and workplace models, respectively. Clients reached via the workplace model were less likely to opt for onsite testing than clients in the community model (8% vs 29%). 6% of onsite workplace testers tested reactive compared to 2% of onsite community testers. Best-case scenario estimated 17,458 (91%) clients self-tested, 633 (4%) received reactive-test results, 606 (96%) linked to confirmatory testing, and 505 (83%) initiated ART. Personnel and HIVST kits represented 60% and 32% of total costs, respectively. Average costs were: per kit distributed US$17.23, per client tested US$18.91, per client with a reactive test US$521.54, per client confirmed positive US$550.83, and per client initiating ART US$708.60. Lower rates for testing, reactivity, and linkage to care in the worst-case scenario resulted in higher average costs along the treatment cascade. CONCLUSION: This study fills a significant evidence gap regarding costs of HIVST provision along the client care cascade in Eswatini. Workplace and community-based distribution of HIVST accompanied with effective linkage to care strategies can support countries to reach cascade objectives.

Provider and female client economic costs of integrated sexual and reproductive health and HIV services in Zimbabwe.

A retrospective facility-based costing study was undertaken to estimate the comparative cost per visit of five integrated sexual and reproductive health and HIV (human immuno-deficiency virus) services (provider perspective) within five clinic sites. These five clinics were part of four service delivery models: Non-governmental-organisation (NGO) directly managed model (Chitungwiza and New Africa House sites), NGO partner managed site (Mutare site), private-public-partnership (PPP) model (Chitungwiza Profam Clinic), and NGO directly managed outreach (operating from New Africa House site. In addition client cost exit interviews (client perspective) were conducted among 856 female clients exiting integrated services at three of the sites. Our costing approach involved first a facility bottom-up costing exercise (February to April 2015), conducted to quantify and value each resource input required to provide individual SRH and HIV services. Secondly overhead financial expenditures were allocated top-down from central office to sites and then respective integrated service based on pre-defined allocation factors derived from both the site facility observations and programme data for the prior 12 months. Costs were assessed in 2015 United States dollars (USD). Costs were assessed for HIV testing and counselling, screening and treatment of sexually transmitted infections, tuberculosis screening with smear microscopy, family planning, and cervical cancer screening and treatment employing visual inspection with acetic acid and cervicography and cryotherapy. Variability in costs per visit was evident across the models being highest for cervical cancer screening and cryotherapy (range: US$6.98-US$49.66). HIV testing and counselling showed least variability (range; US$10.96-US$16.28). In general the PPP model offered integrated services at the lowest unit costs whereas the partner managed site was highest. Significant client costs remain despite availability of integrated sexual and reproductive health and HIV services free of charge in our Zimbabwe study setting. Situating services closer to communities, incentives, transport reimbursements, reducing waiting times and co-location of sexual and reproductive health and HIV services may help minimise impact of client costs.

Do community measures impact the effectiveness of a community led HIV testing intervention. Secondary analysis of an HIV self-testing intervention in rural communities in Zimbabwe.

BACKGROUND: There is a growing body of evidence for the role that communities can have in producing beneficial health outcomes. There is also an increasing recognition of the effectiveness and success of community-led interventions to promote public health efforts. This study investigated whether and how community-level measures facilitate a community-led intervention to achieve improved HIV outcomes. METHODS: This is a secondary analysis of survey data from a cluster randomised trial in 40 rural communities in Zimbabwe. The survey was conducted four months after the intervention was initiated. Communities were randomised 1:1 to either paid distribution arm, where HIV self-test (HIVST) kits were distributed by a paid distributor, or community-led whereby members of the community were responsible for organising and conducting the distribution of HIVST kits. We used mixed effects logistic regression to assess the effect of social cohesion, problem solving, and HIV awareness on HIV testing and prevention. RESULTS: We found no association between community measures and the three HIV outcomes (self-testing, new HIV diagnosis and linkage to VMMC or confirmatory testing). However, the interaction analyses highlighted that in high social cohesion communities, the odds of new HIV diagnosis was greater in the community-led arm than paid distribution arm (OR 2.06 95% CI 1.03-4.19). CONCLUSION: We found some evidence that community-led interventions reached more undiagnosed people living with HIV in places with high social cohesion. Additional research should seek to understand whether the effect of social cohesion is persistent across other community interventions and outcomes. TRIAL REGISTRATION: PACTR201607001701788.

Preferences for oral-fluid-based or blood-based HIV self-testing and provider-delivered testing: an observational study among different populations in Zimbabwe.

BACKGROUND: There is limited data on client preferences for different HIV self-testing (HIVST) and provider-delivered testing options and associated factors. We explored client preferences for oral-fluid-based self-testing (OFBST), blood-based self-testing (BBST) and provider-delivered blood-based testing (PDBBT) among different populations. METHODS: At clinics providing HIV testing services to general populations (1 urban, 1 rural clinic), men seeking voluntary medical male circumcision (VMMC, 1 clinic), and female sex workers (FSW, 1 clinic), clients had the option to test using OFBST, BBST or PDBBT. A pre-test questionnaire collected information on demographics and testing history. Two weeks after collecting a self-test kit, participants responded to a questionnaire. We used logistic regression to determine predictors of choices. We also conducted 20 in-depth interviews to contextualise quantitative findings. RESULTS: May to June 2019, we recruited 1244 participants of whom 249 (20%), 251 (20%), 244 (20%) and 500 (40%) were attending urban general, rural, VMMC and FSW clinics, respectively. Half (n = 619, 50%) chose OFBST, 440 (35%) and 185 (15%) chose BBST and PDBBT, respectively. In multivariable analysis comparing those choosing HIVST (OFBST and BBST combined) versus not, those who had never married aOR 0.57 (95% CI 0.34-0.93) and those previously married aOR0.56 (0.34-0.93) were less likely versus married participants to choose HIVST. HIVST preference increased with education, aOR 2.00 (1.28-3.13), 2.55 (1.28-5.07), 2.76 (1.48-5.14) for ordinary, advanced and tertiary education, respectively versus none/primary education. HIVST preference decreased with age aOR 0.97 (0.96-0.99). Urban participants were more likely than rural ones to choose HIVST, aOR 9.77 (5.47-17.41), 3.38 (2.03-5.62) and 2.23 (1.38-3.61) for FSW, urban general and VMMC clients, respectively. Comparing those choosing OFBST with those choosing BBST, less literate participants were less likely to choose oral fluid tests, aOR 0.29 (0.09-0.92). CONCLUSIONS: Most testing clients opted for OFBST, followed by BBST and lastly, PDBBT. Those who self-assessed as less healthy were more likely to opt for PDBBT which likely facilitated linkage. Results show importance of continued provision of all strategies in order to meet needs of different populations, and may be useful to inform both HIVST kit stock projections and tailoring of HIVST programs to meet the needs of different populations.

Equipping providers to offer novel MPTs: Developing counseling messages for the Dual Prevention Pill in clinical studies and beyond.

Introduction: The pipeline for multi-purpose prevention technologies includes products that simultaneously prevent HIV, pregnancy and/or other sexually transmitted infections. Among these, the Dual Prevention Pill (DPP) is a daily pill co-formulating oral pre-exposure prophylaxis (PrEP), and combined oral contraception (COC). Clinical cross-over acceptability studies for the DPP require training providers to counsel on a combined product. From February 2021-April 2022, a working group of eight HIV and FP experts with clinical and implementation expertise developed counseling recommendations for the DPP based on existing PrEP/COC guidance. Assessment of policy/guidelines options and implications: The working group conducted a mapping of counseling messages from COC and oral PrEP guidance and provider training materials. Six topics were prioritized: uptake, missed pills, side effects, discontinuation and switching, drug interactions and monitoring. Additional evidence and experts were consulted to answer outstanding questions and counseling recommendations for the DPP were developed. Missed pills was the topic with the most complexity, raising questions about whether women could "double up" on missed pills or skip the last week of the pack to recover protection faster. Uptake required aligning the time to reach protective levels for both DPP components and explaining the need to take DPP pills during week 4 of the pack. The potential intensity of DPP side effects, given the combination of oral PrEP with COC, was an important consideration. Discontinuation and switching looked at managing risk of HIV and unintended pregnancy when stopping or switching from the DPP. Guidance on drug interactions contended with differing contraindications for COC and PrEP. Monitoring required balancing clinical requirements with potential user burden. Actionable recommendations: The working group developed counseling recommendations for the DPP to be tested in clinical acceptability studies. Uptake: Take one pill every day for the DPP until the pack is empty. Days 1-21 contain COC and oral PrEP. Days 22-28 do not contain COC to allow for monthly bleeding, but do contain oral PrEP and pills should be taken to maintain HIV protection. Take the DPP for 7 consecutive days to reach protective levels against pregnancy and HIV. Missed pills: If you miss 1 pill multiple times in a month or 2+ consecutive pills, take the DPP as soon as you remember. Do not take more than 2 pills in a day. If 2+ consecutive pills are missed, only take the last missed pill and discard the other missed pills. Side effects: You may experience side effects when you start using the DPP, including changes to monthly bleeding. Side effects are typically mild and go away without treatment. Discontinuation/switching: If you decide to discontinue use of the DPP, but want to be protected from HIV and/or unintended pregnancy, in most cases, you can begin using PrEP or another contraceptive method right away. Drug interactions: There are no drug-drug interactions from combining oral PrEP and COC in the DPP. Certain medications are not recommended due to their contraindication with oral PrEP or COC. Monitoring: You will need to get an HIV test prior to initiating or restarting the DPP, and every 3 months during DPP use. Your provider may recommend other screening or testing. Discussion: Developing recommendations for the DPP as a novel MPT posed unique challenges, with implications for efficacy, cost, and user and provider comprehension and burden. Incorporating counseling recommendations into clinical cross-over acceptability studies allows for real-time feedback from providers and users. Supporting women with information to use the DPP correctly and confidently is critically important for eventual scale and commercialization.

Secondary distribution of HIV self-test kits by HIV index and antenatal care clients: implementation and costing results from the STAR Initiative in South Africa.

BACKGROUND: Partner-delivered HIV self-testing kits has previously been highlighted as a safe, acceptable and effective approach to reach men. However, less is known about its real-world implementation in reaching partners of people living with HIV. We evaluated programmatic implementation of partner-delivered self-testing through antenatal care (ANC) attendees and people newly diagnosed with HIV by assessing use, positivity, linkage and cost per kit distributed. METHODS: Between April 2018 and December 2019, antenatal care (ANC) clinic attendees and people or those newly diagnosed with HIV clients across twelve clinics in three cities in South Africa were given HIVST kits (OraQuick Rapid HIV-1/2 Antibody Test, OraSure Technologies) to distribute to their sexual partners. A follow-up telephonic survey was administered to all prior consenting clients who were successfully reached by telephone to assess primary outcomes. Incremental economic costs of the implementation were estimated from the provider's perspective. RESULTS: Fourteen thousand four hundred seventy-three HIVST kits were distributed - 10,319 (71%) to ANC clients for their male partner and 29% to people newly diagnosed with HIV for their partners. Of the 4,235 ANC clients successfully followed-up, 82.1% (3,475) reportedly offered HIVST kits to their male partner with 98.1% (3,409) accepting and 97.6% (3,328) using the kit. Among ANC partners self-testing, 159 (4.8%) reported reactive HIVST results, of which 127 (79.9%) received further testing; 116 (91.3%) were diagnosed with HIV and 114 (98.3%) initiated antiretroviral therapy (ART). Of the 1,649 people newly diagnosed with HIV successfully followed-up; 1,312 (79.6%) reportedly offered HIVST kits to their partners with 95.8% (1,257) of the partners accepting and 95.9% (1,206) reported that their partners used the kit. Among these index partners, 297 (24.6%) reported reactive HIVST results of which 261 (87.9%) received further testing; 260 (99.6%) were diagnosed with HIV and 258 (99.2%) initiated ART. The average cost per HIVST distributed in the three cities was US$7.90, US$11.98, and US$14.81, respectively. CONCLUSIONS: Partner-delivered HIVST in real world implementation was able to affordably reach many male partners of ANC attendees and index partners of people newly diagnosed with HIV in South Africa. Given recent COVID-19 related restrictions, partner-delivered HIVST provides an important strategy to maintain essential testing services.

Cost-effectiveness of voluntary medical male circumcision for HIV prevention across sub-Saharan Africa: results from five independent models.

BACKGROUND: Voluntary medical male circumcision (VMMC) has been a recommended HIV prevention strategy in sub-Saharan Africa since 2007, particularly in countries with high HIV prevalence. However, given the scale-up of antiretroviral therapy programmes, it is not clear whether VMMC still represents a cost-effective use of scarce HIV programme resources. METHODS: Using five existing well described HIV mathematical models, we compared continuation of VMMC for 5 years in men aged 15 years and older to no further VMMC in South Africa, Malawi, and Zimbabwe and across a range of setting scenarios in sub-Saharan Africa. Outputs were based on a 50-year time horizon, VMMC cost was assumed to be US$90, and a cost-effectiveness threshold of US$500 was used. FINDINGS: In South Africa and Malawi, the continuation of VMMC for 5 years resulted in cost savings and health benefits (infections and disability-adjusted life-years averted) according to all models. Of the two models modelling Zimbabwe, the continuation of VMMC for 5 years resulted in cost savings and health benefits by one model but was not as cost-effective according to the other model. Continuation of VMMC was cost-effective in 68% of setting scenarios across sub-Saharan Africa. VMMC was more likely to be cost-effective in modelled settings with higher HIV incidence; VMMC was cost-effective in 62% of settings with HIV incidence of less than 0·1 per 100 person-years in men aged 15-49 years, increasing to 95% with HIV incidence greater than 1·0 per 100 person-years. INTERPRETATION: VMMC remains a cost-effective, often cost-saving, prevention intervention in sub-Saharan Africa for at least the next 5 years. FUNDING: Bill & Melinda Gates Foundation for the HIV Modelling Consortium.

Engagement in HIV services over time among young women who sell sex in Zimbabwe.

INTRODUCTION: Young female sex workers (FSW) are disproportionately vulnerable to HIV. Zimbabwe data show higher HIV incidence and lower engagement in services compared to older FSW. Utilizing data from a combination HIV prevention and treatment intervention, we describe engagement in the HIV services over time among FSW 18-24 years, compared to those ≥25 years of age. MATERIALS AND METHODS: Data were collected via respondent-driven sampling (RDS) surveys in 14 communities in 2013 and 2016, with >2500 FSW per survey. They included blood samples for HIV and viral load testing. As the intervention had no significant impact on HIV care cascade outcomes, data were aggregated across study arms. Analyses used RDS-II estimation. RESULTS: Mean age in 2013 and 2016 was 31 and 33 years, with 27% and 17% aged 18-24 years. Overall HIV prevalence was 59% at each timepoint, and 35% and 36% among younger FSW. From 2013 to 2016 there was an increase in young HIV-positive FSW knowing their status (38% vs 60%, OR = 2.51, p<0.01). Outcomes for all FSW improved significantly over time at all steps of the cascade, and the relative change over time was similar among older versus younger FSW for most cascade variables. DISCUSSION: Young FSW had improvements in care cascade outcomes, and proportionate improvements similar to older FSW, yet they remain less engaged in services overall. This implies that the dedicated FSW services in Zimbabwe are having a comparably positive impact across age groups, however more is likely required to address young FSW's unique vulnerabilities and needs.

Sensitivity and specificity of OraQuick® HIV self-test compared to a 4th generation laboratory reference standard algorithm in urban and rural Zambia.

BACKGROUND: HIV self-testing (HIVST) has the potential to increase coverage of HIV testing, but concerns exist about intended users' ability to correctly perform and interpret tests, especially in poor communities with low literacy rates. We assessed the clinical performance of the 2016 prototype OraQuick® HIV Self-Test in rural and urban communities in Zambia to assess the sensitivity and specificity of the test compared to the national HIV rapid diagnostic test (RDT) algorithm and a laboratory reference standard using 4th generation enzyme immunoassays and HIV RNA detection. METHODS: Participants were recruited from randomly selected rural and urban households and one urban health facility between May 2016 and June 2017. Participants received a brief demonstration of the self-test, and then self-tested without further assistance. The research team re-read the self-test, repeated the self-test, drew blood for the laboratory reference, and conducted RDTs following the national HIV testing algorithm (Determine™ HIV1/2 (Alere) confirmed using Unigold™ HIV1/2 (Trinity Biotech)). Selected participants (N = 85) were videotaped whilst conducting the testing to observe common errors. RESULTS: Initial piloting showed that written instructions alone were inadequate, and a demonstration of self-test use was required. Of 2,566 self-test users, 2,557 (99.6%) were able to interpret their result. Of participants who were videoed 75/84 (89.3%) completed all steps of the procedure correctly. Agreement between the user-read result and the researcher-read result was 99.1%. Compared to the RDT algorithm, user-conducted HIVST was 94.1% sensitive (95%CI: 90.2-96.7) and 99.7% specific (95%CI: 99.3-99.9). Compared to the laboratory reference, both user-conducted HIVST (sensitivity 87.5%, 95%CI: 82.70-91.3; specificity 99.7%, 95%CI: 99.4-99.9) and the national RDT algorithm (sensitivity 93.4%, 95%CI: 89.7-96.1%; specificity 100% (95%CI: 99.8-100%) had considerably lower sensitivity. CONCLUSIONS: Self-testers in Zambia who used OraQuick® HIV Self-Test achieved reasonable clinical performance compared to the national RDT algorithm. However, sensitivity of the self-test was reduced compared to a laboratory reference standard, as was the national RDT algorithm. In-person demonstration, along with the written manufacturer instructions, was needed to obtain accurate results. Programmes introducing self-care diagnostics should pilot and optimise support materials to ensure they are appropriately adapted to context.

"You have a self-testing method that preserves privacy so how come you cannot give us treatment that does too?" Exploring the reasoning among young people about linkage to prevention, care and treatment after HIV self-testing in Southern Malawi.

BACKGROUND: Young people, aged 16-24, in southern Malawi have high uptake of HIV self-testing (HIVST) but low rates of linking to services following HIVST, especially in comparison, to older generations. The study aim is to explore the barriers and facilitators to linkage for HIV prevention and care following uptake of HIV self-testing among young Malawians. METHODS: We used qualitative methods. Young people aged 16-24 who had received HIVST; community-based distribution agents (CBDAs) and health care workers from the linked facilities were purposively sampled from two villages in rural southern Malawi. RESULTS: We conducted in-depth interviews with thirteen young people (9 female) and held four focus groups with 28 healthcare workers and CBDAs. Young people strongly felt the social consequences associated with inadvertent disclosure of HIV sero-status were a significant deterrent to linkage at their stage in life. They also felt communication on testing benefits and the referral process after testing was poor. In contrast, they valued encouragement from those they trusted, other's positive treatment experiences and having a "strength of mind". CBDAs were important facilitators for young people as they are able to foster a trusting relationship and had more understanding of the factors which prevented young people from linking following HIVST than the healthcare workers. Young people noted contextual barriers to linkage, for example, being seen on the road to the healthcare centre, but also societal gendered barriers. For example, young females and younger adolescents were less likely to have the financial independence to link to services whilst young males (aged 19-24) had the finances but lacked a supportive network to encourage linkage following testing. Overall, it was felt that the primary "responsibility" for linking to formal healthcare following self-testing is shouldered by the young person and not the healthcare system. CONCLUSIONS: Young people are happy to self-test for HIV but faced barriers to link to services following a self-test. Potential interventions for improving linkage suggested by this analysis include the establishment of youth-friendly linkage services, enhanced lines of communication between young people and healthcare providers and prioritising linkage for future interventions when targeting young people following HIVST.

Process evaluation of peer-to-peer delivery of HIV self-testing and sexual health information to support HIV prevention among youth in rural KwaZulu-Natal, South Africa: qualitative analysis.

OBJECTIVE: Peer-to-peer (PTP) HIV self-testing (HIVST) distribution models can increase uptake of HIV testing and potentially create demand for HIV treatment and pre-exposure prophylaxis (PrEP). We describe the acceptability and experiences of young women and men participating in a cluster randomised trial of PTP HIVST distribution and antiretroviral/PrEP promotion in rural KwaZulu-Natal. METHODS: Between March and September 2019, 24 pairs of trained peer navigators were randomised to two approaches to distribute HIVST packs (kits+HIV prevention information): incentivised-peer-networks where peer-age friends distributed packs within their social network for a small incentive, or direct distribution where peer navigators distributed HIVST packs directly. Standard-of-care peer navigators distributed information without HIVST kits. For the process evaluation, we conducted semi-structured interviews with purposively sampled young women (n=30) and men (n=15) aged 18-29 years from all arms. Qualitative data were transcribed, translated, coded manually and thematically analysed using an interpretivist approach. RESULTS: Overall, PTP approaches were acceptable and valued by young people. Participants were comfortable sharing sexual health issues they would not share with adults. Coupled with HIVST, peer (friends) support facilitated HIV testing and solidarity for HIV status disclosure and treatment. However, some young people showed limited interest in other sexual health information provided. Some young people were wary of receiving health information from friends perceived as non-professionals while others avoided sharing personal issues with peer navigators from their community. Referral slips and youth-friendly clinics were facilitators to PrEP uptake. Family disapproval, limited information, daily pills and perceived risks were major barriers to PrEP uptake. CONCLUSION: Both professional (peer navigators) and social network (friends) approaches were acceptable methods to receive HIVST and sexual health information. Doubts about the professionalism of friends and overly exclusive focus on HIVST information materials may in part explain why HIVST kits, without peer navigators support, did not create demand for PrEP.

Did you hear about HIV self-testing? HIV self-testing awareness after community-based HIVST distribution in rural Zimbabwe.

BACKGROUND: Several trials of community-based HIV self-testing (HIVST) provide evidence on the acceptability and feasibility of campaign-style distribution to reach first-time testers, men and adolescents. However, we do not know how many remain unaware of HIVST after distribution campaigns, and who these individuals are. Here we look at factors associated with never having heard of HIVST after community-based campaign-style HIVST distribution in rural Zimbabwe between September 2016 and July 2017. METHODS: Analysis of representative population-based trial survey data collected from 7146 individuals following community-based HIVST distribution to households was conducted. Factors associated with having never heard of HIVST were determined using multivariable mixed-effects logistic regression adjusted for clustered design. RESULTS: Among survey participants, 1308 (18.3%) self-reported having never heard of HIVST. Individuals who were between 20 and 60 years old {20-29 years: [aOR = 0.74, 95% CI (0.58-0.95)], 30-39 years: [aOR = 0.56, 95% CI (0.42-0.74)], 40-49 years: [aOR = 0.50, 95% CI (0.36-0.68)], 50-59 years [aOR = 0.58, 95% CI (0.42-0.82)]}, who had attained at least ordinary level education [aOR = 0.51, 95% CI (0.34-0.76)], and who had an HIV test before [aOR = 0.30, 95% CI (0.25-0.37)] were less likely to have never heard of HIVST compared with individuals who were between 16 and 19 years old, who had a lower educational level and who had never tested for HIV before, respectively. In addition, non-household heads or household head representatives [aOR = 1.21, 95% CI (1.01-1.45)] were more likely to report never having heard of HIVST compared to household head and representatives. CONCLUSIONS: Around one fifth of survey participants remain unaware of HIVST even after an intensive community-based door-to-door HIVST distribution. Of note, those least likely to have heard of self-testing were younger, less educated and less likely to have tested previously. Household heads appear to play an important role in granting or denying access to self-testing to other household members during door-to-door distribution. Differentiated distribution models are needed to ensure access to all. Trial registration PACTR, PACTR201607001701788. Registered 29 June 2016, https://pactr.samrc.ac.za/ PACTR201607001701788.

Understanding mechanisms of impact from community-led delivery of HIV self-testing: Mediation analysis of a cluster-randomised trial in Malawi.

Community HIV strategies are important for early diagnosis and treatment, with new self-care technologies expanding the types of services that can be led by communities. We evaluated mechanisms underlying the impact of community-led delivery of HIV self-testing (HIVST) using mediation analysis. We conducted a cluster-randomised trial allocating 30 group village heads and their catchment areas to the community-led HIVST intervention in addition to the standard of care (SOC) or the SOC alone. The intervention used participatory approaches to engage established community health groups to lead the design and implementation of HIVST campaigns. Potential mediators (individual perceptions of social cohesion, shared HIV concern, critical consciousness, community HIV stigma) and the outcome (HIV testing in the last 3 months) were measured through a post-intervention survey. Analysis used regression-based models to test (i) intervention-mediator effects, (ii) mediator-outcome effects, and (iii) direct and indirect effects. The survey included 972 and 924 participants in the community-led HIVST and SOC clusters, respectively. The community-led HIVST intervention increased uptake of recent HIV testing, with no evidence of indirect effects from changes in hypothesised mediators. However, standardised scores for community cohesion (adjusted mean difference [MD] 0.15, 95% CI -0.03 to 0.32, p = 0.10) and shared concern for HIV (adjusted MD 0.13, 95% CI -0.02 to 0.29, p = 0.09) were slightly higher in the community-led HIVST arm than the SOC arm. Social cohesion, community concern, and critical consciousness also apparently had a quadratic association with recent testing in the community-led HIVST arm, with a positive relationship indicated at lower ranges of each score. We found no evidence of intervention effects on community HIV stigma and its association with recent testing. We conclude that the intervention effect mostly operated directly through community-driven service delivery of a novel HIV technology rather than through intermediate effects on perceived community mobilisation and HIV stigma.

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.

Community-based HIV self-testing: a cluster-randomised trial of supply-side financial incentives and time-trend analysis of linkage to antiretroviral therapy in Zimbabwe.

BACKGROUND: HIV self-testing (HIVST) requires linkage to post-test services to maximise its benefits. We evaluated effect of supply-side incentivisation on linkage following community-based HIVST and evaluated time-trends in facility-based antiretroviral therapy (ART) initiations. METHODS: From August 2016 to August 2017 community-based distributors (CBDs) in 38 rural Zimbabwean communities distributed HIVST door-to-door in 19-25 day campaigns. Communities were allocated (1:1) using constrained randomisation to either one-off US$50 remuneration per CBD (non-incentive arm), or US$50 plus US$0.20 incentive per client visiting mobile-outreach services (conditional-incentive arm). The primary outcome, assessed by population survey 6 weeks later, was self-reported uptake of any clinic service, analysed with random-effects logistic regression. Separately, non-randomised difference-in-differences in monthly ART initiations were analysed for three time periods (6 months baseline; HIVST campaign; 3 months after) at public clinics with (40 clinics) and without (124 clinics) HIVST distribution in catchment area. FINDINGS: A total of 445 conditional-incentive CBDs distributed 39 205 HIVST kits (mean/CBD: 88; 95% CI: 85 to 92) and 447 non-incentive CBDs distributed 41 173 kits (mean/CBD: 93; 95% CI: 89 to 96). Survey participation was 7146/8566 (83.4%), with 3593 (50.3%) reporting self-testing including 1305 (18.3%) previously untested individuals. Use of clinic services post-HIVST was similar in conditional-incentive (1062/3698, 28.7%) and non-incentive (1075/3448, 31.2%) arms (adjusted risk ratio (aRR) 0.94, 95% CI: 0.86 to 1.03). Confirmatory testing by newly diagnosed/untreated HIVST+clients was, however, higher (conditional-incentive: 25/33, 75.8% vs non-incentive: 20/40, 50.0%: aRR: 1.59, 95% CI: 1.05 to 2.39). In total, 12 808 ART initiations occurred, with no baseline or postcampaign differences between initiation rates in HIVST versus non-HIVST clinics, but initiation rates increased from 7.31 to 9.59 initiations per month in HIVST clinics during distribution, aRR: 1.27, 95% CI 1.17 to 1.39. CONCLUSIONS: Community-based HIVST campaigns achieved high testing uptake, temporally associated with increased demand for ART. Small supply-side incentives did not affect general clinic usage but may have increased confirmatory testing for newly diagnosed HIVST positive participants. TRIAL REGISTRATION NUMBER: PACTR201607001701788.

Effect of door-to-door distribution of HIV self-testing kits on HIV testing and antiretroviral therapy initiation: a cluster randomised trial in Malawi.

INTRODUCTION: Reaching high coverage of HIV testing remains essential for HIV diagnosis, treatment and prevention. We evaluated the effectiveness and safety of door-to-door distribution of HIV self-testing (HIVST) kits in rural Malawi. METHODS: This cluster randomised trial, conducted between September 2016 and January 2018, used restricted 1:1 randomisation to allocate 22 health facilities and their defined areas to door-to-door HIVST alongside the standard of care (SOC) or the SOC alone. The study population included residents (≥16 years). HIVST kits were provided door-to-door by community-based distribution agents (CBDAs) for at least 12 months. The primary outcome was recent HIV testing (in the last 12 months) measured through an endline survey. Secondary outcomes were lifetime HIV testing and cumulative 16-month antiretroviral therapy (ART) initiations, which were captured at health facilities. Social harms were reported through community reporting systems. Analysis compared cluster-level outcomes by arm. RESULTS: Overall, 203 CBDAs distributed 273 729 HIVST kits. The endline survey included 2582 participants in 11 HIVST clusters and 2908 participants in 11 SOC clusters. Recent testing was higher in the HIVST arm (68.5%, 1768/2582) than the SOC arm (48.9%, 1422/2908), with adjusted risk difference (RD) of 16.1% (95% CI 6.5% to 25.7%). Lifetime testing was also higher in the HIVST arm (86.9%, 2243/2582) compared with the SOC arm (78.5%, 2283/2908; adjusted RD 6.3%, 95% CI 2.3% to 10.3%). Differences were most pronounced for adolescents aged 16-19 years (adjusted RD 18.6%, 95% CI 7.3% to 29.9%) and men (adjusted RD 10.2%, 95% CI 3.1% to 17.2%). Cumulative incidence of ART initiation was 1187.2 and 909.0 per 100 000 population in the HIVST and SOC arms, respectively (adjusted RD 309.1, 95% CI -95.5 to 713.7). Self-reported HIVST use was 42.5% (1097/2582), with minimal social harms reported. CONCLUSION: Door-to-door HIVST increased recent and lifetime testing at population level and showed high safety, underscoring potential for HIVST to contribute to HIV elimination goals in priority settings. TRIAL REGISTRATION NUMBER: NCT02718274.

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).