Scaling up HIV self-testing in sub-Saharan Africa: a review of technology, policy and evidence.

PURPOSE OF REVIEW: HIV self-testing (HIVST) can provide complementary coverage to existing HIV testing services and improve knowledge of status among HIV-infected individuals. This review summarizes the current technology, policy and evidence landscape in sub-Saharan Africa and priorities within a rapidly evolving field. RECENT FINDINGS: HIVST is moving towards scaled implementation, with the release of WHO guidelines, WHO prequalification of the first HIVST product, price reductions of HIVST products and a growing product pipeline. Multicountry evidence from southern and eastern Africa confirms high feasibility, acceptability and accuracy across many delivery models and populations, with minimal harms. Evidence on the effectiveness of HIVST on increased testing coverage is strong, while evidence on demand generation for follow-on HIV prevention and treatment services and cost-effective delivery is emerging. Despite these developments, HIVST delivery remains limited outside of pilot implementation. SUMMARY: Important technology gaps include increasing availability of more sensitive HIVST products in low and middle-income countries. Regulatory and postmarket surveillance systems for HIVST also require further development. Randomized trials evaluating the effectiveness and cost-effectiveness under multiple distribution models, including unrestricted delivery and with a focus on linkage to HIV prevention and treatment, remain priorities. Diversification of studies from west and central Africa and around blood-based products should be addressed

Uncertainty in tuberculosis clinical decision-making: An umbrella review with systematic methods and thematic analysis

Tuberculosis is a major infectious disease worldwide, but currently available diagnostics have suboptimal accuracy, particularly in patients unable to expectorate, and are often unavailable at the point-of-care in resource-limited settings. Test/treatment decision are, therefore, often made on clinical grounds. We hypothesized that contextual factors beyond disease probability may influence clinical decisions about when to test and when to treat for tuberculosis. This umbrella review aimed to identify such factors, and to develop a framework for uncertainty in tuberculosis clinical decision-making. Systematic reviews were searched in seven databases (MEDLINE, CINAHL Complete, Embase, Scopus, Cochrane, PROSPERO, Epistemonikos) using predetermined search criteria. Findings were classified as barriers and facilitators for testing or treatment decisions, and thematically analysed based on a multi-level model of uncertainty in health care. We included 27 reviews. Study designs and primary aims were heterogeneous, with seven meta-analyses and three qualitative evidence syntheses. Facilitators for decisions to test included providers’ advanced professional qualification and confidence in tests results, availability of automated diagnostics with quick turnaround times. Common barriers for requesting a diagnostic test included: poor provider tuberculosis knowledge, fear of acquiring tuberculosis through respiratory sampling, scarcity of healthcare resources, and complexity of specimen collection. Facilitators for empiric treatment included patients’ young age, severe sickness, and test inaccessibility. Main barriers to treatment included communication obstacles, providers’ high confidence in negative test results (irrespective of negative predictive value). Multiple sources of uncertainty were identified at the patient, provider, diagnostic test, and healthcare system levels. Complex determinants of uncertainty influenced decision-making. This could result in delayed or missed diagnosis and treatment opportunities. It is important to understand the variability associated with patient-provider clinical encounters and healthcare settings, clinicians’ attitudes, and experiences, as well as diagnostic test characteristics, to improve clinical practices, and allow an impactful introduction of novel diagnostics

'I will choose when to test, where I want to test': investigating young people's preferences for HIV self-testing in Malawi and Zimbabwe.

OBJECTIVES: The current study identifies young people's preferences for HIV self-testing (HIVST) delivery, determines the relative strength of preferences and explores underlying behaviors and perceptions to inform youth-friendly services in southern Africa. DESIGN: A mixed methods design was adopted in Malawi and Zimbabwe and includes focus group discussions, in-depth interviews and discrete choice experiments. METHODS: The current study was conducted during the formative phase of cluster-randomized trials of oral-fluid HIVST distribution. Young people aged 16-25 years were purposively selected for in-depth interviews (n = 15) in Malawi and 12 focus group discussions (n = 107) across countries. Representative samples of young people in both countries (n = 341) were administered discrete choice experiments on HIVST delivery, with data analyzed to estimate relative preferences. The qualitative results provided additional depth and were triangulated with the quantitative findings. RESULTS: There was strong concordance across methods and countries based on the three triangulation parameters: product, provider and service characteristics. HIVST was highly accepted by young people, if provided at no or very low cost. Young people expressed mixed views on oral-fluid tests, weighing perceived benefits with accuracy concerns. There was an expressed lack of trust in health providers and preference for lay community distributors. HIVST addressed youth-specific barriers to standard HIV testing, with home-based distribution considered convenient. Issues of autonomy, control, respect and confidentiality emerged as key qualitative themes. CONCLUSION: HIVST services can be optimized to reach young people if products are provided through home-based distribution and at low prices, with respect for them as autonomous individuals

HIV self-testing services for female sex workers, Malawi and Zimbabwe

OBJECTIVE: To present findings from implementation and scale-up of human immunodeficiency virus (HIV) self-testing programmes for female sex workers in Malawi and Zimbabwe, 2013-2018. METHODS: In Zimbabwe, we carried out formative research to assess the acceptability and accuracy of HIV self-testing. During implementation we evaluated sex workers' preferences for, and feasibility of, distribution of test kits before the programme was scaled-up. In Malawi, we conducted a rapid ethnographic assessment to explore the context and needs of female sex workers and resources available, leading to a workshop to define the distribution approach for test kits. Once distribution was implemented, we conducted a process evaluation and established a system for monitoring social harm. FINDINGS: In Zimbabwe, female sex workers were able to accurately self-test. The preference study helped to refine systems for national scale-up through existing services for female sex workers. The qualitative data helped to identify additional distribution strategies and mediate potential social harm to women. In Malawi, peer distribution of test kits was the preferred strategy. We identified some incidents of social harm among peer distributors and female sex workers, as well as supply-side barriers to implementation which hindered uptake of testing. CONCLUSION: Involving female sex workers in planning and ongoing implementation of HIV self-testing is essential, along with strategies to mitigate potential harm. Optimal strategies for distribution and post-test support are context-specific and need to consider existing support for female sex workers and levels of trust and cohesion within their communities

Costs and Cost-Effectiveness of Biomedical, Non-Surgical HIV Prevention Interventions: A Systematic Literature Review.

BACKGROUND: Considerable evidence on the costs and cost-effectiveness of biomedical, non-surgical interventions to prevent human immunodeficiency virus (HIV) transmission has been generated over the last decade. This study aims to synthesize findings and identify remaining knowledge gaps to suggest future research priorities. METHODS: A systematic literature review was carried out in August 2020 using the MEDLINE, Embase, Global Health and EconLit databases to retrieve economic evaluations and costing studies of oral pre-exposure prophylaxis (PrEP), injectable long-acting PrEP, vaginal microbicide rings and gels, HIV vaccines and broadly neutralizing antibodies. Studies reporting costs from the provider or societal perspective were included in the analysis. Those reporting on behavioural methods of prevention, condoms and surgical approaches (voluntary medical male circumcision) were excluded. The quality of reporting of the included studies was assessed using published checklists. RESULTS: We identified 3007 citations, of which 87 studies were retained. Most were set in low- and middle-income countries (LMICs; n = 53) and focused on the costs and/or cost-effectiveness of oral PrEP regimens (n = 70). Model-based economic evaluations were the most frequent study design; only two trial-based cost-effectiveness analyses and nine costing studies were found. Less than half of the studies provided practical details on how the intervention would be delivered by the health system, and only three of these, all in LMICs, explicitly focused on service integration and its implication for delivery costs. 'Real-world' programme delivery mechanisms and costs of intervention delivery were rarely considered. PrEP technologies were generally found to be cost-effective only when targeting high-risk subpopulations. Single-dose HIV vaccines are expected to be cost-effective for all groups despite substantial uncertainty around pricing. CONCLUSIONS: A lack of primary, detailed and updated cost data, including above-service level costs, from a variety of settings makes it difficult to evaluate the cost-effectiveness of specific delivery modes at scale, or to evaluate strategies for services integration. Closing this evidence gap around real-world implementation is vital, not least because the strategies targeting high-risk groups that are recommended by PrEP models may incur substantially higher costs and be of limited practical feasibility in some settings

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

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

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 accessing HIV testing services among rural Malawi communities

ABSTRACTHIV testing is free in Malawi, but users may still incur costs that can deter or delay them accessing these services. We sought to identify and quantify these costs among HIV testing service clients in Malawi. We asked residents of communities participating in a cluster randomised trial investigating the impact of HIV self-testing about their past HIV testing experiences and the direct non-medical and indirect costs incurred to access HIV testing. We recruited 749 participants whose most recent HIV test was within the past 12 months. The mean total cost to access testing was US$2.45 (95$2.11–US$2.70). Men incurred higher costs (US$3.81; 95%CI: US$2.91–US$4.50) than women (US$1.83; 95$1.61–US$2.00). Results from a two-part multivariable regression analysis suggest that age, testing location, time taken to test, visiting a facility specifically for an HIV test and district of residence significantly affected the odds of incurring costs to testing. In addition, gender, wealth, age, education and district of residence were associated with significant user costs

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