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

Investigating interventions to increase uptake of HIV testing and linkage into care or prevention for male partners of pregnant women in antenatal clinics in Blantyre, Malawi: study protocol for a cluster randomised trial.

BACKGROUND: Despite large-scale efforts to diagnose people living with HIV, 54% remain undiagnosed in sub-Saharan Africa. The gap in knowledge of HIV status and uptake of follow-on services remains wide with much lower rates of HIV testing among men compared to women. Here, we design a study to investigate the effect on uptake of HIV testing and linkage into care or prevention of partner-delivered HIV self-testing alone or with an additional intervention among male partners of pregnant women. METHODS: A phase II, adaptive, multi-arm, multi-stage cluster randomised trial, randomising antenatal clinic (ANC) days to six different trial arms. Pregnant women accessing ANC in urban Malawi for the first time will be recruited into either the standard of care (SOC) arm (invitation letter to the male partner offering HIV testing) or one of five intervention arms offering oral HIV self-test kits. Three of the five intervention arms will additionally offer the male partner a financial incentive (fixed or lottery amount) conditional on linkage after self-testing with one arm testing phone call reminders. Assuming that 25% of male partners link to care or prevention in the SOC arm, six clinic days, with a harmonic mean of 21 eligible participants, per arm will provide 80% power to detect a 0.15 absolute difference in the primary outcome. Cluster proportions will be analysed by a cluster summaries approach with adjustment for clustering and multiplicity. DISCUSSION: This trial applies adaptive methods which are novel and efficient designs. The methodology and lessons learned here will be important as proof of concept of how to design and conduct similar studies in the future. Although small, this trial will potentially present good evidence on the type of effective interventions for improving linkage into ART or prevention. The trial results will also have important policy implications on how to implement HIVST targeting male partners of pregnant women who are accessing ANC for the first time while paying particular attention to safety concerns. Contamination may occur if women in the intervention arms share their self-test kits with women in the SOC arm. TRIAL REGISTRATION: ISRCTN, ID: 18421340 . Registered on 31 March 2016

Cost and quality of life analysis of HIV self-testing and facility-based HIV testing and counselling in Blantyre, Malawi.

BACKGROUND: HIV self-testing (HIVST) has been found to be highly effective, but no cost analysis has been undertaken to guide the design of affordable and scalable implementation strategies. METHODS: Consecutive HIV self-testers and facility-based testers were recruited from participants in a community cluster-randomised trial ( ISRCTN02004005 ) investigating the impact of offering HIVST in addition to facility-based HIV testing and counselling (HTC). Primary costing studies were undertaken of the HIVST service and of health facilities providing HTC to the trial population. Costs were adjusted to 2014 US$and INT$. Recruited participants were asked about direct non-medical and indirect costs associated with accessing either modality of HIV testing, and additionally their health-related quality of life was measured using the EuroQol EQ-5D. RESULTS: A total of 1,241 participants underwent either HIVST (n = 775) or facility-based HTC (n = 446). The mean societal cost per participant tested through HIVST (US$9.23; 95$9.14-US$9.32) was lower than through facility-based HTC (US$11.84; 95 % CI: US$10.81-12.86). Although the mean health provider cost per participant tested through HIVST (US$8.78) was comparable to facility-based HTC (range: US$7.53-US$10.57), the associated mean direct non-medical and indirect cost was lower (US$2.93; 95$1.90-US$3.96). The mean health provider cost per HIV positive participant identified through HIVST was higher (US$97.50) than for health facilities (range: US$25.18-US$76.14), as was the mean cost per HIV positive individual assessed for anti-retroviral treatment (ART) eligibility and the mean cost per HIV positive individual initiated onto ART. In comparison to the facility-testing group, the adjusted mean EQ-5D utility score was 0.046 (95 % CI: 0.022-0.070) higher in the HIVST group. CONCLUSIONS: HIVST reduces the economic burden on clients, but is a costlier strategy for the health provider aiming to identify HIV positive individuals for treatment. The provider cost of HIVST could be substantially lower under less restrictive distribution models, or if costs of oral fluid HIV test kits become comparable to finger-prick kits used in health facilities

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

Linkage to HIV care following HIV self‑testing among men : systematic review of quantitative and qualitative studies from six countries in Sub‑Saharan Africa

DATA AVAILABILITY : All the data analysed and reported in this paper were from published literature, which is already in the public domain.Gender disparities are pervasive throughout the HIV care continuum in sub-Saharan Africa, with men testing, receiving treatment, and achieving viral suppression at lower rates, and experiencing mortality at higher rates, compared with women. HIV self-testing (HIVST) has been shown to be highly acceptable among men in sub-Saharan Africa. However, evidence on linkage to HIV care following a reactive HIVST result is limited. In this systematic review, we aimed to synthesize the quantitative and qualitative literature from sub-Saharan Africa on men’s rates of linkage to HIV care after receiving a reactive HIVST result. We systematically searched 14 bibliometric databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) fow diagram was used to document the screening results. The Mixed Methods Appraisal Tool (MMAT) was used to assess the methodological quality of the included studies. Of 22,446 references screened, 15 articles were eligible for inclusion in this review. Linkage to HIV care following a reactive HIVST result was subject to several barriers: fnancial constraints due to travelling costs, potential long waiting hours at the clinics, stigma, discrimination, and privacy concerns. Men’s rates of seeking confrmatory testing and linking to HIV care following a reactive HIVST result were inconsistent across studies. Combining fnancial incentives with HIVST was found to increase the likelihood of linking to HIV care following a reactive HIVST result. The variable rates of linkage to HIV care following a reactive HIVST result suggest a need for further research and development into strategies to increase linkage to HIV care.http://link.springer.com/journal/10461School of Health Systems and Public Health (SHSPH

Stigmatising Attitudes among People Offered Home-Based HIV Testing and Counselling in Blantyre, Malawi: Construction and Analysis of a Stigma Scale

BACKGROUND: HIV/AIDS related stigma is a major barrier to uptake of HIV testing and counselling (HTC). We assessed the extent of stigmatising attitudes expressed by participants offered community-based HTC, and their anticipated stigma from others to assess relationship with HIV test uptake. From these data, we constructed a brief stigma scale for use around the time of HIV testing. METHODS AND FINDINGS: Adult members of 60 households in urban Blantyre, Malawi, were selected using population-weighted random cluster sampling and offered HTC with the option to self-test before confirmatory HTC. Prior to HTC a 15-item HIV stigma questionnaire was administered. We used association testing and principal components analysis (PCA) to construct a scale measure of stigma. Of 226 adults invited to participate, 216 (95.6%) completed questionnaires and 198/216 (91.7%) opted to undergo HTC (all self-tested). Stigmatising attitudes were uncommon, but anticipated stigma was common, especially fearing verbal abuse (22%) or being abandoned by their partner (11%). Three questions showed little association or consistency with the remaining 12 stigma questions and were not included in the final scale. For the 12-question final scale, Cronbach's alpha was 0.75. Level of stigma was not associated with previously having tested for HIV (p = 0.318) or agreeing to HTC (p = 0.379), but was associated with expressed worry about being or becoming HIV infected (p = 0.003). CONCLUSIONS: Anticipated stigma prior to HTC was common among both men and women. However, the high uptake of HTC suggests that this did not translate into reluctance to accept community-based testing. We constructed a brief scale to measure stigma at the time of HIV testing that could rapidly identify individuals requiring additional support following diagnosis and monitor the impact of increasing availability of community-based HTC on prevalence of stigma

Ethical issues in cluster randomized trials conducted in low- and middle-income countries: an analysis of two case studies.

BACKGROUND: Cluster randomized trials are common in health research in low- and middle-income countries raising issues that challenge interpretation of standard ethical guidelines. While the Ottawa Statement on the ethical design and conduct of cluster randomized trials provides guidance for researchers and research ethics committees, it does not explicitly focus on low- and middle-income settings. MAIN BODY: In this paper, we use the lens of the Ottawa Statement to analyze two cluster randomized trials conducted in low- and middle-income settings in order to identify gaps or ethical issues requiring further analysis and guidance. The PolyIran trial was a parallel-arm, cluster trial examining the effectiveness of a polypill for prevention of cardiovascular disease in Golestan province, Iran. The PASTAL trial was an adaptive, multistage, parallel-arm, cluster trial evaluating the effect of incentives for human immunodeficiency virus self-testing and follow-up on male partners of pregnant women in Malawi. Through an in-depth case analysis of these two studies we highlight several issues in need of further exploration. First, standards for verbal consent and waivers of consent require methods for operationalization if they are to be employed consistently. Second, the appropriate choice of a control arm remains contentious. Particularly in the case of implementation interventions, locally available care is required as the comparator to address questions of comparative effectiveness. However, locally available care might be lower than standards set out in national guidelines. Third, while the need for access to effective interventions post-trial is widely recognized, it is often not possible to guarantee this upfront. Clarity on what is required of researchers and sponsors is needed. Fourth, there is a pressing need for ethics education and capacity building regarding cluster randomized trials in these settings. CONCLUSION: We identify four issues in cluster randomized trials conducted in low- and middle-income countries for which further ethical analysis and guidance is required

Uptake, Accuracy, Safety, and Linkage into Care over Two Years of Promoting Annual Self-Testing for HIV in Blantyre, Malawi: A Community-Based Prospective Study

Background Home-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population. Methods and Findings Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test) to adult (≥16 y old) residents (n = 16,660) and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA) sample. Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover) residents self-tested during months 1–12, with adolescents (16–19 y) most likely to test. 10,614/14,004 (75.8%) participants shared results with volunteer-counsellors. Of 1,257 (11.8%) HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3%) newly accessed care with a median CD4 count of 250 cells/μl (interquartile range 159–426). HIVST uptake in months 13–24 was more rapid (70.9% uptake by 6 mo), with fewer (7.3%, 95% CI 6.8%–7.8%) positive participants. Being “forced to test”, usually by a main partner, was reported by 2.9% (95% CI 2.6%–3.2%) of 10,017 questionnaire respondents in months 1–12, but satisfaction with HIVST (94.4%) remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1,649 systematically selected (1 in 20) QA participants (99.4%), giving a sensitivity of 93.6% (95% CI 88.2%–97.0%) and a specificity of 99.9% (95% CI 99.6%–100%). Key limitations included use of aggregate data to report uptake of HIVST and being unable to adjust for population turnover. Conclusions Community-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings

Collecting mortality data via mobile phone surveys: A non-inferiority randomized trial in Malawi

Despite the urgent need for timely mortality data in low-income and lower-middle-income countries, mobile phone surveys rarely include questions about recent deaths. Such questions might a) be too sensitive, b) take too long to ask and/or c) generate unreliable data. We assessed the feasibility of mortality data collection using mobile phone surveys in Malawi. We conducted a non-inferiority trial among a random sample of mobile phone users. Participants were allocated to an interview about their recent economic activity or recent deaths in their family. In the group that was asked mortality-related questions, half of the respondents completed an abridged questionnaire, focused on information necessary to calculate recent mortality rates, whereas the other half completed an extended questionnaire that also included questions about symptoms and healthcare. The primary trial outcome was the cooperation rate, i.e., the number of completed interviews divided by the number of mobile subscribers invited to participate. Secondary outcomes included self-reports of negative feelings and stated intentions to participate in future interviews. We called more than 7,000 unique numbers and reached 3,054 mobile subscribers. In total, 1,683 mobile users were invited to participate. The difference in cooperation rates between those asked to complete a mortality-related interview and those asked to answer questions about economic activity was 0.9 percentage points (95% CI = -2.3, 4.1), which satisfied the non-inferiority criterion. The mortality questionnaire was non-inferior to the economic questionnaire on all secondary outcomes. Collecting mortality data required 2 to 4 additional minutes per reported death, depending on the inclusion of questions about symptoms and healthcare. More than half of recent deaths elicited during mobile phone interviews had not been registered with the National Registration Bureau. Including mortality-related questions in mobile phone surveys is feasible. It might help strengthen the surveillance of mortality in countries with deficient civil registration systems. Registration: AEA RCT Registry, #0008065 (14 September 2021).</jats:p

HIV self-testing alone or with additional interventions, including financial incentives, and linkage to care or prevention among male partners of antenatal care clinic attendees in Malawi: An adaptive multi-arm, multi-stage cluster randomised trial

Background Conventional HIV testing services have been less comprehensive in reaching men than in reaching women globally, but HIV self-testing (HIVST) appears to be an acceptable alternative. Measurement of linkage to post-test services following HIVST remains the biggest challenge, yet is the biggest driver of cost-effectiveness. We investigated the impact of HIVST alone or with additional interventions on the uptake of testing and linkage to care or prevention among male partners of antenatal care clinic attendees in a novel adaptive trial. Methods and findings An adaptive multi-arm, 2-stage cluster randomised trial was conducted between 8 August 2016 and 30 June 2017, with antenatal care clinic (ANC) days (i.e., clusters of women attending on a single day) as the unit of randomisation. Recruitment was from Ndirande, Bangwe, and Zingwangwa primary health clinics in urban Blantyre, Malawi. Women attending an ANC for the first time for their current pregnancy (regardless of trimester), 18 years and older, with a primary male partner not known to be on ART were enrolled in the trial after giving consent. Randomisation was to either the standard of care (SOC; with a clinic invitation letter to the male partner) or 1 of 5 intervention arms: the first arm provided women with 2 HIVST kits for their partners; the second and third arms provided 2 HIVST kits along with a conditional fixed financial incentive of $3 or$10; the fourth arm provided 2 HIVST kits and a 10% chance of receiving $30 in a lottery; and the fifth arm provided 2 HIVST kits and a phone call reminder for the women’s partners. The primary outcome was the proportion of male partners who were reported to have tested for HIV and linked into care or prevention within 28 days, with referral for antiretroviral therapy (ART) or circumcision accordingly. Women were interviewed at 28 days about partner testing and adverse events. Cluster-level summaries compared each intervention versus SOC using eligible women as the denominator (intention-to-treat). Risk ratios were adjusted for male partner testing history and recruitment clinic. A total of 2,349/3,137 (74.9$3 (geometric mean 40.9%, adjusted risk ratio [aRR] 3.01 [95% CI 1.63–5.57], p < 0.001), HIVST + $10 (51.7$23.73 and $28.08 for the HIVST +$3 and HIVST + $10 arms, respectively. Notable limitations of the trial included the relatively small number of clusters randomised to each arm, proxy reporting of the male partner testing outcome, and being unable to evaluate retention in care. Conclusions In this study, the odds of men’s linkage to care or prevention increased substantially using conditional fixed financial incentives plus partner-delivered HIVST; combinations were potentially affordable