COVID-19 self-testing: Countries accelerating policies ahead of WHO guidelines during pandemics, a global consultation.

The widespread use of antigen-detection rapid diagnostic tests (Ag-RDTs) has revolutionized SARS-CoV-2 (COVID-19) testing, particularly through the option of self-testing. The full extent of Ag-RDT utilization for self-testing, however, remains largely unexplored. To inform the development of WHO guidance on COVID-19 self-testing, we conducted a global consultation to gather the views and experiences of policy makers, researchers, and implementers worldwide. The consultation was conducted by disseminating a WHO questionnaire through professional networks via email and social media, encouraging onward sharing. We used a cross-sectional design with both closed and open-ended questions related to policy and program information concerning the regulation, availability, target population, indications, implementation, benefits, and challenges of COVID-19 self-testing (C19ST). We defined self-testing as tests performed and interpreted by an untrained individual, often at home. Descriptive summaries, cross-tabulations, and proportions were used to calculate outcomes at the global level and by WHO region and World Bank income classifications. All information was collated and reported according to WHO guideline development standards and practice for global consultations. Between 01 and 11 February 2022, 844 individuals from 139 countries responded to the survey, with 45% reporting affiliation with governments and 47% operating at the national level. 504 respondents from 101 countries reported policies supporting C19ST for a range of use cases, including symptomatic and asymptomatic populations. More respondents from low-and-middle-income countries (LMICs) than high-income countries (HICs) reported a lack of an C19ST policy (61 vs 11 countries) and low population-level reach of C19ST. Respondents with C19ST experience perceived that the tests were mostly acceptable to target populations, provided significant benefits, and highlighted several key challenges to be addressed for increased success. Reported costs varied widely, ranging from specific programmes enabling free access to certain users and others with high costs via the private sector. Based on this consultation, systems for the regulatory review, policy development and implementation of C19ST appeared to be much more common in HIC when compared to LIC in early 2022, though most respondents indicated self-testing was available to some extent (101 out of 139 countries) in their country. Addressing such global inequities is critical for ensuring access to innovative and impactful interventions in the context of a public health emergency of international concern. The challenges and opportunities highlighted by key stakeholders could be valuable to consider as future testing strategies are being set for outbreak-prone diseases.

Do Peer Navigators Improve Initiation and Retention in HIV/VH/STI Treatment Programs for People From Key Populations? A Systematic Review of Effectiveness, Values and Preferences, and Cost.

BACKGROUND: Key populations are disproportionately affected by HIV, viral hepatitis (VH), and sexually transmitted infections (STIs) and face barriers to care. Peer navigation programs are widely used, but evidence supporting their use has not been synthesized. SETTING: Peer navigation programs for sex workers, men who have sex with men, people who inject drugs, prisoners, and trans and gender diverse people globally. METHODS: To inform World Health Organization guidelines, we conducted a systematic review of effectiveness, values and preferences, and cost studies published between January 2010 and May 2021. We searched CINAHL, PsycINFO, PubMed, and EMBASE; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials and comparative observational studies evaluating time to diagnosis or linkage to care, treatment initiation, treatment retention/completion, viral load, cure, or mortality. We assessed risk of bias and summarized findings in GRADE evidence profiles. Values and preferences and cost data were summarized descriptively. RESULTS: Four studies evaluated the effectiveness of peer navigators for key populations. All were focused on HIV; none were designed for VH or STIs. These studies showed mixed effects on linkage to care, treatment retention/completion, and viral load; no studies measured treatment initiation, cure, or mortality. Two values and preferences studies with community-based organization staff and health workers suggested peer navigators for key populations were acceptable and valued, although continued challenges remained. No cost studies were identified. CONCLUSIONS: Although limited, available studies provide moderate certainty evidence for benefits of HIV/VH/STI peer navigation programs for key populations. Further evaluations are needed.

Missed opportunities for HIV testing among those who accessed sexually transmitted infection (STI) services, tested for STIs and diagnosed with STIs: a systematic review and meta-analysis.

INTRODUCTION: Of 37.7 million people living with HIV in 2020, 6.1 million still do not know their HIV status. We synthesize evidence on concurrent HIV testing among people who tested for other sexually transmitted infections (STIs). METHODS: We conducted a systematic review using five databases, HIV conferences and clinical trial registries. We included publications between 2010 and May 2021 that reported primary data on concurrent HIV/STI testing. We conducted a random-effects meta-analysis and meta-regression of the pooled proportion for concurrent HIV/STI testing. RESULTS: We identified 96 eligible studies. Among those, 49 studies had relevant data for a meta-analysis. The remaining studies provided data on the acceptability, feasibility, barriers, facilitators, economic evaluation and social harms of concurrent HIV/STI testing. The pooled proportion of people tested for HIV among those attending an STI service (n = 18 studies) was 71.0% (95% confidence intervals: 61.0-80.1, I2 = 99.9%), people tested for HIV among those who were tested for STIs (n = 15) was 61.3% (53.9-68.4, I2 = 99.9%), people tested for HIV among those who were diagnosed with an STI (n = 13) was 35.3% (27.1-43.9, I2 = 99.9%) and people tested for HIV among those presenting with STI symptoms (n = 3) was 27.1% (20.5-34.3, I2 = 92.0%). The meta-regression analysis found that heterogeneity was driven mainly by identity as a sexual and gender minority, the latest year of study, country-income level and region of the world. DISCUSSION: This review found poor concurrent HIV/STI testing among those already diagnosed with an STI (35.3%) or who had symptoms with STIs (27.1%). Additionally, concurrent HIV/STI testing among those tested for STIs varied significantly according to the testing location, country income level and region of the world. A few potential reasons for these observations include differences in national STI-related policies, lack of standard operation procedures, clinician-level factors, poor awareness and adherence to HIV indicator condition-guided HIV testing and stigma associated with HIV compared to other curable STIs. CONCLUSIONS: Not testing for HIV among people using STI services presents a significant missed opportunity, particularly among those diagnosed with an STI. Stronger integration of HIV and STI services is urgently needed to improve prevention, early diagnosis and linkage to care services.

Counselling behavioural interventions for HIV, STI and viral hepatitis among key populations: a systematic review of effectiveness, values and preferences, and cost studies.

INTRODUCTION: Key populations (sex workers, men who have sex with men, people who inject drugs, people in prisons and other closed settings, and trans and gender diverse individuals) are disproportionately affected by HIV, sexually transmitted infections (STIs) and viral hepatitis (VH). Counselling behavioural interventions are widely used, but their impact on HIV/STI/VH acquisition is unclear. METHODS: To inform World Health Organization guidelines, we conducted a systematic review and meta-analysis of effectiveness, values and preferences, and cost studies about counselling behavioural interventions with key populations. We searched CINAHL, PsycINFO, PubMed and EMBASE for studies published between January 2010 and December 2022; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials (RCTs) with HIV/STI/VH incidence outcomes; secondary review outcomes of unprotected sex, needle/syringe sharing and mortality were captured if studies also included primary review outcomes. We assessed the risk of bias using the Cochrane Collaboration tool, generated pooled risk ratios through random effects meta-analysis and summarized findings in GRADE evidence profiles. Values and preferences and cost data were summarized descriptively. RESULTS: We identified nine effectiveness, two values and preferences, and two cost articles. Meta-analysis of six RCTs showed no statistically significant effect of counselling behavioural interventions on HIV incidence (1280 participants; combined risk ratio [RR]: 0.70, 95% confidence interval [CI]: 0.41-1.20) or STI incidence (3783 participants; RR: 0.99; 95% CI: 0.74-1.31). One RCT with 139 participants showed possible effects on hepatitis C virus incidence. There was no effect on secondary review outcomes of unprotected (condomless) sex (seven RCTs; 1811 participants; RR: 0.82, 95% CI: 0.66-1.02) and needle/syringe sharing (two RCTs; 564 participants; RR 0.72; 95% CI: 0.32-1.63). There was moderate certainty in the lack of effect across outcomes. Two values and preferences studies found that participants liked specific counselling behavioural interventions. Two cost studies found reasonable intervention costs. DISCUSSION: Evidence was limited and mostly on HIV, but showed no effect of counselling behavioural interventions on HIV/VH/STI incidence among key populations. CONCLUSIONS: While there may be other benefits, the choice to provide counselling behavioural interventions for key populations should be made with an understanding of the potential limitations on incidence outcomes.

Understanding the pathways leading to socioeconomic inequalities in HIV testing uptake in 18 sub-Saharan African countries.

OBJECTIVE: To better understand the different pathways linking socioeconomic position and HIV testing uptake in 18 sub-Saharan African countries. DESIGN: We used cross-sectional population-based surveys between 2010 and 2018. METHODS: Using a potential outcomes framework and the product method, we decomposed the total effect linking wealth and recent (<12 months) HIV testing into direct effects, and indirect effects, via internal (related to individual's ability to perceive need for and to seek care) or external (ability to reach, pay for and engage in healthcare) mediators to calculate the proportion mediated (PM) by each mediator. RESULTS: High levels of inequalities were observed in nine and 15 countries among women and men, respectively. The mediator indirect effect varied greatly across countries. The PM tended to be higher for internal than for external mediators. For instance, among women, HIV-related knowledge was estimated to mediate up to 12.1% of inequalities in Côte d'Ivoire; and up to 31.5% for positive attitudes towards people with HIV (PWH) in Senegal. For the four external mediators, the PM was systematically below 7%. Similar findings were found when repeating analyses on men for the internal mediators, with higher PM by attitudes towards PWH (up to 39.9% in Senegal). CONCLUSIONS: Our findings suggest that wealth-related inequalities in HIV testing may be mediated by internal more than external characteristics, with important variability across countries. Overall, the important heterogeneities in the pathways of wealth-related inequalities in HIV testing illustrate that addressing inequalities requires tailored efforts and upstream interventions.

Cost-effectiveness of easy-access, risk-informed oral pre-exposure prophylaxis in HIV epidemics in sub-Saharan Africa: a modelling study.

BACKGROUND: Approaches that allow easy access to pre-exposure prophylaxis (PrEP), such as over-the-counter provision at pharmacies, could facilitate risk-informed PrEP use and lead to lower HIV incidence, but their cost-effectiveness is unknown. We aimed to evaluate conditions under which risk-informed PrEP use is cost-effective. METHODS: We applied a mathematical model of HIV transmission to simulate 3000 setting-scenarios reflecting a range of epidemiological characteristics of communities in sub-Saharan Africa. The prevalence of HIV viral load greater than 1000 copies per mL among all adults (HIV positive and negative) varied from 1·1% to 7·4% (90% range). We hypothesised that if PrEP was made easily available without restriction and with education regarding its use, women and men would use PrEP, with sufficient daily adherence, during so-called seasons of risk (ie, periods in which individuals are at risk of acquiring infection). We refer to this as risk-informed PrEP. For each setting-scenario, we considered the situation in mid-2021 and performed a pairwise comparison of the outcomes of two policies: immediate PrEP scale-up and then continuation for 50 years, and no PrEP. We estimated the relationship between epidemic and programme characteristics and cost-effectiveness of PrEP availability to all during seasons of risk. For our base-case analysis, we assumed a 3-monthly PrEP cost of US$29 (drug $11, HIV test $4, and $14 for additional costs necessary to facilitate education and access), a cost-effectiveness threshold of $500 per disability-adjusted life-year (DALY) averted, an annual discount rate of 3%, and a time horizon of 50 years. In sensitivity analyses, we considered a cost-effectiveness threshold of $100 per DALY averted, a discount rate of 7% per annum, the use of PrEP outside of seasons of risk, and reduced uptake of risk-informed PrEP. FINDINGS: In the context of PrEP scale-up such that 66% (90% range across setting-scenarios 46-81) of HIV-negative people with at least one non-primary condomless sex partner take PrEP in any given period, resulting in 2·6% (0·9-6·0) of all HIV negative adults taking PrEP at any given time, risk-informed PrEP was predicted to reduce HIV incidence by 49% (23-78) over 50 years compared with no PrEP. PrEP was cost-effective in 71% of all setting-scenarios, and cost-effective in 76% of setting-scenarios with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%. In sensitivity analyses with a $100 per DALY averted cost-effectiveness threshold, a 7% per year discount rate, or with PrEP use that was less well risk-informed than in our base case, PrEP was less likely to be cost-effective, but generally remained cost-effective if the prevalence of HIV viral load greater than 1000 copies per mL among all adults was higher than 3%. In sensitivity analyses based on additional setting-scenarios in which risk-informed PrEP was less extensively used, the HIV incidence reduction was smaller, but the cost-effectiveness of risk-informed PrEP was undiminished. INTERPRETATION: Under the assumption that making PrEP easily accessible for all adults in sub-Saharan Africa in the context of community education leads to risk-informed use, PrEP is likely to be cost-effective in settings with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%, suggesting the need for implementation of such approaches, with ongoing evaluation. FUNDING: US Agency for International Development, US President's Emergency Plan for AIDS Relief, and Bill & Melinda Gates Foundation.

Monitoring socioeconomic inequalities across HIV knowledge, attitudes, behaviours and prevention in 18 sub-Saharan African countries.

OBJECTIVES: Socioeconomic inequalities in HIV prevention services coverage constitute important barriers to global prevention targets, especially in sub-Saharan Africa (SSA). We aimed at monitoring these inequalities from population-based survey data in 18 SSA countries between 2010 and 2018. METHODS: We defined eight HIV indicators aimed at capturing uptake of HIV prevention services among adult participants. Country-specific wealth-related inequalities were measured using the Relative and Slope Index of Inequalities (RII and SII, respectively) and then pooled using random-effects meta-analyses. We compared inequalities between African regions using the Wilcoxon rank-sum test. RESULTS: The sample consisted of 358 591 participants (66% women). Despite variability between countries and indicators, the meta-analysis revealed significant levels of relative and absolute inequalities in six out of eight indicators: HIV-related knowledge, positive attitudes toward people with HIV (PWH), condom use at last sexual intercourse, participation to prevention of mother-to-child transmission programs, medical male circumcision and recent HIV testing. The largest inequalities were reported in condom use, with condom use reported five times more among the richest versus the poorest [RII = 5.02, 95% confidence interval (CI) 2.79-9.05] and in positive attitudes toward PWH, with a 32-percentage point difference between the richest and poorest (SII = 0.32, 95% CI 0.26-0.39). Conversely, no significant inequalities were observed in multipartnership and HIV seropositivity among youth. Overall, inequalities tended to be larger in West and Central vs. East and Southern African countries. CONCLUSION: Despite efforts to scale-up HIV-prevention programs, socioeconomic inequalities remain substantial over the continuum of HIV primary and secondary prevention in several SSA countries.

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

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

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

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

Optimizing HIV retesting during pregnancy and postpartum in four countries: a cost-effectiveness analysis.

INTRODUCTION: HIV retesting during late pregnancy and breastfeeding can help detect new maternal infections and prevent mother-to-child HIV transmission (MTCT), but the optimal timing and cost-effectiveness of maternal retesting remain uncertain. METHODS: We constructed deterministic models to assess the health and economic impact of maternal HIV retesting on a hypothetical population of pregnant women, following initial testing in pregnancy, on MTCT in four countries: South Africa and Kenya (high/intermediate HIV prevalence), and Colombia and Ukraine (low HIV prevalence). We evaluated six scenarios with varying retesting frequencies from late in antenatal care (ANC) through nine months postpartum. We compared strategies using incremental cost-effectiveness ratios (ICERs) over a 20-year time horizon using country-specific thresholds. RESULTS: We found maternal retesting once in late ANC with catch-up testing through six weeks postpartum was cost-effective in Kenya (ICER = $166 per DALY averted) and South Africa (ICER=$289 per DALY averted). This strategy prevented 19% (Kenya) and 12% (South Africa) of infant HIV infections. Adding one or two additional retests postpartum provided smaller benefits (1 to 2 percentage point increase in infections averted versus one retest). Adding three retests during the postpartum period averted additional infections (1 to 3 percentage point increase in infections averted versus one retest) but ICERs ($7639 and in Kenya and $11 985 in South Africa) greatly exceeded the cost-effectiveness thresholds. In Colombia and Ukraine, all retesting strategies exceeded the cost-effectiveness threshold and prevented few infant infections (up to 31 and 5 infections, respectively). CONCLUSIONS: In high HIV burden settings with MTCT rates similar to those seen in Kenya and South Africa, HIV retesting once in late ANC, with subsequent intervention, is the most cost-effective strategy for preventing infant HIV infections. In these settings, two HIV retests postpartum marginally reduced MTCT and were less costly than adding three retests. Retesting in low-burden settings with MTCT rates similar to Colombia and Ukraine was not cost-effective at any time point due to very low HIV prevalence and limited breastfeeding.

Cost-effectiveness of dual maternal HIV and syphilis testing strategies in high and low HIV prevalence countries: a modelling study.

BACKGROUND: Dual HIV and syphilis testing might help to prevent mother-to-child transmission (MTCT) of HIV and syphilis through increased case detection and treatment. We aimed to model and assess the cost-effectiveness of dual testing during antenatal care in four countries with varying HIV and syphilis prevalence. METHODS: In this modelling study, we developed Markov models of HIV and syphilis in pregnant women to estimate costs and infant health outcomes of maternal testing at the first antenatal care visit with individual HIV and syphilis tests (base case) and at the first antenatal care visit with a dual rapid diagnostic test (scenario one). We additionally evaluated retesting during late antenatal care and at delivery with either individual tests (scenario two) or a dual rapid diagnosis test (scenario three). We modelled four countries: South Africa, Kenya, Colombia, and Ukraine. Strategies with an incremental cost-effectiveness ratio (ICER) less than the country-specific cost-effectiveness threshold (US$500 in Kenya, $750 in South Africa, $3000 in Colombia, and $1000 in Ukraine) per disability-adjusted life-year averted were considered cost-effective. FINDINGS: Routinely offering testing at the first antenatal care visit with a dual rapid diagnosis test was cost-saving compared with the base case in all four countries (ICER: -$26 in Kenya,-$559 in South Africa, -$844 in Colombia, and -$454 in Ukraine). Retesting during late antenatal care with a dual rapid diagnostic test (scenario three) was cost-effective compared with scenario one in all four countries (ICER: $270 in Kenya, $260 in South Africa, $2207 in Colombia, and $205 in Ukraine). INTERPRETATION: Incorporating dual rapid diagnostic tests in antenatal care can be cost-saving across countries with varying HIV prevalence. Countries should consider incorporating dual HIV and syphilis rapid diagnostic tests as the first test in antenatal care to support efforts to eliminate MTCT of HIV and syphilis. FUNDING: WHO, US Agency for International Development, and the Bill & Melinda Gates Foundation.

Estimates of the global burden of cervical cancer associated with HIV.

BACKGROUND: HIV enhances human papillomavirus (HPV)-induced carcinogenesis. However, the contribution of HIV to cervical cancer burden at a population level has not been quantified. We aimed to investigate cervical cancer risk among women living with HIV and to estimate the global cervical cancer burden associated with HIV. METHODS: We did a systematic literature search and meta-analysis of five databases (PubMed, Embase, Global Health [CABI.org], Web of Science, and Global Index Medicus) to identify studies analysing the association between HIV infection and cervical cancer. We estimated the pooled risk of cervical cancer among women living with HIV across four continents (Africa, Asia, Europe, and North America). The risk ratio (RR) was combined with country-specific UNAIDS estimates of HIV prevalence and GLOBOCAN 2018 estimates of cervical cancer to calculate the proportion of women living with HIV among women with cervical cancer and population attributable fractions and age-standardised incidence rates (ASIRs) of HIV-attributable cervical cancer. FINDINGS: 24 studies met our inclusion criteria, which included 236 127 women living with HIV. The pooled risk of cervical cancer was increased in women living with HIV (RR 6·07, 95% CI 4·40-8·37). Globally, 5·8% (95% CI 4·6-7·3) of new cervical cancer cases in 2018 (33 000 new cases, 95% CI 26 000-42 000) were diagnosed in women living with HIV and 4·9% (95% CI 3·6-6·4) were attributable to HIV infection (28 000 new cases, 20 000-36 000). The most affected regions were southern Africa and eastern Africa. In southern Africa, 63·8% (95% CI 58·9-68·1) of women with cervical cancer (9200 new cases, 95% CI 8500-9800) were living with HIV, as were 27·4% (23·7-31·7) of women in eastern Africa (14 000 new cases, 12 000-17 000). ASIRs of HIV-attributable cervical cancer were more than 20 per 100 000 in six countries, all in southern Africa and eastern Africa. INTERPRETATION: Women living with HIV have a significantly increased risk of cervical cancer. HPV vaccination and cervical cancer screening for women living with HIV are especially important for countries in southern Africa and eastern Africa, where a substantial HIV-attributable cervical cancer burden has added to the existing cervical cancer burden. FUNDING: WHO, US Agency for International Development, and US President's Emergency Plan for AIDS Relief.

Temporal trends in socioeconomic inequalities in HIV testing: an analysis of cross-sectional surveys from 16 sub-Saharan African countries.

BACKGROUND: Overall increases in the uptake of HIV testing in the past two decades might hide discrepancies across socioeconomic groups. We used data from population-based surveys done in sub-Saharan Africa to quantify socioeconomic inequalities in uptake of HIV testing, and to establish trends in testing uptake in the past two decades. METHODS: We analysed data from 16 countries in sub-Saharan Africa where at least one Demographic and Health Survey was done before and after 2008. We assessed the country-specific and sex-specific proportions of participants who had undergone HIV testing in the previous 12 months across wealth and education groups, and quantified socioeconomic inequalities with both the relative and slope indices of inequalities. We assessed time trends in inequalities, and calculated mean results across countries with random-effects meta-analyses. FINDINGS: We analysed data for 537 784 participants aged 15-59 years (most aged 15-49 years) from 32 surveys done between 2003 and 2016 (16 before 2008, and 16 after 2008) in Cameroon, Côte d'Ivoire, DR Congo, Ethiopia, Guinea, Kenya, Lesotho, Liberia, Malawi, Mali, Niger, Rwanda, Sierra Leone, Tanzania, Zambia, and Zimbabwe. A higher proportion of female participants than male participants reported uptake of HIV testing in the previous 12 months in five of 16 countries in the pre-2008 surveys, and in 14 of 16 countries in the post-2008 surveys. After 2008, in the overall sample, the wealthiest female participants were 2·77 (95% CI 1·42-5·40) times more likely to report HIV testing in the previous 12 months than were the poorest female participants, whereas the richest male participants were 3·55 (1·85-6·81) times more likely to report HIV testing than in the poorest male participants. The mean absolute difference in uptake of HIV testing between the richest and poorest participants was 11·1 (95% CI 4·6-17·5) percentage points in female participants and 15·1 (9·6-20·6) in male participants. Over time (ie, when pre-2008 and post-2008 data were compared), socioeconomic inequalities in the uptake of HIV testing in the previous 12 months decreased in male and female participants, whereas absolute inequalities remained similar in female participants and increased in male participants. INTERPRETATION: Although relative socioeconomic inequalities in uptake of HIV testing in sub-Saharan Africa has decreased, absolute inequalities have persisted or increased. Greater priority should be given to socioeconomic equity in assessments of HIV-testing programmes. FUNDING: INSERM-ANRS (France Recherche Nord and Sud Sida-HIV Hépatites).

Economic compensation interventions to increase uptake of voluntary medical male circumcision for HIV prevention: A systematic review and meta-analysis.

BACKGROUND: Economic compensation interventions may help support higher voluntary medical male circumcision (VMMC) coverage in priority sub-Saharan African countries. To inform World Health Organization guidelines, we conducted a systematic review of economic compensation interventions to increase VMMC uptake. METHODS: Economic compensation interventions were defined as providing money or in-kind compensation, reimbursement for associated costs (e.g. travel, lost wages), or lottery entry. We searched five electronic databases and four scientific conferences for studies examining the impact of such interventions on VMMC uptake, HIV testing and safer-sex/risk-reduction counseling uptake within VMMC, community expectations about compensation, and potential coercion. We screened citations, extracted data, and assessed risk of bias in duplicate. We conducted random-effects meta-analysis. We also reviewed studies examining acceptability, values/preferences, costs, and feasibility. RESULTS: Of 2484 citations identified, five randomized controlled trials (RCTs) and three non-randomized controlled trials met our eligibility criteria. Studies took place in Kenya, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. Meta-analysis of four RCTs showed significant impact of any economic compensation on VMMC uptake (relative risk: 5.23, 95% CI: 3.13 to 8.76). RCTs of food/transport vouchers and conditional cash transfers generally showed increases in VMMC uptake, but lotteries, subsidized VMMC, and receiving a gift appeared somewhat less effective. Three non-randomized trials showed mixed impact. Six additional studies suggested economic compensation interventions were generally acceptable, valued for addressing key barriers, and motivating to men. However, some participants felt they were insufficiently motivating or necessary; one study suggested they might raise community suspicions. One study from South Africa found a program cost of US$91 per additional circumcision and US$450-$1350 per HIV infection averted. CONCLUSIONS: Economic compensation interventions, particularly transport/food vouchers, positively impacted VMMC uptake among adult men and were generally acceptable to potential clients. Carefully selected economic interventions may be a useful targeted strategy to enhance VMMC coverage.

HIV immunoprophylaxis: preparing the pathway from proof of concept to policy decision and use.

Various long-awaited efficacy studies of vaccines and broadly neutralising antibodies for prevention of HIV are now well underway in highly endemic settings. One broadly neutralising monoclonal antibody is being assessed for proof of concept, and combinations are in the pipeline. Two multicomponent prime-and-boost vaccine regimens are being evaluated, one of which is designed for global coverage. These multicomponent vaccines present a new level of complexity that will challenge health delivery systems. We recommend that while awaiting the results, which will appear in 2020-22, the target product profiles and full public value proposition for both categories of products should be defined, and the regulatory, policy, and implementation pathways should be prepared. Economic and health benefits, cost of goods, administrative complexity, and user perspectives will be key considerations for the roll-out of effective products. Investments in manufacturing capacity and public-sector delivery systems will be needed to prepare for product introduction and scale-up. We propose a prioritisation of activities on the basis of a broad stakeholder consultation organised by WHO and UNAIDS.

Vaginal ring acceptability and related preferences among women in low- and middle-income countries: A systematic review and narrative synthesis.

The vaginal ring (VR) is a female-initiated drug-delivery platform used for different indications, including HIV pre-exposure prophylaxis (PrEP). We conducted a systematic review of VR acceptability, values and preferences among women in low- and middle-income countries (LMIC) to inform further investment and/or guidance on VR use for HIV prevention. Following PRISMA guidelines, we used structured methods to search, screen, and extract data from randomized controlled trials (RCTs) and observational studies reporting quantitative outcomes of acceptability of the VR for any indication published 1/1970-2/2019 (PROSPERO: CRD42019122220). Of 1,110 records identified, 68 met inclusion criteria. Studies included women 15-50+ years from 25 LMIC for indications including HIV prevention, contraception, abnormal bleeding, and menopause. Overall VR acceptability was high (71-98% across RCTs; 62-100% across observational studies), with 80-100% continuation rates in RCTs and favorable ease of insertion (greater than 85%) and removal 89-99%). Users reported concerns about the VR getting lost in the body (8-43%), although actual expulsions and adverse events were generally infrequent. Most women disclosed use to partners, with some worrying about partner anger/violence. The VR was not felt during intercourse by 70-92% of users and 48-97% of partners. Acceptability improved over time both within studies (as women gained VR experience and worries diminished), and over chronological time (as the device was popularized). Women expressed preferences for accessible, long-acting, partner-approved methods that prevent both HIV and pregnancy, can be used without partner knowledge, and have no impact on sex and few side effects. This review was limited by a lack of standardization of acceptability measures and study heterogeneity. This systematic review suggests that most LMIC women users have a positive view of the VR that increases with familiarity of use; and, that many would consider the VR an acceptable future delivery device for HIV prevention or other indications.

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

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

Cost-per-diagnosis as a metric for monitoring cost-effectiveness of HIV testing programmes in low-income settings in southern Africa: health economic and modelling analysis.

INTRODUCTION: As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost-effective. To guide their HIV testing programmes, countries require appropriate metrics that can be measured. The cost-per-diagnosis is potentially a useful metric. METHODS: We simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of "core" testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) core-testing as above plus additional testing beyond this ("additional-testing"), for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than those without HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosis and the incremental cost-effectiveness ratio (ICER) of the additional-testing policy. The discount rate used in the base case was 3% per annum (costs in 2018 U.S. dollars). RESULTS: There was a strong graded relationship between the cost-per-diagnosis and the ICER. Overall, the ICER was below $500 per-DALY-averted (the cost-effectiveness threshold used in primary analysis) so long as the cost-per-diagnosis was below $315. This threshold cost-per-diagnosis was similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restricting to women, additional-testing did not appear cost-effective even at a cost-per-diagnosis of below $50, while restricting to men additional-testing was cost-effective up to a cost-per-diagnosis of $585. The threshold cost per diagnosis for testing in men to be cost-effective fell to $256 when the cost-effectiveness threshold was $300 instead of $500, and to $81 when considering a discount rate of 10% per annum. CONCLUSIONS: For testing programmes in low-income settings in southern African there is an extremely strong relationship between the cost-per-diagnosis and the cost-per-DALY averted, indicating that the cost-per-diagnosis can be used to monitor the cost-effectiveness of testing programmes.

Universal health coverage and key populations.

PURPOSE OF REVIEW: There is renewed focus at global and national level to adopt commitments to ensure universal access to health services. The present study highlights key considerations to ensure that the commitment to 'leave no one behind' includes key populations, recognizing the specific impact of marginalization, stigma, discrimination, and criminalization on their access to health. RECENT FINDINGS: Universal health coverage (UHC) means that all people can use the promotive, preventive, curative, rehabilitative, and palliative health services they need, of sufficient quality to be effective, while also ensuring that the use of these services does not expose the user to financial hardship. Countries commit to UHC through Sustainable Development Goals (SDG Target 3.8 Achieve universal health coverage, including financial risk protection, access to quality essential health-care services and access to well tolerated, effective, quality, and affordable essential medicines). SUMMARY: UHC cannot be achieved without addressing the needs of key populations. At the same time, the goal of UHC provides new opportunities to improve health equity and the health of key populations. Political commitment, defining and including essential high-impact, evidence-based interventions for key populations, and their full integration into national health benefit packages; integrated, decentralized, and differentiated health services with involvement, ownership, and acceptance of communities to ensure equity and quality; ensuring financing for UHC provides coverage for key populations, including those who may be undocumented, are needed. Developing more effective interventions and service delivery approaches, providing a supportive policy and legal environment; and measuring progress against clear targets for accountability and programme adjustment will also be required for key populations to benefit fully from UHC.

The impact and cost-effectiveness of community-based HIV self-testing in sub-Saharan Africa: a health economic and modelling analysis.

INTRODUCTION: The prevalence of undiagnosed HIV is declining in Africa, and various HIV testing approaches are finding lower positivity rates. In this context, the epidemiological impact and cost-effectiveness of community-based HIV self-testing (CB-HIVST) is unclear. We aimed to assess this in different sub-populations and across scenarios characterized by different adult HIV prevalence and antiretroviral treatment programmes in sub-Saharan Africa. METHODS: The synthesis model was used to address this aim. Three sub-populations were considered for CB-HIVST: (i) women having transactional sex (WTS); (ii) young people (15 to 24 years); and (iii) adult men (25 to 49 years). We assumed uptake of CB-HIVST similar to that reported in epidemiological studies (base case), or assumed people use CB-HIVST only if exposed to risk (condomless sex) since last HIV test. We also considered a five-year time-limited CB-HIVST programme. Cost-effectiveness was defined by an incremental cost-effectiveness ratio (ICER; cost-per-disability-adjusted life-year (DALY) averted) below US$500 over a time horizon of 50 years. The efficiency of targeted CB-HIVST was evaluated using the number of additional tests per infection or death averted. RESULTS: In the base case, targeting adult men with CB-HIVST offered the greatest impact, averting 1500 HIV infections and 520 deaths per year in the context of a simulated country with nine million adults, and impact could be enhanced by linkage to voluntary medical male circumcision (VMMC). However, the approach was only cost-effective if the programme was limited to five years or the undiagnosed prevalence was above 3%. CB-HIVST to WTS was the most cost-effective. The main drivers of cost-effectiveness were the cost of CB-HIVST and the prevalence of undiagnosed HIV. All other CB-HIVST scenarios had an ICER above US$500 per DALY averted. CONCLUSIONS: CB-HIVST showed an important epidemiological impact. To maximize population health within a fixed budget, CB-HIVST needs to be targeted on the basis of the prevalence of undiagnosed HIV, sub-population and the overall costs of delivering this testing modality. Linkage to VMMC enhances its cost-effectiveness.