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The C. elegans nematode worm is a filter-feeder and requires dietary sources of cholesterol. Here, the authors show that the C. elegans pharynx works as a filter to scavenge hydrophobic small molecules from its surrounding liquid environment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Parasitic nematodes negatively impact human and animal health worldwide. The market withdrawal of nematicidal agents due to unfavourable toxicities has limited the available treatment options. In principle, co-administering nematicides at lower doses along with molecules that potentiate their activity could mitigate adverse toxicities without compromising efficacy. Here, we screened for new small molecules that interact with aldicarb, which is a highly effective treatment for plant-parasitic nematodes whose toxicity hampers its utility. From our collection of 638 worm-bioactive compounds, we identified 20 molecules that interact positively with aldicarb to either kill or arrest the growth of the model nematode Caenorhabditis elegans. We investigated the mechanism of interaction between aldicarb and one of these novel nematicides called wact-86. We found that the carboxylesterase enzyme GES-1 hydrolyzes wact-86, and that the interaction is manifested by aldicarb's inhibition of wact-86's metabolism by GES-1. This work demonstrates the utility of C. elegans as a platform to search for new molecules that can positively interact with industrial nematicides, and provides proof-of-concept for prospective discovery efforts.

The proper display of transmembrane receptors on the leading edge of migrating cells and cell extensions is essential for their response to guidance cues. We previously discovered that MADD-4, which is an ADAMTSL secreted by motor neurons in Caenorhabditis elegans, interacts with an UNC-40/EVA-1 co-receptor complex on muscles to attract plasma membrane extensions called muscle arms. In nematodes, the muscle arm termini harbor the post-synaptic elements of the neuromuscular junction. Through a forward genetic screen for mutants with disrupted muscle arm extension, we discovered that a LAMMER kinase, which we call MADD-3, is required for the proper display of the EVA-1 receptor on the muscle's plasma membrane. Without MADD-3, EVA-1 levels decrease concomitantly with a reduction of the late-endosomal marker RAB-7. Through a genetic suppressor screen, we found that the levels of EVA-1 and RAB-7 can be restored in madd-3 mutants by eliminating the function of a p38 MAP kinase pathway. We also found that EVA-1 and RAB-7 will accumulate in madd-3 mutants upon disrupting CUP-5, which is a mucolipin ortholog required for proper lysosome function. Together, our data suggests that the MADD-3 LAMMER kinase antagonizes the p38-mediated endosomal trafficking of EVA-1 to the lysosome. In this way, MADD-3 ensures that sufficient levels of EVA-1 are present to guide muscle arm extension towards the source of the MADD-4 guidance cue.

We recently discovered a secreted and diffusible midline cue called MADD-4 (an ADAMTSL) that guides migrations along the dorsoventral axis of the nematode Caenorhabditis elegans. We showed that the transmembrane receptor, UNC-40 (DCC), whose canonical ligand is the UNC-6 (netrin) guidance cue, is required for extension towards MADD-4. Here, we demonstrate that MADD-4 interacts with an EVA-1/UNC-40 co-receptor complex to attract cell extensions. EVA-1 is a conserved transmembrane protein with predicted galactose-binding lectin domains. EVA-1 functions in the same pathway as MADD-4, physically interacts with both MADD-4 and UNC-40, and enhances UNC-40's sensitivity to the MADD-4 cue. This enhancement is especially important in the presence of UNC-6. In EVA-1's absence, UNC-6 interferes with UNC-40's responsiveness to MADD-4; in UNC-6's absence, UNC-40's responsiveness to MADD-4 is less dependent on EVA-1. By enabling UNC-40 to respond to MADD-4 in the presence of UNC-6, EVA-1 may increase the precision by which UNC-40-directed processes can reach their MADD-4-expressing targets within a field of the UNC-6 guidance cue.

Abstract Introduction Social network‐based testing approaches (SNAs) encourage individuals (“test promoters”) to motivate sexual partners and/or those in their social networks to test for HIV. We conducted a systematic review to examine the effectiveness, acceptability and cost‐effectiveness of SNA. Methods We searched five databases from January 2010 to May 2023, and included studies that compared SNA with non‐SNA. We used random‐effects meta‐analysis to combine effect estimates. Certainty was assessed using the GRADE approach. Results We identified 47 studies. SNA may increase uptake of HIV testing compared to non‐SNA (RR 2.04, 95% CI: 1.06–3.95, Low certainty). The proportion of first‐time testers was probably higher among partners or social contacts of test promoters using SNA compared to non‐SNA (RR 1.49, 95% CI: 1.22–1.81, Moderate certainty). The proportion of people who tested positive for HIV may be higher among partners or social contacts of test promoters using SNA compared to non‐SNA (RR 1.84, 95% CI: 1.01–3.35, Low certainty). There were no reports of any adverse events or harms associated with SNA. Based on six cost‐effectiveness studies, SNA was generally cheaper per person tested and per person diagnosed compared to non‐SNA. Based on 23 qualitative studies, SNA is likely to be acceptable to a variety of populations. Discussion Our review collated evidence for SNA to HIV testing covering the key populations and the general population who may benefit from HIV testing. We summarized evidence for the effectiveness, acceptability and cost‐effectiveness of different models of SNA. While we did not identify an ideal model of SNA that could be immediately scaled up, for each setting and population targeted, we recommend various implementation considerations as our meta‐analysis showed the effectiveness might differ due to factors which include the testing modality (i.e. use of HIV self‐testing), type of test promoters, long or short duration of recruitment and use of financial incentives. Conclusions Social network‐based approaches may enhance HIV testing uptake, increase the proportion of first‐time testers and those testing positive for HIV. Heterogeneity among studies highlights the need for context‐specific adaptations, but the overall positive impact of SNA on HIV testing outcomes could support its integration into existing HIV testing services.

Abstract Introduction In Viet Nam, key populations (KPs) face barriers accessing HIV services. Virtual platforms can be leveraged to increase access for KPs, including for HIV self‐testing (HIVST). This study compares reach and effectiveness of a web‐based HIVST intervention from pilot to scale‐up in Viet Nam. Methods A mixed‐methods explanatory sequential design used cross‐sectional and thematic analysis. The pilot launched in Can Tho in November 2020, followed by Hanoi and Nghe An in April 2021. Scale‐up included Can Tho and Nghe An, with 21 novel provinces from April to December 2022. After risk assessment, participants registered on the website, receiving HIVST (OraQuick®) by courier, peer educator or self‐pick‐up. Test result reporting and completing satisfaction surveys were encouraged. Intervention reach was measured through numbers accessing the testing, disaggregated by demographics, and proportion of individuals reporting self‐testing post‐registration. Effectiveness was measured through numbers reporting self‐test results, testing positive and linking to care, and testing negative and using HIVST to manage pre‐exposure prophylaxis (PrEP) use. Thematic content analysis of free‐text responses from the satisfaction survey synthesized quantitative outcomes. Results In total, 17,589 participants registered on the HIVST website; 11,332 individuals ordered 13,334 tests. Participants were generally young, aged

Abstract Introduction Following HIV testing services (HTS), the World Health Organization recommends prompt linkage to prevention and treatment. Scale‐up of effective linkage strategies is essential to achieving the global 95‐95‐95 goals for maintaining low HIV incidence by 2030 and reducing HIV‐related morbidity and mortality. Whereas linkage to care including same‐day antiretroviral therapy (ART) initiation for all people with HIV is now routinely implemented in testing programmes, linkage to HIV prevention interventions including behavioural or biomedical strategies, for HIV‐negative individuals remains sub‐optimal. This review aims to evaluate effective post‐HTS linkage strategies for HIV overall, and highlight gaps specifically in linkage to prevention. Methods Using the five‐step Arksey and O'Malley framework, we conducted a scoping review searching existing published and grey literature. We searched PubMed, Cochrane Library, CINAHL, Web of Science and EMBASE databases for English‐language studies published between 1 January 2010 and 30 November 2023. Linkage interventions included as streamlined interventions—involving same‐day HIV testing, ART initiation and point‐of‐care CD4 cell count/viral load, case management—involving linkage coordinators developing personalized HIV care and risk reduction plans, incentives—financial and non‐financial, partner services—including contact tracing, virtual—like social media, quality improvement—like use of score cards, and peer‐based interventions. Outcomes of interest were linkage to any form of HIV prevention and/or care including ART initiation. Results Of 2358 articles screened, 66 research studies met the inclusion criteria. Only nine linkage to prevention studies were identified (n = 9/66, 14%)—involving pre‐exposure prophylaxis, voluntary medical male circumcision, sexually transmitted infection and cervical cancer screening. Linkage to care studies (n = 57/66, 86%) focused on streamlined interventions in the general population and on case management among key populations. Discussion Despite a wide range of HIV prevention interventions available, there was a dearth of literature on HIV prevention programmes and on the use of messaging on treatment as prevention strategy. Linkage to care studies were comparatively numerous except those evaluating virtual interventions, incentives and quality improvement. Conclusions The findings give insights into linkage strategies but more understanding of how to provide these effectively for maximum prevention impact is needed.

Objectives In 2015 and 2016, WHO issued guidelines on HIV testing services (HTS) highlighting recommendations for a strategic mix of differentiated HTS approaches. The policy review examines the uptake of differentiated HTS approaches recommendations in national policies.Methods Data were extracted from national policies published between January 2015 and June 2019. The WHO-recommended HTS approaches included facility-based testing, community-based testing, HIV self-testing and provider-assisted referral (or assisted partner notification). Other supportive recommendations include pre-test information, post-test counselling, lay provider testing and rapid testing. Descriptive analyses were conducted to examine inclusion of recommendations in national policies.Results Of 194 countries worldwide, 65 published policies were identified; 24 WHO Africa region (AFR) countries (51%, 24/47), 21 WHO European region (EUR) (40%, 21/53), 6 WHO Eastern Mediterranean region (EMR) (29%, 6/21), 5 Pan-American region (AMR) (14%, 5/35), 5 Western Pacific Region (WPR) (19%, 5/27) and 4 WHO South East Asia Region (SEAR) (36%, 4/11). Only five countries included all recommendations. 63 included a minimum of one. 85% (n=55) included facility-based testing for pregnant women, 75% (n=49) facility-based testing for key populations, 74% (n=48) community-based testing for key populations, 69% (n=45) rapid testing, 57% (n=37) post-test counselling, 45% (n=29) lay provider testing, 38% (n=25) HIV self-testing, 29% (n=19) pre-test information and 25% (n=16) provider-assisted referral. The proportion in each region that included at least one recommendation were: 100% AFR (24/47), 100% EMR (6/6), 100% AMR (5/5), 100% WPR (5/5), 100% SEAR (4/4) and 95% EUR (20/21). AFR followed by EMR included the highest number of reccomendations.Conclusion There was substantial variability in the uptake of the WHO-differentiated HTS recommendations. Those in EMR included the most WHO-differentiated HTS recommendation followed by AFR. Countries within AMR included the least number of recommendations. Ongoing advocacy and efforts are needed to support the uptake of the WHO-differentiated HTS recommendations in country policies as well as their implementation.

Caregiver-assisted testing using HIV self-test (CG-HIVST) kits has been proposed to enhance paediatric HIV case finding and contribute toward ending paediatric HIV/AIDS by 2030. We conducted a systematic review to assess the risks and benefits of CG-HIVST. We searched nine electronic databases and consulted experts to identify relevant articles through 5 February, 2022. Studies comparing CG-HIVST to other testing services among children over 18-months, or to no intervention, were included. Outcomes included uptake, acceptability, diagnostic accuracy, feasibility, HIV positivity, linkage to care, social harm, values and preferences, costs, and cost-effectiveness. Risk of bias was assessed using relevant Cochrane tools and certainty of evidence was evaluated with GRADE. Among 2203 screened articles, nine observational studies from sub-Saharan Africa were included. All studies used and assessed caregiver-assisted testing using oral fluid-based HIVST. In one non-randomized intervention study of 6062 children, overall CG-HIVST uptake was lower than other standard testing services (3.30% vs. 56.71%). In the same study, HIV positivity following CG-HIVST appeared lower or comparable to standard testing (RR = 0.44; 95% CI: 0.06, 3.20). Two single-arm studies reported high linkage to confirmatory testing (97.48%) and treatment initiation (97.7%) among children reported positive with CG-HIVST. Pooled positive predictive value was 36.72% across three non-randomized intervention studies. Reported social harms were rare, and acceptability appeared high among caregivers taking up the intervention, but feasibility was unclear as some reported anxiety in relation to reactive results. Evidence was appraised very low certainty. Average CG-HIVST costs varied widely and were consistently higher than standard testing services. CG-HIVST may be acceptable, but feasibility remains uncertain with potential higher costs. Current evidence favours standard testing for uptake and positivity. Low positive predictive values raise concerns about false positives and potential harm. Programmes should prioritize evidence-based approaches for paediatric case-finding, while research to fully evaluate this approach continues.

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.

Objectives In 2019, the WHO released guidelines on HIV testing service (HTS). We aim to assess the adoption of six of these recommendations on HIV testing strategies among African countries.Design Policy review.Setting 47 countries within the WHO African region.Participants National HTS policies from the WHO African region as of December 2021.Primary and secondary outcome measures: Uptake of WHO recommendations across national HTS policies including the standard three-test strategy; discontinuation of a tiebreaker test to rule in HIV infection; discontinuation of western blotting (WB) for HIV diagnosis; retesting prior to antiretroviral treatment (ART) initiation and the use of dual HIV/syphilis rapid diagnostic tests (RDTs) in antenatal care. Country policy adoption was assessed on a continuum, based on varying levels of complete adoption.Results National policies were reviewed for 96% (n=45/47) of countries in the WHO African region, 38% (n=18) were published before 2019 and 60% (n=28) adopted WHO guidance. Among countries that had not fully adopted WHO guidance, not yet adopting a three-test strategy was the most common reason for misalignment (45%, 21/47); of which 31% and 22% were in low-prevalence (

ABSTRACT: Objectives: Although the World Health Organization recommends ‘frequent’ screening of sexually transmitted infections (STI) for people who use pre-exposure prophylaxis for HIV, there is no evidence for optimal frequency. Methods: We searched five databases and used random-effects meta-analysis to calculate pooled estimates of STI test positivity. We narratively synthesized data on secondary outcomes, including adherence to recommended STI screening frequency and changes in STI epidemiology. Results: Of 7477 studies, we included 38 for the meta-analysis and 11 for secondary outcomes. With 2-3 monthly STI screening, the pooled positivity was 0.20 (95% confidence interval [CI]: 0.15-0.25) for chlamydia, 0.17 (95% CI: 0.12-0.22) for gonorrhea, and 0.07 (95% CI: 0.05-0.08) for syphilis. For chlamydia and gonorrhea, the positivity was approximately 50% and 75% lower, respectively, in studies that screened 4-6 monthly vs 2-3 monthly. There was no significant difference in the positivity for syphilis in studies that screened 4-6 monthly compared to 2-3 monthly. Adherence of clients to recommended screening frequency varied significantly (39-94%) depending on population and country. Modeling studies suggest more frequent STI screening could reduce incidence. Conclusion: Although more frequent STI screening could reduce delayed diagnoses and incidence, there remain significant knowledge gaps regarding the optimal STI screening frequency.

Abstract Background The World Health Organization (WHO) recommends oral pre-exposure prophylaxis (PrEP) for all people at substantial risk of HIV as part of combination prevention. The extent to which this recommendation has been implemented globally for people who inject drugs is unclear. This study mapped global service delivery of PrEP for people who inject drugs. Methods Between October and December 2021, a desk review was conducted to obtain information on PrEP services for people who inject drugs from drug user-led networks and HIV, harm reduction, and human rights stakeholders. Websites of organizations involved in HIV prevention or services for people who inject drugs were searched. Models of service delivery were described in terms of service location, provider, and package. Results PrEP services were identified in 27 countries (15 high-income). PrEP delivery models varied within and across countries. In most services, PrEP services were implemented in healthcare clinics without direct links to other harm reduction services. In three countries, PrEP services were also provided at methadone clinics. In 14 countries, PrEP services were provided through community-based models (outside of clinic settings) that commonly involved peer-led outreach activities and integration with harm reduction services. Conclusions This study indicates limited PrEP availability for people who inject drugs. There is potential to expand PrEP services for people who inject drugs within harm reduction programs, notably through community-based and peer-led services. PrEP should never be offered instead of evidence-based harm reduction programs for people who inject drugs; however, it could be offered as an additional HIV prevention choice as part of a comprehensive harm reduction program.

Abstract Introduction Pre‐exposure prophylaxis (PrEP) is an important HIV prevention option. Two randomized trials have provided efficacy evidence for long‐acting injectable cabotegravir (CAB‐LA) as PrEP. In considering CAB‐LA as an additional PrEP modality for people at substantial risk of HIV, it is important to understand community response to injectable PrEP. We conducted a systematic review of values, preferences and perceptions of acceptability for injectable PrEP to inform global guidance. Methods We searched nine databases and conference websites for peer‐reviewed and grey literature (January 2010−September 2021). There were no restrictions on location. A two‐stage review process assessed references against eligibility criteria. Data from included studies were organized by constructs from the Theoretical Framework of Acceptability. Results We included 62 unique references. Most studies were observational, cross‐sectional and qualitative. Over half of the studies were conducted in North America. Men who have sex with men were the most researched group. Most studies (57/62) examined injectable PrEP, including hypothetical injectables (55/57) or placebo products (2/57). Six studies examined CAB‐LA specifically. There was overall interest in and often a preference for injectable PrEP, though there was variation within and across groups and regions. Many stakeholders indicated that injectable PrEP could help address adherence challenges associated with daily or on‐demand dosing for oral PrEP and may be a better lifestyle fit for individuals seeking privacy, discretion and infrequent dosing. End‐users reported concerns, including fear of needles, injection site pain and body location, logistical challenges and waning or incomplete protection. Discussion Despite an overall preference for injectable PrEP, heterogeneity across groups and regions highlights the importance of enabling end‐users to choose a PrEP modality that supports effective use. Like other products, preference for injectable PrEP may change over time and end‐users may switch between prevention options. There will be a greater understanding of enacted preference as more end‐users are offered anti‐retroviral (ARV)‐containing injectables. Future research should focus on equitable implementation, including real‐time decision‐making and how trained healthcare providers can support choice. Conclusions Given overall acceptability, injectable PrEP should be included as part of a menu of prevention options, allowing end‐users to select the modality that suits their preferences, needs and lifestyle.

Abstract Introduction Data from two randomized controlled trials (RCTs) showed that injectable cabotegravir (CAB) for pre‐exposure prophylaxis (PrEP) was efficacious in reducing HIV acquisition. The US Food and Drug Administration approved CAB for PrEP in December 2021; Australia in August 2022; Zimbabwe in October 2022; South Africa in November 2022; Malawi in March 2023; and regulatory approvals are being sought in additional countries. The World Health Organization (WHO) recommended CAB be offered to people at substantial risk of HIV in July 2022. However, implementation experience beyond RCTs is limited. As countries consider CAB implementation, questions remain regarding delivery and involvement of populations excluded from the trials. A coordinated approach is needed to ensure these are addressed and CAB can be introduced in low‐ and middle‐income countries in timely, acceptable and effective ways. Discussion Beginning in 2018, the Biomedical Prevention Implementation Collaborative (BioPIC) convened over 100 global health experts to develop a comprehensive introduction strategy for CAB. Using this roadmap, country landscaping for CAB introduction and lessons from oral PrEP implementation, AVAC and WHO co‐convened 50 researchers, donors, implementers and civil society in September 2021 to: (1) identify questions and evidence gaps related to CAB across contexts and partners; (2) define the implementation science agenda; and (3) agree on mechanism(s) for future coordination. As a result, CAB‐related questions were identified, including: defining optimal and feasible HIV testing strategies that expand access; delivery models; integration with a range of services, including family planning and antenatal care; and embedding CAB in demand generation for HIV prevention choices. Through convenings and mapping of implementation research, BioPIC identified gaps in populations, geographies and delivery approaches. Conclusions The introduction strategy refined by BioPIC lays the groundwork for future HIV prevention products. Ongoing policy and implementation dialogue is critical to accelerate the design of CAB implementation studies that adequately address priority knowledge gaps. Additional long‐acting HIV prevention products may be available over the next 5 years, increasing choice, but potentially making delivery and stakeholder engagement more complex. Ongoing coordination with WHO will accelerate the adoption of evidence‐based policies and wide‐scale implementation, and lessons from BioPIC can inform introduction processes for long‐acting HIV prevention products.

Abstract 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.

ABSTRACT: Objectives: Molecular testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is costly. Therefore, we appraised the evidence regarding pooling samples from multiple individuals to test for CT/NG. Methods: In this systematic review, we searched 5 databases (2000-2021). Studies were included if they contained primary data describing pooled testing. We calculated the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. Results: We included 22 studies: most were conducted in high-income countries (81.8%, 18 of 22), among women (73.3%, 17 of 22), and pooled urine samples (63.6%, 14 of 22). Eighteen studies provided 25 estimates for the meta-analysis of diagnostic accuracy, with data from 6,913 pooled specimens. The pooled sensitivity for CT was 98.4% (95% confidence intervals [CI]: 96.8-99.2%, I2=77.5, p

Abstract 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.

BackgroundHIV testing services (HTS) are the first steps in reaching the UNAIDS 95-95-95 goals to achieve and maintain low HIV incidence. Evaluating the effectiveness of different demand creation interventions to increase uptake of efficient and effective HTS is useful to prioritize limited programmatic resources. This review was undertaken to inform World Health Organization (WHO) 2019 HIV testing guidelines and assessed the research question, "Which demand creation strategies are effective for enhancing uptake of HTS?" focused on populations globally.Methods and findingsThe following electronic databases were searched through September 28, 2021: PubMed, PsycInfo, Cochrane CENTRAL, CINAHL Complete, Web of Science Core Collection, EMBASE, and Global Health Database; we searched IAS and AIDS conferences. We systematically searched for randomized controlled trials (RCTs) that compared any demand creation intervention (incentives, mobilization, counseling, tailoring, and digital interventions) to either a control or other demand creation intervention and reported HTS uptake. We pooled trials to evaluate categories of demand creation interventions using random-effects models for meta-analysis and assessed study quality with Cochrane's risk of bias 1 tool. This study was funded by the WHO and registered in Prospero with ID CRD42022296947. We screened 10,583 records and 507 conference abstracts, reviewed 952 full texts, and included 124 RCTs for data extraction. The majority of studies were from the African (N = 53) and Americas (N = 54) regions. We found that mobilization (relative risk [RR]: 2.01, 95% confidence interval [CI]: [1.30, 3.09], p < 0.05; risk difference [RD]: 0.29, 95% CI [0.16, 0.43], p < 0.05, N = 4 RCTs), couple-oriented counseling (RR: 1.98, 95% CI [1.02, 3.86], p < 0.05; RD: 0.12, 95% CI [0.03, 0.21], p < 0.05, N = 4 RCTs), peer-led interventions (RR: 1.57, 95% CI [1.15, 2.15], p < 0.05; RD: 0.18, 95% CI [0.06, 0.31], p < 0.05, N = 10 RCTs), motivation-oriented counseling (RR: 1.53, 95% CI [1.07, 2.20], p < 0.05; RD: 0.17, 95% CI [0.00, 0.34], p < 0.05, N = 4 RCTs), short message service (SMS) (RR: 1.53, 95% CI [1.09, 2.16], p < 0.05; RD: 0.11, 95% CI [0.03, 0.19], p < 0.05, N = 5 RCTs), and conditional fixed value incentives (RR: 1.52, 95% CI [1.21, 1.91], p < 0.05; RD: 0.15, 95% CI [0.07, 0.22], p < 0.05, N = 11 RCTs) all significantly and importantly (≥50% relative increase) increased HTS uptake and had medium risk of bias. Lottery-based incentives and audio-based interventions less importantly (25% to 49% increase) but not significantly increased HTS uptake (medium risk of bias). Personal invitation letters and personalized message content significantly but not importantly (ConclusionsMobilization, couple- and motivation-oriented counseling, peer-led interventions, conditional fixed value incentives, and SMS are high-impact demand creation interventions and should be prioritized for programmatic consideration. Reduced duration counseling and video-based interventions are an efficient and effective alternative to address staffing shortages. Investment in demand creation activities should prioritize those with undiagnosed HIV or ongoing HIV exposure. Selection of demand creation interventions must consider risks and benefits, context-specific factors, feasibility and sustainability, country ownership, and universal health coverage across disease areas.

In this Policy Forum, Anna Grimsrud and colleagues discuss the future of HIV testing in eastern and southern Africa, using insights gleaned from a 2021 expert consultation.

Abstract Background Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at genital and extragenital sites is needed for most key populations, but molecular diagnostic tests for CT/NG are costly. We aimed to determine the accuracy of pooled samples from multiple anatomic sites from one individual to detect CT/NG using the testing of a single sample from one anatomic site as the reference. Methods In this systematic review and meta-analysis, we searched five databases for articles published from January 1, 2000, to February 4, 2021. Studies were included if they contained original data describing the diagnostic accuracy of pooled testing compared with single samples, resource use, benefits and harms of pooling, acceptability, and impact on health equity. We present the pooled sensitivities and specificities for CT and NG using a bivariate mixed-effects logistic regression model. The study protocol is registered in PROSPERO, an international database of prospectively registered systematic reviews (CRD42021240793). We used GRADE to evaluate the quality of evidence. Results Our search yielded 7814 studies, with 17 eligible studies included in our review. Most studies were conducted in high-income countries (82.6%, 14/17) and focused on men who have sex with men (70.6%, 12/17). Fourteen studies provided 15 estimates for the meta-analysis for CT with data from 5891 individuals. The pooled sensitivity for multisite pooling for CT was 93.1% [95% confidence intervals (CI) 90.5–95.0], I 2 =43.3, and pooled specificity was 99.4% [99.0–99.6], I 2 =52.9. Thirteen studies provided 14 estimates for the meta-analysis for NG with data from 6565 individuals. The pooled sensitivity for multisite pooling for NG was 94.1% [95% CI 90.9–96.3], I 2 =68.4, and pooled specificity was 99.6% [99.1–99.8], I 2 =83.6. Studies report significant cost savings (by two thirds to a third). Conclusion Multisite pooled testing is a promising approach to improve testing coverage for CT/NG in resource-constrained settings with a small compromise in sensitivity but with a potential for significant cost savings.

BackgroundDespite the growth of web-based interventions for HIV, viral hepatitis (VH), and sexually transmitted infections (STIs) for key populations, the evidence for the effectiveness of these interventions has not been reported. ObjectiveThis study aimed to inform the World Health Organization guidelines for HIV, VH, and STI prevention, diagnosis, and treatment services for key populations by systematically reviewing the effectiveness, values and preferences, and costs of web-based outreach, web-based case management, and targeted web-based health information for key populations (men who have sex with men, sex workers, people who inject drugs, trans and gender-diverse people, and people in prisons and other closed settings). MethodsWe searched CINAHL, PsycINFO, PubMed, and Embase in May 2021 for peer-reviewed studies; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials (RCTs) and observational studies. We assessed the risk of bias using the Cochrane Collaboration tool for RCTs and the Evidence Project and Risk of Bias in Non-randomized Studies of Interventions tools for non-RCTs. Values and preferences and cost data were summarized descriptively. ResultsOf 2711 records identified, we included 13 (0.48%) articles in the effectiveness review (3/13, 23% for web-based outreach; 7/13, 54% for web-based case management; and 3/13, 23% for targeted web-based health information), 15 (0.55%) articles in the values and preferences review, and 1 (0.04%) article in the costs review. Nearly all studies were conducted among men who have sex with men in the United States. These articles provided evidence that web-based approaches are as effective as face-to-face services in terms of reaching new people, use of HIV, VH, and STI prevention services, and linkage to and retention in HIV care. A meta-analysis of 2 RCTs among men who have sex with men in China found increased HIV testing after web-based outreach (relative risk 1.39, 95% CI 1.21-1.60). Among men who have sex with men in the United States, such interventions were considered feasible and acceptable. One cost study among Canadian men who have sex with men found that syphilis testing campaign advertisements had the lowest cost-per-click ratio on hookup platforms compared with more traditional social media platforms. ConclusionsWeb-based services for HIV, VH, and STIs may be a feasible and acceptable approach to expanding services to key populations with similar outcomes as standard of care, but more research is needed in low-resource settings, among key populations other than men who have sex with men, and for infections other than HIV (ie, VH and STIs).

Abstract Introduction The World Health Organization (WHO) is guided by its global programme of work and the goal that a billion more people have universal health coverage (UHC). To achieve UHC, access for those most vulnerable must be guaranteed and prioritized. WHO is committed to developing evidence‐based guidance to work towards UHC for trans and gender diverse (TGD) people. This commentary describes WHO's work related to TGD people over the last decade. Discussion In 2011, WHO developed guidelines for the prevention and treatment of HIV and sexually transmitted infections (STIs) in men who have sex with men and TGD people. In 2013, the “HIV civil society reference group” called on WHO to provide specific guidance for TGD people. Values and preferences of TGD people were considered by WHO for the first time, which informed the development of the 2014 WHO Consolidated Guidelines on HIV Prevention, Diagnosis, Treatment and Care for Key Populations. The 2014 Guidelines included a comprehensive package of HIV‐related health and enabling interventions with specific considerations for TGD people, as well as a specific policy brief in 2015. Regional WHO offices developed and/or supported the development of blueprints on transgender health and HIV in 2014 and 2016. A 2015 WHO report on sexual health, human rights and the law elucidated the harmful impacts of discriminatory laws on the basis of sexual orientation and gender identity. In 2019, the 11th edition of the international classification of diseases saw the removal of “transsexualism” as a mental and behavioural disorder. WHO's first guideline on self‐care interventions, updated in 2021, included key considerations concerning TGD people. In 2022, WHO's updated key populations guidelines include a prioritized package of not just HIV, but also viral hepatitis and STI health interventions for TGD people. Still, a broader and more specific health approach and a greater focus on social issues are needed to better serve the health needs of TGD people. Conclusions WHO's understanding and commitment to TGD people's health has evolved and improved over the past decade. Together with professional and community trans health organizations, WHO should now start developing evidence‐informed global guidance on TGD health as part of its remit to support UHC to all.

Abstract Background Despite the aging HIV epidemic, increasing age can be associated with hesitancy to test. Addressing this gap is a critical policy concern and highlights the urgent need to identify the underlying factors, to improve knowledge of HIV-related risks as well as uptake of HIV testing and prevention services, in midlife-older adults. Methods We conducted five focus group discussions and 12 in-depth interviews between April 2013 and November 2016 among rural and urban Malawian midlife-older (≥30 years) men and women. Using a life-course theoretical framework we explored how age is enacted socially and its implications on HIV testing and sexual risk behaviours. We also explore the potential for HIV self-testing (HIVST) to be part of a broader strategy for engaging midlife-older adults in HIV testing, prevention and care. Thematic analysis was used to identify recurrent themes and variations. Results Midlife-older adults (30–74 years of age) associated their age with respectability and identified HIV as “a disease of youth” that would not affect them, with age protecting them against infidelity and sexual risk-taking. HIV testing was felt to be stigmatizing, challenging age norms, threatening social status, and implying “lack of wisdom”. These norms drove self-testing preferences at home or other locations deemed age and gender appropriate. Awareness of the potential for long-standing undiagnosed HIV to be carried forward from past relationships was minimal, as was understanding of treatment-as-prevention. These norms led to HIV testing being perceived as a threat to status by older adults, contributing to low levels of recent HIV testing compared to younger adults. Conclusions Characteristics associated with age-gender norms and social position encourage self-testing but drive poor HIV-risk perception and unacceptability of conventional HIV testing in midlife-older adults. There is an urgent need to provide targeted messages and services more appropriate to midlife-older adults in sub-Saharan Africa. HIVST which has often been highlighted as a tool for reaching young people, may be a valuable tool for engaging midlife-older age groups who may not otherwise test.

There is limited information on contraceptive values and preferences of sex workers. We conducted a mixed-method study to explore contraceptive values and preferences among sex workers. We conducted an online survey with individuals from 38 countries (n = 239), 6 focus group discussions (FGD, n = 68) in Zimbabwe, and 12 in-depth phone interviews (IDI) across 4 world regions, in June and July of 2019. Participants were asked about awareness of contraceptives, methods they had used in the past, and the determinants of their choices. Differences between respondents from high-, low- and middle- income countries were examined. Qualitative data were analysed thematically. Survey participants reported an awareness of modern contraceptive methods. FGDs found that younger women had lower awareness. Reports of condomless sex were common and modern contraceptive use was inconsistent. Determinants of contraceptive choices differed by setting according to results of the survey, FGD, and IDI. Regardless of country income level, determinants of contraceptive choices included ease of use, ease of access to a contraceptive method, and fewer side effects. Healthcare provider attitudes, availability of methods, and clinic schedules were important considerations. Most sex workers are aware of contraceptives, but barriers include male partners/clients, side effects, and health system factors such as access and clinic attitudes towards sex workers.

Abstract Background We update a previous systematic review to inform new World Health Organization HIV self-testing (HIVST) recommendations. We compared the effects of HIVST to standard HIV testing services to understand which service delivery models are effective for key populations. Methods We did a systematic review of randomised controlled trials (RCTs) which compared HIVST to standard HIV testing in key populations, published from 1 January 2006 to 4 June 2019 in PubMed, Embase, Global Index Medicus, Social Policy and Practice, PsycINFO, Health Management Information Consortium, EBSCO CINAHL Plus, Cochrane Library and Web of Science. We extracted study characteristic and outcome data and conducted risk of bias assessments using the Cochrane ROB tool version 1. Random effects meta-analyses were conducted, and pooled effect estimates were assessed along with other evidence characteristics to determine the overall strength of the evidence using GRADE methodology. Results After screening 5909 titles and abstracts, we identified 10 RCTs which reported on testing outcomes. These included 9679 participants, of whom 5486 were men who have sex with men (MSM), 72 were trans people and 4121 were female sex workers. Service delivery models included facility-based, online/mail and peer distribution. Support components were highly diverse and ranged from helplines to training and supervision. HIVST increased testing uptake by 1.45 times (RR=1.45 95% CI 1.20, 1.75). For MSM and small numbers of trans people, HIVST increased the mean number of HIV tests by 2.56 over follow-up (mean difference = 2.56; 95% CI 1.24, 3.88). There was no difference between HIVST and SoC in regard to positivity among tested overall (RR = 0.91; 95% CI 0.73, 1.15); in sensitivity analysis of positivity among randomised HIVST identified significantly more HIV infections among MSM and trans people (RR = 2.21; 95% CI 1.20, 4.08) and in online/mail distribution systems (RR = 2.21; 95% CI 1.14, 4.32). Yield of positive results in FSW was not significantly different between HIVST and SoC. HIVST reduced linkage to care by 17% compared to SoC overall (RR = 0.83; 95% CI 0.74, 0.92). Impacts on STI testing were mixed; two RCTs showed no decreases in STI testing while one showed significantly lower STI testing in the intervention arm. There were no negative impacts on condom use (RR = 0.95; 95% CI 0.83, 1.08), and social harm was very rare. Conclusions HIVST is safe and increases testing uptake and frequency as well as yield of positive results for MSM and trans people without negative effects on linkage to HIV care, STI testing, condom use or social harm. Testing uptake was increased for FSW, yield of positive results were not and linkage to HIV care was worse. Strategies to improve linkage to care outcomes for both groups are crucial for effective roll-out.

Abstract Background Many southern African countries are nearing the global goal of diagnosing 90% of people with HIV by 2020. In 2016, 84 and 86% of people with HIV knew their status in Malawi and Zimbabwe, respectively. However, gaps remain, particularly among men. We investigated awareness and use of, and willingness to self-test for HIV and explored sociodemographic associations before large-scale implementation. Methods We pooled responses from two of the first cross-sectional Demographic and Health Surveys to include HIV self-testing (HIVST) questions in Malawi and Zimbabwe in 2015–16. We investigated sociodemographic factors and sexual risk behaviours associated with previously testing for HIV, and past use, awareness of, and future willingness to self-test using univariable and multivariable logistic regression, adjusting for the sample design and limiting analysis to participants with a completed questionnaire and valid HIV test result. We restricted analysis of willingness to self-test to Zimbabwean men, as women and Malawians were not systematically asked this question. Results Of 31,385 individuals, 31.2% of men had never tested compared with 16.5% of women (p

Introduction Novel mechanisms of service delivery are needed to expand access to pre-exposure prophylaxis (PrEP) for HIV prevention. Providing PrEP directly through pharmacies could offer an additional option for reaching potential users.Methods We conducted a systematic review of studies examining effectiveness, values and preferences of end users and health workers, and cost of PrEP initiation and continuation through pharmacies (pharmacy access). We searched PubMed, CINAHL, LILACS and EMBASE through 2 December 2020. We also searched clinical trial registries and recent HIV conference abstracts. Standardised methods were used to search, screen and extract data from included studies.Results No studies met the inclusion criteria for the effectiveness review, for either PrEP initiation or continuation. However, six ‘case studies’ presenting non-comparative data from PrEP pharmacy programmes demonstrated feasibility of this model in the USA. Eleven studies reported values and preferences of end users and health workers. In the USA, Kenya and South Africa, potential PrEP clients generally supported pharmacy access, although some preferred clinics. One study of PrEP pharmacy clients found all would ‘definitely recommend’ the programme. Six studies found pharmacists were generally supportive of offering PrEP; one study including doctors found more limited favour, while one study of diverse Kenyan stakeholders found broad support. Three studies reported cost data indicating client willingness to pay in the USA and Kenya and initial sustainability of a clinic financial model in the USA.Conclusion Provision of PrEP through pharmacies has been demonstrated to be feasible in the USA and acceptable to potential end users and stakeholders in multiple settings. Limited evidence on effectiveness and requirements for laboratory testing and assurance of high-quality services may limit enthusiasm for this approach. Further research is needed to determine if pharmacy access is a safe and effective way to help achieve global HIV prevention goals.PROSPERO registration number CRD42021231650.

Objectives In sub-Saharan Africa (SSA) where HIV burden is highest, access to testing, a key entry point for prevention and treatment, remains low for adolescents (aged 10–19). Access may be hampered by policies requiring parental consent for adolescents to receive HIV testing services (HTS). In 2013, the WHO recommended countries to review HTS age of consent policies. Here, we investigate country progress and policies on age of consent for HIV testing.Design Comprehensive policy review.Data sources Policies addressing HTS were obtained through searching WHO repositories and governmental and non-governmental websites and consulting country and regional experts.Eligibility criteria HTS policies published by SSA governments before 2019 that included age of consent.Data extraction and synthesis Data were extracted on HTS age of consent including exceptions based on risk and maturity. Descriptive analyses of included policies were disaggregated by Eastern and Southern Africa (ESA) and Western and Central Africa (WCA) subregions.Results Thirty-nine policies were reviewed, 38 were eligible; 19/38 (50%) permitted HTS for adolescents ≤16 years old without parental consent. Of these, six allowed HTS at ≥12 years old, two at ≥13, two at ≥14, five at ≥15 and four at ≥16. In ESA, 71% (n=15/21) allowed those of ≤16 years old to access HTS, while only 24% (n=6/25) of WCA countries allowed the same. Maturity exceptions including marriage, sexual activity, pregnancy or key population were identified in 18 policies. In 2019, 63% (n=19/30) of policies with clear age-based criteria allowed adolescents of 12–16 years old to access HIV testing without parental consent, an increase from 37% (n=14/38) in 2013.Conclusions While many countries in SSA have revised their HTS policies, many do not specify age of consent. Revision of SSA consent to HTS policies, particularly in WCA, remains a priority to achieve the 2025 goal of 95% of people with HIV knowing their status.

Background: We updated a 2017 systematic review and compared the effects of HIV self-testing (HIVST) to standard HIV testing services to understand effective service delivery models among the general population. Methods: We included randomized controlled trials (RCTs) comparing testing outcomes with HIVST to standard testing in the general population and published between January 1, 2006 and June 4, 2019. Random effects meta-analysis was conducted and pooled risk ratios (RRs) were reported. The certainty of evidence was determined using the GRADE methodology. Findings: We identified 14 eligible RCTs, 13 of which were conducted in sub-Saharan Africa. Support provided to self-testers ranged from no/basic support to one-on-one in-person support. HIVST increased testing uptake overall (RR:2.09; 95% confidence interval: 1.69–2.58; p

Introduction: Offering HIV testing services (HTS) within sexual and reproductive health (SRH) services is a priority, especially for women who have a substantial risk. To reach women with HIV who do not know their status and prevent mother-to-child HIV transmission, the World Health Organization (WHO) recommends routinely offering HTS as part of family planning (FP) service delivery in high HIV burden settings. We conducted a landscape analysis to assess HTS uptake and HIV positivity in the context of FP/SRH services.Assessment of Research and Programs: We searched records from PubMed, four gray literature databases, and 13 organization websites, and emailed 24 organizations for data on HTS in FP/SRH services. We also obtained data from International Planned Parenthood Federation (IPPF) affiliates in Eswatini, Kenya, Lesotho, Malawi, Namibia, Uganda, Zambia, and Zimbabwe. Unique programs/studies from records were included if they provided data on, or barriers/facilitators to, offering HTS in FP/SRH. Overall, 2,197 records were screened and 12 unique programs/studies were eligible, including 10 from sub-Saharan Africa. Four reported on co-delivery of SRH services (including FP), with reported HTS uptake between 17 and 94%. Six reported data on HTS in FP services: four among general FP clients; one among couples; and one among female sex workers, adolescent girls, and young women. Two of the six reported HTS uptake >50% (51%, 419/814 Kenya; 63%, 5,930/9,439 Uganda), with positivity rates of 2% and 4.1%, respectively. Uptake was low (8%, 74/969 Kenya) in the one FP program offering pre-exposure prophylaxis. In the IPPF program, seven countries reported HTS uptake in FP services and ranged from 4% in Eswatini to 90% in Lesotho; between 0.6% (Uganda) and 8% (Eswatini) of those tested were HIV positive.Implications: Data on providing HTS in FP/SRH service delivery were sparse and HTS uptake varied widely across programs.Actionable Recommendations: As countries expand HTS in FP/SRH appropriate to epidemiology, they should ensure data are reported and monitored for progress and impact.

BackgroundUndiagnosed 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 findingsThis 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.ConclusionsIn 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 registrationClinicaltrials.gov NCT03541382.

Summary: 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.

BackgroundPre-exposure prophylaxis (PrEP), a WHO-recommended HIV prevention method for people at high risk for acquiring HIV, is being increasingly implemented in many countries. Setting programmatic targets, particularly in generalised epidemics, could incorporate estimates of the size of the population likely to be eligible for PrEP using incidence-based thresholds. We estimated the proportion of men and women who would be eligible for PrEP and the number of HIV infections that could be averted in Malawi, Mozambique, and Zambia using prioritisation based on age, sex, geography, and markers of risk.Methods and findingsWe analysed the latest nationally representative Demographic and Health Surveys (DHS) of Malawi, Mozambique, and Zambia to determine the proportion of adults who report behavioural markers of risk for HIV infection. We used prevalence ratios (PRs) to quantify the association of these factors with HIV status. Using a multiplier method, we combined these proportions with the number of new HIV infections by district, derived from district-level modelled HIV estimates. Based on these numbers, different scenarios were analysed for the minimum number of person-years on PrEP needed to prevent 1 HIV infection (NNP). An estimated total of 38,000, 108,000, and 46,000 new infections occurred in Malawi, Mozambique, and Zambia in 2016, corresponding with incidence rates of 0.43, 0.63, and 0.57 per 100 person-years. In these countries, 9%-20% of new infections occurred among people with a sexually transmitted infection (STI) in the past 12 months and 40%-42% among people with either an STI or a non-regular sexual partner (NP) in the past 12 months (STINP). The models estimate that around 50% of new infections occurred in districts with incidence rates ≥1.0% in Mozambique and Zambia and ≥0.5% in Malawi. In Malawi, Mozambique, and Zambia, 35.1%, 21.9%, and 12.5% of the population live in these high-incidence districts. In the most parsimonious scenario, if women aged 15-34 years and men 20-34 years with an STI in the past 12 months living in high-incidence districts were to take PrEP, it would take a minimum of 65.8 person-years on PrEP to avert 1 HIV infection per year in Malawi, 35.2 in Mozambique, and 16.4 in Zambia. Our findings suggest that 3,300, 5,200, and 1,700 new infections could be averted per year in the 3 countries, respectively. Limitations of our study are that these values are based on modelled estimates of HIV incidence and self-reported behavioural risk factors from national surveys.ConclusionsA large proportion of new HIV infections in these 3 African countries were estimated to occur among people who had either an STI or an NP in the past year, providing a straightforward means to set PrEP targets. Greater prioritisation of PrEP by district, sex, age, and behavioural risk factors resulted in lower NNPs thereby increasing PrEP cost-effectiveness, but also diminished the overall impact on reducing new infections.

Summary: 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).

Introduction Ensuring a correct and timely HIV diagnosis is critical. WHO publishes guidelines on HIV testing strategies that maximise the likelihood of correctly determining one’s HIV status. A review of national HIV testing policies in 2014 found low adherence to WHO guidelines. We updated this review to determine adherence to current recommendations.Methods We conducted a comprehensive policy review through April 2018. We extracted data on HIV testing strategies, recommendations on HIV retesting prior to antiretroviral therapy (ART) initiation and pre-exposure prophylaxis (PrEP)-related HIV testing information. Descriptive analyses disaggregated by region were conducted to ascertain adherence to recommendations and to describe testing strategy characteristics.Results Of 91 policies included, 26% (n=24/91) adhered to WHO recommendations. Having a two-assay testing strategy to rule-in HIV infection as opposed to the recommended three-assay testing strategy was a major reason for non-adherence. Of 72 country policies providing sufficient information, 31% (n=22) recommended retesting for HIV prior to initiating ART. Of 25 countries and two regions reporting PrEP-related HIV testing guidelines, almost all recommended testing prior to initiating PrEP and every 3 months during PrEP use.Conclusions Global adherence to WHO recommendations for HIV testing strategies have improved since 2014 but remain low. We found adherence existed on a continuum. Such a system provides insights into how countries can move towards adherence by making relatively minor changes to testing strategies. Guidance from WHO on the role of new HIV testing technologies within testing algorithms and identifying ways to simplify testing guidance is warranted.

BackgroundEconomic 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.MethodsEconomic 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.ResultsOf 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.ConclusionsEconomic 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.

BackgroundVoluntary medical male circumcision (VMMC) remains an essential component of combination HIV prevention services, particularly in priority countries in sub-Saharan Africa. As VMMC programs seek to maximize impact and efficiency, and to support World Health Organization guidance, specific uptake-enhancing strategies are critical to identify.MethodsWe systematically reviewed the literature to evaluate the impact of service delivery interventions (e.g., facility layout, service co-location, mobile outreach) on VMMC uptake among adolescent and adult men. For the main effectiveness review, we searched for publications or conference abstracts that measured VMMC uptake or uptake of HIV testing or risk reduction counselling within VMMC services. We synthesized data by coding categories and outcomes. We also reviewed studies assessing acceptability, values/preferences, costs, and feasibility.ResultsFour randomized controlled trials and five observational studies were included in the effectiveness review. Studies took place in South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. They assessed a range of service delivery innovations, including community-, school-, and facility-based interventions. Overall, interventions increased VMMC uptake; some successfully improved uptake among age-specific subpopulations, but urban-rural stratification showed no clear trends. Interventions that increased adult men's uptake included mobile services (compared to static facilities), home-based testing with active referral follow-up, and facility-based HIV testing with enhanced comprehensive sexual education. Six acceptability studies suggested interventions were generally perceived to help men choose to get circumcised. Eleven cost studies suggested interventions create economies-of-scale and efficiencies. Three studies suggested such interventions were feasible, improving facility preparedness, service quality and quantity, and efficiencies.ConclusionsInnovative changes in male-centered VMMC services can improve adult men's and adolescent boys' VMMC uptake. Limited evidence on interventions that enhance access and acceptability show promising results, but evidence gaps persist due to inconsistent intervention definition and delivery, due in part to contextual relevance and limited age disaggregation.

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.

Abstract Surveillance for human immunodeficiency virus (HIV) in low- and middle-income countries started in the 1980s. However, the questions of whether the results of HIV tests should be given to participants, and if so how, has still not been resolved. In the absence of effective treatment, it was considered acceptable to withhold results from HIV-positive participants. However, when antiretroviral treatment is available, some argue for beneficence - that it is the researcher's duty to return the test results to all those who provide samples for surveillance. The corollary is that only participants who wish to receive their test results would be eligible to participate in surveys. Others argue for autonomy - that to obtain a more representative result for the general population, surveys should not exclude participants who do not wish to receive their test results. This round table discussion takes a closer look at those two arguments. We believe that the global community should work towards routine feedback of HIV surveillance while ensuring that participants receive and understand their test results.

Introduction HIV testing is the entry point for the elimination of mother‐to‐child transmission of HIV. Decreasing external funding for the HIV response in some low‐ and middle‐income countries has triggered the question of whether a focused approach to HIV testing targeting pregnant women in high‐burden areas should be considered. This study aimed at determining and comparing the cost‐effectiveness of universal and focused HIV testing approaches for pregnant women across high to very low HIV prevalence settings. Methods We conducted a modelling analysis on health and cost outcomes of HIV testing for pregnant women using four country‐based case scenarios (Namibia, Kenya, Haiti and Viet Nam) to illustrate high, intermediate, low and very low HIV prevalence settings. We used subnational prevalence data to divide each country into high‐, medium‐ and low‐burden areas, and modelled different antenatal and testing coverage in each. Results When HIV testing services were only focused in high‐burden areas within a country, mother‐to‐child transmission rates remained high ranging from 18 to 23%, resulting in a 25 to 69% increase in new paediatric HIV infections and increased future treatment costs for children. Universal HIV testing was found to be dominant (i.e. more QALYs gained with less cost) compared to focused approaches in the Namibia, Kenya and Haiti scenarios. The universal approach was also very cost‐effective compared to focused approaches, with $ 125 per quality‐adjusted life years gained in the Viet Nam‐based scenario of very low HIV prevalence. Sensitivity analysis further supported the findings. Conclusions Universal approach to antenatal HIV testing achieves the best health outcomes and is cost‐saving or cost‐effective in the long term across the range of HIV prevalence settings. It is further a prerequisite for quality maternal and child healthcare and for the elimination of mother‐to‐child transmission of HIV.

Introduction The remarkable expansion in availability of antiretroviral therapy (ART) over the past two decades has transformed HIV infection into a manageable chronic condition. People with HIV infection now live long and healthy lives on treatment that is simpler, safer and cheaper. According to UNAIDS estimates, the global coverage of ART reached 46% in 2015, resulting in a 26% decrease in annual HIV‐related deaths since 2010. Such success has positioned treatment access at the centre of the global HIV response as a way to prevent mortality, morbidity and HIV transmission through a “Treat All” approach. Continuing expansion of treatment is needed to further reduce HIV‐related mortality. This progress with treatment, however, masks a stagnation in the estimated annual number of new HIV infections. Continuing levels of HIV incidence despite treatment scale‐up stem from several factors, which should be addressed in order to prevent new infections and decrease the numbers of people requiring treatment in the future. Discussion ART can only reach those already diagnosed, and although it is unclear what proportion of new infections occur during acute and early infection prior to treatment initiation, phylogenetic studies suggest that it might be substantial. Thus, better testing approaches to reach the 40% of people with undiagnosed HIV infection as early as possible are critical. New approaches to reach men, young people and key populations, where HIV risk is highest and HIV prevention, testing and treatment coverage is lowest, are also needed. Overall coverage of effective prevention interventions remains low, enabling HIV transmission to occur, or time is required to show population‐level effects. For example, the full impact of the medical male circumcision intervention will be seen once a larger proportion of men in age cohorts with high incidence are circumcised. Finally, strategically focused pre‐exposure prophylaxis interventions have the potential to prevent HIV acquisition among populations at substantial risk, averting treatment costs in coming years. Conclusions The United Nations (UN) targets to end AIDS include the “90‐90‐90” targets for HIV diagnosis, treatment and viral suppression. While 90‐90‐90 has been widely emphasized and adopted by countries and international funders, the focus thus far has largely been on increasing access to ART – the second “90.” A similar emphasis on achieving UN HIV prevention targets and adequate funding for meeting these is essential, alongside treatment, in order to reduce population‐level incidence and change the trajectory of the HIV epidemic over the long term.

This paper examines the ethical, economic and social issues that should be considered when antiretroviral interventions are being planned to reduce mother-to-child transmission of the human immunodeficiency virus. Interventions aiming to reduce mother-to-child transmission should be concerned with the rights of both the child and the mother. Women should not be seen as vectors of transmission but as people entitled to adequate health care and social services in their own right. For women accepting mother-to-child transmission interventions it is important to consider their medical and emotional needs and to ensure that they are not stigmatized or subjected to abuse or abandonment following voluntary counselling and testing. Seropositive women who do not wish to continue with pregnancy should have access to facilities for safe termination if this is legal in the country concerned. Problems arise in relation to the basic requirements for introducing such interventions via the health services in developing countries. A framework is given for making decisions about implementation of interventions in health care systems with limited resources where there is a relatively high prevalence of human immunodeficiency virus infection among pregnant women.