Background: HIV 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 findings: The 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 (<25% increase) increased HTS uptake (medium risk of bias). Reduced duration counseling had comparable performance to standard duration counseling (low risk of bias) and video-based interventions were comparable or better than in-person counseling (medium risk of bias). Heterogeneity of effect among pooled studies was high. This study was limited in that we restricted to randomized trials, which may be systematically less readily available for key populations; additionally, we compare only pooled estimates for interventions with multiple studies rather than single study estimates, and there was evidence of publication bias for several interventions. Conclusions: Mobilization, 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.

Introduction: Predictors of neurodevelopment among children who are HIV‐exposed uninfected (CHEU) are poorly understood.Methods: Mothers with and without HIV and their children were enrolled during 6‐week postnatal care visits across seven sites in Kenya between March 2021 and June 2022. Infant neurodevelopment was assessed using the Malawi Developmental Assessment Tool, including social, language, fine motor and gross motor domains. We used multivariate linear mixed effects models to identify associations between 1‐year neurodevelopment scores, HIV and antiretroviral therapy (ART) exposures, and household factors, adjusted for potential confounders and clustered by the site.Results: At 1‐year evaluation, CHEU (n = 709) and children who are HIV‐unexposed uninfected (CHUU) (n = 715) had comparable median age (52 weeks) and sex distribution (49% vs. 52% female). Mothers living with HIV were older (31 vs. 27 years), had lower education (50% vs. 26% primary) and were more likely to be report moderate‐to‐severe food insecurity (26% vs. 9%) (p < 0.01 for all). Compared to CHUU, CHEU had higher language scores (adjusted coeff: 0.23, 95% CI: 0.06, 0.39) and comparable social, fine and gross motor scores. Among all children, preterm birth was associated with lower gross motor scores (adjusted coeff: −1.38, 95% CI: −2.05, −0.71), food insecurity was associated with lower social scores (adjusted coeff: −0.37, 95% CI: −0.73, −0.01) and maternal report of intimate partner violence (IPV) was associated with lower fine motor (adjusted coeff: −0.76, 95% CI: −1.40, −0.13) and gross motor scores (adjusted coeff: −1.07, 95% CI: −1.81, −0.33). Among CHEU, in utero efavirenz (EFV) exposure during pregnancy was associated with lower gross motor scores compared to dolutegravir (DTG) exposure (adjusted coeff: −0.51, 95% CI: −1.01, −0.03). Lower fine and gross motor scores were also associated with having a single or widowed mother (adjusted coeff: −0.45, 95% CI: −0.87, −0.03) or a deceased or absent father (adjusted coeff: −0.81, 95% CI: −1.58, −0.05), respectively.Conclusions: Biologic and social factors were associated with child neurodevelopment. Despite socio‐demographic differences between CHEU and CHUU, 1‐year neurodevelopment was similar. Addressing IPV and food insecurity may provide benefits regardless of maternal HIV status. DTG use was associated with higher neurodevelopmental scores in CHEU, compared to EFV regimens, potentially contributing to a lack of neurodevelopmental difference between CHEU and CHUU.

Background: Secondary distribution of HIV self-testing kits (HIVST) to pregnant women attending antenatal care (ANC) clinics to give to their male partners is a promising strategy to increase testing coverage among men, but its costs are unknown. Methods: We conducted micro-costing of a trial evaluating secondary distribution of HIVST on pregnant women living with HIV (PWLHIV) in an ANC in Kampala, Uganda. Costs (2019 USD) were collected from program budgets, expenditure records, time and motion observations, and staff interviews and estimated for three scenarios: as-studied, reflecting full costs of the research intervention, Ministry of Health (MOH) implementation, reflecting the research intervention if implemented by the MOH, and MOH roll-out, the current strategy being used to roll out HIVST distribution. Results: In the as-studied scenario, cost of HIVST provision was $13.96/PWLHIV reached, and $11.89 and $10.55 per HIV-positive and HIV-negative male partner, respectively, who linked to a clinic for facility-based testing. In the MOH implementation scenario, costs were $9.45/PWLHIV, and $7.87 and $6.99, respectively, per HIV-positive and HIV-negative male partner linking to the clinic. In the MOH roll-out scenario, the cost of HIVST provision to pregnant women regardless of HIV status was $3.70/woman, and $6.65/HIV-positive male partner. Conclusion: Secondary distribution of HIVST from pregnant women can be implemented at reasonable cost to increase testing among men in Uganda and similar settings in Africa.

Background: The number of people living with HIV (PLHIV) in need of treatment monitoring in low-and-middle-income countries is rapidly expanding, straining existing laboratory capacity. Point-of-care viral load (POC VL) testing can alleviate the burden on centralized laboratories and enable faster delivery of results, improving clinical outcomes. However, implementation costs are uncertain and will depend on clinic testing volume. We sought to estimate the costs of decentralized POC VL testing compared to centralized laboratory testing for adults and children receiving HIV care in Kenya. Methods: We conducted microcosting to estimate the per-patient costs of POC VL testing compared to known costs of centralized laboratory testing. We completed time-and-motion observations and stakeholder interviews to assess personnel structures, staff time, equipment costs, and laboratory processes associated with POC VL administration. Capital costs were estimated using a 5 year lifespan and a 3% annual discount rate. Results: We estimated that POC VL testing cost USD $24.25 per test, assuming a clinic is conducting 100 VL tests per month. Test cartridge and laboratory equipment costs accounted for most of the cost (62% and 28%, respectively). Costs varied by number of VL tests conducted at the clinic, ranging from $54.93 to $18.12 per test assuming 20 to 500 VL tests per month, respectively. A VL test processed at a centralized laboratory was estimated to cost USD $25.65. Conclusion: POC VL testing for HIV treatment monitoring can be feasibly implemented in clinics within Kenya and costs declined with higher testing volumes. Our cost estimates are useful to policymakers in planning resource allocation and can inform cost-effectiveness analyses evaluating POC VL testing.

Introduction: Secondary distribution of HIV self‐tests (HIVST) by HIV‐negative pregnant women to male partners increases men's testing rates. We examined whether this strategy promotes male partner testing for pregnant women living with HIV (PWLHIV).Methods: We conducted an open‐label individually randomized trial in Kampala, Uganda, in which PWLHIV ≥18 years who reported a partner of unknown HIV status were randomized 2:1 to secondary distribution of HIVST for male partner(s) or standard‐of‐care (SOC; invitation letter to male partner for fast‐track testing). Women were followed until 12 months post‐partum. Male partners were offered confirmatory HIV testing and facilitated linkage to antiretroviral treatment (ART) or oral pre‐exposure prophylaxis (PrEP). Using intention‐to‐treat analysis, primary outcomes were male partner testing at the clinic and initiation on PrEP or ART evaluated through 12 months post‐partum (ClinicalTrials.gov, NCT03484533).Results: From November 2018 to March 2020, 500 PWLHIV were enrolled with a median age of 27 years (interquartile range [IQR] 23–30); 332 were randomized to HIVST and 168 to SOC with 437 PWLHIV (87.4%) completing 12 months follow‐up post‐partum. Of 236 male partners who tested at the clinic and enrolled (47.2%), their median age was 31 years (IQR 27–36), 45 (88.3%) men with HIV started ART and 113 (61.1%) HIV‐negative men started PrEP. There was no intervention effect on male partner testing (hazard ratio [HR] 1.04; 95% confidence interval [CI]: 0.79–1.37) or time to ART or PrEP initiation (HR 0.96; 95% CI: 0.69–1.33). Two male partners and two infants acquired HIV for an incidence of 0.99 per 100 person‐years (95% CI: 0.12–3.58) and 1.46 per 100 person‐years (95% CI: 0.18%–5.28%), respectively. Social harms related to study participation were experienced by six women (HIVST = 5, SOC = 1).Conclusions: Almost half of the partners of Ugandan PWLHIV tested for HIV with similar HIV testing rates and linkage to ART or PrEP among the secondary distribution of HIVST and SOC arms. Although half of men became aware of their HIV serostatus and linked to services, additional strategies to reach male partners of women in antenatal care are needed to increase HIV testing and linkage to services among men.

Background. The burden of the coronavirus disease 2019 (COVID-19) pandemic has been geographically disproportionate. Certain weather factors and population characteristics are thought to drive transmission, but studies examining these factors are limited. We aimed to identify weather, sociodemographic, and geographic drivers of COVID-19 at the global scale using a comprehensive collection of country/territory-level data, and to use discovered associations to estimate the timing of community transmission. Methods. We examined COVID-19 cases and deaths reported up to May 2, 2020 across 205 countries and territories in relation to weather data collected from capital cities for the eight weeks prior to and four weeks after the date of the first reported case, as well as country/territory-level population, geographic, and planetary data. We performed univariable and multivariable regression modeling and odds ratio analyses to investigate associations with COVID-19 cases, deaths, and epidemic growth rate. We also conducted maximum likelihood analysis to estimate the timing of initial community spread. Findings. Lower temperature (p<0.0001), lower humidity (p=0.006), higher altitude (p=0.0080), higher percentage of urban population (p<0.0001), increased air travelers (p=0.00019), and higher prevalence of obesity (p<0.0001) were strong independent predictors of national COVID-19 incidence, mortality, and epidemic growth rate. Temperature at 5-7 weeks before the first reported case best predicted epidemic growth, suggesting that significant community transmission was occurring on average 1-2 months prior to detection. Interpretation. The results of this ecologic analysis demonstrate that global COVID-19 burden and timing of country-level epidemic growth can be predicted by weather and population factors. In particular, we find that cool, dry, and higher altitude environments, as well as more urban and obese populations, may be conducive to more rapid epidemic spread. Funding sources: None.