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IntroductionHIV self-testing (HIVST) is an innovative strategy that has been shown to increase uptake of HIV testing compared to conventional facility-based testing. HIVST implementation with digital-based supports may help facilitate testing accessibility and linkage to care after a reactive self-test. Economic evidence around community-based implementation of HIVST is growing; however, economic evidence around digital-based HIVST approaches remains limited.MethodsWe used previously published cost and efficacy data from HIVST interventions, with the specific intervention model differing between scenarios. Digital-based interventions included text messaging campaigns and online websites that promoted uptake and linkage to HIVST care. Community-based interventions included door-to-door distribution, peer-incentivized distribution, and mobile testing units. Using data obtained from the literature, we parameterized a combined Markov and decision analytic model to evaluate the cost-utility of digital-based HIVST implementation across Malawi, South Africa, and Brazil compared to both community-based HIVST and facility-based testing.ResultsWe found that HIVST was cost-effective compared to facility-based testing in all settings investigated. Our scenarios predicted that digital-based HIVST was associated with an incremental cost in the range of $769–$17,839/DALY (disability-adjusted life year) averted compared to facility-based testing across Malawi, South Africa, and Brazil. Digital-based HIVST cost savings had an incremental cost of $7,300/DALY averted compared to community-based HIVST. The main drivers of cost-utility included HIV test and treatment costs, HIV test-positivity, rates of linkage to care, and antiretroviral therapy (ART) initiation rates. Digital-based supports were associated with an increased cost compared to facility-based testing, but they also had increased utility, which led to favorable cost-utility estimates.DiscussionHIVST with digital supports has the potential to be a highly cost-effective approach, with the potential to make HIV testing more available and accessible, thereby increasing overall uptake and coverage of HIV testing. Digital supports can also support linkage to care, which we have identified as a major driver of cost-utility. Strategies to improve cost-utility include reducing testing costs, targeting key populations with increased rates of HIV test-positivity, and ensuring strong support for linkage to care.

[This corrects the article DOI: 10.1371/journal.ppat.1006939.].

Once considered a phenotypically monomorphic bacterium, there is a growing body of work demonstrating heterogeneity among Mycobacterium tuberculosis (Mtb) strains in clinically relevant characteristics, including virulence and response to antibiotics. However, the genetic and molecular basis for most phenotypic differences among Mtb strains remains unknown. To investigate the basis of strain variation in Mtb, we performed genome-wide transposon mutagenesis coupled with next-generation sequencing (TnSeq) for a panel of Mtb clinical isolates and the reference strain H37Rv to compare genetic requirements for in vitro growth across these strains. We developed an analytic approach to identify quantitative differences in genetic requirements between these genetically diverse strains, which vary in genomic structure and gene content. Using this methodology, we found differences between strains in their requirements for genes involved in fundamental cellular processes, including redox homeostasis and central carbon metabolism. Among the genes with differential requirements were katG, which encodes the activator of the first-line antitubercular agent isoniazid, and glcB, which encodes malate synthase, the target of a novel small-molecule inhibitor. Differences among strains in their requirement for katG and glcB predicted differences in their response to these antimicrobial agents. Importantly, these strain-specific differences in antibiotic response could not be predicted by genetic variants identified through whole genome sequencing or by gene expression analysis. Our results provide novel insight into the basis of variation among Mtb strains and demonstrate that TnSeq is a scalable method to predict clinically important phenotypic differences among Mtb strains.

ObjectivesHIV self-testing (HIVST) has been proposed as an innovative strategy to diagnose human immunodeficiency virus (HIV). While HIVST offers the potential to broaden accessibility of early HIV diagnosis and treatment initiation, this testing strategy incurs additional cost and requires confirmatory testing and treatment. We have conducted the first systematic review to summarize the current economic literature for HIVST in low- and middle-income countries (LMICs).DesignA search strategy was developed including key terms for HIV, self-testing and cost-effectiveness and was conducted in Medline and Embase databases. Studies were included that reported costs per outcome and included both cost-effectiveness and cost-utility outcome measures. The search strategy identified publications up until August 15, 2023 were included. Abstract and full text screening was conducted and a standardized data abstraction form was used for included studies. Costs are reported in USD, 2020.ResultsOur search strategy identified 536 total titles from the search strategy, which were screened down to 25 relevant studies that provided both cost and outcome data on HIVST. There was significant heterogeneity in the HIVST intervention, study population, costs and outcomes reported among included studies. Cost per person tested ranged from $1.09–155. Cost per case diagnosed ranged from $20–1,277. Cost-utility estimates ranged from cost-saving to $1846 per DALY averted. Higher cost-effectiveness estimates were associated with more expensive testing algorithms with increased support for linkage to care and post-test counseling.ConclusionAll studies considered HIVST cost-effective although major drivers were identified included underlying HIV prevalence, testing cost and linkage to care. HIVST is likely to be cost-effective in a LMIC context, however policy makers should be aware of the drivers of cost-effectiveness when implementing HIVST programs as these underlying factors can impact the overall cost-effectiveness of HIVST.

Background: HIV self-testing (HIVST) is recommended by the WHO as an innovative strategy to reach UNAIDS targets to end HIV by 2030. HIVST with digital supports is defined as the use of digital interventions (e.g., website-based, social media, mobile HIVST applications (apps), text messaging (SMS), digital vending machines (digital VMs)) to improve the efficiency and impact of HIVST. HIVST deployment and integration in health services is an emerging priority. We conducted a systematic review aiming to close the gap in evidence that summarizes the impact of digitally supported HIVST and to inform policy recommendations. Methods: We searched PubMed and Embase for articles and abstracts on HIVST with digital supports published during the period February 1st, 2010 to June 15th, 2021, following Cochrane guidelines and PRISMA methodology. We assessed feasibility, acceptability, preference, and impact outcomes across all populations and study designs. Metrics reported were willingness to use HIVST, preferences for HIVST delivery, proportion of first-time testers, HIVST uptake, HIVST kit return rate, and linkage to care. Heterogeneity of the interventions and reported metrics precluded us from conducting a meta-analysis. Findings: 46 studies were narratively synthesized, of which 72% were observational and 28% were RCTs. Half of all studies (54%, 25/46) assessed web-based innovations (e.g., study websites, videos, chatbots), followed by social media (26%, 12/46), HIVST-specific apps (7%, 3/46), SMS (9%, 4/46), and digital VMs (4%, 2/46). Web-based innovations were found to be acceptable (77–97%), preferred over in-person and hybrid options by more first-time testers (47–48%), highly feasible (93–95%), and were overall effective in supporting linkage to care (53–100%). Social media and app-based innovations also had high acceptability (87–95%) and linkage to care proportions (80–100%). SMS innovations increased kit return rates (54–94%) and HIVST uptake among hard-to-reach groups. Finally, digital VMs were highly acceptable (54–93%), and HIVST uptake was six times greater when using digital VMs compared to distribution by community workers. Interpretation: HIVST with digital supports was deemed feasible, acceptable, preferable, and was shown to increase uptake, engage first-time testers and hard-to-reach populations, and successfully link participants to treatment. Findings pave the way for greater use of HIVST interventions with digital supports globally. Funding: This work was funded by the Foundation for Innovative New Diagnostics. The agency had no role in the decision to submit it for publication, however the funders contributing to the writing of the manuscript. NPP also acknowledges support from the Fonds de recherche du Quebec Sante (Senior scientist scholar award), The Canadian Institutes of Health Research (PJT 153149 and HBR 422155), Grand Challenges Canada (Transition to Scale award, 071005), the India-Canada centre for Innovative Multidisciplinary Partnerships to Accelerate Community Transformation and Sustainability (IC-IMPACTS), and the MUHC Foundation.