Children are highly susceptible to tuberculosis; thus, there is need for safe and effective preventive interventions. Our objective was to evaluate the efficacy of isoniazid in prevention of tuberculosis morbidity and mortality in children aged 15 years or younger by performing a meta-analysis of randomized controlled trials. To our knowledge, this is the first meta-analysis evaluating efficacy of isoniazid prophylaxis in prevention of tuberculosis in children.

Despite substantial progress, gaps in the HIV care cascade remain large: globally, while about 36.7 million people were living with HIV in 2015, 11.9 million of these individuals did not know their HIV status, 12.7 million were in need of antiretroviral therapy (ART) and 13.0 million were not virally suppressed. We sought to deepen understanding of the barriers to care engagement at three critical steps of the care cascade proposed to make greatest impact for attaining the UNAIDS 90-90-90 targets aimed at shutting down the HIV epidemic. Analyses were conducted among HIV-infected adults in rural East Africa. Qualitative data were collected using in-depth interviews among 63 individuals participating in an ongoing test-and treat trial (NCT01864683) in its baseline year (July 2013-June 2014). Audio recordings were transcribed, translated into English, and coded using Atlas.ti software. Data were analyzed using a thematic framework for explaining barriers to care engagement that drew upon both theory and prior empirical research in similar settings. Multiple barriers to engagement in care were observed. HIV-related stigma across dimensions of anticipated, internalized and enacted stigma manifested in denial and fears of disclosure, and influenced lapses in care engagement across multiple steps in the cascade. Poverty (lack of food and transport), lack of social support, work interference, prior negative experiences with health services, drug side effects, and treatment fatigue also negatively affected ART adherence and viral suppression. Gender differences were observed, with work interference and denial disproportionately affecting men compared to women. Multiple barriers to HIV care engagement still pervade rural sub-Saharan settings threatening the realization of the UNAIDS 90-90-90 targets. To control the epidemic, efforts need to be accelerated to combat stigma. Patient economic empowerment, innovative drug formulations, as well as more patient-responsive health systems, may help overcome barriers to engagement in care.

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Introduction: Optimizing HIV prevention may require structured approaches for providing client‐centred choices as well as community‐based entry points and delivery. We evaluated the effect of a dynamic choice model for HIV prevention, delivered by community health workers (CHWs) with clinician support, on the use of biomedical prevention among persons at risk of HIV in rural East Africa.Methods: We conducted a cluster randomized trial among persons (≥15 years) with current or anticipated HIV risk in 16 villages in Uganda and Kenya (SEARCH; NCT04810650). The intervention was a client‐centred HIV prevention model, including (1) structured client choice of product (pre‐exposure prophylaxis [PrEP] or post‐exposure prophylaxis [PEP]), service location (clinic or out‐of‐clinic) and HIV testing modality (self‐test or rapid test), with the ability to switch over time; (2) a structured assessment of patient barriers and development of a personalized support plan; and (3) phone access to a clinician 24/7. The intervention was delivered by CHWs and supported by clinicians who oversaw PrEP and PEP initiation and monitoring. Participants in control villages were referred to local health facilities for HIV prevention services, delivered by Ministry of Health staff. The primary outcome was biomedical prevention coverage: a proportion of 48‐week follow‐up with self‐reported PrEP or PEP use.Results: From May to July 2021, we enrolled 429 people (212 intervention; 217 control): 57% women and 35% aged 15–24 years. Among intervention participants, 58% chose PrEP and 58% chose PEP at least once over follow‐up; self‐testing increased from 52% (baseline) to 71% (week 48); ≥98% chose out‐of‐facility service delivery. Among 413 (96%) participants with the primary outcome ascertained, average biomedical prevention coverage was 28.0% in the intervention versus 0.5% in the control: a difference of 27.5% (95% CI: 23.0–31.9%, p<0.001). Impact was larger during periods of self‐reported HIV risk: 36.6% coverage in intervention versus 0.9% in control, a difference of 35.7% (95% CI: 27.5–43.9, p<0.001). Intervention effects were seen across subgroups defined by sex, age group and alcohol use.Conclusions: A client‐centred dynamic choice HIV prevention intervention, including the option to switch between products and CHW‐based delivery in the community, increased biomedical prevention coverage by 27.5%. However, substantial person‐time at risk of HIV remained uncovered.

Introduction: Antiretroviral‐based HIV prevention, including pre‐exposure prophylaxis (PrEP), is expanding in generalized epidemic settings, but additional prevention options are needed for individuals with periodic, high‐risk sexual exposures. Non‐occupational post‐exposure prophylaxis (PEP) is recommended in global guidelines. However, in Africa, awareness of and access to PEP for sexual exposures are limited. We assessed feasibility, acceptability, uptake and adherence in a pilot study of a patient‐centred PEP programme with options for facility‐ or community‐based service delivery.Methods: After population‐level HIV testing with universal access to PrEP for persons at elevated HIV risk (SEARCH Trial:NCT01864603), we conducted a pilot PEP study in five rural communities in Kenya and Uganda between December 2018 and May 2019. We assessed barriers to PEP in the population and implemented an intervention to address these barriers, building on existing in‐country PEP protocols. We used community leaders for sensitization. Test kits and medications were acquired through the Ministry of Health supply chain and healthcare providers based at the Ministry of Health clinics were trained on PEP delivery. Additional intervention components were (a)PEP availability seven days/week, (b)PEP hotline staffed by providers and (c)option for out‐of‐facility medication delivery. We assessed implementation using the Proctor framework and measured seroconversions via repeat HIV testing. Successful “PEP completion” was defined as self‐reported adherence over four weeks of therapy with post‐PEP HIV testing.Results: Community leaders were able to sensitize and mobilize for PEP. The Ministry of Health supplied test kits and PEP medications; after training, healthcare providers delivered the 28‐day regimen with high completion rates. Among 124 persons who sought PEP, 66% were female, 24% were ≤25 years and 42% were fisherfolk. Of these, 20% reported exposure with a serodifferent partner, 72% with a new or existing relationship and 7% from transactional sex. 12% of all visits were conducted at out‐of‐facility community‐based sites; 35% of participants had ≥1 out‐of‐facility visit. No serious adverse events were reported. Overall, 85% met the definition of PEP completion. There were no HIV seroconversions.Conclusions: Among individuals with elevated‐risk exposures in rural East African communities, patient‐centred PEP was feasible, acceptable and provides a promising addition to the current prevention toolkit.

Introduction: As countries move toward universal HIV treatment, many individuals fail to link to care after diagnosis of HIV. Efficient and effective linkage strategies are needed. Methods: We implemented a patient-centered, multicomponent linkage strategy in the SEARCH “test-and-treat” trial (NCT 01864603) in Kenya and Uganda. After population-based, community-wide HIV testing, eligible participants were (1) introduced to clinic staff after testing, (2) provided a telephone “hot-line” for enquiries, (3) provided an appointment reminder phone call, (4) given transport reimbursement on linkage, and (5) tracked if linkage appointment was missed. We estimated the proportion linked to care within 1 year and evaluated factors associated with linkage at 7, 30, and 365 days after diagnosis. Results: Among 71,308 adults tested, 6811 (9.6%) were HIV-infected; of these, 4760 (69.9%) were already in HIV care, and 30.1% were not. Among 2051 not in care, 58% were female, median age was 32 (interquartile range 26–40) years, and median CD4 count was 493 (interquartile range 331–683) cells/µL. Half (49.7%) linked within 1 week, and 73.4% linked within 1 year. Individuals who were younger [15–34 vs. >35 years, adjusted Risk Ratio (aRR) 0.83, 95% confidence interval (CI): 0.74 to 0.94], tested at home vs. community campaign (aRR = 0.87, 95% CI: 0.81 to 0.94), had a high HIV-risk vs. low-risk occupation (aRR = 0.81, 95% CI: 0.75 to 0.88), and were wealthier (aRR 0.90, 95% CI: 0.83 to 0.97) were less likely to link. Linkage did not differ by marital status, stable residence, level of education, or having a phone contact. Conclusions: Using a multicomponent linkage strategy, high proportions of people living with HIV but not in care linked rapidly after HIV testing.