Disease Progression in Children With Perinatal Human Immunodeficiency Virus Correlates With Increased PD-1+ CD8 T Cells That Coexpress Multiple Immune Checkpoints.

BACKGROUND: PD-1 marks exhausted T cells, with weak effector functions. Adults living with human immunodeficiency virus (HIV) have increased levels of PD-1+ CD8 T cells that correlate with HIV disease progression, yet little is known about the role of PD-1+ CD8 T cells in children with perinatal HIV. METHODS: We enrolled 76 Kenyan children with perinatal HIV and 43 children who were HIV unexposed and quantified PD-1 levels on CD8 T cells; their coexpression with immune checkpoints (ICs) 2B4, CD160, and TIM3; correlates with immune activation and HIV disease progression; and HIV-specific and -nonspecific proliferative responses. RESULTS: PD-1+ CD8 T-cell frequencies are elevated in children with perinatal HIV and associated with disease progression. The majority of PD-1+ CD8 T cells coexpress additional ICs. ART initiation lowers total PD-1 levels and coexpression of multiple ICs. The frequency of PD-1+2B4+CD160+TIM3- in PD-1+ CD8 T cells predicts weaker HIV-specific proliferative responses, suggesting that this subset is functionally exhausted. CONCLUSIONS: Children with perinatal HIV have high levels of PD-1+ CD8 T cells that are a heterogeneous population differentially coexpressing multiple ICs. Understanding the complex interplay of ICs is essential to guide the development of PD-1-directed immunotherapies for pediatric HIV remission and cure.

Correlations between oral Pre-Exposure Prophylaxis (PrEP) initiations and policies that enable the use of PrEP to address HIV globally.

Policies facilitating access to HIV prevention services, specifically for pre-exposure prophylaxis (PrEP), can foster enabling environments for service uptake. This analysis aims to establish whether policies enabling broad PrEP eligibility, HIV self-testing, and lowered age of consent to HIV testing and treatment services are correlated with PrEP uptake. Ages of consent vary by country, therefore this analysis focused on how age of consent policies, in general, affect adolescent PrEP uptake. Data was collected from the HIV Policy Lab and AVAC's Global PrEP Tracker, a database of approximately 334 PrEP projects operating across 95 countries, and linear regression and correlation analyses were conducted via STATA to examine relationships amongst national oral PrEP eligibility, HIV self-testing, lowered age of consent, and national cumulative oral PrEP initiations, as of December 2021. Of all 194 countries tracked by the HIV Policy Lab, only about 7% have adopted all three policies (HIV self-testing, lowered age of consent, and PrEP eligibility policies). Less than 50% have adopted have adopted at least one of these policies. Of the 54 countries that have fully adopted PrEP eligibility policies, less than 30% have co-adopted HIV self-testing or lowered age of consent policies. About 30% of these 194 countries have yet to adopt any of these policies, of which about 14% have indicated information is "unavailable" for at least one of the policies. Analyses conducted for the 91 countries tracked by both the HIV Policy Lab and the Global PrEP Tracker revealed a significant and positive relationship between cumulative individuals initiated on oral PrEP and adoption of HIV self-testing policies (p = 0.01, r = 0.26), lowered age of consent policies (p = 0.01, r = 0.25), and PrEP eligibility policies (p = 0.01, r = 0.26). Stronger advocacy efforts towards approving public health policies, such as those outlined in our analysis, that enshrine and enable access to HIV prevention are necessary.

Client and healthcare worker experiences with differentiated HIV treatment models in Eswatini.

INTRODUCTION: Universal access to antiretroviral therapy (ART) is a cornerstone of Eswatini's national HIV strategy, and the number of people on ART in the country more than tripled between 2010 and 2019. Building on these achievements, the Ministry of Health (MOH) is scaling up differentiated service delivery, including less-intensive differentiated ART (DART) models for people doing well on treatment. We conducted a mixed-methods study to explore client and health care worker (HCW) perceptions of DART in Eswatini. METHODS: The study included structured site assessments at 39 purposively selected health facilities (HF), key informant interviews with 20 HCW, a provider satisfaction survey with 172 HCW and a client satisfaction survey with 270 adults. RESULTS: All clients had been on ART for more than a year; 69% were on ART for ≥ 5 years. The most common DART models were Fast-Track (44%), Outreach (26%) and Community ART Groups (20%). HCW and clients appreciated DART, noting that the models often decrease provider workload and client wait time. Clients also reported that DART models helped them to adhere to ART, 96% said they were "very satisfied" with their current model, and 90% said they would recommend their model to others, highlighting convenience, efficiency and cost savings. The majority of HCW (52%) noted that implementation of DART reduced their workload, although some models, such as Outreach, were more labor-intensive. Each model had advantages and disadvantages; for example, clients concerned about stigma and inadvertent disclosure of HIV status were less interested in group models. CONCLUSIONS: Clients in DART models were very satisfied with their care. HCW were also supportive of the new approach to HIV treatment delivery, noting its advantages to HF, HCW and to clients. Given the heterogeneous needs of people living with HIV, no single DART model will suit every client; a diverse portfolio of DART models is likely the best strategy.