Pediatric Antiretroviral Therapy Coverage and AIDS Deaths in the "Treat All" Era.

OBJECTIVES: In 2015, CD4-based clinical staging criteria for antiretroviral therapy (ART) initiation were removed, expanding ART eligibility ("Treat All") for children, who shoulder an outsized burden of HIV-related deaths. To quantify the impact of "Treat All" on pediatric HIV outcomes, we examined shifts in pediatric ART coverage and AIDS mortality before and after "Treat All" implementation. METHODS: We abstracted country-level ART coverage (proportion of children <15 years on ART) and AIDS mortality (deaths per 100 000 population) estimates over 11 years. For 91 countries, we also abstracted the year "Treat All" was incorporated into national guidelines. We used multivariable 2-way fixed effects negative binomial regression to estimate changes in pediatric ART coverage and AIDS mortality potentially attributable to "Treat All" expansion, reported as adjusted incidence rate ratios (adj.IRR) with 95% confidence intervals (95% CI). RESULTS: From 2010 to 2020, pediatric ART coverage tripled (16% to 54%), and AIDS-related deaths were halved (240 000 to 99 000). Compared with the pre-implementation period, observed ART coverage continued increasing after "Treat All" adoption, but this rate of increase declined by 6% (adj.IRR = 0.94, 95% CI: 0.91-0.98). AIDS mortality continued declining after "Treat All" adoption, but this rate of decline decreased by 8% (adj.IRR = 1.08, 95% CI: 1.05-1.11) in the post-implementation period. CONCLUSIONS: Although "Treat All" called for increased HIV treatment equity, ART coverage continues lagging in children and comprehensive approaches that address structural issues, including family-based services and intensified case-finding, are needed to close pediatric HIV treatment gaps.

Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunction.

Fibroblasts are a major cell population that perform critical functions in the wound healing process. In response to injury, they proliferate and migrate into the wound space, engaging in extracellular matrix (ECM) production, remodeling, and contraction. However, there is limited knowledge of how fibroblast functions are altered in diabetes. To address this gap, several state-of-the-art microscopy techniques were employed to investigate morphology, migration, ECM production, 2D traction, 3D contraction, and cell stiffness. Analysis of cell-derived matrix (CDM) revealed that diabetic fibroblasts produce thickened and less porous ECM that hindered migration of normal fibroblasts. In addition, diabetic fibroblasts were found to lose spindle-like shape, migrate slower, generate less traction force, exert limited 3D contractility, and have increased cell stiffness. These changes were due, in part, to a decreased level of active Rac1 and a lack of co-localization between F-actin and Waskott-Aldrich syndrome protein family verprolin homologous protein 2 (WAVE2). Interestingly, deletion of thrombospondin-2 (TSP2) in diabetic fibroblasts rescued these phenotypes and restored normal levels of active Rac1 and WAVE2-F-actin co-localization. These results provide a comprehensive view of the extent of diabetic fibroblast dysfunction, highlighting the regulatory role of the TSP2-Rac1-WAVE2-actin axis, and describing a new function of TSP2 in regulating cytoskeleton organization.

"She is the one who knows": A qualitative exploration of oral and injectable PrEP as part of a community empowerment approach to HIV prevention among female sex workers in the Dominican Republic and Tanzania.

Despite documented interest among female sex workers (FSW), uptake of oral pre-exposure prophylaxis (PrEP) for HIV prevention has been low. Recent trials and regulatory approval of long-acting injectable (LAI) PrEP offer new hope for the potential of this biomedical intervention. We examined FSW's PrEP-related interest and preferences regarding both oral and LAI PrEP situating these dynamics within their specific social and occupational realities. We conducted this work using qualitative methods across two distinct contexts by conducting 40 in-depth interviews with FSW in Tanzania and the Dominican Republic. Textual data was coded using iterative thematic content analysis. Analytic summaries were developed and reviewed to identify recurring themes. We systematically organized themes within each country and then compared across settings. Women in both settings expressed strong interest in PrEP seeing it as an important option to protect themselves in their work. Most participants preferred LAI PrEP due to expectations of reduced stigma and concerns about daily pill adherence and side effects. Occupational factors such as alcohol use, overnight dates with clients, and fear of violence from clients were identified as barriers to daily oral PrEP. LAI PrEP was seen as having the potential to reduce stress related to oral PrEP. Women who preferred pills discussed fear of needles, skepticism about the injections, and others relayed that taking a daily pill would not be challenging for them. There was a pre-dominant sentiment that women know best whether they are better suited for oral or LAI PrEP. Participants stressed the importance of FSW understanding both options to ensure informed decision-making around PrEP and described community-led peer education as key to delivering trusted information. Community empowerment approaches led by FSW which address structural and psychosocial constraints and promote safe work environments may facilitate equitable access and uptake of PrEP among FSW across settings.

"A dream come true": Perspectives on long-acting injectable antiretroviral therapy among female sex workers living with HIV from the Dominican Republic and Tanzania.

BACKGROUND: Long-acting injectable antiretroviral therapy (LA ART) was found to be non-inferior to daily oral ART in Phase 3 clinical trials. LA ART may offer an important alternative for people living with HIV with challenges adhering to daily oral ART or preferences for non-pill-based regimens. METHODS: Using a mixed methods approach integrating survey, in-depth interview and biological data from female sex workers (FSW) living with HIV in Tanzania (N = 208) and the Dominican Republic (DR) (N = 201), we assessed factors associated with the potential likelihood of LA ART use if it were available. We conducted multivariate logistic regression and thematic content analysis. RESULTS: Likelihood of LA ART use was high with 84.92% of FSW from the DR and 92.27% of FSW from Tanzania reporting they would be "likely" or "very likely" to use LA ART if available (p = 0.02). In Tanzania better HIV-related patient-provider communication (AOR 4.58; 95% CI 1.90-11.05) and quality of HIV clinical care (AOR 3.68; 95% CI 1.05-12.86) were positively associated with the high likelihood of LA ART use. In the DR, easier clinic access was associated with a higher likelihood of LA ART use (AOR 3.04; 95% CI 1.41-6.56), as was greater monthly income from sex work (AOR 2.37; 95% CI 1.27-4.41). In both settings, years on ART was significantly associated with a strong likelihood of LA ART use (TZ: AOR 1.16 per year; 95% CI 1.00-1.34/DR: AOR 1.07 per year; 95% CI 1.00-1.14). Qualitative findings underscored enthusiasm for LA ART and reinforced its potential to address sex work-specific barriers to daily oral ART adherence including work-related schedules and substance use. CONCLUSIONS: We found a high likelihood of LA ART use if available among FSW in two diverse settings and documented barriers to future uptake. Community-driven approaches which include tailored health education and improved patient-provider communication and quality of care, as well as strategies to facilitate appointment adherence are needed to optimize LA ART use among FSW.

Essential elements of a community empowerment approach to HIV prevention among female sex workers engaged in project Shikamana in Iringa, Tanzania.

Globally, female sex workers bear a disproportionate burden of HIV, with those in sub-Saharan Africa being among the most affected. Community empowerment approaches have proven successful at preventing HIV among this population. These approaches facilitate a process whereby sex workers take collective ownership over programmes to address the barriers they face in accessing their health and human rights. Limited applications of such approaches have been documented in Africa. We describe the community empowerment process among female sex workers in Iringa, Tanzania, in the context of a randomised controlled trial of a community empowerment-based model of combination HIV prevention. We conducted 24 in-depth interviews with participants from the intervention community and 12 key informant interviews with HIV care providers, police, venue managers, community advisory board members and research staff. Content analysis was employed, and salient themes were extracted. Findings reveal that the community empowerment process was facilitated by the meaningful engagement of sex workers in programme development, encouraging sex worker ownership over the programme, providing opportunities for solidarity and capacity building, and forming partnerships with key stakeholders. Through this process, sex workers mobilised their collective agency to access their health and human rights including HIV prevention, care and treatment.