Temporal Trends and Determinants of HIV Testing at Antenatal Care in Sub-Saharan Africa: A Pooled Analysis of Population-Based Surveys (2005-2021).

BACKGROUND: In sub-Saharan Africa (SSA), integrating HIV testing into antenatal care (ANC) has been crucial toward reducing mother-to-child transmission of HIV. With the introduction of new testing modalities, we explored temporal trends in HIV testing within and outside of ANC and identified sociodemographic determinants of testing during ANC. METHODS: We analyzed data from 139 nationally representative household surveys conducted between 2005 and 2021, including more than 2.2 million women aged 15-49 years in 41 SSA countries. We extracted data on women's recent HIV testing history (<24 months), by modality (ie, at ANC versus outside of ANC) and sociodemographic variables (ie, age, socioeconomic status, education level, number of births, urban/rural). We used Bayesian generalized linear mixed models to estimate HIV testing coverage and the proportion of those that tested as part of ANC. RESULTS: HIV testing coverage (<24 months) increased substantially between 2005 and 2021 from 8% to 38%, with significant variations between countries and subregions. Two percent of women received an HIV test in the 24 months preceding the survey interview as part of ANC in 2005 and 11% in 2021. Among women who received an HIV test in the 24 months preceding the survey, the probability of testing at ANC was significantly greater for multiparous, adolescent girls, rural women, women in the poorest wealth quintile, and women in West and Central Africa. CONCLUSION: ANC testing remains an important component to achieving high levels of HIV testing coverage and benefits otherwise underserved women, which could prove instrumental to progress toward universal knowledge of HIV status in SSA.

Mechanisms of metabolic stress induced cell death of human oligodendrocytes: relevance for progressive multiple sclerosis.

Oligodendrocyte (OL) injury and loss are central features of evolving lesions in multiple sclerosis. Potential causative mechanisms of OL loss include metabolic stress within the lesion microenvironment. Here we use the injury response of primary human OLs (hOLs) to metabolic stress (reduced glucose/nutrients) in vitro to help define the basis for the in situ features of OLs in cases of MS. Under metabolic stress in vitro, we detected reduction in ATP levels per cell that precede changes in survival. Autophagy was initially activated, although ATP levels were not altered by inhibitors (chloroquine) or activators (Torin-1). Prolonged stress resulted in autophagy failure, documented by non-fusion of autophagosomes and lysosomes. Consistent with our in vitro results, we detected higher expression of LC3, a marker of autophagosomes in OLs, in MS lesions compared to controls. Both in vitro and in situ, we observe a reduction in nuclear size of remaining OLs. Prolonged stress resulted in increased ROS and cleavage of spectrin, a target of Ca2+-dependent proteases. Cell death was however not prevented by inhibitors of ferroptosis or MPT-driven necrosis, the regulated cell death (RCD) pathways most likely to be activated by metabolic stress. hOLs have decreased expression of VDAC1, VDAC2, and of genes regulating iron accumulation and cyclophilin. RNA sequencing analyses did not identify activation of these RCD pathways in vitro or in MS cases. We conclude that this distinct response of hOLs, including resistance to RCD, reflects the combined impact of autophagy failure, increased ROS, and calcium influx, resulting in metabolic collapse and degeneration of cellular structural integrity. Defining the basis of OL injury and death provides guidance for development of neuro-protective strategies.

Regional and country-level trends in cervical cancer screening coverage in sub-Saharan Africa: A systematic analysis of population-based surveys (2000-2020).

BACKGROUND: Sub-Saharan Africa (SSA) has the highest cervical cancer (CC) burden globally-worsened by its HIV epidemics. In 2020, the World Health Organization (WHO) introduced a CC elimination strategy with goals for vaccination, screening, and treatment. To benchmark progress, we examined temporal trends in screening coverage, percent screened at least twice by the age of 45, screening coverage among women living with HIV (WLHIV), and pre-cancer treatment coverage in SSA. METHODS AND FINDINGS: We conducted a systematic analysis of cross-sectional population-based surveys. It included 52 surveys from 28 countries (2000 to 2020) with information on CC screening among women aged 25 to 49 years (N = 151,338 women). We estimated lifetime and past 3-year screening coverage by age, year, country, and HIV serostatus using a Bayesian multilevel model. Post-stratification and imputations were done to obtain aggregate national, regional, and SSA-level estimates. To measure re-screening by age 45, a life table model was developed. Finally, self-reported pre-cancer treatment coverage was pooled across surveys using a Bayesian meta-analysis. Overall, an estimated 14% (95% credible intervals [95% CrI]: 11% to 21%) of women aged 30 to 49 years had ever been screened for CC in 2020, with important regional and country-level differences. In Eastern and Western/Central Africa, regional screening coverages remained constant from 2000 to 2020 and WLHIV had greater odds of being screened compared to women without HIV. In Southern Africa, however, screening coverages increased and WLHIV had equal odds of screening. Notably this region was found to have higher screening coverage in comparison to other African regions. Rescreening rates were high among women who have already been screened; however, it was estimated that only 12% (95% CrI: 10% to 18%) of women had been screened twice or more by age 45 in 2020. Finally, treatment coverage among 4 countries with data was 84% (95% CrI: 70% to 95%). Limitations of our analyses include the paucity of data on screening modality and the few countries that had multiple surveys. CONCLUSION: Overall, CC screening coverage remains sub-optimal and did not improve much over the last 2 decades, outside of Southern Africa. Action is needed to increase screening coverage if CC elimination is to be achieved.

Population sizes, HIV prevalence, and HIV prevention among men who paid for sex in sub-Saharan Africa (2000-2020): A meta-analysis of 87 population-based surveys.

BACKGROUND: Key populations, including sex workers, are at high risk of HIV acquisition and transmission. Men who pay for sex can contribute to HIV transmission through sexual relationships with both sex workers and their other partners. To characterize the population of men who pay for sex in sub-Saharan Africa (SSA), we analyzed population size, HIV prevalence, and use of HIV prevention and treatment. METHODS AND FINDINGS: We performed random-effects meta-analyses of population-based surveys conducted in SSA from 2000 to 2020 with information on paid sex by men. We extracted population size, lifetime number of sexual partners, condom use, HIV prevalence, HIV testing, antiretroviral (ARV) use, and viral load suppression (VLS) among sexually active men. We pooled by regions and time periods, and assessed time trends using meta-regressions. We included 87 surveys, totaling over 368,000 male respondents (15-54 years old), from 35 countries representing 95% of men in SSA. Eight percent (95% CI 6%-10%; number of surveys [Ns] = 87) of sexually active men reported ever paying for sex. Condom use at last paid sex increased over time and was 68% (95% CI 64%-71%; Ns = 61) in surveys conducted from 2010 onwards. Men who paid for sex had higher HIV prevalence (prevalence ratio [PR] = 1.50; 95% CI 1.31-1.72; Ns = 52) and were more likely to have ever tested for HIV (PR = 1.14; 95% CI 1.06-1.24; Ns = 81) than men who had not paid for sex. Men living with HIV who paid for sex had similar levels of lifetime HIV testing (PR = 0.96; 95% CI 0.88-1.05; Ns = 18), ARV use (PR = 1.01; 95% CI 0.86-1.18; Ns = 8), and VLS (PR = 1.00; 95% CI 0.86-1.17; Ns = 9) as those living with HIV who did not pay for sex. Study limitations include a reliance on self-report of sensitive behaviors and the small number of surveys with information on ARV use and VLS. CONCLUSIONS: Paying for sex is prevalent, and men who ever paid for sex were 50% more likely to be living with HIV compared to other men in these 35 countries. Further prevention efforts are needed for this vulnerable population, including improved access to HIV testing and condom use initiatives. Men who pay for sex should be recognized as a priority population for HIV prevention.