A decade of PrEP: the evolution of HIV pre-exposure prophylaxis content and sentiments in South African print news media, 2012-2021.

After nearly a decade of HIV pre-exposure prophylaxis (PrEP) rollout in sub-Saharan Africa, there has been limited study of PrEP messaging in news media. We selected twenty South African newspapers with the highest circulation volumes to retrieve articles published in 2012-2021 mentioning PrEP (N = 249). Using inductive content analysis, we developed a structured codebook to characterise PrEP-related content and sentiments, as well as their evolution over time, in the South African press. Many articles espoused favourable attitudes towards PrEP (52%), but a sizeable fraction espoused unfavourable attitudes (11%). Relative to PrEP-favourable articles, PrEP-unfavourable articles were significantly more likely to emphasise the drawbacks/consequences of PrEP use, including adherence/persistence requirements (52% vs. 24%, p = .007), cost (48% vs. 11%, p < .001), and risk compensation (52% vs. 5%, p < .001). Nevertheless, the presence of these drawbacks/consequences in print media largely declined over time. Key populations (e.g. adolescents, female sex workers) were frequently mentioned potential PrEP candidates. Despite message variations over time, prevention effectiveness and adherence/persistence requirements were the most widely cited PrEP benefits and drawbacks, respectively. Study findings demonstrate the dynamic nature of PrEP coverage in the South African press, likely in response to PrEP scale-up and real-world PrEP implementation during the study period.

Estimating the mortality risk correcting for high loss to follow-up among female sex workers with HIV in Durban, South Africa, 2018-2021.

PURPOSE: This study assesses risk factors of loss to follow-up (LTFU) and estimates mortality risk among female sex workers (FSW) with HIV in Durban, South Africa, in 2018-2021. METHODS: We used data from the Siyaphambili trial, which evaluated strategies for improved viral suppression. FSW with HIV aged ≥ 18 years with viral load ≥ 50 copies/mL were followed up for 18 months. LTFU was defined as absence from study or intervention visits for 6 months. We traced LTFU participants by calling/in-person visit attempts to ascertain their vital status. We used Cox regression to determine risk factors of LTFU and inverse probability of tracing weights to correct mortality risk. RESULTS: Of 777 participants, 10 (1.3%) had died and 578 (74.4%) were initially LTFU. Among those LTFU, 36.3% (210/578) were traced successfully, with 6 additional deaths ascertained. Recent physical and sexual violence, and non-viral suppression were associated with increased LTFU. The unweighted and weighted 18-month mortality risks were 2.4% (95% CI: 0.8%-3.9%) and 3.7% (95% CI: 1.8%-5.9%), respectively. CONCLUSIONS: LTFU is common among FSW with HIV in South Africa with additional investigation of vital status demonstrating under-ascertained mortality. These data suggest the need for comprehensively addressing risks for mortality among FSW.

Polysubstance Use Profiles and HIV Viremia in a South African Cohort of Female Sex Workers: A Latent Class Analysis.

BACKGROUND: Given intersecting social and structural factors, female sex workers (FSW) exhibit elevated risk of HIV and substance use. However, there is limited study of how distinct substance use typologies influence HIV treatment outcomes among FSW. SETTING: A cross-sectional survey with objective viral load assessments of 1391 FSW enrolled into a treatment optimization-focused trial in Durban, South Africa (2018-2020). METHODS: We used latent class analysis to uncover discrete patterns in past-month self-reported use of the following substances: heavy alcohol use, cannabis, cocaine, crack, ecstasy, methamphetamine, heroin, and Whoonga . We used Wald tests to identify multilevel predictors of latent class membership and multivariable mixture modeling to quantify associations of substance use classes with HIV viremia (≥50 RNA copies/mL). RESULTS: Substance use (87%) and HIV viremia (62%) were highly prevalent. Latent class analysis uncovered 3 polysubstance use profiles: Heavy Alcohol Use Only (∼54%); Cannabis, Heavy Alcohol, & Crack Use (∼28%); and Whoonga & Crack Use (∼18%). Whoonga & Crack Use was associated with social and structural adversities, including homelessness, outdoor/public sex work, HIV stigma, and violence. Relative to Heavy Alcohol Use Only , HIV viremia was significantly higher in the Whoonga & Crack Use class (adjusted odds ratio 1.97, 95% confidence interval: 1.13 to 3.43), but not in the Cannabis, Heavy Alcohol, & Crack Use class (adjusted odds ratio 1.17, 95% confidence interval: 0.74 to 1.86). CONCLUSION: HIV viremia differed significantly across identified polysubstance use profiles among South African FSW. Integrating drug treatment and harm reduction services into HIV treatment programs is key to improving virologic outcomes in marginalized communities.

Effect of implementation strategies on pre-exposure prophylaxis persistence among female sex workers in South Africa: an interrupted time series study.

BACKGROUND: A disproportionate number of new HIV infections in South Africa are among female sex workers; pre-exposure prophylaxis (PrEP) for HIV prevention is freely available to female sex workers in the country, but unique barriers challenge PrEP persistence. TB HIV Care, a large South African non-profit organisation that provides daily oral PrEP (tenofovir disoproxil fumarate and emtricitabine), has implemented multiple strategies to improve PrEP persistence. We aimed to evaluate the effect of different implementation strategies on PrEP persistence in a large-scale real-world setting. METHODS: In this interrupted time series study, we estimated level changes in 1-month oral PrEP persistence associated with roll-out of various implementation strategies among female sex workers across nine districts in South Africa. We used routinely collected data from TB HIV Care programme files from June 7, 2016, to April 30, 2021. Poisson regression of 1-month persistence was used to assess the effect of these strategies. In secondary analyses, we tested the association between each of the strategies and 4-month persistence. FINDINGS: The median 1-month PrEP persistence for female sex workers was 33% (IQR 27-40). SMS support and refill reminders were associated with an 11% relative increase in 1-month persistence (risk ratio [RR] 1·11, 95% CI 1·02-1·26) and clinical mentoring for PrEP providers was associated with a 127% relative increase (RR 2·27, 95% CI 1·94-2·66) among female sex workers. The loyalty rewards programme was negatively associated with 1-month persistence (RR 0·71, 95% CI 0·67-0·83). Although clinical mentoring improved 4-month persistence, SMS support text messages had no significant effect. INTERPRETATION: Identification and subsequent use of clinical mentoring for PrEP providers and SMS support and refill reminders might improve the usefulness of PrEP overall to prevent new HIV infections among female sex workers. PrEP persistence remains an important issue, and strategies to build on our findings are needed. FUNDING: National Institute of Mental Health and National Institute of Allergy and Infectious Diseases.

Latent Classes of Polysubstance Use and Associations with HIV Risk and Structural Vulnerabilities among Cisgender Women Who Engage in Street-Based Transactional Sex in Baltimore City.

We describe patterns of polysubstance use and associations with HIV risk-related behaviors among women engaged in street-based transactional sex, an understudied yet important population and area of research. This sample was restricted to cisgender women who reported drug use (n = 244) in the baseline of the longitudinal SAPPHIRE cohort study. Latent class analysis (LCA) was conducted using drug use measures (route of administration (injection/non-injection); type of drug (specific opioids, stimulants)) and selection based on fit statistics and qualitative interpretation of the classes. Polysubstance use was prevalent (89% ≥ 2), and 68% had injected drugs in the past 3 months. A three-class solution was selected: Class 1 ("heroin/cocaine use", 48.4% of sample), Class 2 ("poly-opioid use", 21.3%), and Class 3 ("poly-route, polysubstance use", 30.3%). Class 3 was significantly younger, and Class 2 was disproportionately non-White. Women reported high levels of housing (63%) and food (55%) insecurity, condomless sex with clients (40%), and client-perpetrated violence (35%), with no significant differences by class. Obtaining syringes from syringe services programs differed significantly by class, despite injection behaviors in all classes. Tailored HIV and overdose prevention programming that considers drug use patterns would strengthen their impact.

Altered 3D chromatin structure permits inversional recombination at the IgH locus.

Immunoglobulin heavy chain (IgH) genes are assembled by two sequential DNA rearrangement events that are initiated by recombination activating gene products (RAG) 1 and 2. Diversity (DH) gene segments rearrange first, followed by variable (VH) gene rearrangements. Here, we provide evidence that each rearrangement step is guided by different rules of engagement between rearranging gene segments. DH gene segments, which recombine by deletion of intervening DNA, must be located within a RAG1/2 scanning domain for efficient recombination. In the absence of intergenic control region 1, a regulatory sequence that delineates the RAG scanning domain on wild-type IgH alleles, VH and DH gene segments can recombine with each other by both deletion and inversion of intervening DNA. We propose that VH gene segments find their targets by distinct mechanisms from those that apply to DH gene segments. These distinctions may underlie differential allelic choice associated with each step of IgH gene assembly.

Low temperature decreases bone mass in mice: Implications for humans.

OBJECTIVES: Humans exhibit significant ecogeographic variation in bone size and shape. However, it is unclear how significantly environmental temperature influences cortical and trabecular bone, making it difficult to recognize adaptation versus acclimatization in past populations. There is some evidence that cold-induced bone loss results from sympathetic nervous system activation and can be reduced by nonshivering thermogenesis (NST) via uncoupling protein (UCP1) in brown adipose tissue (BAT). Here we test two hypotheses: (1) low temperature induces impaired cortical and trabecular bone acquisition and (2) UCP1, a marker of NST in BAT, increases in proportion to degree of low-temperature exposure. METHODS: We housed wildtype C57BL/6J male mice in pairs at 26 °C (thermoneutrality), 22 °C (standard), and 20 °C (cool) from 3 weeks to 6 or 12 weeks of age with access to food and water ad libitum (N = 8/group). RESULTS: Cool housed mice ate more but had lower body fat at 20 °C versus 26 °C. Mice at 20 °C had markedly lower distal femur trabecular bone volume fraction, thickness, and connectivity density and lower midshaft femur cortical bone area fraction versus mice at 26 °C (p < .05 for all). UCP1 expression in BAT was inversely related to temperature. DISCUSSION: These results support the hypothesis that low temperature was detrimental to bone mass acquisition. Nonshivering thermogenesis in brown adipose tissue increased in proportion to low-temperature exposure but was insufficient to prevent bone loss. These data show that chronic exposure to low temperature impairs bone architecture, suggesting climate may contribute to phenotypic variation in humans and other hominins.