Delayed circadian rhythms in older Africans living with human immunodeficiency virus (HIV).

The increasing number of people living with human immunodeficiency virus, HIV, (PLWH) have an elevated incidence of risk for noncommunicable comorbidities, the aetiology of which remains incompletely understood. While sleep disturbances are often reported in PLWH, it is unknown to what extent they relate to changes in the circadian and/or sleep homeostatic processes. We studied the relationship between sleep characteristics, circadian phase, and HIV status in older adults from the HAALSI (Health and Ageing in Africa: a Longitudinal Study of an INDEPTH Community in South Africa) subsample of the Agincourt Health and Demographic Surveillance System in South Africa (n = 187, 36 human immunodeficiency virus positive [HIV+], age: 66.7 ± 11.5 years, range 45-93 years), where HIV prevalence is high and (in contrast to the global north) does not associate significantly with potentially confounding behavioural differences. In participants with valid actigraphy data (n = 172), regression analyses adjusted for age and sex indicated that HIV+ participants had slightly later sleep onset (ß = .16, p = .039), earlier sleep offset times (ß = -.16, p = .049) and shorter total sleep times (ß = -.20, p = .009) compared to the HIV negative (HIV-) participants. In a subset of participants (n = 51, 11 HIV+), we observed a later dim light melatonin onset (DLMO) in HIV+ (21:16 ± 01:47) than in HIV- (20:06 ± 00:58) participants (p = .006). This substantial difference remained when adjusted for age and sex (ß = 1.21; p = .006). In 36 participants (6 HIV+) with DLMO and actigraphy data, median phase angle of entrainment was -6 min in the HIV+ group and +1 h 25 min in the HIV- group. DLMO time correlated with sleep offset (ρ = 0.47, p = .005) but not sleep onset (ρ = -0.086, p = .623). Collectively, our data suggest that the sleep phase occurred earlier than what would be biologically optimal among the HIV+ participants. This is the first report of a mistimed circadian phase in PLWH, which has important potential implications for their health and well-being, especially given the well-established relationships between circadian asynchrony and sleep deprivation with poorer health outcomes.

HIV Related Behaviors Among Male Partners of Adolescent Girls and Young Women in Rural South Africa.

Improving men's engagement in HIV prevention is not only essential for reducing their own HIV risk but also the risk of transmitting HIV to their female partners. We conducted a cross-sectional survey using a population-based sample of men (age 18-30) who reported being a partner of an adolescent girls and young women (AGYW) in South Africa (N = 2827). We used logit-binomial regression models to examine associations among men's partnership characteristics, HIV risk perceptions, and HIV-related behaviors and examine differences by male partner age (younger men (18-24) vs. older men (25-30)) and age difference between partners (age-concordant (< 5 years) vs. age-disparate (≥ 5 years)). Most men reported inconsistent condom use (85%) and nearly half reported engaging in transactional sex (48%). Older men were just as likely as younger men, and men with age-disparate and age-concordant partners, to inconsistently use condoms, engage in transactional sex, and perpetrate intimate partner violence. Most men also reported a very high interest in pre-exposure prophylaxis (PrEP) (77%) and half reported having an HIV test in the past year (50%). There were no differences by male partner age or age difference between partners in PrEP interest but older men and men in age-discordant relationships were more likely than younger men and men in age-concordant relationships to have an HIV test in the past year. Male partners of AGYW in South Africa are engaging in HIV-related behaviors and need HIV prevention interventions to reduce risk for themselves and their female partners.

Validity of Self-Report for Ascertaining HIV Status Among Circular Migrants and Permanent Residents in South Africa: A Cross-Sectional, Population-Based Analysis.

While expanded HIV testing is needed in South Africa, increasing accurate self-report of HIV status is an essential parallel goal in this highly mobile population. If self-report can ascertain true HIV-positive status, persons with HIV (PWH) could be linked to life-saving care without the existing delays required by producing medical records or undergoing confirmatory testing, which are especially burdensome for the country's high prevalence of circular migrants. We used Wave 1 data from The Migration and Health Follow-Up Study, a representative adult cohort, including circular migrants and permanent residents, randomly sampled from the Agincourt Health and Demographic Surveillance System in a rural area of Mpumalanga Province. Within the analytic sample (n = 1,918), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of self-report were calculated with dried blood spot (DBS) HIV test results as the standard. Among in-person participants (n = 2,468), 88.8% consented to DBS-HIV testing. HIV prevalence was 25.3%. Sensitivity of self-report was 43.9% (95% CI: 39.5-48.5), PPV was 93.4% (95% CI: 89.5-96.0); specificity was 99.0% (95% CI: 98.3-99.4) and NPV was 83.9% (95% CI: 82.8-84.9). Self-report of an HIV-positive status was predictive of true status for both migrants and permanent residents in this high-prevalence setting. Persons who self-reported as living with HIV were almost always truly positive, supporting a change to clinical protocol to immediately connect persons who say they are HIV-positive to ART and counselling. However, 56% of PWH did not report as HIV-positive, highlighting the imperative to address barriers to disclosure.

Understanding the effects of universal test and treat on longitudinal HIV care outcomes among South African youth: a retrospective cohort study.

INTRODUCTION: Little is known about the effects of universal test and treat (UTT) policies on HIV care outcomes among youth living with HIV (YLHIV). Moreover, there is a paucity of information regarding when YLHIV are most susceptible to disengagement from care under the newest treatment guidelines. The longitudinal HIV care continuum is an underutilized tool that can provide a holistic understanding of population-level HIV care trajectories and be used to compare treatment outcomes across groups. We aimed to explore effects of the UTT policy on longitudinal outcomes among South African YLHIV and identify temporally precise opportunities for re-engaging this priority population in the UTT era. METHODS: Using medical record data, we conducted a retrospective cohort study among youth aged 18-24 diagnosed with HIV from August 2015-December 2018 in nine health care facilities in South Africa. We used Fine and Gray sub-distribution proportional hazards models to characterize longitudinal care continuum outcomes in the population overall and stratified by treatment era of diagnosis. We estimated the proportion of individuals in each stage of the continuum over time and the restricted mean time spent in each stage in the first year following diagnosis. Sub-group estimates were compared using differences. RESULTS: A total of 420 YLHIV were included. By day 365 following diagnosis, just 23% of individuals had no 90-or-more-day lapse in care and were virally suppressed. Those diagnosed in the UTT era spent less time as ART-naïve (mean difference=-19.3 days; 95% CI: -27.7, -10.9) and more time virally suppressed (mean difference = 17.7; 95% CI: 1.0, 34.4) compared to those diagnosed pre-UTT. Most individuals who were diagnosed in the UTT era and experienced a 90-or-more-day lapse in care disengaged between diagnosis and linkage to care or ART initiation and viral suppression. CONCLUSIONS: Implementation of UTT yielded modest improvements in time spent on ART and virally suppressed among South African YLHIV- however, meeting UNAIDS' 95-95-95 targets remains a challenge. Retention in care and re-engagement interventions that can be implemented between diagnosis and linkage to care and between ART initiation and viral suppression (e.g., longitudinal counseling) may be particularly important to improving care outcomes among South African YLHIV in the UTT era.

SARS-CoV-2 Seroprevalence after Third Wave of Infections, South Africa.

By November 2021, after the third wave of severe acute respiratory syndrome coronavirus 2 infections in South Africa, seroprevalence was 60% in a rural community and 70% in an urban community. High seroprevalence before the Omicron variant emerged may have contributed to reduced illness severity observed in the fourth wave.

Twin epidemics: the effects of HIV and systolic blood pressure on mortality risk in rural South Africa, 2010-2019.

BACKGROUND: Sub-Saharan African settings are experiencing dual epidemics of HIV and hypertension. We investigate effects of each condition on mortality and examine whether HIV and hypertension interact in determining mortality. METHODS: Data come from the 2010 Ha Nakekela population-based survey of individuals ages 40 and older (1,802 women; 1,107 men) nested in the Agincourt Health and socio-Demographic Surveillance System in rural South Africa, which provides mortality follow-up from population surveillance until mid-2019. Using discrete-time event history models stratified by sex, we assessed differential mortality risks according to baseline measures of HIV infection, HIV-1 RNA viral load, and systolic blood pressure. RESULTS: During the 8-year follow-up period, mortality was high (477 deaths). Survey weighted estimates are that 37% of men (mortality rate 987.53/100,000, 95% CI: 986.26 to 988.79) and 25% of women (mortality rate 937.28/100,000, 95% CI: 899.7 to 974.88) died. Over a quarter of participants were living with HIV (PLWH) at baseline, over 50% of whom had unsuppressed viral loads. The share of the population with a systolic blood pressure of 140mm Hg or higher increased from 24% at ages 40-59 to 50% at ages 75-plus and was generally higher for those not living with HIV compared to PLWH. Men and women with unsuppressed viral load had elevated mortality risks (men: adjusted odds ratio (aOR) 3.23, 95% CI: 2.21 to 4.71, women: aOR 2.05, 95% CI: 1.27 to 3.30). There was a weak, non-linear relationship between systolic blood pressure and higher mortality risk. We found no significant interaction between systolic blood pressure and HIV status for either men or women (p>0.05). CONCLUSIONS: Our results indicate that HIV and elevated blood pressure are acting as separate, non-interacting epidemics affecting high proportions of the older adult population. PLWH with unsuppressed viral load were at higher mortality risk compared to those uninfected. Systolic blood pressure was a mortality risk factor independent of HIV status. As antiretroviral therapy becomes more widespread, further longitudinal follow-up is needed to understand how the dynamics of increased longevity and multimorbidity among people living with both HIV and high blood pressure, as well as the emergence of COVID-19, may alter these patterns.

"The sky is the limit; I am going there": experiences of hope among young women receiving a conditional cash transfer in rural South Africa.

Young women in South Africa face elevated risk of HIV infection compared to male peers. Cash transfers may mitigate their risk for HIV; however, there is limited understanding of mechanisms of impact. We explored hope as one potential mechanism. Longitudinal qualitative analysis was used to explore how cash transfer recipients in the HPTN 068 study conceptualised hope and how the intervention influenced their hope over time. We found the intervention increased confidence, alleviated financial stressors and instilled in young women the belief that a better life, defined as being educated, independent and supportive to family, was attainable. Findings support hope as a critical outcome of cash transfer and other economic strengthening interventions.

Modeling Combination Interventions to Prevent Human Immunodeficiency Virus in Adolescent Girls and Young Women in South Africa (HIV Prevention Trials Network 068).

BACKGROUND: Combination interventions may be an effective way to prevent human immunodeficiency virus (HIV) in adolescent girls and young women. However, current studies are not designed to understand which specific interventions and combinations will be most effective. We estimate the possible impacts of interventions on a combination of factors associated with HIV. METHODS: We used the g-formula to model interventions on combinations of HIV risk factors to identify those that would prevent the most incident HIV infections, including low school attendance, intimate partner violence, depression, transactional sex, and age-disparate partnerships. We used data from the HIV Prevention Trials Network (HPTN) 068 study in rural South Africa from 2011 to 2017. We estimated HIV incidence under a potential intervention that reduced each risk factor and compared this to HIV incidence under the current distribution of these risk factors. RESULTS: Although many factors had strong associations with HIV, potential intervention estimates did not always suggest large reductions in HIV incidence because the prevalence of risk factors was low. When modeling combination effects, an intervention to increase schooling, decrease depression, and decease transactional sex showed the largest reduction in incident infection (risk difference, -1.4%; 95% confidence interval [CI], -2.7% to -.2%), but an intervention on only transactional sex and depression still reduced HIV incidence by -1.3% (95% CI, -2.6% to -.2%). CONCLUSIONS: To achieve the largest reductions in HIV, both prevalence of the risk factor and strength of association with HIV must be considered. Additionally, intervening on more risk factors may not necessarily result in larger reductions in HIV incidence.

SARS-CoV-2 Seroprevalence in a Rural and Urban Household Cohort during First and Second Waves of Infections, South Africa, July 2020-March 2021.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections may be underestimated because of limited access to testing. We measured SARS-CoV-2 seroprevalence in South Africa every 2 months during July 2020-March 2021 in randomly selected household cohorts in 2 communities. We compared seroprevalence to reported laboratory-confirmed infections, hospitalizations, and deaths to calculate infection-case, infection-hospitalization, and infection-fatality ratios in 2 waves of infection. Post-second wave seroprevalence ranged from 18% in the rural community children <5 years of age, to 59% in urban community adults 35-59 years of age. The second wave saw a shift in age distribution of case-patients in the urban community (from persons 35-59 years of age to persons at the extremes of age), higher attack rates in the rural community, and a higher infection-fatality ratio in the urban community. Approximately 95% of SARS-CoV-2 infections were not reported to national surveillance.

Associations of Father and Adult Male Presence with First Pregnancy and HIV Infection: Longitudinal Evidence from Adolescent Girls and Young Women in Rural South Africa (HPTN 068).

This study, a secondary analysis of the HPTN 068 randomized control trial, aimed to quantify the association of father and male presence with HIV incidence and first pregnancy among 2533 school-going adolescent girls and young women (AGYW) in rural South Africa participating in the trial between March 2011 and April 2017. Participants' ages ranged from 13-20 years at study enrollment and 17-25 at the post-intervention visit. HIV and pregnancy incidence rates were calculated for each level of the exposure variables using Poisson regression, adjusted for age using restricted quadratic spline variables, and, in the case of pregnancy, also adjusted for whether the household received a social grant. Our study found that AGYW whose fathers were deceased and adult males were absent from the household were most at risk for incidence of first pregnancy and HIV (pregnancy: aIRR = 1.30, Wald 95% CI 1.05, 1.61, Wald chi-square p = 0.016; HIV: aIRR = 1.27, Wald 95% CI 0.84, 1.91, Wald chi-square p = 0.263) as compared to AGYW whose biological fathers resided with them. For AGYW whose fathers were deceased, having other adult males present as household members seemed to attenuate the incidence (pregnancy: aIRR = 0.92, Wald 95% CI 0.74, 1.15, Wald chi-square p = 0.462; HIV: aIRR = 0.90, Wald 95% CI 0.58, 1.39, Wald chi-square p = 0.623) such that it was similar, and therefore not statistically significantly different, to AGYW whose fathers were present in the household.