SA-MRC/Wits Agincourt Unit (Research Outputs/Publications)
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Item A community mobilization intervention to improve engagement in HIV testing, linkage to care, and retention in care in South Africa: a cluster-randomized controlled trial(2022-09) Sheri A. Lippman; Audrey Pettifor; Mi-Suk Kang Dufour; Chodziwadziwa Whiteson Kabudula; Rhian Twine; Dean Peacock; Rhandzekile Mathebula; Aimée Julien; Rebecca West; Torsten B. Neilands; Ryan Wagner; Ann Gottert; F. Xavier Gómez Olivé; Dumisani Rebombo; Nicole Haberland; Julie Pulerwitz; Louis Pappie Majuba; Stephen Tollman; Kathleen KahnBackground: Community Mobilization (CM), engaging communities in a process to collectively enact change, could improve HIV testing and care engagement. We assessed whether CM increased HIV testing, linkage to, and retention in care over time in intervention relative to control communities. Methods: Fifteen communities in Mpumalanga, South Africa were randomized to either a CM intervention engaging residents to address social barriers to HIV testing and treatment or to control. Implementation occurred from August 2015-July 2018. Outcomes included quarterly rates of HIV testing, linkage to care, and retention in care documented from health facility records among 18-49 year-old residents of intervention and control communities over the three years of study. Intention-to-treat analyses employed generalized estimating equations stratified by sex. ClinicalTrials.gov number NCT02197793. Findings: Residents in eight intervention communities (N=20,544) and seven control communities (N=17,848) contributed data. Among men, HIV testing increased quarterly by 12·1% (Relative Change (RC):1·121, 95%CI:1·099-1·143) in intervention communities and 9·5% (RC:1·095, 95%CI:1·075-1·114) in control communities; differences by arm were marginally significant (exponentiated interaction coefficient:1·024, 95%CI:0·997-1·052, p-value=0·078). Among women, HIV testing increased quarterly by 10·6% (RC:1·106, 95%CI:1·097-1·114) in intervention and 9·3% (RC:1·093, 95%CI:1·084-1·102) in control communities; increases were greater in intervention communities (exponentiated interaction coefficient:1·012, 95%CI:1·001-1·023, p-value=0·043). Quarterly linkage increased significantly among intervention community women (RC:1·013, 95%CI:1·002-1·023) only. Quarterly retention fell among women in both arms; however, reductions were tempered among intervention women (exponentiated interaction coefficient:1·003, 95%CI:<1·000-1·006, p-value=0·062). No significant differences were detected in linkage or retention among men. Interpretation: CM was associated with modest improvements in select trial outcomes. The sum of these incremental, quarterly improvements achieved by addressing social barriers to HIV care engagement can impact epidemic control. However, achieving optimal impacts will likely require integrated efforts addressing both social barriers through CM and provision of improved service delivery.Item A prospective study of asymptomatic SARS-CoV-2 infection among individuals involved in academic research under limited operations during the COVID-19 pandemic(2022-04-25) Audrey Pettifor; Bethany L DiPrete; Bonnie E Shook-Sa; Lakshmanane Premkumar; Kriste Kuczynski; Dirk Dittmer; Allison Aiello; Shannon Wallet; Robert Maile; Joyce Tan; Ramesh Jadi; Linda Pluta; Aravinda M de Silva; David J Weber; Min Kim; Arlene C Seña; Corbin D JonesBackground: Early in the pandemic, transmission risk from asymptomatic infection was unclear, making it imperative to monitor infection in workplace settings. Further, data on SARS-CoV-2 seroprevalence within university populations has been limited. Methods: We performed a longitudinal study of University research employees on campus July-December 2020. We conducted questionnaires on COVID-19 risk factors, RT-PCR testing, and SARS-CoV-2 serology using an in-house spike RBD assay, laboratory-based Spike NTD assay, and standard nucleocapsid platform assay. We estimated prevalence and cumulative incidence of seroconversion with 95% confidence intervals using the inverse of the Kaplan-Meier estimator. Results: 910 individuals were included in this analysis. At baseline, 6.2% (95% CI 4.29-8.19) were seropositive using the spike RBD assay; four (0.4%) were seropositive using the nucleocapsid assay, and 44 (4.8%) using the Spike NTD assay. Cumulative incidence was 3.61% (95% CI: 2.04-5.16). Six asymptomatic individuals had positive RT-PCR results. Conclusions: Prevalence and incidence of SARS-CoV-2 infections were low; however, differences in target antigens of serological tests provided different estimates. Future research on appropriate methods of serological testing in unvaccinated and vaccinated populations is needed. Frequent RT-PCR testing of asymptomatic individuals is required to detect acute infections, and repeated serosurveys are beneficial for monitoring subclinical infection.Item Access to Social Protection by People Living with, at Risk of, or Afected by HIV in Eswatini, Malawi, Tanzania, and Zambia: Results from Population‑Based HIV Impact Assessments(2022-09) David Chipanta; Audrey Pettifor; Jessie Edwards; Danielle Giovenco; Hillary Mariko Topazian; Rachel M. Bray; Monique C. Millington; Janne Estill; Olivia Keiser; Jessica E. JustmanWe aimed to measure social protection coverage among the general population, women and men living with HIV (WLHIV, MLHV), female and male sex workers (FSW, MSW), men who have sex with men (MSM), adolescent girls young women (AGYW), and orphans vulnerable children (OVC) in Eswatini, Malawi, Tanzania, and Zambia. We used Population-Based HIV Impact Assessment data. We operationalised social protection benefits as external economic support from private and public sources to the household in the last three or 12 months. We estimated survey-weighted proportions and 95% confidence intervals (CI) for each population receiving social protection benefits. The sample size ranged from 10,233 adults ages 15-59 years in Eswatini to 29,638 in Tanzania. In the surveyed countries, social protection coverage among the general population was lower than the global average of 45%, ranging from 7.7% (95% CI 6.7%-8.8%) in Zambia to 39.6% (95% CI 36.8%-42.5%) in Eswatini. In Malawi and Zambia, social protection coverage among OVC, AGYW, SW, MSM, and people living with HIV (PLHIV) was similar to the general population. In Eswatini, more AGWY reported receiving social projection benefits than older women and more men not living with HIV reported receiving social protection benefits than MLHIV. In Tanzania, more WLHIV than women not living with HIV, MLHIV than men not living with HIV, and FSW than women who were not sex workers reported receiving social protection benefits. More data on access to social protection benefits by PLHIV or affected by HIV are needed to estimate better their social protection coverage.Item Addressing alcohol use among blood pressure patients in Thai primary care: Lessons from a survey-based stakeholder consultation(2022) Julia M. Lemp; Supa Pengpid; Doungjai Buntup; Till W. Barnighausen; Pascal Geldsetzerf; Karl Peltzer; Jürgen Rehm; Bundit Sornpaisarn; Charlotte Probstblood pressure. Given that brief intervention can effectively reduce hazardous alcohol consumption, this study aimed to investigate how hypertensive patients with concomitant alcohol use are identified and treated in Thai primary care settings and what this may mean for screening and lifestyle intervention strategies. In a crosssectional, mixed-method design, we surveyed 91 participants from three different groups of Thai stakeholders: policy- and decisionmakers; healthcare practitioners; and patients diagnosed with hypertension. Data was collected between December 2020 and May 2021. Responses were analyzed descriptively and using open coding tools to identify current practices, barriers, facilitators, and implications for interventions. All stakeholder groups regarded alcohol use as an important driver of hypertension. While lifestyle interventions among hypertensive patients were perceived as beneficial, current lifestyle support was limited. Barriers included limited resources in primary healthcare facilities, lack of continuous monitoring or follow-up, missing tools or procedures for risk assessment and lifestyle intervention, and stigmatization of alcohol use. Our results suggest that although screening for lifestyle risk factors (including alcohol use) and lifestyle interventions are not yet sufficiently established, a wide range of stakeholders still recognize the potential of interventions targeted at hazardous alcohol use among hypertensive patients. Future interventions may establish standardized assessment tools, be tailored to high-risk groups, and include electronic or remote elements.Item Adolescent sleep health in Africa: a scoping review protocol(2023-08-17) Oluwatosin Eunice Olorunmoteni; F Xavier Gómez-Olivé; Biliamin O Popoola; Adesegun Olayiwola Fatusi; Karine ScheuermaierIntroduction Problematic sleep is a major threat to health and quality of life among adolescents. Hence, to provide directions for research and interventions, there is a need to examine the literature on adolescent sleep health in Africa. However, available studies on adolescent sleep health in Africa have not been properly mapped. Thus, this scoping review aims to investigate the extent and type of available evidence concerning sleep health among adolescents in Africa and to highlight the relationship of adolescent sleep health with adverse mental health outcomes and cardiometabolic risk factors. The review will further highlight areas of agreement and controversies on adolescent sleep health, and identify evidence gaps that require research attention across the continent. Methods and analysis This scoping review will be conducted using Arksey and O’Malley’s six-step procedure. Thus, we have prepared this protocol according to the framework for scoping reviews developed by the Joanna Briggs Institute. To identify eligible studies, we will search MEDLINE, Scopus, PsycINFO, AJOL, JSTOR, HINARI and Google Scholar. The review will include all published articles in English, French, Spanish, Portuguese and Italian languages on adolescent sleep health in Africa from the inception of the databases, while relevant information will be extracted from included studies using an adapted data extraction tool. The results will be presented using tables and charts as appropriate. Ethics and dissemination The scoping review does not require ethical approval because the publications to be used for the review are publicly available and the study does not involve contact with humans or other animals as research participants. Furthermore, clinical records will not be used for the study. Upon completion, findings from the study will be disseminated through presentations at scientific meetings and publication in a relevant peer reviewed journal.Item Age-incidence and prevalence of HIV among intact and circumcised men: an analysis of PHIA surveys in Southern Africa(2022-10-05) Michel GarenneThe study investigates the statistical relationship between male circumcision and HIV prevalence in Africa, in the context of the Voluntary Medical Male Circumcision (VMMC) campaigns in place since 2008. Data from the Population-based HIV Impact Assessment (PHIA) surveys conducted in African countries in 2017-2018 were utilized. Six countries with high HIV prevalence, low traditional circumcision and large VMMC programs were selected: Eswatini, Lesotho, Malawi, Namibia, Zambia, Zimbabwe. The statistical analysis investigated the relative risk (RR) of HIV prevalence by circumcision status (circumcised vs intact) among men age 20-59, and the age-incidence of HIV in the two groups among men age 20-49, defined as the linear-logistic slope of the relationship between prevalence and age. Results show that the standardized RR was not different from 1 at older ages (50-59): RR = 0.923, 95% CI = 0.769-1.108, P = 0.390. Furthermore, the age-incidence was at least as high or higher among the circumcised groups than among the intact groups. The standardized RR was lower than 1 at younger ages, and this could be explained by selection biases. HIV prevalence at age 40-59 (27.3%) was also the same in the four groups of circumcision status (intact, traditional, medical, unknown). Results matched earlier observations made in South Africa that circumcised and intact men had similar levels of HIV infection. The study questions the current strategy of large scale VMMC campaigns to control the HIV epidemic. These campaigns also raise a number of ethical issuesItem Age-incidence and prevalence of HIV among intact and circumcised men: an analysis of PHIA surveys in Southern Africa(2022-10-05) Michel GarenneThe study investigates the statistical relationship between male circumcision and HIV prevalence in Africa, in the context of the Voluntary Medical Male Circumcision (VMMC) campaigns in place since 2008. Data from the Population-based HIV Impact Assessment (PHIA) surveys conducted in African countries in 2017-2018 were utilized. Six countries with high HIV prevalence, low traditional circumcision and large VMMC programs were selected: Eswatini, Lesotho, Malawi, Namibia, Zambia, Zimbabwe. The statistical analysis investigated the relative risk (RR) of HIV prevalence by circumcision status (circumcised vs intact) among men age 20-59, and the age-incidence of HIV in the two groups among men age 20-49, defined as the linear-logistic slope of the relationship between prevalence and age. Results show that the standardized RR was not different from 1 at older ages (50-59): RR = 0.923, 95% CI = 0.769-1.108, P = 0.390. Furthermore, the age-incidence was at least as high or higher among the circumcised groups than among the intact groups. The standardized RR was lower than 1 at younger ages, and this could be explained by selection biases. HIV prevalence at age 40-59 (27.3%) was also the same in the four groups of circumcision status (intact, traditional, medical, unknown). Results matched earlier observations made in South Africa that circumcised and intact men had similar levels of HIV infection. The study questions the current strategy of large scale VMMC campaigns to control the HIV epidemic. These campaigns also raise a number of ethical issues.Item All-cause mortality of hospitalised patients with suspected COVID-19 in Sierra Leone: a prospective cohort study(2023-02-05) Olivia Farrant; Mamadu Baldeh; Joseph Baio Kamara; Emma Bailey; Stephen Sevalie; Gibrilla Deen; James Baligeh Walter Russell; Daniel Youkee; Andy JM Leather; Justine Davies; Sulaiman LakohObjectives To study the mortality of patients with COVID-19 in Sierra Leone, to explore the factors associated with mortality during the COVID-19 pandemic and to highlight the complexities of treating patients with a novel epidemic disease in a fragile health system. Study design A prospective single-centre cohort study. Data were extracted from paper medical records and transferred onto an electronic database. Specific indicators were compared between survivors and non-survivors, using descriptive statistics in Stata V.17. Study setting The infectious diseases unit (IDU) at Connaught Hospital in Freetown, Sierra Leone Participants Participants were all patients admitted to the IDU between March and July 2020. Aims of study The primary outcome of the study was to examine the all-cause mortality of hospitalised patients with suspected COVID-19 in Sierra Leone and the secondary outcome measures were to examine factors associated with mortality in patients positive for COVID-19. Results 261 participants were included in the study. Overall, 41.3% of those admitted to the IDU died, compared with prepandemic in-hospital mortality of 23.8%. Factors contributing to the higher mortality were COVID-19 infection (aOR 5.61, 95% CI 1.19 to 26.30, p=0.02) and hypertension (aOR 9.30, 95% CI 1.18 to 73.27, p=0.03) Conclusions This study explores the multiple factors underpinning a doubling in facility mortality rate during the COVID-19 pandemic in Sierra Leone . It provides an insight into the realities of providing front-line healthcare during a pandemic in a fragile health system.Item Anthropometric criteria for best-identifying children at high risk of mortality: a pooled analysis of twelve cohorts(2023-02-03) Tanya Khara; Mark Myatt; Kate Sadler; Paluku Bahwere; James A Berkley; James A Berkley; Robert E Black; Erin Boyd; Michel Garenne; Sheila Isanaka; Natasha Lelijveld; Christine McDonald; Andrew Mertens; Martha Mwangome; Kieran O’Brien; Heather Stobaugh; Sunita Taneja; Keith P West; André BriendObjective: To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications. Design: A multiple cohort individual data meta-analysis of mortality risk (within 6 months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences were modelled. Setting: Community-based cohort studies in twelve low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread. Participants: Children aged 6 to 59 months. Results: Of the twelve anthropometric case definitions examined, four (weight-forage Z-score (WAZ) <−2), (mid-upper arm circumference (MUAC) <125 mm), (MUAC < 115 mm or WAZ < −3) and (WAZ < −3) had the highest informedness in predicting mortality. A combined case definition (MUAC < 115 mm or WAZ < −3) was better at predicting deaths associated with weight-for-height Z-score <−3 and concurrent wasting and stunting (WaSt) than the single WAZ < −3 case definition. After the assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC < 115 mm or WAZ < −3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1·87 times larger than programmes admitting on MUAC < 115 mm alone. Conclusions: A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.Item Anthropometric deficits and the associated risk of death by age and sex in children aged 6-59 months: A meta-analysis(2023-08) Susan Thurstans; Stephanie V. Wrottesley; Bridget Fenn; Tanya Khara; Paluku Bahwere; James A. Berkley; Robert E. Black; Erin Boyd; Michel Garenne; Sheila Isanaka; Natasha Lelijveld; Christine M. McDonald; Andrew Mertens; Martha Mwangome; Kieran S. O'Brien; Heather Stobaugh; Sunita Taneja; Keith P. West; Saul Guerrero; Marko Kerac; André Briend; Mark MyattRisk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6-59 months by age and sex. We categorised children into younger (6-23 months) and older (24-59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC < 125 mm; RR 1.35, p = 0.272 for WHZ < -2). For underweight and stunting, absolute risk of death was higher in younger (RR 2.57, p < 0.001) compared with older children (RR 2.83, p < 0.001). For all deficits, there were no differences in mortality risk for girls compared with boys. There were no differences in the risk of mortality between younger and older wasted children, supporting continued inclusion of all children under-five in wasting treatment programmes. The risk of mortality associated with underweight and stunting was higher among younger children, suggesting that prevention programmes might be justified in focusing on younger children where resources are limited. There were no sex differences by age in mortality risk for all deficits.Item Antiretroviral Drug Use and HIV Drug Resistance Among Young Women in Rural South Africa: HPTN 068(2018-11-01) Zhang, Yinfeng PhD; Sivay, Mariya V. PhD; Hudelson, Sarah E. BS; Clarke, William PhD; Breaud, Autumn MS; Wang, Jing MS, MA; Piwowar-Manning, Estelle BS, MT (ASCP); Agyei, Yaw MPH, BS, MT (ASCP); Fogel, Jessica M. PhD; Hamilton, Erica L. MPH; Selin, Amanda MHS; MacPhail, Catherine PhD; Kahn, Kathleen MD, PhD; Gómez-Olivé, Francesc Xavier MD, PhD; Hughes, James P. PhD; Pettifor, Audrey PhD, MPH; Eshleman, Susan H. MD, PhDBackground: Antiretroviral (ARV) drugs are used for HIV treatment and prevention. We analyzed ARV drug use and HIV drug resistance in a cohort of young women in rural South Africa enrolled in the HIV Prevention Trials Network (HPTN) 068 study, which evaluated the use of a cash transfer conditional on school attendance to reduce HIV incidence. Methods: ARV drug testing was performed using plasma samples from 2526 young women. This included 2526 enrollment samples (80 HIV-infected and 2446 HIV-uninfected) and 162 seroconversion samples (first HIV-positive study visit). Testing was performed using a qualitative assay that detects 20 ARV drugs from 5 drug classes. HIV drug resistance testing was performed with the ViroSeq HIV-1 Genotyping System for samples that had HIV viral loads ≥400 copies per milliliter. Results: At enrollment, ARV drugs were detected in 10 (12.5%) of 80 HIV-infected young women. None of 2446 HIV-uninfected young women had ARV drugs detected at enrollment. ARV drugs were also detected in 16 (9.9%) of 162 seroconverters. At enrollment, 9 (13.4%) of 67 young women with genotyping results had HIV drug resistance; resistance was also detected in 9 (6.9%) of 131 seroconverters with genotyping results. Conclusions: Most of the HIV-infected young women in this cohort from rural South Africa were not taking ARV drugs, suggesting they were unaware of their HIV status or were not in care. HIV drug resistance was detected in young women with both prevalent and new HIV infection.Item Antiretroviral therapy and aging as resources for managing and resisting HIV-related stigma in rural South Africa(2022-12) Danielle Denardo; Sanyu A. Mojolab; Enid Schatzc; F. Xavier Gómez-OlivéThe widespread roll-out of antiretroviral therapy (ART) in Africa has contributed to a large population of adults aging with HIV. However, little is known about how HIV-related stigma interacts with aging in the ART era. This study uses in-depth interviews with middle-aged and older South Africans living with HIV to explore stigma-related experiences and response strategies. Participants describe a persistence of stigma which requires the deployment of a range of common and age-based stigma management and resistance strategies. We find that participants minimize their exposure to stigma through selective disclosure of their HIV status; neutralize HIV-related stigma through comparisons to chronic illnesses common among older adults, and deflect stigma through asserting an ART-adherent identity and othering younger non-adherent adults. Overall, our study highlights the roles of ART and aging as resources for managing and resisting HIV-related stigma.Item Antiretroviral therapy based HIV prevention targeting young women who sell sex: A mixed method approach to understand the implementation of PrEP in a rural area of KwaZulu-Natal, South Africa(2022-02) Natsayi Chimbindi; Nondumiso Mthiyane; Thembelihle Zuma; Kathy Baisley; Deenan Pillay; Nuala McGrath; Guy Harling; Lorraine Sherr; Isolde Birdthistle; Sian Floyd; Jaco Dreyer; Sarah Nakasone; Janet Seeley; Maryam Shahmanesh§Pre-Exposure Prophylaxis (PrEP) is a potential game-changer for HIV. We used PrEP introduction for Young Women Who Sell Sex (YWSS) in a rural South Africa district to understand community norms and PrEP coverage in YWSS. Between 2017 and 2018, we measured awareness and uptake of PrEP in a representative cohort of 2184 Adolescent Girls and Young Women (AGYW) aged 13-22. We conducted group discussions with young people and community members (19); key informant interviews (9), in-depth interviews with 15-24 year-olds (58) and providers (33). Interviews were analysed using thematic analysis. PrEP awareness increased from 2% to 9%. Among 965 AGYW sexually-active by 2018, 13.4% (95%CI: 11.4%-15.7%) reported transactional sex and 10.6% (95%CI: 8.85-12.7%) sex for money. Of the 194 YWSS, 21 were aware of PrEP, but none had used it. Youth were enthusiastic about PrEP as tool for HIV prevention; whilst older community members were cautious about a technology they had limited experience with but could benefit select groups. Teachers and healthcare providers were concerned that PrEP would lower personal responsibility for sexual health. In conclusion, the narrow and limited introduction of PrEP to YWSS reduced the accessibility and reach. Introducing PrEP as part of sexual healthcare may improve demand and access for YWSS.Item Apolipoprotein L1 High-Risk Genotypes and Albuminuria in Sub-Saharan African Populations(2022-06) Jean-Tristan Brandenburg; Melanie A. Govender; Winkler, Cheryl A.; Boua, Palwende Romuald; Agongo, Godfred; Fabian, June; Ramsay, MichèleBackground and objectives: Recessive inheritance of African-specific APOL1 kidney risk variants is associated with higher risk of nondiabetic kidney disease, progression to kidney failure, and early-onset albuminuria that precedes eGFR decline. The effect of APOL1 risk variants on kidney disease in continental Africans is understudied. Objectives of this study were to determine APOL1 risk allele prevalence and associations between APOL1 genotypes and kidney disease in West, East, and South Africa. Design, setting, participants, & measurements: This cross-sectional population-based study in four African countries included 10,769 participants largely aged 40-60 years with sociodemographic and health information, anthropometry data, and blood and urine tests for biomarkers of kidney disease. APOL1 risk alleles were imputed from the H3Africa genotyping array, APOL1 risk allele and genotype frequencies were determined, and genetic associations were assessed for kidney disease. Kidney disease was defined as the presence of eGFR <60 ml/min per 1.73 m2, albuminuria, or a composite end point including eGFR <60 ml/min per 1.73 m2 and/or albuminuria. Results: High G1 allele frequencies occurred in South and West Africa (approximately 7%-13%). G2 allele frequencies were highest in South Africa (15%-24%), followed by West Africa (9%-12%). Associations between APOL1 risk variants and albuminuria were significant for recessive (odds ratio, 1.63; 95% confidence interval, 1.25 to 2.12) and additive (odds ratio, 1.39; 95% confidence interval, 1.09 to 1.76) models. Associations were stronger for APOL1 G1/G1 genotypes versus G0/G0 (odds ratio, 3.87; 95% confidence interval, 2.16 to 6.93) compared with either G2/G2 (odds ratio, 1.65; 95% confidence interval, 1.09 to 2.51) or G1/G2 (odds ratio, 1.24; 95% confidence interval, 0.83 to 1.87). No association between APOL1 risk variants and eGFR <60 ml/min per 1.73 m2 was observed. Conclusions: APOL1 G1 and G2 alleles and high-risk genotype frequencies differed between and within West and South Africa and were almost absent from East Africa. APOL1 risk variants were associated with albuminuria but not eGFR <60 ml/min per 1.73 m2. There may be differential effects of homozygous G1 and G2 genotypes on albuminuria that require further investigation.Item Are cardiovascular health measures heritable across three generations of families in Soweto, South Africa? A cross-sectional analysis using the random family method(2022-09-23) Lisa J Ware; Innocent Maposa; Andrea Kolkenbeck-Ruh; Shane A Norris; Larske Soepnel; Simone Crouch; Juliana Kagura; Sanushka Naidoo; Wayne Smith; Justine DaviesObjectives: Cardiovascular disease is increasing in many low and middle-income countries, including those in Africa. To inform strategies for the prevention of cardiovascular disease in South Africa, we sought to determine the broad heritability of phenotypic markers of cardiovascular risk across three generations. Design: A cross-sectional study conducted in a longitudinal family cohort. Setting: Research unit within a tertiary hospital in a historically disadvantaged, large urban township of South Africa. Participants: 195 individuals from 65 biological families with all three generations including third-generation children aged 4-10 years were recruited from the longest running intergenerational cohort study in Africa, the Birth to Twenty Plus cohort. All adults (grandparents and parents) were female while children were male or female. Primary and secondary outcome measures: The primary outcome was heritability of blood pressure (BP; brachial and central pressures). Secondary outcomes were heritability of arterial stiffness (pulse wave velocity), carotid intima media thickness (cIMT) and left ventricular mass indexed to body surface area (LVMI). Results: While no significant intergenerational relationships of BP or arterial stiffness were found, there were significant relationships in LVMI across all three generations (p<0.04), and in cIMT between grandparents and parents (p=0.0166). Heritability, the proportion of phenotypic trait variation attributable to genetics, was estimated from three common statistical methods and ranged from 23% to 44% for cIMT and from 21% to 39% for LVMI. Conclusions: Structural indicators of vascular health, which are strong markers of future clinical cardiovascular outcomes, transmit between generations within African families. Identification of these markers in parents may be useful to trigger assessments of preventable risk factors for cardiovascular disease in offspring.Item Assessing risk for HIV infection among adolescent girls in SouthAfrica: an evaluation of the VOICE risk score (HPTN 068)(2019-07) Danielle Giovenco; Audrey Pettifor; Catherine MacPhail; Kathleen Kahn; Ryan Wagner; Estelle Piwowar-Manning; Jing Wang; James P HughesAbstractIntroduction:To maximize impact and minimize costs, antiretroviral pre-exposure prophylaxis (PrEP) interventions should beoffered to those at highest risk for HIV infection. The risk score derived from the VOICE trial is one tool currently being uti-lized to determine eligibility in adolescent PrEP trials in sub-Saharan Africa. This study is aimed at evaluating the utility of therisk score in predicting HIV incidence among a cohort of adolescent girls in rural South Africa.Methods:We utilized data from HIV Prevention Trials Network (HPTN) 068, a phase III randomized controlled trial con-ducted in rural Mpumalanga province, South Africa. School-attending young women aged 13 to 20 years were enrolled intothe trial from 2011 to 2012 and followed for up to three years. A risk score based on individual-level risk factors measuredat enrolment was calculated for HPTN 068 participants who completed a one-year follow-up visit and were HIV seronegativeat enrolment. Possible scores ranged from 0 to 10. A proportional hazards model was then used to determine if risk score atenrolment was predictive of incident HIV infection at follow-up and an area under the curve analysis was used to examine thepredictive ability of the score.Results and Discussion:The risk score had limited variability in the HPTN 068 sample. Scores≥5 identified 85% of incidentinfections from 94% of the sample, compared to the VOICE sample in which scores≥5 identified 91% of incident infectionsfrom only 64% of participants. The risk score did not predict HIV incidence after one year of follow-up (hazardratio=1.029; 95% confidence interval (CI): 0.704, 1.503,p=.884) and showed poor predictive ability (area under thecurve=0.55; 95% CI: 0.44, 0.65). Certain individual risk factors that comprise the risk score may be context specific or notrelevant for adolescent populations. Additional factors should be considered when assessing risk for the purposes of deter-mining PrEP eligibility.Conclusions:The VOICE risk score demonstrated low utility to predict HIV incidence in the HPTN 068 sample. Findings high-light the need for an age and developmentally appropriate tool for assessing risk for HIV infection among adolescents. Use ofthe VOICE risk score for determining PrEP eligibility in younger populations should be carefully considered.Item Assessing the prevalence of young children living in households prepared for COVID-19 in 56 low- and middle-income countries(2022) Chunling Lu; Yiqun Luan; Sara N. Naicker; S. V. Subramanian; Jere R. Behrman; Jody Heymann; Alan Stein; Linda M. RichterItem Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study(2022-08-20) Jose Villar; Roseline Ochieng; Robert B Gunier; Aris T Papageorghiou; Stephen Rauch; Rose McGready; Julia M Gauglitz; Fernando C Barros; Manu Vatish; Michelle Fernandes; Victor Zammit; Verena I Carrara; Shama Munim; Rachel Craik; Hellen C Barsosio; Maria Carvalho; James A Berkley; Leila I Cheikh Ismail; Shane A Norris; Chrystelle O O Tshivuila-Matala; Francois Nosten; Eric O Ohuma; Alan Stein; Ann Lambert; Adele Winsey; Ricardo Uauy; Brenda Eskenazi; Zulfiqar A Bhutta; Stephen H KennedyBackground: Obesity predominantly affects populations in high-income countries and those countries facing epidemiological transition. The risk of childhood obesity is increased among infants who had overweight or obesity at birth, but in low-resource settings one in five infants are born small for gestational age. We aimed to study the relationships between: (1) maternal metabolite signatures; (2) fetal abdominal growth; and (3) postnatal growth, adiposity, and neurodevelopment. Methods: In the prospective, multinational, observational INTERBIO-21st fetal study, conducted in maternity units in Pelotas (Brazil), Nairobi (Kenya), Karachi (Pakistan), Soweto (South Africa), Mae Sot (Thailand), and Oxford (UK), we enrolled women (≥18 years, with a BMI of less than 35 kg/m2, natural conception, and a singleton pregnancy) who initiated antenatal care before 14 weeks' gestation. Ultrasound scans were performed every 5±1 weeks until delivery to measure fetal growth and feto-placental blood flow, and we used finite mixture models to derive growth trajectories of abdominal circumference. The infants' health, growth, and development were monitored from birth to age 2 years. Early pregnancy maternal blood and umbilical cord venous blood samples were collected for untargeted metabolomic analysis. Findings: From Feb 8, 2012, to Nov 30, 2019, we enrolled 3598 pregnant women and followed up their infants to 2 years of age. We identified four ultrasound-derived trajectories of fetal abdominal circumference growth that accelerated or decelerated within a crucial 20-25 week gestational age window: faltering growth, early accelerating growth, late accelerating growth, and median growth tracking. These distinct phenotypes had matching feto-placental blood flow patterns throughout pregnancy, and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood. There were 709 maternal metabolites with positive effect for the faltering growth phenotype and 54 for the early accelerating growth phenotype; 31 maternal metabolites had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype. Metabolites associated with the faltering growth phenotype had statistically significant odds ratios close to 1·5 (ie, suggesting upregulation of metabolic pathways of impaired fetal growth). The metabolites had a reciprocal relationship with the early accelerating growth phenotype, with statistically significant odds ratios close to 0.6 (ie, suggesting downregulation of fetal growth acceleration). The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid, and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was highly abundant in the early accelerating growth phenotype group. Interpretation: Early pregnancy lipid biology associated with fetal abdominal growth trajectories is an indicator of patterns of growth, adiposity, vision, and neurodevelopment up to the age of 2 years. Our findings could contribute to the earlier identification of infants at risk of obesity.Item Association of alcohol use and multimorbidity among adults aged 40 years and above in rural South Africa(2023-05-14) MafunoG. Mpinganjira; Tobias Chirwa; Chodziwadziwa.W. Kabudula; Francesc XavierGómez‑Olivé; StephenTollman3; Joel Msafri Francis1We assessed the prevalence of reported alcohol use and its association with multimorbidity among adults aged 40 years and above in a rural, transitioning South African setting. Findings could potentially inform alcohol interventions integration in the prevention and treatment of chronic conditions. We analysed data from the frst wave of The Health and Ageing in Africa—a longitudinal Study in an INDEPTH community (HAALSI) nested within the Agincourt Health and Demographic Surveillance Systems, conducted between November 2014 and November 2015 (n= 5059). We computed descriptive statistics and performed univariate analysis to determine factors independently associated with multimorbidity. Age, Body Mass Index, education, sex, and household wealth status and variables with a p-value < 0.20 in univariate analysis were included in multivariable Modifed Poisson regression models. Any factors with a p-value of < 0.05 in the fnal models were considered statistically signifcant. The frst wave of HAALSI was completed by 5059 participants aged 40 years and above and included 2714 (53.6%) females. The prevalence of reported ever alcohol use was 44.6% (n= 2253) and of these 51.9% (n= 1171) reported alcohol use in the last 30 days. The prevalence of HIV multimorbidity was 59.6% (3014/5059) and for multimorbidity without HIV 52.5% (2657/5059). Alcohol use was associated with HIV multimorbidity among all participants (RR: 1.05, 95% CI: 1.02– 1.08), and separately for males (RR: 1.05, 95% CI: 1.00–1.10) and females (RR: 1.06, 95%CI: 1.02– 1.11). Similarly, alcohol use was associated with multimorbidity without HIV among all participants (RR: 1.05, 95% CI: 1.02–1.09), and separately for males (RR: 1.06, 95% CI: 1.00–1.12) and females (RR: 1.06, 95% CI: 1.01–1.11). Reported alcohol use was common and associated with HIV multimorbidity and multimorbidity without HIV among older adults in rural northeast South Africa. There is a need to integrate Screening, Brief Interventions, and Referral for alcohol Treatment in the existing prevention and treatment of multimorbidity in South Africa.Item Association of socioeconomic status with hypertension prevalence and control in Nanjing: a cross-sectional study(2022-03-02) Zhenzhen Qin; Chao Li; Shengxiang Qi; Hairong Zhou; Jie Wu; Weiwei Wang; Qing Ye; Huafeng Yang; Chenchen Wang & Xin HongBackground The role of socioeconomic status (SES) on hypertension prevalence and hypertension control has gotten much attention but with conflicting results. This paper aimed to quantify the association of SES with both hypertension prevalence and hypertension control rate in Nanjing, China. Methods A community-based cross-sectional study was conducted using multistage random sampling on 60,283 adults aged more than 18 years between March 2017 and June 2018. Hypertension was defined as systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or self-reported diagnosis of hypertension or respondent's report of taking antihypertensive medications. The controlled hypertension was defined by systolic BP < 140 mmHg and diastolic BP of < 90 mmHg among the subjects that self-reported exhibiting hypertensive and taking antihypertensive medications. The associations between SES with hypertension prevalence and hypertension control were quantified using generalized mixed model regression analysis and reported as odds ratios (ORs) and 95% confidence interval (CI). Results There was a high prevalence of subjects with primary educational level (49.6%) or unemployed and retired (49.5%) or lower annual household income level (44.9%) in each SES group, respectively. After adjustments for potential confounding factors, there were higher odds of hypertension among those with primary educational level (OR = 1.56), but lower odds for controlled BP (OR = 0.51). Higher odds of hypertension could be found among unemployed and retired, and higher odds of controlled BP was observed in the mental laborers or students (OR = 1.30), compared with the other categories, respectively. The lower-income group was more likely to be hypertensive (OR = 1.35) and less likely to have controlled hypertension (OR = 0.73). Conclusion Socioeconomic status played an important role in hypertension prevalence and hypertension control among adults in Nanjing, China. Strategies for hypertension prevention and control should especially focus on people in the vulnerable lower SES groups.