Tinofa Mutevedzi

Cohort Profile: Africa Centre Demographic Information System (ACDIS) and population-based HIV survey

The health and demography of the South African population has been undergoing substantial changes as a result of the rapidly progressing HIV epidemic. Researchers at the University of KwaZulu-Natal and the South African Medical Research Council established The Africa Centre for Health and Population Studies in 1997 funded by a large core grant from The Wellcome Trust, UK. Given the urgent need for high quality longitudinal data with which to monitor these changes, and with which to evaluate interventions to mitigate impact, a demographic surveillance system (DSS) was established in a rural South African population facing a rapid and severe HIV epidemic. 1 The DSS, referred to as the Africa Centre Demographic Information System (ACDIS), started in 2000. In 2003, population-based HIV testing (also funded by the Wellcome Trust, UK) was started in ACDIS through annual surveys. In this article, we seek to describe the most salient features of ACDIS and the population-based HIV cohort and briefly present some of the most important results to date.

Mass HIV Treatment and Sex Disparities in Life Expectancy: Demographic Surveillance in Rural South Africa.

Background Women have better patient outcomes in HIV care and treatment than men in sub-Saharan Africa. We assessed—at the population level—whether and to what extent mass HIV treatment is associated with changes in sex disparities in adult life expectancy, a summary metric of survival capturing mortality across the full cascade of HIV care. We also determined sex-specific trends in HIV mortality and the distribution of HIV-related deaths in men and women prior to and at each stage of the clinical cascade. Methods and Findings Data were collected on all deaths occurring from 2001 to 2011 in a large population-based surveillance cohort (52,964 women and 45,688 men, ages 15 y and older) in rural KwaZulu-Natal, South Africa. Cause of death was ascertained by verbal autopsy (93% response rate). Demographic data were linked at the individual level to clinical records from the public sector HIV treatment and care program that serves the region. Annual rates of HIV-related mortality were assessed for men and women separately, and female-to-male rate ratios were estimated in exponential hazard models. Sex-specific trends in adult life expectancy and HIV-cause-deleted adult life expectancy were calculated. The proportions of HIV deaths that accrued to men and women at different stages in the HIV cascade of care were estimated annually. Following the beginning of HIV treatment scale-up in 2004, HIV mortality declined among both men and women. Female adult life expectancy increased from 51.3 y (95% CI 49.7, 52.8) in 2003 to 64.5 y (95% CI 62.7, 66.4) in 2011, a gain of 13.2 y. Male adult life expectancy increased from 46.9 y (95% CI 45.6, 48.2) in 2003 to 55.9 y (95% CI 54.3, 57.5) in 2011, a gain of 9.0 y. The gap between female and male adult life expectancy doubled, from 4.4 y in 2003 to 8.6 y in 2011, a difference of 4.3 y (95% CI 0.9, 7.6). For women, HIV mortality declined from 1.60 deaths per 100 person-years (95% CI 1.46, 1.75) in 2003 to 0.56 per 100 person-years (95% CI 0.48, 0.65) in 2011. For men, HIV-related mortality declined from 1.71 per 100 person-years (95% CI 1.55, 1.88) to 0.76 per 100 person-years (95% CI 0.67, 0.87) in the same period. The female-to-male rate ratio for HIV mortality declined from 0.93 (95% CI 0.82–1.07) in 2003 to 0.73 (95% CI 0.60–0.89) in 2011, a statistically significant decline (p = 0.046). In 2011, 57% and 41% of HIV-related deaths occurred among men and women, respectively, who had never sought care for HIV in spite of the widespread availability of free HIV treatment. The results presented here come from a poor rural setting in southern Africa with high HIV prevalence and high HIV treatment coverage; broader generalizability is unknown. Additionally, factors other than HIV treatment scale-up may have influenced population mortality trends. Conclusions Mass HIV treatment has been accompanied by faster declines in HIV mortality among women than men and a growing female–male disparity in adult life expectancy at the population level. In 2011, over half of male HIV deaths occurred in men who had never sought clinical HIV care. Interventions to increase HIV testing and linkage to care among men are urgently needed.

From HIV infection to therapeutic response: a population-based longitudinal HIV cascade-of-care study in KwaZulu-Natal, South Africa

BACKGROUND Standard approaches to estimation of losses in the HIV cascade of care are typically cross-sectional and do not include the population stages before linkage to clinical care. We used indiviual-level longitudinal cascade data, transition by transition, including population stages, both to identify the health-system losses in the cascade and to show the differences in inference between standard methods and the longitudinal approach. METHODS We used non-parametric survival analysis to estimate a longitudinal HIV care cascade for a large population of people with HIV residing in rural KwaZulu-Natal, South Africa. We linked data from a longitudinal population health surveillance (which is maintained by the Africa Health Research Institute) with patient records from the local public-sector HIV treatment programme (contained in an electronic clinical HIV treatment and care database, ARTemis). We followed up all people who had been newly detected as having HIV between Jan 1, 2006, and Dec 31, 2011, across six cascade stages: three population stages (first positive HIV test, HIV status knowledge, and linkage to care) and three clinical stages (eligibility for antiretroviral therapy [ART], initiation of ART, and therapeutic response). We compared our estimates to cross-sectional cascades in the same population. We estimated the cumulative incidence of reaching a particular cascade stage at a specific time with Kaplan-Meier survival analysis. FINDINGS Our population consisted of 5205 individuals with HIV who were followed up for 24 031 person-years. We recorded 598 deaths. 4539 individuals gained knowledge of their positive HIV status, 2818 were linked to care, 2151 became eligible for ART, 1839 began ART, and 1456 had successful responses to therapy. We used Kaplan-Meier survival analysis to adjust for censorship due to the end of data collection, and found that 8 years after testing positive in the population health surveillance, 16% had died. Among living patients, 82% knew their HIV status, 45% were linked to care, 39% were eligible for ART, 35% initiated ART, and 33% had reached therapeutic response. Median times to transition for these cascade stages were 52 months, 52 months, 20 months, 3 months, and 9 months, respectively. Compared with the population stages in the cascade, the transitions across the clinical stages were fast. Over calendar time, rates of linkage to care have decreased and patients presenting for the first time for care were, on average, healthier. INTERPRETATION HIV programmes should focus on linkage to care as the most important bottleneck in the cascade. Cascade estimation should be longitudinal rather than cross-sectional and start with the population stages preceding clinical care. FUNDING Wellcome Trust, PEPFAR.

Preventing Unintended Pregnancy and HIV Transmission: Effects of the HIV Treatment Cascade on Contraceptive Use and Choice in Rural KwaZulu-Natal

Background:For women living with HIV, contraception using condoms is recommended because it prevents not only unintended pregnancy but also acquisition of other sexually transmitted infections and onward transmission of HIV. Dual-method dual-protection contraception (condoms with other contraceptive methods) is preferable over single-method dual-protection contraception (condoms alone) because of its higher contraceptive effectiveness. We estimate the effect of progression through the HIV treatment cascade on contraceptive use and choice among HIV-infected women in rural South Africa. Methods:We linked population-based surveillance data on contraception collected by the Wellcome Trust Africa Centre for Health and Population Studies to data from the local antiretroviral treatment (ART) program in Hlabisa subdistrict, KwaZulu-Natal. In bivariate probit regression, we estimated the effects of progressing through the cascade on contraceptive choice among HIV-infected sexually active women aged 15–49 years (N = 3169), controlling for a wide range of potential confounders. Findings:Contraception use increased across the cascade from <40% among HIV-infected women who did not know their status to >70% among women who have been on ART for 4–7 years. Holding other factors equal (1) awareness of HIV status, (2) ART initiation, and (3) being on ART for 4–7 years increased the likelihood of single-method/dual-method dual protection by the following percentage points (pp), compared with women who were unaware of their HIV status: (1) 4.6 pp (P = 0.030)/3.5 pp (P = 0.001), (2) 10.3 pp (P = 0.003)/5.2 pp (P = 0.007), and (3) 21.6 pp (P < 0.001)/11.2 pp (P < 0.001). Conclusions:Progression through the HIV treatment cascade significantly increased the likelihood of contraception in general and contraception with condoms in particular. ART programs are likely to contribute to HIV prevention through the behavioral pathway of changing contraception use and choice.

Assessing the validity of respondents' reports of their partners' ages in a rural South African population-based cohort.

Objectives This study evaluated the validity of using respondents’ reports of age disparity in their sexual relationships (perceived disparity), compared to age disparity based on each partners report of their own date of birth (actual disparity). Setting The study was conducted using data from a longitudinal population-based cohort in rural KwaZulu-Natal, South Africa, between 2005 and 2012. Participants The study used 13 831 reports of partner age disparity within 7337 unique conjugal relationships. 10 012 (72.4%) reports were made by women. Primary and secondary outcome measures The primary outcome was the Lin concordance correlation of perceived and actual age disparities. Secondary outcomes included the sensitivity/specificity of perceived disparities to assess whether the man in the relationship was more than five or more than 10 years older than the woman. Results Mean relationship age disparity was 6 years. On average, respondents slightly underestimated their partners’ ages (male respondents: 0.50 years; female respondents: 0.85 years). Almost three-quarters (72.3%) of age disparity estimates fell within 2 years of the true values, although a small minority of reports were far from correct. The Lin concordance correlation of perceived and actual age disparities (men: ρ=0.61; women: ρ=0.78), and assessments of whether the man in the relationship was more than five, or more than 10 years older than the woman (sensitivity >60%; specificity >75%), were relatively high. Accuracy was higher for spouses and people living in the same household, but was not affected by relationship duration. Conclusions Rural South Africans reported their sexual partners’ ages imperfectly, but with less error than in some other African settings. Further research is required to determine how generalisable these findings are. Self-reported data on age disparity in sexual relationships can be used with caution for research, intervention design, and targeting in this and similar settings.

Structural barriers to antiretroviral treatment: a study using population-based CD4 cell count and linked antiretroviral treatment programme data

Abstract Background The promise of an AIDS-free generation rests on treatment as prevention to reduce HIV incidence. Treatment as prevention depends critically on high antiretroviral treatment (ART) coverage. However, even under current national ART guidelines coverage remains far from universal in sub-Saharan Africa. We examined structural barriers to ART access in a community in rural South Africa, which has a very high adult HIV prevalence (28%) and incidence (approximately three new infections per 100 person-years). Methods We did a population-based survey of CD4 cell count among 5000 randomly selected participants in the 2010 round of a longitudinal, population-based HIV surveillance study. The study was carried out by the Africa Centre for Health and Population Studies in the Hlabisa subdistrict of KwaZula-Natal. We identified the people needing ART among the HIV-infected surveillance participants as those who were either enrolled in the local ART programme (ie, people needing and receiving ART) or people who were not enrolled in the programme but had a CD4 cell count below a certain threshold (ie, people needing ART but not yet receiving it). We applied two different CD4 cell count thresholds (≤200 and ≤350 cells per μL), leading to two different samples of people needing ART (n=376 and n=610). We then used logistic regression to explore the effect of socioeconomic factors (sex, age, education, wealth, distance to the nearest ART clinic, urban/rural residence, and migration status) on the binary outcome of ART enrolment in relation to ART need. Findings ART coverage was 72% in the 376 individuals who were either on ART or had a CD4 count of 200 cells per μL or fewer, and 45% in the 610 individuals who were either on ART or had a CD4 count of 350 cells per μL or fewer. Women who needed ART were significantly more likely to receive treatment than were men who needed it (48% vs 34%; p=0·003 for the ≤350 cells per μL threshold). The age pattern of ART coverage increased from approximately 20% at age 20 years to 60% at age 45 years, declining to 40% at age 70 years for the 350 cells per μL or fewer threshold. Controlling for other factors, among those needing ART, women were more than twice as likely to be taking ART than were men (adjusted odds ratio 2·43, 95% CI 1·36–4·33; p=0·003) and every additional km distance from the nearest clinic decreased the likelihood of ART used by approximately 20% (adjusted odds ratio 0·79, 95% CI 0·67–0·94; p=0·007). Education, wealth, and migration did not affect ART access. When we separated women into those who had not been pregnant since inception of the ART programme in 2004, and those who had been pregnant, pregnancy was a significant determinant of ART access, but explained only a small fraction ( Interpretation Working towards universal coverage goals, ART programmes need to improve access for men, young and old people, and remote populations. Interventions improving geographical accessibility of ART programmes, such as subsidised transport or the opening of more ART clinics in remote areas, are likely to help to overcome important structural barriers to access. Funding The Africa Centre for Health and Population Studies demographic and HIV surveillance is funded by the Wellcome Trust. TB and FT received financial support from the Wellcome Trust and through 1R01-HD058482-01 from the National Institute of Child Health and Human Development, National Institutes of Health.

Do Gifts Increase Consent to Home-based HIV Testing? A Difference-in-Differences Study in Rural KwaZulu-Natal, South Africa

Abstract Background: Despite the importance of HIV testing for controlling the HIV epidemic, testing rates remain low. Efforts to scale up testing coverage and frequency in hard-to-reach and at-risk populations commonly focus on home-based HIV testing. This study evaluates the effect of a gift (a US

Prevalence of sexually transmitted infections among young people in South Africa: A nested survey in a health and demographic surveillance site

5 food voucher for families) on consent rates for home-based HIV testing. Methods: We use data on 18 478 individuals (6 418 men and 12 060 women) who were successfully contacted to participate in the 2009 and 2010 population-based HIV surveillance carried out by the Wellcome Trusts Africa Health Research Institute in rural KwaZulu-Natal, South Africa. Of 18 478 potential participants contacted in both years, 35% (6 518) consented to test in 2009, and 41% (7 533) consented to test in 2010. Our quasi-experimental difference-in-differences approach controls for unobserved confounding in estimating the causal effect of the intervention on HIV-testing consent rates. Results: Allocation of the gift to a family in 2010 increased the probability of family members consenting to test in the same year by 25 percentage points [95% confidence interval (CI) 21–30 percentage points; P < 0.001]. The intervention effect persisted, slightly attenuated, in the year following the intervention (2011). Conclusions: In HIV hyperendemic settings, a gift can be highly effective at increasing consent rates for home-based HIV testing. Given the importance of HIV testing for treatment uptake and individual health, as well as for HIV treatment-as-prevention strategies and for monitoring the population impact of the HIV response, gifts should be considered as a supportive intervention for HIV-testing initiatives where consent rates have been low.

The Impact of Self-Interviews on Response Patterns for Sensitive Topics: A Randomized Trial of Electronic Delivery Methods for a Sexual Behaviour Questionnaire in Rural South Africa

Background Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are associated with increased transmission of HIV, and poor reproductive and sexual health. The burden of STIs/BV among young people is unknown in many high HIV prevalence settings. We conducted an acceptability, feasibility, and prevalence study of home-based sampling for STIs/BV among young men and women aged 15–24 years old in a health and demographic surveillance site (HDSS) in rural KwaZulu-Natal, South Africa. Methods and findings A total of 1,342 young people, stratified by age (15–19 and 20–24 years) and sex were selected from the HDSS sampling frame; 1,171/1,342 (87%) individuals had ≥1 attempted home visit between 4 October 2016 and 31 January 2017, of whom 790 (67%) were successfully contacted. Among the 645 who were contacted and eligible, 447 (69%) enrolled. Consenting/assenting participants were interviewed, and blood, self-collected urine (men), and vaginal swabs (women) were tested for herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis, trichomoniasis, and BV. Both men and women reported that sample collection was easy. Participants disagreed that sampling was painful; more than half of the participants disagreed that they felt anxious or embarrassed. The weighted prevalence of STIs/BV among men and women, respectively, was 5.3% and 11.2% for chlamydia, 1.5% and 1.8% for gonorrhoea, 0% and 0.4% for active syphilis, 0.6% and 4.6% for trichomoniasis, 16.8% and 28.7% for HSV-2, and 42.1% for BV (women only). Of the women with ≥1 curable STI, 75% reported no symptoms. Factors associated with STIs/BV included having older age, being female, and not being in school or working. Among those who participated in the 2016 HIV serosurvey, the prevalence of HIV was 5.6% among men and 19% among women. Feasibility was impacted by the short study duration and the difficulty finding men at home. Conclusions A high prevalence of STIs/BV was found in this rural setting with high HIV prevalence in South Africa. Most STIs and HIV infections were asymptomatic and would not have been identified or treated under national syndromic management guidelines. A nested STI/BV survey within a HDSS proved acceptable and feasible. This is a proof of concept for population-based STI surveillance in low- and middle-income countries that could be utilised in the evaluation of STI/HIV prevention and control programmes.

Persistently high incidence of HIV and poor service uptake in adolescent girls and young women in rural KwaZulu-Natal, South Africa prior to DREAMS

BackgroundSelf-interviews, where the respondent rather than the interviewer enters answers to questions, have been proposed as a way to reduce social desirability bias associated with interviewer-led interviews. Computer-assisted self-interviews (CASI) are commonly proposed since the computer programme can guide respondents; however they require both language and computer literacy. We evaluated the feasibility and acceptability of using electronic methods to administer quantitative sexual behaviour questionnaires in the Somkhele demographic surveillance area (DSA) in rural KwaZulu-Natal, South Africa.MethodsWe conducted a four-arm randomized trial of paper-and-pen-interview, computer-assisted personal-interview (CAPI), CASI and audio-CASI with an age-sex-urbanicity stratified sample of 504 adults resident in the DSA in 2015. We compared respondents’ answers to their responses to the same questions in previous surveillance rounds. We also conducted 48 cognitive interviews, dual-coding responses using the Framework approach.ResultsThree hundred forty (67%) individuals were interviewed and covariates and participation rates were balanced across arms. CASI and audio-CASI were significantly slower than interviewer-led interviews. Item non-response rates were higher in self-interview arms. In single-paper meta-analysis, self-interviewed individuals reported more socially undesirable sexual behaviours. Cognitive interviews found high acceptance of both self-interviews and the use of electronic methods, with some concerns that self-interview methods required more participant effort and literacy.ConclusionsElectronic data collection methods, including self-interview methods, proved feasible and acceptable for completing quantitative sexual behaviour questionnaires in a poor, rural South African setting. However, each method had both benefits and costs, and the choice of method should be based on context-specific criteria.