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Background List randomization (LR), a survey method intended to mitigate biases related to sensitive true/false questions, has received recent attention from researchers. However, tests of its validity are limited, with no study comparing LR-elicited results with individually known truths. We conducted a test of LR for HIV-related responses in a high HIV prevalence setting in KwaZulu-Natal. By using researcher-known HIV serostatus and HIV test refusal data, we were able to assess how LR and direct questionnaires perform against individual known truth. Methods Participants were recruited from the participation list from the 2016 round of the Africa Health Research Institute demographic surveillance system, oversampling individuals who were HIV positive. Participants were randomized to two study arms. In Arm A, participants were presented five true/false statements, one of which was the sensitive item, the others non-sensitive. Participants were then asked how many of the five statements they believed were true. In Arm B, participants were asked about each statement individually. LR estimates used data from both arms, while direct estimates were generated from Arm B alone. We compared elicited responses to HIV testing and serostatus data collected through the demographic surveillance system. Results We enrolled 483 participants, 262 (54%) were randomly assigned to Arm A, and 221 (46%) to Arm B. LR estimated 56% (95% CI: 40 to 72%) of the population to be HIV-negative, compared to 47% (95% CI: 39 to 54%) using direct estimates; the population-estimate of the true value was 32% (95% CI: 28 to 36%). LR estimates yielded HIV test refusal percentages of 55% (95% CI: 37 to 73%) compared to 13% (95% CI: 8 to 17%) by direct estimation, and 15% (95% CI: 12 to 18%) based on observed past behavior. Conclusions In this context, LR performed poorly when compared to known truth, and did not improve estimates over direct questioning methods when comparing with known truth. These results may reflect difficulties in implementation or comprehension of the LR approach, which is inherently complex. Adjustments to delivery procedures may improve LR’s usefulness. Further investigation of the cognitive processes of participants in answering LR surveys is warranted.

Objectives: We investigate the effect of immediate antiretroviral therapy (ART) eligibility on HIV incidence among HIV-uninfected household members. Design: Regression discontinuity study arising from a population-based cohort. Methods: Household members of patients seeking care at the Hlabisa HIV Treatment and Care Programme in rural KwaZulu-Natal South Africa between January 2007 and August 2011 with CD4+ cell counts up to 350 cells/μl were eligible for inclusion if they had at least two HIV tests and were HIV-uninfected at the time the index patient linked to care (N = 4115). Regression discontinuity was used to assess the intention-to-treat effect of immediate versus delayed ART eligibility on HIV incidence among household members. Exploiting the CD4+ cell count-based threshold rule for ART initiation (CD4+ < 200 cells/μl until August 2011), we used Cox proportional hazards models to compare outcomes for household members of patients who presented for care with CD4+ cell counts just above versus just below the ART initiation threshold. Results: Characteristics of household members of index patients initiating HIV care were balanced between those with an index patient immediately eligible for ART (N = 2489) versus delayed for ART (N = 1626). There were 337 incident HIV infections among household members, corresponding to an HIV incidence of 2.4 infections per 100 person-years (95% confidence interval 2.5–3.1). Immediate eligibility for treatment reduced HIV incidence in households by 47% in our optimal estimate (hazard ratio = 0.53, 95% confidence interval 0.30–0.96), and by 32–60% in alternate specifications of the model. Conclusion: Immediate eligibility of ART led to substantial reductions in household-level HIV incidence.

Background. Antiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in “real-life” population-based settings in hyperendemic communities of sub-Saharan Africa, where health systems are typically resource-poor and overburdened, adherence to ART is often low, and partners commonly do not disclose their HIV status to each other. Methods. Data arose from a population-based open cohort in KwaZulu-Natal, South Africa. A total of 17 016 HIV-uninfected individuals present between January 2005 and December 2013 were included. Interval-censored time-updated proportional hazards regression was used to assess how the ART status affected HIV transmission risk in stable serodiscordant relationships. Results. We observed 1619 HIV seroconversions in 17 016 individuals, over 60 349 person-years follow-up time. During the follow-up period, 1846 individuals had an HIV-uninfected and 196 had an HIV-infected stable partner HIV incidence was 3.8/100 person-years (PY) among individuals with an HIV-infected partner (95% confidence interval [CI], 2.3–5.6), 1.4/100 PY (.4–3.5) among those with HIV-infected partners receiving ART, and 5.6/100 PY (3.5–8.4) among those with HIV-infected partners not receiving ART. Use of ART was associated with a 77% decrease in HIV acquisition risk among serodiscordant couples (adjusted hazard ratio, 0.23; 95% CI, .07–.80). Conclusions. ART initiation was associated with a very large reduction in HIV acquisition in serodiscordant couples in rural KwaZulu-Natal. However, this “real-life” effect was substantially lower than the effect observed in the HPTN-052 trial. To eliminate HIV transmission in serodiscordant couples, additional prevention interventions are probably needed.

Background: The effect of the rapid scale-up of vertical antiretroviral treatment (ART) programs for HIV in sub-Saharan Africa on the overall health system is under intense debate. Some have argued that these programs have reduced access for people suffering from diseases unrelated to HIV because ART programs have drained human and physical resources from other parts of the health system; others have claimed that the investments through ART programs have strengthened the general health system and the population health impacts of ART have freed up health care capacity for the treatment of diseases that are not related to HIV. To establish the population-level impact of ART programs on health care utilization in the public-sector health system, we compared trends in health care utilization among HIV-infected people receiving and not receiving ART with HIV-uninfected people during a period of rapid ART scale-up. Methods and Findings: We used data from the Wellcome Trust Africa Centre for Population Health, which annually elicited information on health care utilization from all surveillance participants over the period 2009–2012 (N = 32,319). We determined trends in hospitalization, and public-sector and private-sector primary health care (PHC) clinic visits for HIV-infected and -uninfected people over a time period of rapid ART scale-up (2009–2012) in this community. We regressed health care utilization on HIV status and ART status in different calendar years, controlling for sex, age, and area of residence. The proportion of people who reported to have visited a public-sector primary health care (PHC) clinic in the last 6 months increased significantly over the period 2009–2012, for both HIV-infected people (from 59% to 67%; p<0.001), and HIV-uninfected people (from 41% to 47%; p<0.001). In contrast, the proportion of HIV-infected people visiting a private-sector PHC clinic declined from 22% to 12% (p<0.001) and hospitalization rates declined from 128 to 82 per 1000 PY (p<0.001). For HIV-uninfected people, the proportion visiting a private-sector PHC clinic declined from 16% to 9%, and hospitalization rates declined from 78 to 44 per 1000 PY (p<0.001). After controlling for potential confounding factors, all trends remained of similar magnitude and significance. Conclusions: Our results indicate that the ART scale-up in this high HIV prevalence community has shifted health care utilization from hospitals and private-sector primary care to public-sector primary care. Remarkably, this shift is observed for both HIV-infected and -uninfected populations, supporting and extending hypotheses of ‘therapeutic citizenship’ whereby HIV-infected patients receiving ART facilitate primary care access for family and community members. One explanation of our findings is that ART has improved the capacity or quality of primary care in this community and, as a consequence, increasingly met overall health care needs at the primary care level rather than at the secondary level. Future research needs to confirm this causal interpretation of our findings using qualitative work to understand causal mechanisms or quasi-experimental quantitative studies to increase the strength of causal inference.

Background: High BMI and blood pressure are leading chronic disease risk factors in South Africa. Longterm effects of HIV and ART on adiposity and blood pressure are poorly understood, and direct comparisons of risk factor trajectories in HIV- versus HIV+ populations are rare. Methods: In 2003 and 2010, height, weight, and blood pressure were recorded in a study population (n = 505) in KwaZulu-Natal, South Africa (30% adult HIV prevalence). We modeled change in BMI and BP longitudinally in HIV- individuals (n = 315), seroconverters (n = 32), HIV+ patients not on ART (HIV+ART−; n = 52), HIV+ patients on ART for 0–<2 years as of 2010 (HIV+ART0–<2 yrs; n = 18), patients on ART for 2–5 years (HIV+ART2–5yrs; n = 44), and a subgroup with unknown HIV status (n = 44). Difference-in-differences were assessed in reference to the HIV- population. Results: Between 2003 and 2010, BMI increased significantly in the HIV- group, by 0.874 (95% CI 0.339, 1.41; p = 0.001), to 30.4. BMI drop was significantly greater in HIV+ART0-<2yrs than in HIV+ART2–5yrs (p = 0.005). DID in BMI in HIV+ART0-<2yrs versus the reference was -5.21 (95% CI -7.53, -2.90; p = 0.001), and DID in HIV+ART2–5yrs versus reference was -1.35 (95% CI -2.89, 0.189; p = 0.086). DID in SBP in HIV+ART−vs HIV- DID was -7.55 mmHg (95% CI -13.2 to -1.90; p = 0.009). Conclusion: Short-term ART (0–<2 years) was associated with larger weight loss than either no ART or long-term ART. Once on ART for 2+ years, individuals ‘caught up’ on weight gain with the HIV- population. Our results showcase the importance of health system readiness to address the burgeoning double burden of disease in South Africa.

Background: Cross-sectional, biomarker methods to determine HIV infection recency present a promising and cost-effective alternative to the repeated testing of uninfected individuals. We evaluate a viral-based assay that uses a measure of pairwise distances (PwD) to identify HIV infection recency, and compare its performance with two serologic incidence assays, BED and LAg. In addition, we assess whether combination BED plus PwD or LAg plus PwD screening can improve predictive accuracy by reducing the likelihood of a false-recent result. Methods: The data comes from 854 time-points and 42 participants enrolled in a primary HIV-1C infection study in Botswana. Time points after treatment initiation or with evidence of multiplicity of infection were excluded from the final analysis. PwD was calculated from quasispecies generated using single genome amplification and sequencing. We evaluated the ability of PwD to correctly classify HIV infection recency within <130, <180 and <360 days post-seroconversion using Receiver Operator Characteristics (ROC) methods. Following a secondary PwD screening, we quantified the reduction in the relative false-recency rate (rFRR) of the BED and LAg assays while maintaining a sensitivity of either 75, 80, 85 or 90%. Results: The final analytic sample consisted of 758 time-points from 40 participants. The PwD assay was more accurate in classifying infection recency for the 130 and 180-day cut-offs when compared with the recommended LAg and BED thresholds. A higher AUC statistic confirmed the superior predictive performance of the PwD assay for the three cut-offs. When used for combination screening, the PwD assay reduced the rFRR of the LAg assay by 52% and the BED assay by 57.8% while maintaining a 90% sensitivity for the 130 and 180-day cut-offs respectively. Conclusion: PwD can accurately determine HIV infection recency. A secondary PwD screening reduces misclassification and increases the accuracy of serologic-based assays.

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 partner's 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.

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.