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The scale-up of antiretroviral therapy (ART) is expected to raise adult life expectancy in populations with high HIV prevalence. Using data from a population cohort of over 101,000 individuals in rural KwaZulu-Natal, South Africa, we measured changes in adult life expectancy for 2000—2011. In 2003, the year before ART became available in the public-sector health system, adult life expectancy was 49.2 years; by 2011, adult life expectancy had increased to 60.5 years—an 11.3-year gain. Based on standard monetary valuation of life, the survival benefits of ART far outweigh the costs of providing treatment in this community. These gains in adult life expectancy signify the social value of ART and have implications for the investment decisions of individuals, governments, and donors.

Introduction: To systematically review the literature on mother‐to‐child transmission in breastfed infants whose mothers received antiretroviral therapy and support the process of updating the World Health Organization infant feeding guidelines in the context of HIV and ART. Methods: We reviewed experimental and observational studies; exposure was maternal HIV antiretroviral therapy (and duration) and infant feeding modality; outcomes were overall and postnatal HIV transmission rates in the infant at 6, 9, 12 and 18 months. English literature from 2005 to 2015 was systematically searched in multiple electronic databases. Papers were analysed by narrative synthesis; data were pooled in random effects meta‐analyses. Postnatal transmission was assessed from four to six weeks of life. Study quality was assessed using a modified Newcastle‐Ottawa Scale (NOS) and GRADE. Results and discussion: Eleven studies were identified, from 1439 citations and review of 72 s. Heterogeneity in study methodology and pooled estimates was considerable. Overall pooled transmission rates at 6 months for breastfed infants with mothers on antiretroviral treatment (ART) was 3.54% (95% CI: 1.15–5.93%) and at 12 months 4.23% (95% CI: 2.97–5.49%). Postnatal transmission rates were 1.08 (95% CI: 0.32–1.85) at six and 2.93 (95% CI: 0.68–5.18) at 12 months. ART was mostly provided for PMTCT only and did not continue beyond six months postpartum. No study provided data on mixed feeding and transmission risk. Conclusions: There is evidence of substantially reduced postnatal HIV transmission risk under the cover of maternal ART. However, transmission risk increased once PMTCT ART stopped at six months, which supports the current World Health Organization recommendations of life‐long ART for all.

ObjectivesTo identify and investigate complex pathways to stunting among children aged 6–24 months to determine the mediating effects of dietary diversity and continued breast feeding on the association between socioeconomic factors and child stunting.Design, setting and participantsWe analysed the most recent cross-sectional Demographic and Health Survey data from Cambodia (2014). We applied structural path analysis on a sample of 1365 children to model the complex and inter-related pathways of factors determining children’s height for age. Explanatory variables included a composite indicator of maternal employment, household wealth, maternal education, current breastfeeding status and dietary diversity score. Results are presented both in terms of non-standardised and standardised coefficients.Outcome measureThe primary outcome measure was height-for-age Z-scores as a continuous measure.ResultsFindings suggest that children’s dietary diversity and continued breast feeding mediate the association between socioeconomic status and children’s height. While there was no significant direct effect of maternal education on children’s height, results suggested significant indirect pathways through which maternal education effects children’s height; operating through household wealth, maternal employment, dietary diversity and continued breastfeeding status (p<0.001). Most notably, 41% of the effect of maternal employment on children’s height was mediated by either dietary diversity or continued breast feeding.ConclusionWe provide evidence to support targeted nutrition interventions which account for the different ways in which underlying socioeconomic factors influence infant and young child feeding practices, and the potential impact on child nutritional status.

Hypertension and excess body weight are major risk factors of cardiovascular morbidity and mortality in developing countries. In countries with a high HIV prevalence, it is unknown how increased antiretroviral treatment and care (ART) coverage has affected the prevalence of overweight, obesity, and hypertension. We conducted a health survey in 2010 based on the WHO STEPwise approach in 14,198 adult resident participants of a demographic surveillance area in rural South Africa to investigate factors associated with hypertension and excess weight including HIV infection and ART status. Women had a significantly higher median body mass index (BMI) than men (26.4 vs. 21.2 kg/m(2), p<0.001). The prevalence of obesity (BMI ≥ 30 kg/m(2)) in women (31.3%, 95% confidence interval (CI) 30.2-32.4) was 6.5 times higher than in men (4.9%, 95% CI 4.1-5.7), whereas prevalence of hypertension (systolic or diastolic blood pressure ≥ 140 or 90 mm Hg, respectively) was 1.4 times higher in women than in men (28.5% vs 20.8%, p<0.001). In multivariable regression analysis, both hypertension and obesity were significantly associated with sex, age, HIV and ART status. The BMI of women and men on ART was on average 3.8 (95% CI 3.2-3.8) and 1.7 (95% CI 0.9-2.5) kg/m(2) lower than of HIV-negative women and men, respectively. The BMI of HIV-infected women and men not on ART was on average 1.2 (95% CI 0.8-1.6) and 0.4 (95% CI -0.1-0.9) kg/m(2) lower than of HIV-negative women and men, respectively. Obesity was a bigger risk factor for hypertension in men (adjusted odds ratio (aOR) 2.99, 95% CI 2.00-4.48) than in women (aOR 1.64, 95% CI 1.39-1.92) and overweight (25 ≤ BMI<30) was a significant risk factor for men only (aOR 1.53 95% CI 1.14-2.06). Our study suggests that, cardiovascular risk factors of hypertension and obesity differ substantially between women and men in rural South Africa.

Exclusive breastfeeding, though better than other forms of infant feeding and associated with improved child survival, is uncommon. We assessed the HIV-1 transmission risks and survival associated with exclusive breastfeeding and other types of infant feeding. 2722 HIV-infected and uninfected pregnant women attending antenatal clinics in KwaZulu Natal, South Africa (seven rural, one semiurban, and one urban), were enrolled into a non-randomised intervention cohort study. Infant feeding data were obtained every week from mothers, and blood samples from infants were taken monthly at clinics to establish HIV infection status. Kaplan-Meier analyses conditional on exclusive breastfeeding were used to estimate transmission risks at 6 weeks and 22 weeks of age, and Cox's proportional hazard was used to quantify associations with maternal and infant factors. 1132 of 1372 (83%) infants born to HIV-infected mothers initiated exclusive breastfeeding from birth. Of 1276 infants with complete feeding data, median duration of cumulative exclusive breastfeeding was 159 days (first quartile [Q1] to third quartile [Q3], 122–174 days). 14·1% (95% CI 12·0–16·4) of exclusively breastfed infants were infected with HIV-1 by age 6 weeks and 19·5% (17·0–22·4) by 6 months; risk was significantly associated with maternal CD4-cell counts below 200 cells per μL (adjusted hazard ratio [HR] 3·79; 2·35–6·12) and birthweight less than 2500 g (1·81, 1·07–3·06). Kaplan-Meier estimated risk of acquisition of infection at 6 months of age was 4·04% (2·29–5·76). Breastfed infants who also received solids were significantly more likely to acquire infection than were exclusively breastfed children (HR 10·87, 1·51–78·00, p=0·018), as were infants who at 12 weeks received both breastmilk and formula milk (1·82, 0·98–3·36, p=0·057). Cumulative 3-month mortality in exclusively breastfed infants was 6·1% (4·74–7·92) versus 15·1% (7·63–28·73) in infants given replacement feeds (HR 2·06, 1·00–4·27, p=0·051). The association between mixed breastfeeding and increased HIV transmission risk, together with evidence that exclusive breastfeeding can be successfully supported in HIV-infected women, warrant revision of the present UNICEF, WHO, and UNAIDS infant feeding guidelines.

The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART. Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/μl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded. In all, 12,894 adults were registered as eligible for participation (5,790 in intervention arm; 7,104 in control arm), of whom 9,927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569 ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known HIV-positive status). Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤ 350 cells/μl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/μl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded. Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population. ClinicalTrials.gov NCT01509508.

Concurrent sexual partnerships are widely believed to be one of the main drivers of the HIV epidemic in sub-Saharan Africa. This view is supported by theoretical models predicting that increases in prevalence of concurrent partnerships could substantially increase the rate of spread of the disease. However, the effect of concurrent partnerships on HIV incidence has not been appropriately tested in a sub-Saharan African setting. For this population-based cohort study, we used data from the Africa Centre demographic surveillance site in KwaZulu-Natal, South Africa, to try to find support for the concurrency hypothesis. We used a moving-window approach to construct estimates of the geographical variation in reported concurrent and lifetime partners in sexually active men aged 15–55 years (n=2153) across the study area. We then followed up 7284 HIV-negative women (≥15 years of age) in the population and quantified the effect of the sexual behaviour profiles of men in the surrounding local community on a woman's hazard of HIV acquisition. During 5 years' follow-up, 693 new female HIV infections occurred (incidence 3·60 cases per 100 person-years). We identified substantial intercommunity heterogeneity in the estimated point-prevalence of partnership concurrency (range 4·0–76·3%; mean 31·5%) and mean number of lifetime sexual partners (3·4–12·9; mean 6·3) in sexually active men in this population. After adjustment for individual-level sexual behaviour and demographic, socioeconomic, and environmental factors associated with HIV acquisition, mean lifetime number of partners of men in the immediate local community was predictive of hazard of HIV acquisition in women (adjusted hazard ratio [HR] 1·08, 95% CI 1·03–1·14, p=0·004), whereas a high prevalence of partnership concurrency in the same local community was not associated with any increase in risk of HIV acquisition (adjusted HR 1·02, 95% CI 0·95–1·09, p=0·556). We find no evidence to suggest that concurrent partnerships are an important driver of HIV incidence in this typical high-prevalence rural African population. Our findings suggest that in similar hyperendemic sub-Saharan African settings, there is a need for straightforward, unambiguous messages aimed at the reduction of multiple partnerships, irrespective of whether those partnerships overlap in time. US National Institute of Child Health and Human Development; Wellcome Trust.

The success of potent antiretroviral treatment for HIV infection is primarily determined by adherence. We systematically review the evidence of effectiveness of interventions to increase adherence to antiretroviral treatment in sub-Saharan Africa. We identified 27 relevant reports from 26 studies of behavioural, cognitive, biological, structural, and combination interventions done between 2003 and 2010. Despite study diversity and limitations, evidence suggests that treatment supporters, directly observed therapy, mobile-phone text messages, diary cards, and food rations can effectively increase adherence in sub-Saharan Africa. However, some interventions are unlikely to have large or lasting effects, and others are effective only in specific settings. These findings emphasise the need for more research, particularly for randomised controlled trials, to examine the effect of context and specific features of intervention content on effectiveness. Future work should assess intervention targeting and selection of interventions based on behavioural theories relevant to sub-Saharan Africa.

Background In South Africa, HIV prevalence among youth aged 15-24 is among the world's highest. Given the urgent need to identify effective HIV prevention approaches, this review assesses the evidence base for youth HIV prevention in South Africa. Methods Systematic, analytical review of HIV prevention interventions targeting youth in South Africa since 2000. Critical assessment of interventions in 4 domains: 1) study design and outcomes, 2) intervention design (content, curriculum, theory, adaptation process), 3) thematic focus and HIV causal pathways, 4) intervention delivery (duration, intensity, who, how, where). Results Eight youth HIV prevention interventions were included; all were similar in HIV prevention content and objectives, but varied in thematic focus, hypothesised causal pathways, theoretical basis, delivery method, intensity and duration. Interventions were school- (5) or group-based (3), involving in- and out-of-school youth. Primary outcomes included HIV incidence (2), reported sexual risk behavior alone (4), or with alcohol use (2). Interventions led to reductions in STI incidence (1), and reported sexual or alcohol risk behaviours (5), although effect size varied. All but one targeted at least one structural factor associated with HIV infection: gender and sexual coercion (3), alcohol/substance use (2), or economic factors (2). Delivery methods and formats varied, and included teachers (5), peer educators (5), and older mentors (1). School-based interventions experienced frequent implementation challenges. Conclusions Key recommendations include: address HIV social risk factors, such as gender, poverty and alcohol; target the structural and institutional context; work to change social norms; and engage schools in new ways, including participatory learning.

Introduction HIV treatment guidelines now recommend antiretroviral therapy (ART) initiation regardless of CD4 count to maximize benefit both for the individual and society. It is unknown whether the initiation of ART at higher CD4 counts would affect adherence levels. We investigated whether initiating ART at higher CD4 counts was associated with sub‐optimal adherence (<95%) during the first 12 months of ART. Methods A prospective cohort study nested within a two‐arm cluster‐randomized trial of universal test and treat was implemented from March 2012 to June 2016 to measure the impact of ART on HIV incidence in rural KwaZulu‐Natal. ART was initiated regardless of CD4 count in the intervention arm and according to national guidelines in the control arm. ART adherence was measured monthly using a visual analogue scale (VAS) and pill counts (PC). HIV viral load was measured at ART initiation, three and six months, and six‐monthly thereafter. We pooled data from participants in both arms and used random‐effects logistic regression models to examine the association between CD4 count at ART initiation and sub‐optimal adherence, and assessed if adherence levels were associated with virological suppression. Results Among 900 individuals who initiated ART ≥12 months before study end, median (IQR) CD4 at ART initiation was 350 cells/mm3 (234, 503); median age was 34.6 years (IQR 27.4 to 46.4) and 71.7% were female. Adherence was sub‐optimal in 14.7% of visits as measured by VAS and 20.7% by PC. In both the crude analyses and after adjusting for potential confounders, adherence was not significantly associated with CD4 count at ART initiation (adjusted OR for linear trend in sub‐optimal adherence with every 100 cells/mm3 increase in CD4 count: 1.00, 95% CI 0.95 to 1.05, for VAS, and 1.03, 95% CI 0.99 to 1.07, for PC). Virological suppression at 12 months was 97%. Optimal adherence by both measures was significantly associated with virological suppression (p < 0.001 for VAS; p = 0.006 for PC). Conclusions We found no evidence that higher CD4 counts at ART initiation were associated with sub‐optimal ART adherence in the first 12 months. Our findings should alleviate concerns about adherence in individuals initiating ART at higher CD4 counts, however long‐term outcomes are needed. ClinicalTrials.gov NCT01509508.