We tested whether a multisectoral household agricultural and finance intervention increased the dietary intake and improved the nutritional status of HIV-affected children. Two hospitals in rural Kenya were randomly assigned to be either the intervention or the control arm. The intervention comprised a human-powered water pump, microfinance loan for farm commodities, and training in sustainable farming practices and financial management. In each arm, 100 children (0-59 mo of age) were enrolled from households with HIV-infected adults 18-49 y old. Children were assessed beginning in April 2012 and every 3 mo for 1 y for dietary intake and anthropometry. Children in the intervention arm had a larger increase in weight (β: 0.025 kg/mo, P = 0.030), overall frequency of food consumption (β: 0.610 times · wk^-1 · mo^-1, P = 0.048), and intakes of staples (β: 0.222, P = 0.024), fruits and vegetables (β: 0.425, P = 0.005), meat (β: 0.074, P < 0.001), and fat (β: 0.057, P = 0.041). Livelihood interventions have potential to improve the nutrition of HIV-affected children. This trial was registered at clinicaltrials.gov as NCT01548599.

Exclusive breastfeeding (EBF) provides infants with optimal nutrition, and together with appropriate antiretroviral therapy has also been shown to decrease mother-to-child transmission of HIV from 45 to less than 1 %. However, rates of EBF are particularly low in South Africa, where rates of HIV are some of the highest in the world. Although perinatal depression has been identified as a potential barrier to EBF, little is known about its impact on EBF among HIV-infected women. A cohort study was conducted as part of a pilot randomized controlled trial (RCT) examining the effect of an Information, Motivation and Behavioral skills-based intervention promoting EBF among South African women living with HIV in their third trimester (28-42 weeks) of pregnancy. At baseline and follow-up, participants were interviewed on depression symptoms (PHQ-9), and breastfeeding intentions and behavior. Multivariate logistic regressions were conducted to determine predictors of EBF at 6-weeks postpartum. A total of 68 women were enrolled and 58 women completed both baseline and follow-up assessments. Most (80.9 %) of the sample reported at least some symptoms of depression prenatally. Rates of depression were lower postpartum (47.1 %). In multivariate models, higher prenatal depression scores significantly predicted lower likelihood of EBF at 6-weeks postpartum after adjusting for demographics, condition, and intentions (AOR = 0.68, p < 0.05). Postpartum depression was not a significant predictor of EBF rates (AOR = 0.99, p = 0.96). These findings demonstrate the negative impact of prenatal depression on breastfeeding behavior. Future interventions focused on depression are warranted to identify those at risk for sub-optimal EBF. Improving maternal psychosocial well-being could be a new frontier to improving infant and young child feeding and reducing pre/postnatal transmission.

In the eastern Democratic Republic of the Congo, ongoing armed conflict increases the incidence of gender-based violence (GBV) and presents a distinct and major barrier to care delivery for all survivors of GBV. A specific challenge is providing emergency contraception, HIV prophylaxis and treatment for sexually transmitted infections to all survivors within 72 hours of violence. To address the multiple barriers to providing this time-sensitive medical care, Global Strategies and Panzi Hospital implemented the Prevention Pack Program. The Prevention Pack is a pre-packaged post-rape medical kit containing antiretroviral post-exposure prophylaxis, antibiotics for treatment of sexually transmitted infections and emergency contraception. The Prevention Pack Program combines community sensitisation about post-rape medical care with the provision of Prevention Packs and the implementation of a cloud-based and Global Positioning System (GPS)-enabled inventory management system. The Panzi Hospital gender-based violence team implemented the Prevention Pack Program at Panzi Hospital and 12 rural clinics in the South Kivu Province. The data manager took GPS coordinates of each site, provided an initial stock of Prevention Packs and then called all sites daily to determine demand for post-rape care and Prevention Pack consumption. Inventory data were entered into the GPS-enabled cloud-based inventory management system. Project personnel used the consumption rate, trends and geolocation of sites to guide Prevention Pack restocking strategy. Between 2013 and 2017, a total of 8206 individuals presented for care following rape at the study sites. Of the 1414 individuals who presented in the rural areas, 1211 (85.6%) did so within the first 72 hours of reported rape. Care was delivered continuously and without a single stockout of medication across all sites. The Prevention Pack Program provided timely and consistent access to emergency contraception, HIV prophylaxis and treatment for sexually transmitted infections for rape survivors in the eastern Democratic Republic of the Congo.

Little is known about the association of gender-based power imbalances and health and health behaviors among women with HIV (WWH). We examined cross-sectional baseline data among WWH in a cluster-randomized control trial (NCT02815579) in rural Kenya. We assessed associations between the Sexual Relationship Power Scale (SRPS) and ART adherence, physical and mental health, adjusting for sociodemographic and social factors. SRPS consists of two subscales: relationship control (RC) and decision-making dominance. Women in the highest and middle tertiles for RC had a 7.49 point and 8.88 point greater Medical Outcomes Study-HIV mental health score, and a 0.27 and 0.29 lower odds of depression, respectively, compared to women in the lowest tertile. We did not find associations between SPRS or its subscales and ART adherence. Low sexual relationship power, specifically low RC, may be associated with poor mental health among WWH. Intervention studies aimed to improve RC among WWH should be studied to determine their effect on improving mental health.

Objectives

Food insecurity and HIV/AIDS outcomes are inextricably linked in sub-Saharan Africa. We report on health and nutritional outcomes of a multisectoral agricultural intervention trial among HIV-infected adults in rural Kenya.

Design

This is a pilot cluster randomized controlled trial.

Methods

The intervention included a human-powered water pump, a microfinance loan to purchase farm commodities, and education in sustainable farming practices and financial management. Two health facilities in Nyanza Region, Kenya were randomly assigned as intervention or control. HIV-infected adults 18 to 49 years' old who were on antiretroviral therapy and had access to surface water and land were enrolled beginning in April 2012 and followed quarterly for 1 year. Data were collected on nutritional parameters, CD4 T-lymphocyte counts, and HIV RNA. Differences in fixed-effects regression models were used to test whether patterns in health outcomes differed over time from baseline between the intervention and control arms.

Results

We enrolled 72 and 68 participants in the intervention and control groups, respectively. At 12 months follow-up, we found a statistically significant increase in CD4 cell counts (165 cells/μl, P < 0.001) and proportion virologically suppressed in the intervention arm compared with the control arm (comparative improvement in proportion of 0.33 suppressed, odds ratio 7.6, 95% confidence interval: 2.2-26.8). Intervention participants experienced significant improvements in food security (3.6 scale points higher, P < 0.001) and frequency of food consumption (9.4 times per week greater frequency, P = 0.013) compared to controls.

Conclusion

Livelihood interventions may be a promising approach to tackle the intersecting problems of food insecurity, poverty and HIV/AIDS morbidity.

This longitudinal qualitative study sought to understand how and why a livelihood intervention affected the health and health behaviors of HIV-infected Kenyan adults. The intervention included a microfinance loan, agricultural and financial training, and a human-powered water pump. In-depth interviews were conducted at two time points with intervention and control participants and program staff. We double coded interviews (n = 117) and used thematic content analysis of transcripts following an integrative inductive-deductive approach. Intervention participants described improvements in HIV health, including increased CD4 counts and energy, improved viral suppression, and fewer HIV-related symptoms. Better health was linked to improved clinic attendance and ART adherence through several mechanisms: (1) reductions in food insecurity and abject hunger; (2) improved financial stability; (3) improved productivity which enhanced social support; (4) better control over work situations; and, (5) renewed desire to prioritize their own health. Livelihood interventions may improve health by influencing upstream determinants of health behavior including food security and poverty.

Reliable access to safe and acceptable water in sufficient quantities (i.e., water security) is important for medication adherence and limiting pathogen exposure, yet prior studies have only considered the role of food security as a social determinant of HIV-related health. Therefore, the objective of this analysis was to assess the relationships between household water insecurity and HIV-related outcomes among adults living with HIV in western Kenya (N = 716). We conducted a cross-sectional analysis of baseline data from Shamba Maisha (NCT02815579), a cluster randomized controlled trial of a multisectoral agricultural and asset loan intervention. Baseline data were collected from June 2016 to December 2017. We assessed associations between water insecurity and HIV-related outcomes, adjusting for clinical and behavioral confounders, including food insecurity. Each five-unit higher household water insecurity score (range: 0-51) was associated with 1.21 higher odds of having a viral load ≥ 1000 copies/mL (95% CI 1.07, 1.36) and 1.26 higher odds of AIDS-defining illness (95% CI 1.11, 1.42). Household water insecurity was not associated with CD4 cell count (B: 0.27; 95% CI -3.59, 13.05). HIV treatment and support programs should consider assessing and addressing water insecurity in addition to food insecurity to optimize HIV outcomes.

In prostate cancer, androgen receptor (AR)-targeting agents are very effective in various disease stages. However, therapy resistance inevitably occurs, and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multiomics analyses on tissues isolated before and after 3 months of AR-targeting enzalutamide monotherapy from patients with high-risk prostate cancer enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors toward a neuroendocrine-like disease state. Additionally, epigenomic profiling revealed massive enzalutamide-induced reprogramming of pioneer factor FOXA1 from inactive chromatin sites toward active cis-regulatory elements that dictate prosurvival signals. Notably, treatment-induced FOXA1 sites were enriched for the circadian clock component ARNTL. Posttreatment ARNTL levels were associated with patients' clinical outcomes, and ARNTL knockout strongly decreased prostate cancer cell growth. Our data highlight a remarkable cistromic plasticity of FOXA1 following AR-targeted therapy and revealed an acquired dependency on the circadian regulator ARNTL, a novel candidate therapeutic target.

Significance

Understanding how prostate cancers adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenomic plasticity toward prosurvival signaling and uncovered the circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel lead for therapeutic development. See related commentary by Zhang et al., p. 2017. This article is highlighted in the In This Issue feature, p. 2007.

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.