The heterogeneous effect of short-term transfers for improving ART adherence among HIV-infected Tanzanian adults

A recently concluded randomized study in Tanzania found that short-term conditional cash and food transfers significantly improved HIV-infected patients' possession of antiretroviral therapy (ART) and reduced patient loss to follow-up (LTFU) (McCoy, S. I., Njau, P. F., Fahey, C., Kapologwe, N., Kadiyala, S., Jewell, N. P., & Padian, N. S. (2017). Cash vs. food assistance to improve adherence to antiretroviral therapy among HIV-infected adults in Tanzania. AIDS, 31(6), 815­825. doi:10.1097/QAD.0000000000001406 ). We examined whether these transfers had differential effects within population subgroups. In the parent study, 805 individuals were randomized to one of three study arms: standard-of-care (SOC) HIV services, food assistance, or cash transfer. We compared achievement of the medication possession ratio (MPR) ≥ 95% at 6 and 12 months and patient LTFU at 12 months between those receiving the SOC and those receiving food or cash (combined). Using a threshold value of p < 0.20 to signal potential effect measure modifiers (EMM), we compared intervention effects, expressed as risk differences (RD), within subgroups characterized by: sex, age, wealth, and time elapsed between HIV diagnosis and ART initiation. Short-term transfers improved 6 and 12-month MPR ≥ 95% and reduced 12-month LTFU in most subgroups. Study results revealed wealth and time elapsed between HIV diagnosis and ART initiation as potential EMMs, with greater effects for 6-month MPR ≥ 95% in the poorest patients (RD: 32, 95% CI: (9, 55)) compared to those wealthier (RD: 16, 95% CI: (5, 27); p = 0.18) and in newly diagnosed individuals (<90 days elapsed since diagnosis) (RD: 25, 95% CI: (13, 36)) compared to those with ≥90 days (RD: 0.3, 95% CI (−17, 18); p = 0.02), patterns which were sustained at 12 months. Results suggest that food and cash transfers may have stronger beneficial effects on ART adherence in the poorest patients. We also provide preliminary data suggesting that targeting interventions at patients more recently diagnosed with HIV may be worthwhile. Larger and longer-term assessments of transfer programs for the improvement of ART adherence and their potential heterogeneity by sub-population are warranted.

Rationale and design of a randomized study of short-term food and cash assistance to improve adherence to antiretroviral therapy among food insecure HIV-infected adults in Tanzania.

BACKGROUND: Food insecurity is an important barrier to retention in care and adherence to antiretroviral therapy (ART) among people living with HIV infection (PLHIV). However, there is a lack of rigorous evidence about how to improve food security and HIV-related clinical outcomes. To address this gap, this randomized trial will evaluate three delivery models for short-term food and nutrition support for food insecure PLHIV in Shinyanga, Tanzania: nutrition assessment and counseling (NAC) alone, NAC plus food assistance, and NAC plus cash transfers. METHODS/DESIGN: At three HIV care and treatment sites, 788 participants will be randomized into one of three study arms in a 3:3:1 ratio, stratified by site: NAC plus food assistance, NAC plus cash transfer, and NAC only. Eligible participants are: 1) at least 18 years of age; 2) living with HIV infection; 3) initiated ART in the past 90 days; and 4) food insecure, as measured with the Household Hunger Scale. PLHIV who are severely malnourished (body mass index (BMI) < 16 kg/m(2)) will be excluded. Participants randomized to receive food or cash transfers are eligible to receive assistance for up to six months, conditional on attending regularly scheduled visits with their HIV care provider. Participants will be followed for 12 months: the initial 6-month intervention period and then for another 6 months post-intervention. The primary outcome is ART adherence measured with the medication possession ratio. Secondary outcomes include 1) retention in care; 2) nutritional indicators including changes in food security, BMI, and weight gain; 3) viral suppression and self-reported ART adherence; and 4) participation in the labor force. DISCUSSION: This rigorously designed trial will inform policy decisions regarding supportive strategies for food insecure PLHIV in the early stages of treatment. The study will measure outcomes immediately after the period of support ends as well as 6 months later, providing information on the duration of the interventions' effect. The comparison of food to cash transfers will better inform policies favoring cash assistance or will provide rationale for the continued investment in food and nutrition interventions for PLHIV. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01957917.

Facility-based delivery in the context of Zimbabwe's HIV epidemic--missed opportunities for improving engagement with care: a community-based serosurvey.

BACKGROUND: In developing countries, facility-based delivery is recommended for maternal and neonatal health, and for prevention of mother-to-child HIV transmission (PMTCT). However, little is known about whether or not learning one's HIV status affects one's decision to deliver in a health facility. We examined this association in Zimbabwe. METHODS: We analyzed data from a 2012 cross-sectional community-based serosurvey conducted to evaluate Zimbabwe's accelerated national PMTCT program. Eligible women (≥16 years old and mothers of infants born 9-18 months before the survey) were randomly sampled from the catchment areas of 157 health facilities in five of ten provinces. Participants were interviewed about where they delivered and provided blood samples for HIV testing. RESULTS: Overall 8796 (77 %) mothers reported facility-based delivery; uptake varied by community (30-100%). The likelihood of facility-based delivery was not associated with maternal HIV status. Women who self-reported being HIV-positive before delivery were as likely to deliver in a health facility as women who were HIV-negative, irrespective of when they learned their status - before (adjusted prevalence ratio (PRa) = 1.04, 95% confidence interval (CI) = 1.00-1.09) or during pregnancy (PRa = 1.05, 95% CI = 1.01-1.09). Mothers who had not accessed antenatal care or tested for HIV were most likely to deliver outside a health facility (69%). Overall, however 77% of home deliveries occurred among women who had accessed antenatal care and were HIV-tested. CONCLUSIONS: Uptake of facility-based delivery was similar among HIV-infected and HIV-uninfected mothers, which was somewhat unexpected given the substantial technical and financial investment aimed at retaining HIV-positive women in care in Zimbabwe.

Food insecurity is a barrier to prevention of mother-to-child HIV transmission services in Zimbabwe: a cross-sectional study.

BACKGROUND: Food insecurity (FI) is the lack of physical, social, and economic access to sufficient food for dietary needs and food preferences. We examined the association between FI and women's uptake of services to prevent mother-to-child HIV transmission (MTCT) in Zimbabwe. METHODS: We analyzed cross-sectional data collected in 2012 from women living in five of ten provinces. Eligible women were ≥16 years old, biological mothers of infants born 9-18 months before the interview, and were randomly selected using multi-stage cluster sampling. Women and infants were tested for HIV and interviewed about health service utilization during pregnancy, delivery, and post-partum. We assessed FI in the past four weeks using a subset of questions from the Household Food Insecurity Access Scale and classified women as living in food secure, moderately food insecure, or severely food insecure households. RESULTS: The weighted population included 8,790 women. Completion of all key steps in the PMTCT cascade was reported by 49%, 45%, and 38% of women in food secure, moderately food insecure, and severely food insecure households, respectively (adjusted prevalence ratio (PRa) = 0.95, 95% confidence interval (CI): 0.90, 1.00 (moderate FI vs. food secure), PRa = 0.86, 95% CI: 0.79, 0.94 (severe FI vs. food secure)). Food insecurity was not associated with maternal or infant receipt of ART/ARV prophylaxis. However, in the unadjusted analysis, among HIV-exposed infants, 13.3% of those born to women who reported severe household food insecurity were HIV-infected compared to 8.2% of infants whose mothers reported food secure households (PR = 1.62, 95% CI: 1.04, 2.52). After adjustment for covariates, this association was attenuated (PRa = 1.42, 95% CI: 0.89, 2.26). There was no association between moderate food insecurity and MTCT in unadjusted or adjusted analyses (PRa = 0.68, 95% CI: 0.43, 1.08). CONCLUSIONS: Among women with a recent birth, food insecurity is inversely associated with service utilization in the PMTCT cascade and severe household food insecurity may be positively associated with MTCT. These preliminary findings support the assessment of FI in antenatal care and integrated food and nutrition programs for pregnant women to improve maternal and child health.

Social network recruitment for Yo Puedo: an innovative sexual health intervention in an underserved urban neighborhood­sample and design implications.

Most existing evidence-based sexual health interventions focus on individual-level behavior, even though there is substantial evidence that highlights the influential role of social environments in shaping adolescents' behaviors and reproductive health outcomes. We developed Yo Puedo, a combined conditional cash transfer and life skills intervention for youth to promote educational attainment, job training, and reproductive health wellness that we then evaluated for feasibility among 162 youth aged 16-21 years in a predominantly Latino community in San Francisco, CA. The intervention targeted youth's social networks and involved recruitment and randomization of small social network clusters. In this paper we describe the design of the feasibility study and report participants' baseline characteristics. Furthermore, we examined the sample and design implications of recruiting social network clusters as the unit of randomization. Baseline data provide evidence that we successfully enrolled high risk youth using a social network recruitment approach in community and school-based settings. Nearly all participants (95%) were high risk for adverse educational and reproductive health outcomes based on multiple measures of low socioeconomic status (81%) and/or reported high risk behaviors (e.g., gang affiliation, past pregnancy, recent unprotected sex, frequent substance use; 62%). We achieved variability in the study sample through heterogeneity in recruitment of the index participants, whereas the individuals within the small social networks of close friends demonstrated substantial homogeneity across sociodemographic and risk profile characteristics. Social networks recruitment was feasible and yielded a sample of high risk youth willing to enroll in a randomized study to evaluate a novel sexual health intervention.

Are hormonal contraceptive users more likely to misreport unprotected sex? Evidence from a biomarker validation study in Zimbabwe.

We analyzed biomarker validation data of unprotected sex from women in Zimbabwe to determine whether condom and sexual behavior misreporting differs between users of different contraceptive methods. Self-reported sexual behavior was compared with the presence of prostate-specific antigen (PSA) in vaginal fluid, a biomarker of semen exposure. Of the 195 women who were PSA positive, 94 (48 %) reported no sex or only condom-protected sex. Hormonal contraceptive users misreported sexual behavior less than women using non-hormonal methods (45 vs. 67 %, P = 0.03). This misclassification pattern could have implications on the elevated risk of HIV infection associated with hormonal contraception in some studies.

Food insecurity, socioeconomic status, and HIV-related risk behavior among women in farming households in Tanzania.

Food insecurity (FI) is associated with higher-risk sexual behavior in some studies. However, the overlap between FI and socioeconomic status (SES) has been poorly described. The study objectives were to: (1) determine the relationship between household FI and four dimensions of SES among sexually active Tanzanian women in farming households: expenditures, assets, flooring material of the home, and land ownership; and (2) determine whether FI is associated with higher-risk sexual behavior and relationship power. In male-headed households, FI was associated with assets, flooring material, and land ownership but not expenditures. There was no association between FI and the four dimensions of SES in female-headed households. Among women in male-headed households, but not female household heads themselves, severe FI was associated with a non-significant increase in the likelihood of being in a relationship because of material goods [adjusted prevalence ratio (PRa) = 1.76, 95 % confidence interval (CI) 0.81, 3.81] and was inversely associated with being able to ask partners to use condoms (PRa = 0.47, 95 % CI 0.25, 0.88). There was not a strong association between food security and relationship power. Our findings suggest that the association between FI and HIV risk behavior may differ depending on the type of household.

HIV treatment as prevention: considerations in the design, conduct, and analysis of cluster randomized controlled trials of combination HIV prevention.

The rigorous evaluation of the impact of combination HIV prevention packages at the population level will be critical for the future of HIV prevention. In this review, we discuss important considerations for the design and interpretation of cluster randomized controlled trials (C-RCTs) of combination prevention interventions. We focus on three large C-RCTs that will start soon and are designed to test the hypothesis that combination prevention packages, including expanded access to antiretroviral therapy, can substantially reduce HIV incidence. Using a general framework to integrate mathematical modelling analysis into the design, conduct, and analysis of C-RCTs will complement traditional statistical analyses and strengthen the evaluation of the interventions. Importantly, even with combination interventions, it may be challenging to substantially reduce HIV incidence over the 2- to 3-y duration of a C-RCT, unless interventions are scaled up rapidly and key populations are reached. Thus, we propose the innovative use of mathematical modelling to conduct interim analyses, when interim HIV incidence data are not available, to allow the ongoing trials to be modified or adapted to reduce the likelihood of inconclusive outcomes. The preplanned, interactive use of mathematical models during C-RCTs will also provide a valuable opportunity to validate and refine model projections.

HIV prevention transformed: the new prevention research agenda.

We have entered a new era in HIV prevention whereby priorities have expanded from biomedical discovery to include implementation, effectiveness, and the effect of combination prevention at the population level. However, gaps in knowledge and implementation challenges remain. In this Review we analyse trends in the rapidly changing landscape of HIV prevention, and chart a new path for HIV prevention research that focuses on the implementation of effective and efficient combination prevention strategies to turn the tide on the HIV pandemic.