A comparison of all-cause and cause-specific mortality by household socioeconomic status across seven INDEPTH network health and demographic surveillance systems in sub-Saharan Africa

Background: Understanding socioeconomic disparities in all-cause and cause-specific mortality can help inform prevention and treatment strategies. Objectives: To quantify cause-specific mortality rates by socioeconomic status across seven health and demographic surveillance systems (HDSS) in five countries (Ethiopia, Kenya, Malawi, Mozambique, and Nigeria) in the INDEPTH Network in sub-Saharan Africa. Methods: We linked demographic residence data with household survey data containing living standards and education information we used to create a poverty index. Person-years lived and deaths between 2003 and 2016 (periods varied by HDSS) were stratified in each HDSS by age, sex, year, and number of deprivations on the poverty index (0–8). Causes of death were assigned to each death using the InterVA-4 model based on responses to verbal autopsy questionnaires. We estimated rate ratios between socioeconomic groups (2–4 and 5–8 deprivations on our poverty index compared to 0–2 deprivations) for specific causes of death and calculated life expectancy for the deprivation groups. Results: Our pooled data contained almost 3.5 million person-years of observation and 25,038 deaths. All-cause mortality rates were higher among people in households with 5–8 deprivations on our poverty index compared to 0–2 deprivations, controlling for age, sex, and year (rate ratios ranged 1.42 to 2.06 across HDSS sites). The poorest group had consistently higher death rates in communicable, maternal, neonatal, and nutritional conditions (rate ratios ranged 1.34–4.05) and for non-communicable diseases in several sites (1.14–1.93). The disparities in mortality between 5–8 deprivation groups and 0–2 deprivation groups led to lower life expectancy in the higher-deprivation groups by six years in all sites and more than 10 years in five sites. Conclusions: We show large disparities in mortality on the basis of socioeconomic status across seven HDSS in sub-Saharan Africa due to disparities in communicable disease mortality and from non-communicable diseases in some sites. Life expectancy gaps between socioeconomic groups within sites were similar to the gaps between high-income and lower-middle-income countries. Prevention and treatment efforts can benefit from understanding subpopulations facing higher mortality from specific conditions

The Association between Sexual Behavior and Adherence to Hiv Pre-exposure Prophylaxis Medication in Hiv Serodiscordant Couples

High levels of adherence have been identified as a key factor for effective pre-exposure prophylaxis medication (PrEP). Because PrEP is a new concept in HIV prevention, there are limited data on predictors of adherence, though initial findings indicate that sexual behavior could be an influencing factor. This study examines different aspects of sexual behavior and their associations with monthly rates and patterns of adherence. We enrolled 1147 HIV-negative individuals living in long-term serodiscordant relationships at three sites in Uganda. Sexual behavior was assessed via monthly in-person interviews and adherence was measured through electronic monitoring of pill bottle openings. We used generalized estimation equations to adjust for risk factors of low adherence to PrEP medication. Fifty-three percent of participants were male, 51% were aged between 18 and 34 years, the median number of years they had lived with the HIV-positive partner was 8.5 years and 24.2% were in polygamous relationships. Participants who had sex with other partners and also had less than 100% use of condoms were more than twice as likely to have less than 80% adherence (OR=2.48, 95%CI=1.70-3.62). Per electronic monitoring, 54.7% of cohort participants had at least one 72-hour consecutive gap in adherence. Participants who had sex with other partners and were also had also reported less than 100% use of condoms had a 50% increase in odds of having a 72-hour gap in adherence (OR=1.50, 95%CI=1.19-31.91). Low overall adherence and extended gaps in adherence were more common in participants that abstained from sex and those that reported sex outside their primary partnership. Despite high monthly adherence rates, many study participants had long periods of non-adherence during which they engaged in risky sexual behavior with potential for HIV acquisition

Sexual Relationships Outside Primary Partnerships and Abstinence are Associated with Lower Adherence and Adherence Gaps: Data from the Partners PrEP Ancillary Adherence Study

Objective—To assess the role of sexual relationships on levels and patterns of adherence to medication for pre-exposure prophylaxis (PrEP) against HIV. Methods—We enrolled 1,147 HIV-negative individuals in long-term serodiscordant relationships at three sites in Uganda from the Partners PrEP Study- a randomized placebo-controlled trial of daily oral tenofovir and emtricitabine/tenofovir. We used generalized estimation equations to assess the effects of sexual relationships on low adherence ( Results—Fifty-three percent were male, 51% were 18-34 years and 24% were polygamous. Participants who reported sex in the past month with someone other than their primary partner and with Conclusions—Risk of low overall adherence was higher in participants who reported sex outside primary partnerships and suboptimal condom use, as well as in those who abstained from sex. Adherence gaps were common, potentially creating risk for HIV acquisition

Noncommunicable Disease (NCD) strategic plans in low- and lower-middle income Sub-Saharan Africa: framing and policy response

Background Global efforts to address NCDs focus primarily on 4-by-4 interventions – interventions to prevent and treat four groups of conditions affecting mainly older adults (some cardiovascular disease and cancers, type 2 diabetes, chronic respiratory disease) and four associated risk factors (alcohol, tobacco, poor diets, and physical inactivity). However, the NCD burden in Sub-Saharan Africa (SSA) is composed of a more diverse set of conditions, driven by a more complex group of risks, and impacting all segments of the population. Objective To document the NCD priorities identified by NCD strategic plans, to characterize the proposed policy response, and to assess the alignment between the two. Methods Using a two-part conceptual framework, we undertook a descriptive study to characterize the framing and overall policy response of strategic plans from 24 low- and lower-middle-income countries across SSA. Results The national situation assessments that ground strategic plans emphasize a diversity of conditions that range in terms of severity and frequency. These assessments also highlight a wide diversity of factors that shape this burden. Most include discussions of a broad range of behavioral, structural, genetic, and infectious risk factors. Plans endorse a more narrow response to this diverse burden, with a focus on primary and secondary prevention that is generally convergent with the objectives established in global policy documents. Conclusions Broadly, we observe that plans developed by countries in SSA recognize the heterogeneity of the NCD burden in this region. However, they emphasize interventions that are consistent with global strategies focused on preventing a narrower set of cardiometabolic risk factors and their associated diseases. In comparison, relatively few countries detail plans to prevent, treat, and palliate the full scope of the needs they identify. There is a need for increased support for bottom-up planning efforts to address local priorities

What's Love Got to Do With It? Explaining Adherence to Oral Antiretroviral Pre-Exposure Prophylaxis for HIV-Serodiscordant Couples

OBJECTIVE(S): Adherence may be the “Achilles heel” of pre-exposure prophylaxis (“PrEP”), a promising biomedical approach to HIV prevention. This paper presents an explanation of PrEP adherence for African serodiscordant couples derived from qualitative data. DESIGN: Explaining quantitative findings is one way qualitative investigation contributes to research in medicine and public health. This qualitative interview study was nested in the Partners PrEP Study, a phase III randomized trial evaluating oral tenofovir and emtricitabine/tenofovir PrEP to prevent HIV acquisition by HIV-uninfected partners in serodiscordant heterosexual couples. METHODS: In-depth qualitative interviews were provided by 60 Partners PrEP Study participants in Uganda. Interviews used open-ended questions eliciting information on adherence experiences, barriers, and facilitators. An inductive approach informed by grounded theory methodology was used to analyze study data. RESULTS: The proposed explanation may be summarized as follows. Serodiscordance de-stabilizes couples, as the HIV-negative partner reacts with anger, fear and sadness to the implication of infidelity represented by HIV infection. A ‘discordance dilemma’ ensues, as the desire to avoid acquiring HIV and the advantages of preserving the relationship become competing priorities. PrEP is seen as a solution – a means of safeguarding health without ending the relationship. PrEP users benefit from the support of partners, who reinforce adherence. Where discord in the relationship persists, adherence suffers. CONCLUSION: PrEP adherence in serodiscordant couples may be understood as a function of the desire to reduce risk while preserving a partnered relationship. PrEP use in stable couples may be associated with improved adherence and thus, greater effectiveness

Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. METHODS: This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov, number NCT02842086. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07-0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17-0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23-1·26]). Approximately 78-82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p\u3c0·0001). INTERPRETATION: Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. FUNDING: Gilead Sciences

Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial

In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov, number NCT02842086. Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07–0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17–0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23–1·26]). Approximately 78–82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p<0·0001). Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. Gilead Sciences