Showing papers in "Journal of Acquired Immune Deficiency Syndromes in 2014"

Epidemiology of HIV and AIDS among adolescents: current status, inequities, and data gaps.

Abstract: Objectives: To examine levels and patterns of HIV prevalence knowledge sexual behavior and coverage of selected HIV services among adolescents aged 10-19 years and highlight data gaps and challenges. Methods: Data were reviewed from Joint United Nations Programme on HIV / AIDS HIV estimates nationally representative household surveys behavioral surveillance surveys and published literature. Results: A number of gaps exist for adolescent-specific HIV-related data; however important implications for programming can be drawn. Eighty-two percent of the estimated 2.1 million adolescents aged 10-19 years living with HIV in 2012 were in sub-Saharan Africa and the majority of these (58%) were females. Comprehensive accurate knowledge about HIV condom use HIV testing and antiretroviral treatment coverage remain low in most countries. Early sexual debut (sex before 15 years of age) is more common among adolescent girls than boys in low- and middle-income countries consistent with early marriage and early childbirth in these countries. In low and concentrated epidemic countries HIV prevalence is highest among key populations. Conclusions: Although the available HIV-related data on adolescents are limited increased HIV vulnerability in the second decade of life is evident in the data. Improving data gathering analysis and reporting systems specific to adolescents is essential to monitoring progress and improving health outcomes for adolescents. More systematic and better quality disaggregated data are needed to understand differences by sex age geography and socioeconomic factors and to address equity and human rights obligations especially for key populations.

HIV Protective Efficacy and Correlates of Tenofovir Blood Concentrations in a Clinical Trial of PrEP for HIV Prevention

Abstract: Background Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence. Methods In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate (TDF) and TDF with emtricitabine (FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly selected controls who remained uninfected. Results Among controls, 71% of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared with 21% of cases at the visit HIV was first detected. Pill count data indicated that 96% of controls and 66% of cases had >80% adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88% (95% confidence interval: 60 to 96, P 40 ng/mL at month 1, 75% maintained this concentration at month 12. Only 5 of 29 seroconverters seemed to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations ≤40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner. Conclusions Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP seemed to have high and consistent adherence.

Health Behavior Change Models for HIV Prevention and AIDS Care: Practical Recommendations for a Multi-Level Approach

Abstract: Despite increasing recent emphasis on the social and structural determinants of HIV-related behavior, empirical research and interventions lag behind, partly because of the complexity of social-structural approaches. This article provides a comprehensive and practical review of the diverse literature on multi-level approaches to HIV-related behavior change in the interest of contributing to the ongoing shift to more holistic theory, research, and practice. It has the following specific aims: (1) to provide a comprehensive list of relevant variables/factors related to behavior change at all points on the individual-structural spectrum, (2) to map out and compare the characteristics of important recent multi-level models, (3) to reflect on the challenges of operating with such complex theoretical tools, and (4) to identify next steps and make actionable recommendations. Using a multi-level approach implies incorporating increasing numbers of variables and increasingly context-specific mechanisms, overall producing greater intricacies. We conclude with recommendations on how best to respond to this complexity, which include: using formative research and interdisciplinary collaboration to select the most appropriate levels and variables in a given context; measuring social and institutional variables at the appropriate level to ensure meaningful assessments of multiple levels are made; and conceptualizing intervention and research with reference to theoretical models and mechanisms to facilitate transferability, sustainability, and scalability.

Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: A randomized phase 2 study

Abstract: OBJECTIVES To evaluate the safety and efficacy of the novel tenofovir prodrug, tenofovir alafenamide (TAF), as part of a single-tablet regimen (STR) for the initial treatment of HIV-1 infection. DESIGN Phase 2, randomized, double-blind, double-dummy, multicenter, active-controlled study. METHODS Antiretroviral naive adults with HIV-1 RNA ≥5000 copies per milliliter and a CD4 count ≥50 cells per microliter were randomized 2:1 to receive an STR of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), plus placebo for 48 weeks. RESULTS Patients on both E/C/F/TAF (n = 112) and E/C/F/TDF (n = 58) had high rates of virologic suppression (<50 HIV copies per milliliter) at week 24 (86.6%; 89.7%) and at week 48 (88.4%; 87.9%), and had similar improvements in CD4 at week 48 (177; 204), respectively. Both treatments were well tolerated, and most adverse events were self-limiting and of mild to moderate severity. Compared with patients on E/C/F/TDF, patients on E/C/F/TAF had smaller reductions in estimated creatinine clearance (-5.5 vs. -10.1 mL/min, P = 0.041), significantly less renal tubular proteinuria, and smaller changes in bone mineral density for hip (-0.62% vs. -2.39%, P < 0.001) and spine (-1.00% vs. -3.37%, P < 0.001). Patients on E/C/F/TAF had higher increases in total cholesterol, low-density lipoprotein, and high-density lipoprotein, but the total cholesterol/high-density lipoprotein ratio was unchanged for both. CONCLUSIONS Treatment-naive patients given the STR that contained either TAF or TDF achieved a high rate of virologic success. Compared with those receiving TDF, patients on E/C/F/TAF experienced significantly smaller changes in estimated creatinine clearance, renal tubular proteinuria, and bone mineral density.

Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care.

Abstract: Background We sought to clarify the association of HIV infection and immunodeficiency on myocardial infarction (MI) risk. Methods We conducted a cohort study from 1996 to 2009 of HIV-positive (HIV) and demographically matched HIV-negative (HIV) Kaiser Permanente California health plan members. Rate ratios (RRs) were obtained from Poisson regression models comparing MI incidence rates between HIV (overall and stratified by recent and nadir CD4 count, and recent HIV RNA levels) and HIV subjects, adjusting for age, sex, calendar era, race/ethnicity, census-based socioeconomic status, smoking, alcohol/drug abuse, overweight/obesity, diabetes, hypertension, and lipid-lowering therapy. Among HIV subjects, we also evaluated the independent association of CD4, HIV RNA, and antiretroviral therapy (ART) use. Results The study population included 22,081 HIV and 230,069 HIV subjects. The crude MI incidence rate per 100,000 person-years was 283 and 165 for HIV and HIV subjects, respectively, with an adjusted RR of 1.4 [95% confidence interval (CI): 1.3 to 1.6]. Compared with HIV subjects (reference), MI rates were similar for HIV subjects with recent CD4 ≥500 cells per microliter (RR = 1.18; 95% CI: 0.96 to 1.45) and those with nadir CD4 ≥500 cells per microliter (RR = 0.85; 95% CI: 0.55 to 1.33). Among HIV subjects, nadir CD4 was the only HIV-specific factor associated with MIs (RR per 100 cells = 0.88; 95% CI: 0.81 to 0.96), whereas recent CD4 and HIV RNA, prior ART use, and duration of protease inhibitors and nonnucleoside reverse transcriptase inhibitors were not associated with MIs. Conclusion HIV subjects with recent or nadir CD4 ≥500 cells per microliter had similar MI rates compared with HIV subjects. Lower nadir CD4, in particular, seems to be independently associated with MIs. These results strengthen recommendations for earlier ART initiation.

Prevalence and incidence of HIV infection, trends, and risk factors among persons aged 15-64 years in Kenya: results from a nationally representative study

Abstract: Background Enhanced HIV surveillance using demographic, behavioral, and biologic data from national surveys can provide information to evaluate and respond to HIV epidemics efficiently. Methods From October 2012 to February 2013, we conducted a 2-stage cluster sampling survey of persons aged 18 months to 64 years in 9 geographic regions in Kenya. Participants answered questionnaires and provided blood for HIV testing. We estimated HIV prevalence, HIV incidence, described trends in HIV prevalence over the past 5 years, and identified factors associated with HIV infection. This analysis was restricted to persons aged 15-64 years. Results HIV prevalence was 5.6% [95% confidence interval (CI): 4.9 to 6.3] in 2012, a significant decrease from 2007, when HIV prevalence, excluding the North Eastern region, was 7.2% (95% CI: 6.6 to 7.9). HIV incidence was 0.5% (95% CI: 0.2 to 0.9) in 2012. Among women, factors associated with undiagnosed HIV infection included being aged 35-39 years, divorced or separated, from urban residences and Nyanza region, self-perceiving a moderate risk of HIV infection, condom use with the last partner in the previous 12 months, and reporting 4 or more lifetime number of partners. Among men, widowhood, condom use with the last partner in the previous 12 months, and lack of circumcision were associated with undiagnosed HIV infection. Conclusions HIV prevalence has declined in Kenya since 2007. With improved access to treatment, HIV prevalence has become more challenging to interpret without data on new infections and mortality. Correlates of undiagnosed HIV infection provide important information on where to prioritize prevention interventions to reduce transmission of HIV in the broader population.

"What they wanted was to give birth; nothing else": barriers to retention in option B+ HIV care among postpartum women in South Africa

Abstract: BACKGROUND: Women initiating antiretroviral therapy during pregnancy have high rates of dropout particularly after delivery. We aimed to identify challenges to postpartum retention in care under Option B+ which expands antiretroviral therapy access to all HIV-positive pregnant women regardless of CD4 count. METHODOLOGY: We performed 2 semi-structured interviews (SSI n = 50) and 1 focus group discussion (n = 8) with HIV-positive women at Witkoppen Health and Welfare Centre a primary care facility in Johannesburg South Africa that is one of the only clinics offering Option B+ in South Africa. RESULTS: Fifty women completed the SSI before delivery and 48 (96%) completed the second SSI within 3 months of delivery. Median age was 28 years (interquartile range: 26-34); most women worked (62%) or had worked in the previous year (18%). Postpartum women attending HIV care perceived that barriers to HIV care after delivery among other women included the belief that mothers care more about the babys health than their own (29.2% 14/48) women were "ignorant" or "irresponsible" (16.7% 8/48) negative clinic staff treatment (12.5% 6/48) and denial or lack of disclosure of HIV status (10.4% each 5/48). Experienced barriers included lack of money (18.0% 9/50) work conflict (6.0% 3/50) and negative staff treatment (6.0% 3/50). During the focus group discussion 3 main themes emerged: conflict with work commitment negative treatment from health-care workers and lack of disclosure related to stigma. CONCLUSIONS: We identified a complex set of interconnected barriers to retaining postpartum women in HIV care under Option B+ including structural personal and societal barriers. The importance of postpartum HIV care for the mothers own health must be embraced by health-care workers and public health programs.

FEM-PrEP: adherence patterns and factors associated with adherence to a daily oral study product for pre-exposure prophylaxis.

Abstract: Background Several clinical trials have demonstrated the safety and effectiveness of oral tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), as pre-exposure prophylaxis (PrEP) for reducing the risk of HIV acquisition. Adherence to the study product was insufficient to demonstrate the effectiveness of FTC/TDF in 2 PrEP clinical trials conducted among women (FEM-PrEP and the Vaginal and Oral Interventions to Control the Epidemic study), but further analyses of adherence in these studies may inform PrEP demonstration projects and future HIV prevention clinical trials. Methods We randomly selected a subcohort of 150 participants randomized to FTC/TDF in 3 FEM-PrEP sites (Bondo, Kenya; Bloemfontein, South Africa; and Pretoria, South Africa) to examine adherence levels over time and to assess factors associated with adherence, based on plasma tenofovir and intracellular tenofovir diphosphate drug concentrations in specimens collected at 4-week visit intervals. Results We observed drug concentrations consistent with good adherence in 28.5% of all visit intervals when drug was available to use, but only 12% of participants achieved good adherence throughout their study participation. In multivariate analysis, the Bloemfontein site [odds ratio (OR): 2.43; 95% confidence interval (CI): 1.32 to 4.48] and liking the pill color (OR: 2.93; 95% CI: 1.18 to 7.27) were positively associated with good adherence, whereas using oral contraceptive pills at enrollment was negatively associated with good adherence (OR: 0.37; 95% CI: 0.18 to 0.74). Conclusions Most participants did not regularly adhere to the study product throughout their trial participation, although a small minority did. Few factors associated with good adherence to the study product were identified in FEM-PrEP.

GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

Abstract: BACKGROUND: GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. METHODS: This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. RESULTS: Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from <8% to 28% of corresponding plasma concentrations. CONCLUSIONS: These data suggest 744 LA injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

Mental, neurological, and substance use disorders in people living with HIV/AIDS in low- and middle-income countries.

Abstract: Depression, alcohol use disorders (AUD), and neurocognitive disorders are the 3 most prevalent mental, neurological, and substance use disorders in people living with HIV infection in low- and middle-income countries (LMICs). Importantly, they have an impact on everyday functions and on HIV outcomes. Many LMICs have validated tools to screen for and diagnose depression and AUD in the general population that can be used among people living with HIV infection. Current screening and diagnostic methods for HIV-associated neurocognitive disorders in the era of antiretroviral therapy are suboptimal and require further research. In our view, 2 research priorities are most critical. One is the development of an integrated screening approach for depression, AUD, and neurocognitive disorders that can be used by nonspecialists in LMICs. Second, research is needed on interventions for depression and AUD that also target behavior change, as these could impact on adherence to antiretroviral therapy and improve mental symptoms. Mentorship and fellowship schemes at an individual and institutional level need to be further supported to build capacity and provide platforms for research on HIV and mental, neurological, and substance use disorders in LMICs.

HIV and noncommunicable disease comorbidities in the era of antiretroviral therapy: a vital agenda for research in low- and middle-income country settings.

Abstract: In this special 2014 issue of JAIDS, international investigator teams review a host of noncommunicable diseases (NCDs) that are often reported among people living and aging with HIV in sub-Saharan Africa. With the longer lifespans that antiretroviral therapy programs have made possible, NCDs are occurring due to a mix of chronic immune activation, medication side effects, coinfections, and the aging process itself. Cancer; cardiovascular and pulmonary diseases; metabolic, body, and bone disorders; gastrointestinal, hepatic, and nutritional aspects; mental, neurological, and substance use disorders; and renal and genitourinary diseases are discussed. Cost-effectiveness, key research methods, and issues of special importance in Asia, Latin America, and the Caribbean are also addressed. In this introduction, we present some of the challenges and opportunities for addressing HIV and NCD comorbidities in low- and middle-income countries, and preview the research agenda that emerges from the articles that follow.

Cervical inflammation and immunity associated with hormonal contraception, pregnancy, and HIV-1 seroconversion.

Abstract: OBJECTIVE: Hormonal contraception (HC) younger age and pregnancy have been associated with increased HIV risk in some studies. We sought to elucidate the biological mechanisms for these associations. DESIGN: Case-control selection of specimens from a large prospective clinical study. METHODS: We enrolled and followed 4531 HIV-negative women from Uganda and Zimbabwe using either the injectable depo-medroxyprogesterone acetate (DMPA) combined oral contraception or no HC (NH). Innate immunity mediators were measured in cervical samples collected from women at their visit before HIV seroconversion (n = 199) and matched visits from women remaining HIV uninfected (n = 633). Generalized linear models were applied after Box-Cox power transformation. RESULTS: Higher RANTES and lower secretory leukocyte protease inhibitor (SLPI) levels were associated with HIV seroconversion. DMPA users had higher RANTES and lower BD-2 levels. Most inflammation-promoting and/or inflammation-inducible mediators were higher [interleukin (IL)-1beta IL-6 IL-8 MIP-3alpha vascular endothelial growth factor and SLPI] and the protective BD-2 and IL-1RA:IL-1beta ratio were lower among combined oral contraception users. Pregnant women showed a similar cervical immunity status (higher IL-1beta IL-6 IL-8 vascular endothelial growth factor SLPI and IL-1RA; lower IL-1RA:IL-1beta). Age <25 years was associated with lower SLPI IL-8 MIP-3alpha but higher IL-1RA:IL-1beta. Zimbabwean women (with higher HIV seroconversion rates) had overall higher pro-inflammatory and lower anti-inflammatory protein levels than Ugandan women. CONCLUSIONS: HC use pregnancy and young age alter cervical immunity in different ways known to increase risk of HIV for example through increased levels of pro-inflammatory cytokines or decreased levels of SLPI. Higher levels of RANTES may be one factor underlying a possible association between DMPA use and risk of HIV acquisition.

Accurate early infant HIV diagnosis in primary health clinics using a point-of-care nucleic acid test.

Abstract: Objective To evaluate the accuracy of a point-of-care (POC) nucleic acid-based test (NAT) for early infant HIV diagnosis (EID) in primary health clinics in Mozambique. Methods POC and laboratory NAT EID tests were conducted on matched blood samples collected from 827 HIV-exposed infants younger than 18 months who were enrolled consecutively at 4 periurban primary health clinics and the central hospital in Maputo. Lancet heel draw blood collected by nurses was tested on site for HIV-1/-2 RNA on the Alere HIV NAT POC device and also used to create dried blood spots for later laboratory EID testing on the Roche Cobas Taqman/Ampliprep instrument. Results were used to determine the sensitivity, specificity, and agreement between the POC and laboratory NAT EID tests. Results The sensitivity and specificity of POC NAT EID testing were 98·5% (95% confidence interval (CI): 91.7 to 99.9, n = 65) and 99·9% (95% CI: 99.3 to 100, n = 762), respectively, compared with laboratory EID tests. Overall agreement was high (Cohen kappa = 0·981; 95% CI: 0.96 to 1.00). Positive (98·5%; 95% CI: 96·3 to 100) and negative 99.9% (95% CI: 99.7 to 100) test agreement was also high. Conclusions Primary health care nurses accurately performed POC NAT EID testing within primary health care clinics. On-site nucleic acid-based EID testing is technically feasible in clinic settings and could be used in efforts to improve access to pediatric HIV antiretroviral treatment.

Pharmacokinetics, safety, and tolerability with repeat doses of GSK1265744 and rilpivirine (TMC278) long-acting nanosuspensions in healthy adults.

Abstract: Objective Pharmacokinetics, safety, and tolerability of GSK1265744 (744) and rilpivirine (RPV) (TMC278) were assessed after repeat dosing of long-acting (LA) injectable formulations in healthy subjects. Methods Subjects received a 14-day lead-in of oral 744 (30 mg/d) to assess safety and tolerability before injectable administration. Subjects were randomized into 4 cohorts: 800 mg of 744 LA intramuscularly (IM) followed by 3 monthly doses of (1) 200 mg subcutaneously, (2) 200 mg IM, (3) 400 mg IM, or (4) a second injection of 800 mg IM after 12 weeks. Cohorts 2 and 3 also received IM doses of RPV LA at months 3 (1200 mg) and 4 (900 or 600 mg). Pharmacokinetics and safety were assessed throughout the trial. Results Forty-seven subjects enrolled; 40 received ≥1 LA injection with 37 completing all planned injections. Seven subjects discontinued 744 oral (non-drug-related, n = 6; dizziness, n = 1). The 744 LA and RPV LA injections were generally well tolerated, with grade 1 injection site reactions most commonly reported. Three subjects discontinued during injection phase (consent withdrawn, n = 2; self-limited rash, n = 1). There were no grade 3 or 4 adverse events and no clinically significant trends in laboratory abnormalities, electrocardiograms, or vital signs. All dose cohorts achieved therapeutically relevant plasma concentrations of each drug within 3 days with prolonged exposure over the dosing interval. Plasma concentrations of 744 exceeded the protein-adjusted IC90 and RPV plasma concentrations and were comparable to steady-state oral RPV 25 mg/d. Conclusions These data support the potential application of dual-therapy 744 LA and RPV LA for treatment of HIV-1 infection.

Do age-disparate relationships drive HIV incidence in young women? Evidence from a population cohort in Rural KwaZulu-Natal, South Africa

Abstract: Background: Based on ethnographic investigations and mathematical models, older sexual partners are often considered a major risk factor for HIV for young women in sub-Saharan Africa. Numerous public health campaigns have been conducted to discourage young women from relationships with older men. However, longitudinal evidence relating sex partner age disparity to HIV acquisition in women is limited. Methods: Using data from a population-based open cohort in rural KwaZulu-Natal, South Africa, we studied 15- to 29-year-old women who were HIV seronegative at first interview between January 2003 and June 2012 (n = 2444). We conducted proportional hazards analysis to establish whether the age disparity of women's most recent sexual partner, updated at each surveillance round, was associated with subsequent HIV acquisition. Results: A total of 458 HIV seroconversions occurred over 5913 person-years of follow-up (incidence rate: 7.75 per 100 person-years). Age disparate relationships were common in this cohort; 37.7% of women reported a partner 5 or more years older than themselves. The age disparity of women's partners was not associated with HIV acquisition when measured either continuously [hazard ratio (HR) for 1-year increase in partner's age: 1.00, 95% confidence interval (CI): 0.97 to 1.03] or categorically (man ≥5 years older: HR, 0.98; 95% CI: 0.81 to 1.20; man ≥10 years older: HR, 0.98; 95% CI: 0.67 to 1.43). These results were robust to adjustment for known sociodemographic and behavioral HIV risk factors and did not vary significantly by women's age, marital status, education attainment, or household wealth. Conclusions: HIV incidence in young women was very high in this rural community in KwaZulu-Natal. Partner age disparity did not predict HIV acquistion. Campaigns to reduce age-disparate sexual relationships may not be a cost-effective use of HIV prevention resources in this setting.

Kenya AIDS Indicator Survey 2012.

Abstract: Surveillance—the routine, systematic collection of data about disease frequency and distribution; the analysis of those data; and the dissemination of that information to those who need to know—is a cornerstone of public health action. Surveillance has played an important historical role in the global response to HIV/AIDS, alerting the world to the gravity of the pandemic, providing data on which major funding decisions were based, allowing appropriate targeting of intervention efforts, and evaluating and monitoring the response. Despite the complexity of measuring HIV infection, morbidity, and mortality, data on the global distribution of HIV/AIDS are among the most robust in all of global health. Traditionally, estimates of national and global burdens of HIV infection have been derived from mathematical modeling applied to sentinel HIV prevalence data among pregnant women. Early on, sentinel studies among persons with sexually transmitted infections and blood donors contributed additional information. So-called “second generation surveillance” introduced in the early 2000s emphasized adapting approaches to local country contexts, addressing the surveillance needs of key populations at high risk of exposure to HIV infection, collecting information to monitor and measure the impact of HIV services, and incorporating appropriate behavioral measurements to give integrated insight into biomedical data. Despite these improvements, increasing experience with population-based surveys showed that extrapolations from sentinel surveillance data frequently yielded excessively high estimates of population HIV prevalence, and the role and utility of these national HIV prevalence surveys quickly became recognized. The substantial downsizing of global estimates of HIV infection that the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) undertook in 2007 can largely be ascribed to the insights provided by population-based surveys in different countries. Over 30 countries, most in sub-Saharan Africa, have conducted population-based surveys of HIV infection, with Botswana, South Africa and Kenya standing out by having supported 4 such studies this century. In Kenya, 2 surveys incorporated HIV testing into routine Demographic and Health Surveys, and 2 were special AIDS Indicator Surveys. These surveys have yielded nationally representative data on HIV prevalence in men, women, and for the first time in 2012 in Kenya, in children. Clear insights have been provided into the complex age-specific, urban–rural, and regional differences within the country; the impact of male circumcision; behavioral and other factors associated with HIV infection; HIV testing behaviors and knowledge of HIV serostatus, including within stable relationships; blood and injection safety; and the association at a population level of HIV with previous tuberculosis and sexually transmitted infection syndromes. The 2012 Kenya AIDS Indicator Survey (KAIS 2012) also examined orphans and vulnerable children as well as key populations. These surveys have given representative insights into the trends in national epidemics. KAIS 2012 was innovative in several ways. Data were collected by trained field staff using robust tablet devices that allowed real-time data entry and transmission to a central location on a daily basis, thus facilitating data quality enhancement and oversight, and shortening the time required for survey completion. Blood was collected from study participants for later testing for HIV, CD4 counts, and viral load at the central reference laboratory, but participants who wished to know their HIV and CD4 status were offered point-of-care testing with immediate return of results, and if necessary, referral for care.

Enhancing reporting of behavior change intervention evaluations.

Abstract: Many behavior change interventions for the prevention and treatment of HIV have been evaluated, but suboptimal reporting of evaluations hinders the accumulation of evidence and the replication of interventions. In this article, we address 4 practices contributing to this problem. First, detailed descriptions of the interventions and their implementation are often unavailable. Second, content of active control group content (such as usual care or support designed by researchers) often varies markedly between trials; yet, descriptions of this content are routinely omitted. Third, detailed process evaluations revealing the mechanisms by which interventions generate their effects, and among whom, frequently are not available. Fourth, there is a lack of replication in other contexts, which limits knowledge of external validity. This article advances recommendations made by an international group of scholars constituting the Workgroup for Intervention Development and Evaluation Research (WIDER), which has developed brief guidance to journal editors to improve the reporting of evaluations of behavior change interventions, thereby serving as an addition to reporting statements such as CONSORT. Improved reporting standards would facilitate and accelerate the development of the science of behavior change and its application in implementation science to improve public health.

Lessons learned from early implementation of option B+: the Elizabeth Glaser Pediatric AIDS Foundation experience in 11 African countries.

Abstract: BACKGROUND: "Option B+" is a World Health Organization-recommended approach to prevent mother-to-child HIV transmission whereby all HIV-positive pregnant and lactating women initiate lifelong antiretroviral therapy (ART). This review of early Option B+ implementation experience is intended to inform Ministries of Health and others involved in implementing Option B+. METHODS: This implementation science study analyzed data from 11 African countries supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) to describe early experience implementing Option B+. Data are from 4 sources: (1) national guidelines for prevention of mother-to-child HIV transmission and Option B+ implementation plans (2) aggregated service delivery data between January 2013 and March 2014 from EGPAF-supported sites (3) field visits to Option B+ implementation sites and (4) relevant EGPAF research quality improvement and evaluation studies. RESULTS: Rapid adoption of Option B+ led to large increases in percentage of HIV-positive pregnant women accessing ART in antenatal care. By the end of 2013 most programs reached at least 50% of HIV-positive women in antenatal care with ART even in countries using a phased approach to implementation. Scaling up Option B+ through integrating ART in maternal and child health settings has required expansion of the workforce and task shifting to allow nurse-led ART initiation has created staffing pressure on lower-level cadres for counseling and community follow-up. Complex data collection needs may be impairing data quality. DISCUSSION: Early experiences with Option B+ implementation demonstrate promise. Continued program evaluation is needed as is specific attention to counseling and support around initiation of lifetime ART in the context of pregnancy and lactation.

Effectiveness of mass media interventions for HIV prevention, 1986-2013: a meta-analysis.

Abstract: Objectives: This meta-analysis was conducted to synthesize evaluations of mass media-delivered HIV prevention interventions assess the effectiveness of interventions in improving condom use and HIV-related knowledge and identify moderators of effectiveness. Study Selection: We systematically searched electronic databases relevant Web sites related journals and reference lists of previous reviews and included studies. Studies that quantitatively evaluated the effectiveness of mass media-delivered HIV prevention using pre-/post-campaign assessments targeted the general population reported outcomes of interest and were available as of September 30 2013 were eligible for inclusion. Data Extraction and Synthesis: Raters coded report intervention and sample characteristics. The standardized mean difference d comparing pretest and posttest assessments was calculated for each study sample. Effect sizes were analyzed incorporating random-effects assumptions. Results: Of the 433 obtained and screened reports 54 reports containing evaluations of 72 interventions using 93 samples (N = 142196) met the selection criteria and were included. Campaigns were associated with increases in condom use [d+ = 0.25 95% confidence interval (CI) = 0.18 to 0.21] transmission knowledge (d+ = 0.30 95% CI = 0.18 to 0.41) and prevention knowledge (d+ = 0.39 95% CI = 0.25 to 0.52). Increases in condom use were larger for longer campaigns and in nations that scored lower on the human development index. Increases in transmission knowledge were larger to the extent that respondents reported greater campaign exposure for more recent campaigns and for nations that scored lower on the human development index.

The importance of context in implementation research.

Abstract: This article describes the pertinence of context in HIV/ AIDS implementation research. Without attending to context and how it interacts with interventions, national protocols for HIV/AIDS interventions are likely to fail or underperform. With its focus on what works, for whom, under what contextual circumstances, and whether interventions are scalable, implementation research yields context-sensitive designs and enhances the likelihood of scale-up for equitable outcomes. A framework for implementation science is presented alongside a review of published HIV/AIDS protocols for complex interventions. A case study of the South African Prevention of Mother-to-Child Transmission of HIV program highlights the application of complex system improvement principles in develop- ing adaptive and context-sensitive scale-up designs. Preliminary recommendations are provided that can be used to characterize context when reporting interventions and describing how context can be accounted for in implementation strategies.

A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF versus single-tablet regimen efavirenz/emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results.

Abstract: INTRODUCTION The first integrase inhibitor-based single-tablet regimen combines elvitegravir (an integrase inhibitor), cobicistat (a pharmacoenhancer), emtricitabine (FTC), and tenofovir DF (TDF) (EVG/ COBI/FTC/TDF). In 2 phase 3 randomized trials, EVG/COBI/FTC/TDF demonstrated noninferior efficacy at week 48 to efavirenz (EFV)/FTC/TDF (study 102) and to ritonavir-boosted atazanavir ATV + RTV + FTC/TDF (study 103) with durable efficacy through week 96. We present week 144 data from study 102. METHODS A full description of the methods has been published. A brief description is provided below.

HIV and noncommunicable cardiovascular and pulmonary diseases in low- and middle-income countries in the ART era: what we know and best directions for future research.

Abstract: With the advent of effective antiretroviral therapy (ART), HIV is becoming a chronic disease. HIV-seropositive (+) patients on ART can expect to live longer and, as a result, they are at risk of developing chronic noncommunicable diseases related to factors, such as aging, lifestyle, long-term HIV infection, and the potential adverse effects of ART. Although data are incomplete, evidence suggests that even in low- and middle-income countries (LMICs), chronic cardiovascular and pulmonary diseases are increasing in HIV-positive patients. This review summarizes evidence-linking HIV infection to the most commonly cited chronic cardiovascular and pulmonary conditions in LMICs: heart failure, hypertension, coronary artery disease/myocardial infarction, stroke, obstructive lung diseases, and pulmonary arterial hypertension. We describe the observed epidemiology of these conditions, factors affecting expression in LMICs, and key populations that may be at higher risk (ie, illicit drug users and children), and finally, we suggest that strategic areas of research and training intended to counter these conditions effectively. As access to ART in LMICs increases, long-term outcomes among HIV-positive persons will increasingly be determined by a range of associated chronic cardiovascular and pulmonary complications. Actions taken now to identify those conditions that contribute to long-term morbidity and mortality optimize early recognition and diagnosis and implement effective prevention strategies and/or disease interventions are likely to have the greatest impact on limiting cardiovascular and pulmonary disease comorbidity and improving population health among HIV-positive patients in LMICs.

Phylogenetic studies of transmission dynamics in generalized HIV epidemics: an essential tool where the burden is greatest?

Abstract: Efficient and effective HIV prevention measures for generalized epidemics in sub-Saharan Africa have not yet been validated at the population level. Design and impact evaluation of such measures requires fine-scale understanding of local HIV transmission dynamics. The novel tools of HIV phylogenetics and molecular epidemiology may elucidate these transmission dynamics. Such methods have been incorporated into studies of concentrated HIV epidemics to identify proximate and determinant traits associated with ongoing transmission. However, applying similar phylogenetic analyses to generalized epidemics, including the design and evaluation of prevention trials, presents additional challenges. Here we review the scope of these methods and present examples of their use in concentrated epidemics in the context of prevention. Next, we describe the current uses for phylogenetics in generalized epidemics and discuss their promise for elucidating transmission patterns and informing prevention trials. Finally, we review logistic and technical challenges inherent to large-scale molecular epidemiological studies of generalized epidemics and suggest potential solutions.

Enhancing benefits or increasing harms: community responses for HIV among men who have sex with men, transgender women, female sex workers, and people who inject drugs.

Abstract: Studies completed over the past 15 years have consistently demonstrated the importance of community-level determinants in potentiating or mitigating risks for the acquisition and transmission of HIV. Structural determinants are especially important in mediating HIV risk among key populations, including men who have sex with men, people who inject drugs, sex workers of all genders, and transgender women. The objective of this systematic review was to synthesize the evidence characterizing the community-level determinants that potentiate or mitigate HIV-related outcomes for key populations. The results of the review suggest that although health communication programs represent community-level strategies that have demonstrated the effectiveness in increasing the uptake of HIV testing and decreasing the experienced stigma among people living with HIV, there are limited studies focused on key populations in low- and middle-income settings. Moreover, interpretation from the 22 studies that met inclusion and exclusion criteria reinforce the importance of the continued measurement of community-level determinants of HIV risks and of the innovation in tools to effectively address these risks as components of the next generation of the HIV response. Consequently, the next generation of effective HIV prevention science research must improve our understanding of the multiple levels of HIV risk factors, while programming for key populations must address each of these risk levels. Failure to do so will cost lives, harm communities, and undermine the gains of the HIV response.

Reliability and validity of depression assessment among persons with HIV in sub-Saharan Africa: systematic review and meta-analysis.

Abstract: Objective The aim of this study was to systematically review the reliability and validity of instruments used to screen for major depressive disorder or assess depression symptom severity among persons with HIV in sub-Saharan Africa. Design Systematic review and meta-analysis. Methods A systematic evidence search protocol was applied to 7 bibliographic databases. Studies examining the reliability and/or validity of depression assessment tools were selected for inclusion if they were based on the data collected from HIV-positive adults in any African member state of the United Nations. A random-effects meta-analysis was used to calculate pooled estimates of depression prevalence. In a subgroup of studies of criterion-related validity, the bivariate random-effects model was used to calculate pooled estimates of sensitivity and specificity. Results Of 1117 records initially identified, I included 13 studies of 5373 persons with HIV in 7 sub-Saharan African countries. Reported estimates of Cronbach alpha ranged from 0.63 to 0.95, and analyses of internal structure generally confirmed the existence of a depression-like construct accounting for a substantial portion of variance. The pooled prevalence of probable depression was 29.5% [95% confidence interval (CI): 20.5 to 39.4], whereas the pooled prevalence of major depressive disorder was 13.9% (95% CI: 9.7 to 18.6). The Center for Epidemiologic Studies Depression scale was the most frequently studied instrument, with a pooled sensitivity of 0.82 (95% CI: 0.73 to 0.87) for detecting major depressive disorder. Conclusions Depression-screening instruments yielded relatively high false positive rates. Overall, few studies described the reliability and/or validity of depression instruments in sub-Saharan Africa.

Disrespect and abuse during childbirth in Tanzania: are women living with HIV more vulnerable?

Abstract: HIV-related stigma and discrimination and disrespect and abuse during childbirth are barriers to use of essential maternal and HIV health services. Greater understanding of the relationship between HIV status and disrespect and abuse during childbirth is required to design interventions to promote women's rights and to increase uptake of and retention in health services; however, few comparative studies of women living with HIV (WLWH) and HIV-negative women exist. Mixed methods included interviews with postpartum women (n = 2000), direct observation during childbirth (n = 208), structured questionnaires (n = 50), and in-depth interviews (n = 18) with health care providers. Bivariate and multivariate regressions analyzed associations between HIV status and disrespect and abuse, whereas questionnaires and in-depth interviews provided insight into how provider attitudes and workplace culture influence practice. Of the WLWH and HIV-negative women, 12.2% and 15.0% reported experiencing disrespect and abuse during childbirth (P = 0.37), respectively. In adjusted analyses, no significant differences between WLWH and HIV-negative women's experiences of different types of disrespect and abuse were identified, with the exception of WLWH having greater odds of reporting non-consented care (P = 0.03). None of the WLWH reported violations of HIV confidentiality or attributed disrespect and abuse to their HIV status. Provider interviews indicated that training and supervision focused on prevention of vertical HIV transmission had contributed to changing the institutional culture and reducing HIV-related violations. In general, WLWH were not more likely to report disrespect and abuse during childbirth than HIV-negative women. However, the high overall prevalence of disrespect and abuse measured indicates a serious problem. Similar institutional priority as has been given to training and supervision to reduce HIV-related discrimination during childbirth should be focused on ensuring respectful maternity care for all women.

Antiretroviral Concentrations in Small Hair Samples as a Feasible Marker of Adherence in Rural Kenya

Abstract: Antiretroviral hair levels objectively quantify drug exposure over time and predict virologic responses. We assessed the acceptability and feasibility of collecting small hair samples in a rural Kenyan cohort. Ninety-five percentage of participants (354/373) donated hair. Although median self-reported adherence was 100% (interquartile range, 96%-100%), a wide range of hair concentrations likely indicates overestimation of self-reported adherence and the advantages of a pharmacologic adherence measure. Higher nevirapine hair concentrations observed in women and older adults require further study to unravel behavioral versus pharmacokinetic contributors. In resource-limited settings, hair antiretroviral levels may serve as a low-cost quantitative biomarker of adherence.

HIV infection and its association with an excess risk of clinical fractures: a nationwide case-control study.

Abstract: BACKGROUND: Different studies have reported an association between HIV infection, antiretroviral therapies, and impaired bone metabolism, but data on their impact on fracture risk are scarce. We studied the association between a clinical diagnosis of HIV infection and fracture risk. METHODS: We conducted a case-control study using data from the Danish National Health Service registries, including 124,655 fracture cases and 373,962 age- and gender-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. RESULTS: A total of 50 (0.40/1000) patients in the fracture group and 52 (0.14/1000) controls had an HIV diagnosis. The risk of any fracture was thus significantly increased among HIV-infected patients (age- and gender-matched OR = 2.89, 95% CI: 1.99 to 4.18). Similarly, significant increases in the risk of hip (OR = 8.99, 95% CI: 1.39 to 58.0), forearm (OR = 3.50, 95% CI: 1.26 to 9.72), and spine fractures (OR = 9.00, 95% CI: 1.39 to 58.1) were observed. CONCLUSIONS: HIV infection is associated with an almost 3-fold increase in fracture risk compared with that of age- and gender-matched uninfected patients. HIV patients are also at an almost 9-fold higher risk of hip fracture.

An adapted frailty-related phenotype and the VACS index as predictors of hospitalization and mortality in HIV-infected and uninfected individuals.

Abstract: Background Frailty is a geriatric syndrome of decreased physiologic reserve and a risk factor for hospitalization and mortality. We hypothesized that an adapted, survey-based frailty-related phenotype (aFRP) predicts hospitalization and mortality among HIV-infected and uninfected individuals in adjusted models but is uncommon among those achieving undetectable HIV-1 RNA.

Infrequent HIV testing and late HIV diagnosis are common among a cohort of black men who have sex with men in 6 US cities.

Abstract: OBJECTIVE US guidelines recommend at least annual HIV testing for those at risk. This analysis assessed frequency and correlates of infrequent HIV testing and late diagnosis among black men who have sex with men (BMSM). METHODS HIV testing history was collected at enrollment from participants in HPTN 061, an HIV prevention trial for at-risk US BMSM. Two definitions of late HIV diagnosis were assessed: CD4 cell count <200 cells per cubic millimeter or <350 cells per cubic millimeter at diagnosis. RESULTS HPTN 061 enrolled 1553 BMSM. HIV testing questions were completed at enrollment by 1284 (98.7%) of 1301 participants with no previous HIV diagnosis; 272 (21.2%) reported no HIV test in previous 12 months (infrequent testing); 155 of whom (12.1% of the 1284 with testing data) reported never testing. Infrequent HIV testing was associated with: not seeing a medical provider in the previous 6 months (relative risk [RR]: 1.08, 95% confidence interval [CI]: 1.03 to 1.13), being unemployed (RR: 1.04, CI: 1.01 to 1.07), and having high internalized HIV stigma (RR: 1.03, CI: 1.0 to 1.05). New HIV diagnoses were more likely among infrequent testers compared with men tested in the previous year (18.4% vs. 4.4%; odds ratio: 4.8, 95% CI: 3.2 to 7.4). Among men with newly diagnosed HIV, 33 (39.3%) had a CD4 cell count <350 cells per cubic millimeter including 17 (20.2%) with CD4 <200 cells per cubic millimeter. CONCLUSIONS Infrequent HIV testing, undiagnosed infection, and late diagnosis were common among BMSM in this study. New HIV diagnoses were more common among infrequent testers, underscoring the need for additional HIV testing and prevention efforts among US BMSM.