Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study

Background: Nondaily dosing of oral preexposure prophylaxis (PrEP) may provide equivalent coverage of sex events compared with daily dosing. Methods: At-risk men and transgender women who have sex with men were randomly assigned to 1 of 3 dosing regimens: 1 tablet daily, 1 tablet twice weekly with a postsex dose (time-driven), or 1 tablet before and after sex (event-driven), and were followed for coverage of sex events with pre- and postsex dosing measured by weekly self-report, drug concentrations, and electronic drug monitoring. Results: From July 2012 to May 2014, 357 participants were randomized. In Bangkok, the coverage of sex events was 85% for the daily arm compared with 84% for the time-driven arm (P = .79) and 74% for the event-driven arm (P = .02). In Harlem, coverage was 66%, 47% (P = .01), and 52% (P = .01) for these groups. In Bangkok, PrEP medication concentrations in blood were consistent with use of ≥2 tablets per week in >95% of visits when sex was reported in the prior week, while in Harlem, such medication concentrations occurred in 48.5% in the daily arm, 30.9% in the time-driven arm, and 16.7% in the event-driven arm (P < .0001). Creatinine elevations were more common in the daily arm (P = .050), although they were not dose limiting. Conclusions: Daily dosing recommendations increased coverage and protective drug concentrations in the Harlem cohort, while daily and nondaily regimens led to comparably favorable outcomes in Bangkok, where participants had higher levels of education and employment

Improving Antiretroviral Therapy Adherence in Resource-Limited Settings at Scale: a Discussion of Interventions and Recommendations

INTRODUCTION: Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings. METHODS: In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource-limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta-analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low- and middle-income countries. Interventions are categorized broadly as education and counselling; information and communication technology-enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described. RESULTS AND DISCUSSION: The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource-limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi-media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement. CONCLUSION: The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS

Predictors of adherence to antiretroviral therapy among HIV-infected persons: a prospective study in Southwest Ethiopia

BACKGROUND: The devastating impact of AIDS in the world especially in sub-Saharan Africa has led to an unprecedented global effort to ensure access to antiretroviral (ARV) drugs. Given that medication-taking behavior can immensely affect an individual's response; ART adherence is now widely recognized as an 'Achilles heel' for the successful outcome. The present study was undertaken to investigate the rate and predictors of adherence to antiretroviral therapy among HIV-infected persons in southwest Ethiopia. METHODS: The study was conducted in the antiretroviral therapy unit of Jimma University Specialized Hospital. A prospective study was undertaken on a total of 400 HIV infected person. Data were collected using a pre-tested interviewer-administered structured questionnaire at first month (M0) and third month (M3) follow up visits. RESULTS: A total of 400 and 383 patients at baseline (M0) and at follow up visit (M3) respectively were interviewed. Self-reported dose adherence in the study area was 94.3%. The rate considering the combined indicator (dose, time and food) was 75.7%. Within a three month follow up period, dose adherence decreased by 2% and overall adherence rate decreased by more than 3%. Adherence was common in those patients who have a social support (OR, 1.82, 95%CI, 1.04, 3.21). Patients who were not depressed were two times more likely to be adherent than those who were depressed (OR, 2.13, 95%CI, 1.18, 3.81). However, at the follow up visit, social support (OR, 2.42, 95%CI, 1.29, 4.55) and the use of memory aids (OR, 3.29, 95%CI, 1.44, 7.51) were found to be independent predictors of adherence. The principal reasons reported for skipping doses in this study were simply forgetting, feeling sick or ill, being busy and running out of medication in more than 75% of the cases. CONCLUSION: The self reported adherence rate was high in the study area. The study showed that adherence is a dynamic process which changes overtime and cannot reliably be predicted by a few patient characteristics that are assumed to vary with time. Adherence is a process, not a single event, and adherence support should be integrated into regular clinical follow up

Patient and Regimen Characteristics Associated with Self-Reported Nonadherence to Antiretroviral Therapy

BACKGROUND: Nonadherence to antiretroviral therapy (ARVT) is an important behavioral determinant of the success of ARVT. Nonadherence may lead to virological failure, and increases the risk of development of drug resistance. Understanding the prevalence of nonadherence and associated factors is important to inform secondary HIV prevention efforts. METHODOLOGY/PRINCIPAL FINDINGS: We used data from a cross-sectional interview study of persons with HIV conducted in 18 U.S. states from 2000-2004. We calculated the proportion of nonadherent respondents (took <95% of prescribed doses in the past 48 hours), and the proportion of doses missed. We used multivariate logistic regression to describe factors associated with nonadherence. Nine hundred and fifty-eight (16%) of 5,887 respondents reported nonadherence. Nonadherence was significantly (p<0.05) associated with black race and Hispanic ethnicity; age <40 years; alcohol or crack use in the prior 12 months; being prescribed >or=4 medications; living in a shelter or on the street; and feeling "blue" >or=14 of the past 30 days. We found weaker associations with having both male-male sex and injection drug use risks for HIV acquisition; being prescribed ARVT for >or=21 months; and being prescribed a protease inhibitor (PI)-based regimen not boosted with ritonavir. The median proportion of doses missed was 50%. The most common reasons for missing doses were forgetting and side effects. CONCLUSIONS/SIGNIFICANCE: Self-reported recent nonadherence was high in our study. Our data support increased emphasis on adherence in clinical settings, and additional research on how providers and patients can overcome barriers to adherence

Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination

Characterising HIV transmission risk among US patients with HIV in care: a cross-sectional study of sexual risk behaviour among individuals with viral load above 1500 copies/mL

ObjectivesViral load and sexual risk behaviour contribute to HIV transmission risk. High HIV viral loads present greater transmission risk than transient viral ‘blips’ above an undetectable level. This paper therefore characterises sexual risk behaviour among patients with HIV in care with viral loads>1500 copies/mL and associated demographic characteristics.MethodsThis cross-sectional study was conducted at six HIV outpatient clinics in USA. The study sample comprises 1315 patients with HIV with a recent viral load >1500 copies/mL. This study sample was drawn from a larger sample of individuals with a recent viral load >1000 copies/mL who completed a computer-assisted self-interview (CASI) regarding sexual risk practices in the last 2 months. The study sample was 32% heterosexual men, 38% men who have sex with men (MSM) and 30% women.ResultsNinety per cent of the sample had their viral load assay within 60 days of the CASI. Thirty-seven per cent reported being sexually active (vaginal or anal intercourse) in the last 2 months. Most of the sexually active participants reported always using condoms (56.9%) or limiting condomless sex to seroconcordant partners (serosorting; 29.2% overall and 42.9% among MSM). Among sexually active participants who reported condomless anal or vaginal sex with an at-risk partner (14%), most had viral loads>10 000 copies/mL (62%).ConclusionsA relatively small number of patients with HIV in care with viral loads above 1500 copies/mL reported concurrent sexual transmission risk behaviours. Most of the individuals in this small group had markedly elevated viral loads, increasing the probability of transmission. Directing interventions to patients in care with high viral loads and concurrent risk behaviour could strengthen HIV prevention and reduce HIV infections.Trial registration numberNCT02044484, completed

Gaps Up To 9 Months Between HIV Primary Care Visits Do Not Worsen Viral Load

Current guidelines specify that visit intervals with viral monitoring should not exceed 6 months for HIV patients. Yet, gaps in care exceeding 6 months are common. In an observational cohort using US patients, we examined the association between gap length and changes in viral load status and sought to determine the length of the gap at which significant increases in viral load occur. We identified patients with gaps in care greater than 6 months from 6399 patients from six US HIV clinics. Gap strata were >6 to <7, 7 to <8, 8 to <9, 9 to <12, and ≥12 months, with viral load measurements matched to the opening and closing dates for the gaps. We examined visit gap lengths in association with two viral load measurements: continuous (log 10 viral load at gap opening and closing) and dichotomous (whether patients initially suppressed but lost viral suppression by close of the care gap). Viral load increases were nonsignificant or modest when gap length was <9 months, corresponding to 10% or fewer patients who lost viral suppression. For gaps ≥12 months, there was a significant increase in viral load as well as a much larger loss of viral suppression (in 23% of patients). Detrimental effects on viral load after a care gap were greater in young patients, black patients, and those without private health insurance. On average, shorter gaps in care were not detrimental to patient viral load status. HIV primary care visit intervals of 6 to 9 months for select patients may be appropriate

HIV incidence in a multinational cohort of men and transgender women who have sex with men in sub-Saharan Africa: Findings from HPTN 075.

Few studies have assessed HIV incidence in men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa (SSA). We assessed HIV incidence and its correlates among MSM and TGW in SSA enrolled in the prospective, multi-country HIV Prevention Trials Network (HPTN) 075 study, conducted from 2015 to 2017. Participants were enrolled at four sites in SSA (Kisumu, Kenya; Blantyre, Malawi; Cape Town and Soweto, South Africa). Eligible participants reported male sex assignment at birth, were 18 to 44 years of age, and had engaged in anal intercourse with a man in the preceding three months. Participation involved five study visits over 12 months. Visits included behavioral assessments and testing for HIV and sexually transmitted infections. Twenty-one of 329 persons acquired HIV during the study [incidence rate: 6.96/100 person-years (PY) (95% CI: 4.3, 10.6)]. Among TGW, HIV incidence was estimated to be 8.4/100 PY (95% CI: 2.3, 21.5). Four participants were found to have acute HIV infection at their first HIV-positive visit. HIV incidence varied among the four study sites, ranging from 1.3/100 PY to 14.4/100 PY. In multivariate longitudinal analysis, factors significantly associated with HIV acquisition were engagement in unprotected receptive anal intercourse [adjusted hazard ratio (AHR) 5.8, 95% confidence interval (CI): 2.4, 14.4] and incident rectal gonorrhea and/or chlamydia (AHR: 2.7, 95% CI: 1.1, 6.8). The higher HIV incidence in Cape Town compared to Blantyre could be explained by the higher prevalence of several risk factors for HIV infection among participants in Cape Town. Annual HIV incidence observed in this study is substantially higher than reported HIV incidence in the general populations in the respective countries and among MSM in the United States. Intensification of HIV prevention efforts for MSM and TGW in SSA is urgently needed

Single Viral Load Measurements Overestimate Stable Viral Suppression Among HIV Patients in Care: Clinical and Public Health Implications

The HIV continuum of care paradigm uses a single viral load test per patient to estimate the prevalence of viral suppression. We compared this single-value approach with approaches that used multiple viral load tests to examine the stability of suppression. The retrospective analysis included HIV patients who had at least 2 viral load tests during a 12-month observation period. We assessed the (1) percent with suppressed viral load (<200 copies/mL) based on a single test during observation, (2) percent with suppressed viral loads on all tests during observation, (3) percent who maintained viral suppression among patients whose first observed viral load was suppressed, and (4) change in viral suppression status comparing first with last measurement occasions. Prevalence ratios compared demographic and clinical subgroups. Of 10,942 patients, 78.5% had a suppressed viral load based on a single test, whereas 65.9% were virally suppressed on all tests during observation. Of patients whose first observed viral load was suppressed, 87.5% were suppressed on all subsequent tests in the next 12 months. More patients exhibited improving status (13.3% went from unsuppressed to suppressed) than worsening status (5.6% went from suppressed to unsuppressed). Stable suppression was less likely among women, younger patients, black patients, those recently diagnosed with HIV, and those who missed ≥1 scheduled clinic visits. Using single viral load measurements overestimated the percent of HIV patients with stable suppressed viral load by 16% (relative difference). Targeted clinical interventions are needed to increase the percent of patients with stable suppression