Challenges in the design of HIV prevention trials in the United States.
Ontology highlight
ABSTRACT:
SUBMITTER: Donnell D
PROVIDER: S-EPMC3298818 | biostudies-other | 2010 Dec
REPOSITORIES: biostudies-other
Publications
Challenges in the design of HIV prevention trials in the United States.
Donnell Deborah D Hughes James P JP Fleming Thomas R TR
Journal of acquired immune deficiency syndromes (1999) 20101201
The design of studies evaluating the safety and efficacy of interventions for HIV prevention is challenging in the US context, where there is low generalized prevalence. HIV incidence is sufficiently high in the at-risk US population of men who have sex with men that prevention trials using HIV infection end points are feasible. In other US populations at higher risk of HIV exposure, efficacy trials of HIV prevention are likely not feasible. However, for interventions where efficacy is already e ...[more]
Similar Datasets
Project description:Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009-2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1-4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals.
| S-EPMC4596522 | biostudies-other
Project description:Despite the recent success of antiretrovirals for HIV prevention, additional, more effective, or more acceptable biomedical interventions will ultimately be needed to end the HIV epidemic. Designing clinical trials to evaluate the efficacy of new products that reduce HIV infection risk is challenging because of the existence of highly effective interventions to prevent HIV. However, the implementation of these interventions is uneven, and the fact that multiple HIV prevention efficacy trials are currently evaluating new products means the field confronts uncertainty in the emerging standard of prevention. In this Viewpoint, we take stock of the current state of HIV prevention, and subsequently discuss the key challenges in designing future trials to evaluate the next generation of HIV prevention products. We also highlight gaps in the knowledge base that need to be addressed to advance the design of research. Future trials are tenable, even in the context of existing and effective interventions, and should involve careful statistical approaches and multidisciplinary collaborative design.
| S-EPMC6612578 | biostudies-literature
Project description:ObjectivesVigorous discussions are ongoing about future efficacy trial designs of candidate human immunodeficiency virus (HIV) prevention interventions. The study design challenges of HIV prevention interventions are considerable given rapid evolution of the prevention landscape and evidence of multiple modalities of highly effective products; future trials will likely be 'active-controlled', i.e., not include a placebo arm. Thus, novel design approaches are needed to accurately assess new interventions against these highly effective active controls.MethodsTo discuss active control design challenges and identify solutions, an initial virtual workshop series was hosted and supported by the International AIDS Enterprise (October 2020-March 2021). Subsequent symposia discussions continue to advance these efforts. As the non-inferiority design is an important conceptual reference design for guiding active control trials, we adopt several of its principles in our proposed design approaches.ResultsWe discuss six potential study design approaches for formally evaluating absolute prevention efficacy given data from an active-controlled HIV prevention trial including using data from: 1) a registrational cohort, 2) recency assays, 3) an external trial placebo arm, 4) a biomarker of HIV incidence/exposure, 5) an anti-retroviral drug concentration as a mediator of prevention efficacy, and 6) immune biomarkers as a mediator of prevention efficacy.ConclusionsOur understanding of these proposed novel approaches to future trial designs remains incomplete and there are many future statistical research needs. Yet, each of these approaches, within the context of an active-controlled trial, have the potential to yield reliable evidence of efficacy for future biomedical interventions.
| S-EPMC10798828 | biostudies-literature
Project description:To ensure generalizability of clinical research results, it is important to enroll a heterogeneous population that is representative of the target clinical population. Earlier studies have found regional variation in participation in human immunodeficiency virus (HIV) clinical trials, with the lowest rates seen in the southern United States. Rates of new HIV diagnoses are highest in the South, highlighting the need for in-depth understanding of disparities in clinical trial participation. We evaluated whether regional variation in study participation remains, and describe factors that facilitate or prevent HIV clinical trial participation by region.A one-time, anonymous, bilingual, self-administered survey was conducted among HIV-infected adults receiving HIV care at all 47 domestic AIDS Clinical Trials Group clinical research sites, with a goal of completing 50 surveys per site. ?(2) tests were used to evaluate differences in knowledge of and participation in HIV clinical trials by region, including Northeast, Midwest, South, and West regions. Multivariable logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for the effect of region on knowledge of and participation in HIV clinical trials.Of 2263 completed surveys, 2125 were included in this analysis. The proportion of respondents in the South who reported knowledge of studies (66%) was significantly lower than in the Northeast (76%), Midwest (77%), and West (73%) (P = 0.001). Respondents in the South also were the least likely group to report ever having tried to or having participated in a research study (51%) compared with respondents in the Northeast (60%), Midwest (57%), and West (69%; P < 0.001). After adjusting for age, sex, education, race/ethnicity, tobacco use, and alcohol use, the odds ratio for knowledge of and participation in clinical trials for the Northeast (1.36; 95% CI 1.07-1.72) and West (1.85; 95% CI 1.39-2.45) remained significant compared with the South. African American respondents in the South were the most likely population group to report not understanding research studies (15%) as a reason for not participating, compared with the Northeast (9%), Midwest (8%), and West (6%; P < 0.001).Significant regional variations in knowledge of and participation in HIV clinical trials exist. Our results suggest that increasing awareness and understanding of research studies, particularly among African Americans in the South, may facilitate HIV clinical trial participation that is more representative of the HIV-infected population across the United States.
| S-EPMC4356522 | biostudies-literature
Project description:Gay bathhouses (including sex clubs) contributed to HIV prevention from the early days of the AIDS epidemic, but the extent to which prevention interventions are implemented in bathhouses is unknown. Using telephone survey methodology, bathhouse managers provided data about HIV prevention in their bathhouses. All the bathhouses provided free condoms, and nearly all displayed educational posters in public areas and had informational pamphlets available for patrons. A few of the bathhouses offered outreach services and counseling services. Almost all promoted testing for HIV/sexually transmitted infection (which included providing information about where to get tested), and 75.5% had HIV testing programs in their venues. Most of the HIV testing programs were started during the past 5 years, initiated by the bathhouse management or a community agency, and operated by community-based agencies. About one third of the programs offered rapid HIV testing. The results of the telephone survey revealed that all the bathhouses engaged in prevention and many offered a wide range of prevention services, suggesting that managers have embraced the issue of HIV and collaborated in bringing prevention to high-risk men. The absence of studies evaluating these prevention efforts remains a concern and an obstacle for efficient use of the prevention resources.
| S-EPMC3079177 | biostudies-literature
Project description:Reliable methods for estimating the incidence of human immunodeficiency virus (HIV) infection are needed to monitor the epidemic, identify at-risk populations, and evaluate HIV prevention strategies. We used a multifaceted approach to estimate HIV incidence in the HIV Prevention Trials Network (HPTN) 064 study.The HPTN 064 study enrolled 2067 HIV-seronegative women and 32 HIV-seropositive women with no prior HIV infection diagnosis. Women were followed for up to 12 months. HIV incidence estimates were based on (1) detection of acute HIV infection, (2) documentation of HIV seroconversion, and (3) detection of recent HIV infection, using a multiassay algorithm (MAA).Two women had acute HIV infection at enrollment, 4 seroconverted, and 2 were identified as recently infected at enrollment using the MAA. The annual HIV incidence estimate based on acute infection at enrollment (2.52% [95% confidence interval {CI}, .17%-9.33%], using a 14-day window period) was higher than the estimate based on seroconversion (0.24% [95% CI, .07%-.62%]; P = .027). Incidence estimates obtained using the MAA at enrollment and at the end of study were 0.25% (95% CI, .03%-.93%) and 0.13% (95% CI, .006%-.76%), respectively.We detected a high frequency of acute infection at enrollment. Cross-sectional HIV incidence estimates obtained using the MAA were similar to the longitudinal estimate based on HIV seroconversion.NCT00995176.
| S-EPMC3532822 | biostudies-literature
Project description:To provide a synopsis of past, current, and potential next-generation approaches to prevention for positives (PfP) interventions in the United States. For a variety of reasons, PfP interventions, with the goals of limiting HIV transmission from people living with HIV/AIDS (PLWHA) to others and protecting the health of PLWHA, did not appear with any frequency in the United States until about 2000. Even today, the number and breadth of evidence-based PfP interventions is very limited. Nevertheless, meta-analytic evidence demonstrates that such interventions can be effective, perhaps even more so than interventions targeting HIV-uninfected individuals. We review early and more recent PfP interventions and suggest that next-generation PfP interventions must involve behavioral and biologic components and target any element that affects HIV risk behavior and/or infectivity. Next-generation PfP interventions should include increased HIV testing to identify additional PLWHA, components to initiate and maintain HIV care, to initiate antiretroviral therapy and promote adherence, and to reduce sexual and injection drug use risk behavior, as well as ancillary treatments and referrals to services. Comprehensive next-generation PfP interventions, including all of these elements and effective linkages among them, are discussed.
| S-EPMC3076002 | biostudies-literature
Project description:Racial and ethnic minorities are disproportionately affected by HIV/AIDS in the United States despite advances in prevention methodologies. The goal of this study was to systematically review the past 30 years of HIV prevention interventions addressing racial disparities. We conducted electronic searches of Medline, PsycINFO, CINAHL, and Cochrane Review of Clinical Trials databases, supplemented by manual searches and expert review. Studies published before June 5, 2011 were eligible. Prevention interventions that included over 50% racial/ethnic minority participants or sub-analysis by race/ethnicity, measured condom use only or condom use plus incident sexually transmitted infections or HIV as outcomes, and were affiliated with a health clinic were included in the review. We stratified the included articles by target population and intervention modality. Reviewers independently and systematically extracted all studies using the Downs and Black checklist for quality assessment; authors cross-checked 20% of extractions. Seventy-six studies were included in the final analysis. The mean DB score was 22.44--high compared to previously published means. Most of the studies were randomized controlled trials (87%) and included a majority of African-American participants (83%). No interventions were designed specifically to reduce disparities in HIV acquisition between populations. Additionally, few interventions targeted men who have sex with men or utilized HIV as a primary outcome. Interventions that combined skills training and cultural or interactive engagement of participants were superior to those depending on didactic messaging. The scope of this review was limited by the exclusion of non-clinic based interventions and intermediate risk endpoints. Interactive, skills-based sessions may be effective in preventing HIV acquisition in racial and ethnic minorities, but further research into interventions tailored to specific sub-populations, such as men who have sex with men, is warranted.
| S-EPMC3403151 | biostudies-literature
Project description:ObjectiveThe aim of this study was to investigate the value of coformulated Tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) for preexposure prophylaxis (PrEP) for conception in the U.S. and to identify scenarios in which 'Undetectable = Untransmittable' (U = U) may not be adequate, and rather, PrEP or assisted reproduction would improve outcomes.DesignWe developed a Markov cohort simulation model to estimate the incremental benefits and cost-effectiveness of PrEP compared with alternative safer conception strategies, including combination antiretroviral therapy (cART) alone for the HIV-infected partner and assisted reproductive technologies. We modelled various scenarios in which HIV RNA suppression in the male partner was less than perfect.SettingU.S. healthcare sector perspective.ParticipantsSerodiscordant couples in the U.S. was composed of an HIV-infected male and HIV-uninfected female seeking conception.InterventionEconomic analysis.Main outcome measure(s)Cumulative risks of HIV transmission to women and babies, maternal life expectancy, discounted quality-adjusted life years (QALY), discounted lifetime medical costs and incremental cost-effectiveness ratios.ResultscART with condomless intercourse limited to ovulation was the preferred HIV prevention strategy among women seeking to conceive with an HIV-infected partner who is HIV-suppressed. PrEP was not cost-effective for women who had partners who were virologically suppressed. When the probability of male partner HIV suppression was low and we assumed generic pricing of PrEP, PrEP was cost-effective, and sometimes even cost-saving compared with cART alone.ConclusionFrom a U.S. healthcare sector perspective, when the male partner was not reliably suppressed, PrEP became economically attractive, and in some cases, cost-saving.
| S-EPMC6805137 | biostudies-literature
Project description:An inherent challenge to clinical trials that aim to test the efficacy of experimental therapeutics for patients with amyotrophic lateral sclerosis (ALS) is the relative rarity of the disease. A promising solution to this problem is a multi-center approach that ideally includes sites distributed across a broad geographic area. In support of such an approach, the European E-RARE program and the United States National Institutes of Health (NIH) partnered to support the investigator-initiated ROCK-ALS trial (Eudra-CT-Nr.: 2017-003676-31, NCT03792490) as a multi-national collaboration between centers in Europe and North America that is led by European investigators. During the set-up of this international trial, however, a number of unanticipated legal, administrative, and financial complexities emerged that required significant adaptation of the proposed trial scheme. Here, we report our experience navigating these obstacles and describe the potential solutions that we explored. Our experience may inform future efforts to implement multi-national investigator-initiated trials that involve both European and United States centers.
| S-EPMC8289747 | biostudies-literature