JAIDS Journal of Acquired Immune Deficiency Syndromes:
Intentions to Use Preexposure Prophylaxis Among Current Phase 2B Preventive HIV-1 Vaccine Efficacy Trial Participants
Fuchs, Jonathan D. MD, MPH*,†; Sobieszczyk, Magdalena E. MD, MPH‡; Madenwald, Tamra MA, MPH§; Grove, Doug MS‖; Karuna, Shelly T. MD§; Andrasik, Michele PhD§; Sherwat, Adam MD¶; Broder, Gail MHS§; Mayer, Kenneth MD#; Koblin, Beryl PhD**; Hammer, Scott MD‡; the HVTN 505 Protocol Team
*San Francisco Department of Public Health, San Francisco, CA;
†Department of Medicine, University of California, San Francisco, CA;
‡Division of Infectious Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY;
§HIV Vaccine Trials Network;
‖Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA;
¶National Institutes of Allergy and Infectious Diseases, Bethesda, MD;
#Fenway Health and the Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; and
**Laboratory of Infectious Disease Prevention, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY.
Correspondence to: Jonathan D. Fuchs, MD, MPH, San Francisco Department of Public Health, 25 Van Ness Avenue, Suite 100, San Francisco, CA 94102 (e-mail: email@example.com).
Preliminary analyses were presented at AIDS Vaccine 2011, Bangkok, Thailand.
The HVTN is supported through a cooperative agreement with the National Institute of Allergy and Infectious Diseases Grant AI068614AI068635, which supports T.M., D.G., S.K., M.A., and G.B.; J.F. is supported under a Division of AIDS CTU Award UO1AI069496; M.S. and S.H. are supported under CTU and CTSA Awards UO1AI69470 and UL1RR024156; K.M. is supported under CTU Awards UM1AI069480-05 and UO1AI069412 and unrestricted research grant support from Gilead Sciences, Inc; B.K. is supported under a CTU Award UO1AI69470.
HVTN 505 Protocol Team members and clinical research site investigators have been listed in Acknowledgments section.
The authors have no conflicts of interest to disclose.
Received January 02, 2013
Accepted March 22, 2013
Abstract: In November 2010, the iPrEx study reported that preexposure prophylaxis (PrEP) with daily tenofovir disoproxil fumarate/emtricitabine reduced HIV infections by 44% among men who have sex with men and subsequent trials corroborated efficacy among heterosexual men and women. During regularly scheduled follow-up visits from January to March 2011, participants in an ongoing phase 2b vaccine efficacy trial completed an anonymous Web survey about PrEP. Among 376 respondents, 17% reported they were very likely to use PrEP in the next year. Nonwhite participants were more likely to use PrEP. Among those with some level of interest, intent to use PrEP was greatest if the drug were available through the clinical trial or health insurance. Most (91%) believed taking PrEP would not change their willingness to stay in the vaccine trial and few thought it would affect recruitment. As key stakeholders, currently enrolled trial participants can offer vital input about emerging prevention technologies that may affect the design of future HIV vaccine and nonvaccine prevention trials.
Over the past few years, the HIV prevention landscape has rapidly changed, with several independent trials reporting the benefits of antiretroviral medications to reduce HIV acquisition and transmission.1–6 Guidelines for good participatory practice in biomedical HIV prevention trials highlight the need for protocol teams involved with ongoing studies, in close collaboration with community stakeholders, to assess new data and to determine how they may affect trial conduct.7 In late 2010, the global iPrEx trial reported that preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) reduced HIV infection by 44% in HIV-uninfected men who have sex with men (MSM) and transgender (TG) women at sexual risk for HIV acquisition.1 However, several questions remain concerning PrEP, including the regimen’s long-term safety and the lack of clear mechanisms for patients to access the drug and associated clinical monitoring in many settings. The HVTN 505 study is an ongoing, blinded, randomized, and placebo-controlled phase 2b vaccine efficacy trial evaluating a DNA prime, adenovirus subtype 5 vector boost vaccine regimen in HIV-uninfected MSM and TG female participants from 21 clinical sites in the United States. After the iPrEx study results were released, the HVTN protocol team gathered input from several external stakeholder groups and assessed the possible implications of these results on the vaccine trial’s design. For example, if a substantial proportion of participants started taking PrEP, the observed HIV seroincidence in the enrolled cohort could decrease, requiring increases in sample size and/or longer follow-up to accrue the necessary number of incident infections to establish a reliable estimate of vaccine efficacy. Although knowledge and use of PrEP in the community was limited before and immediately after the results were released,8–10 awareness of and interest in taking PrEP by HVTN 505 participants were unknown. Thus, the HVTN 505 protocol team asked enrolled participants about their intention to use PrEP and assessed the potential impact of the iPrEx results on trial retention and recruitment.
From January through March 2011, enrolled HVTN 505 participants were invited to complete a short Web-based survey during their regularly scheduled study visits. Given that the protocol requires visits every 3 months, a majority of enrolled participants had the opportunity to participate during this 3-month window. The brief survey assessed the perceived significance of the iPrEx results, personal intent to use PrEP, access to health care, and potential impact on study recruitment and retention. The supplemental survey was approved by the institutional review boards of participating research sites. To reinforce the anonymity of their responses, participants were informed that survey data were de-linked from other information collected as part of the HVTN 505 protocol, including questions about behavioral risks. Study staff offered a brief presentation of the iPrEx efficacy and safety results to participants before survey completion. Staff described the importance of daily adherence to PrEP and that HIV testing was required before PrEP initiation and at regular intervals during use; that a start-up syndrome including nausea was seen more commonly with FTC/TDF compared with placebo; that elevations in serum creatinine were observed but improved with study drug discontinuation; and that longer-term side effects of PrEP, if any, were unknown. A 5-point Likert scale was used to assess intent to use PrEP. Descriptive analyses were performed to assess participant intent to use and access to PrEP, perceived significance of the iPrEx study results, and their influence on continued participation or the participation of others in the HIV vaccine trial. Multiple logistic regression was performed to identify correlates of any intent to take PrEP including age, race/ethnicity, insurance status, and having a regular medical provider. Covariates were included in the model if significant on bivariate analysis with a P < 0.1.
Of the 693 active participants enrolled in HVTN 505 before January 1, 2011, 487 had a study visit during the 3-month survey period. Among those, 65 individuals were not offered the survey because of time constraints or omission, 41 provided incomplete survey data, and responses from the small number of self-identified TG females (n = 5) were excluded, giving a total of 376 (77%) for this analysis. The median age was 29 years and a majority of respondents were white, non-Hispanic (73%); 51 respondents (14%) were African American, and 10% were Hispanic. The demographics of the respondents were comparable with the full HVTN 505 cohort at the time (data not shown). Three-fourths (74%) of respondents had health insurance, mostly through private insurers, whereas only 6% of those insured had coverage through a public program. In this sample, 65% reported having a regular medical provider, and among those, only 4% had spoken to that provider about the PrEP results in the few months after they were released.
A majority of respondents (67%) reported that the PrEP results were either very (35%) or moderately (32%) important to them. Overall, 17% stated they were very likely to take PrEP in the next year, whereas 39% stated that they were not likely to take it at all (Fig. 1). Among those who expressed any intent to take PrEP in the next year (n = 231), 13% stated they would be very likely to take PrEP if required to pay out of pocket, whereas 54% would be very likely to take it if made available through the clinical trial and 54% through a provider or health insurance. As seen in Table 1, in multiple logistic regression analysis, nonwhite identification was associated with any intent to use PrEP (adjusted odds ratio: 2.23, 95% CI: 1.35 to 3.68, P = 0.002). When asked “would taking PrEP change your willingness to stay in HVTN 505,” almost all (91%) said it would not affect their participation in the trial. Moreover, only 16% felt that PrEP would affect others’ willingness to enroll.
We conducted a brief, Web-based survey of MSM enrolled in an ongoing, blinded vaccine efficacy trial that offered a valuable snapshot of their interest in PrEP shortly after the iPrEx results were released. Our study showed that less than a fifth of respondents reported they would be very likely to take PrEP in the coming year. However, more than half expressed strong interest in taking PrEP if it were provided through the trial or were available through their health care providers and covered by insurance. Notably, participants from communities of color were more likely to express intent to use PrEP. In addition, we found that PrEP would minimally influence enrollees’ willingness to remain in HVTN 505 and that they believed it would be unlikely to hamper study recruitment.
To date, few studies nested within ongoing HIV prevention trials have assessed the perspectives of currently enrolled participants about emerging HIV prevention technologies, and as far as we are aware, none have produced results that directly influenced the design of the ongoing trial. In 2011, the sample size of HVTN 505 was expanded from 1350 to 2200 participants. This new enrollment target accounted for a conservative estimate of 20% PrEP uptake gleaned from our survey and, informed by the promising RV144 trial results,11 increased the statistical power to detect an impact on HIV acquisition and early viral load setpoint. Survey data supplemented the substantial input sought from community stakeholders that led to the decision to offer education about PrEP to study participants and to include active behavioral and biologic monitoring of PrEP use in the vaccine trial. In addition, the study team is working closely with trial sites to ensure community providers can accommodate referred participants interested in PrEP and that HIV test results obtained at the site are readily shared with these providers to avoid misdiagnosis of HIV infection or unblinding to treatment assignment from vaccine-induced seropositivity.
Although the stated willingness to use PrEP was modest in the months following the release of the iPrEx results, we recognize that demand for PrEP may evolve over time. This study and others10 have found that interest in PrEP use was affected by many contextual factors including perceptions about accessibility and cost. Since the survey went into the field, the U.S. Centers for Disease Control and Prevention released interim guidance on PrEP,12 and new trial data were released in the summer of 2011 establishing the safety and efficacy of TDF/FTC in other populations including serodiscordant couples and at risk heterosexuals.3,4 On July 16, 2012, the U.S. Food and Drug Administration approved TDF/FTC to be taken daily as PrEP in combination with safer sex practices to reduce the risk of sexually acquired HIV infection in adults at high risk.13 This new prevention indication is likely to spur both private and public insurers to cover the costs of PrEP.14 In addition, government-funded PrEP demonstration projects are being initiated or planned in several U.S. cities, which may increase access for some communities.
This study has some limitations. Participants represent a convenience sample of current HVTN 505 enrollees seen in the months following the release of the iPrEx results, which may not reflect the perspectives of the entire cohort nor be generalizable to all MSM and TG communities at risk. This limitation is mitigated to a reasonable extent by the innovation of surveying participants shortly after the release of a major clinical research result and the desire for the study team to get valuable input from its enrollees, which guided how HVTN 505 adapted to the iPrEx results. In addition, we may have underestimated the intent to take PrEP or to remain in the vaccine trial as some respondents may have been reluctant to disclose their interest in PrEP, believing it could threaten their ability to remain in the trial. We tried to reduce social desirability bias through the use of an anonymous, Web-based survey and by reinforcing with our study volunteers that the decision to use PrEP would not in any way preclude continued involvement in the trial. Finally, several potential correlates of interest were not measured in this study, such as sexual risk behaviors, which have been shown to predict willingness to use PrEP.10 Planned analyses will consider these correlates in the assessment of actual PrEP use in HVTN 505.
These analyses reinforce the need for reliable mechanisms to access PrEP at low or no cost, particularly for minority American MSM.15–17 PrEP availability in these communities should be prioritized. Although increased access may enhance PrEP uptake, providers have identified a number of challenges to PrEP implementation in clinical settings, including the need for additional training and definitive guidance from normative bodies.18 Furthermore, ongoing community concerns about adherence, risk compensation, viral resistance, and longer-term safety will likely influence the demand for PrEP as we await prospective data from open label studies.19,20 As our understanding of these issues continue to evolve, we have shown that it is feasible, and desirable, to gather input systematically from actively enrolled trial participants about new HIV prevention strategies.
This input can directly inform changes to the trial’s design and conduct. It is an exciting and increasingly complex time in HIV prevention science as we determine how best to incorporate new tools to limit the spread of HIV. Future HIV vaccine trials, such as prevention trials investigating other modalities, must thoughtfully consider these advances as researchers iteratively reevaluate the standards of prevention.21 Emerging data should be bolstered by effective and transparent engagement with key stakeholders, including trial participants.
The authors thank Dr. Albert Liu for his helpful comments on an early draft of this article. In addition, they would like to gratefully acknowledge the study participants and the work and contributions of HVTN 505 trial site staff and community advisory boards.
HVTN 505 Protocol Team and Clinical Research Site Investigators (in addition to named authors):
Annandale, MD—Donald Poretz; Atlanta, GA—Mark Mulligan, Sri Edupunganti; Bethesda, MD—Barney Graham, Julie Ledgerwood; Birmingham, AL—Paul Goepfert; Boston, MA—Lindsey Baden, Doug Krakower; Chicago, IL—Richard Novak; Cleveland, OH—Michael Lederman, Benigno Rodriguez; Dallas, TX—Mamta Jain; Denver, CO—Thomas Campbell; Houston, TX—Hana El Sahly; Los Angeles, CA—Stephen Brown; Nashville, TN—Spyros Kalams; New York, NY—Demetre Daskalakis; Orlando, FL—Edwin DeJesus; Philadelphia, PA—Ian Frank; Rochester, NY—Michael Keefer; San Francisco, CA—Susan Buchbinder, Darpun Sachdev; Seattle, WA—Juliana McElrath, Janine Maenza; HIV Vaccine Trials Network—Soyon Im, Jim Maynard, Niles Eaton, Steve Wakefield, Shelly Mahilum, Peter Gilbert, Jim Kublin, Larry Corey; National Institute of Allergy and Infectious Diseases—Elizabeth Adams; and Community representatives—Rick Church, Richard Trevino, Jason Roberts, Coco Alinsug.
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clinical trials; HIV vaccines; HIV prevention; preexposure prophylaxis; good participatory practice
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