Current HIV Research. 2013 Apr;11(3):238-45.

Barriers to participation in actual HIV vaccine trials.

Dhalla S, Poole G.

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

 

Abstract

Cognitive barriers to participation in actual HIV vaccine trials have not been previously comprehensively reviewed. In this review article, barriers in actual early phase, phase 2B, and phase 3 HIV vaccine trials are quantified and categorized, and compared between the Organization for Economic Co-operation and Development (OECD) countries and the non-OECD countries. Participation rates were standardized to allow for comparisons. In both the OECD and the non-OECD countries, barriers included subjective norms and discrimination, vaccine safety concerns, and logistical concerns.  More actual HIV vaccine trials can incorporate questions about and quantify barriers to participation, and this may aid future recruitment strategies.

PMID: 23721228

 

Supplement:

Large-scale HIV vaccine trials to prevent HIV infection have been conducted since 1998.  These include the AIDSVAX B/B and AIDSVAX B/E studies (1), the STEP Study (2) and the Phambili study (3), the RV144 study (4), and HIV vaccine trials network (HVTN) 505 (5).  Apart from RV144, these vaccine trials have shown that the HIV vaccines were not able to prevent HIV infection.

The internationally-based STEP Study was stopped in 2007. This was because the HIV vaccine was not effective in preventing HIV infection.  There was also an increased rate of infection in the vaccine group in those men who were uncircumcised and adenovirus type 5 (Ad5) seropositive, compared to the placebo group (did not receive the vaccine). Similarly, the Phambili study in South Africa was halted in 2007.

The RV144 study in Thailand that was completed in 2009 showed a moderate efficacy of 31.2% of the HIV vaccines (ALVAC with rgp120 boost), compared to the placebo group. The recent HVTN 505 HIV vaccine trial in the US was halted in 2013, as the vaccine combination (DNA vaccine with Ad5 boost) did not prevent HIV infection and there was a non-statistically significant increase in HIV infection in the vaccinated group compared to the placebo group.

In 2005, researchers at the University of British   Columbia in Vancouver, Canada, developed the concept of conducting literature reviews examining willingness to participate and factors associated with willingness to participate in HIV vaccine trials.  These included literature reviews on motivators and barriers to participation in actual HIV vaccine trials.  Our review of barriers to participation was one of the first studies to comprehensively review barriers in actual HIV vaccine trials and compare these barriers between the Organization for Economic Co-operation and Development (OECD) countries and the non-OECD countries.

shayesta dhalla-fig1Figure 1 shows the results of our literature review, yielding 20 studies of early phase as well as larger scale HIV vaccine trials examining barriers. The most common barriers in the OECD countries were subjective norms (6 studies); vaccine-induced seropositivity (VISP) (5 studies); logistical concerns (5 studies); and vaccine safety (4 studies). The most common barriers in the non-OECD countries were subjective norms (5 studies); discimination/stigma (3 studies); and vaccine safety (3 studies).  Subjective norms refer to our perceptions of what others would do or what they would want us to do.  Vaccine-induced seropositivity (VISP) refers to the fact that the vaccinated person would test HIV-positive, despite not having the disease.

The percentages of respondents choosing a given barrier were calculated for each study. We standardized the denominators to the number of participants responding to a particular item, independent of their willingness to participate in the HIV vaccine trial.

Social harms were found to be important in both the OECD and the non-OECD countries.

With regards to negative social impacts, these were more prominent in the AIDSVAX B/B trial in men who have sex with men (MSM) and high-risk women, than in the complementary AIDSVAX B/E trial in injection drug users (IDU) in Thailand.  We hypothesized that this result could be because of socially desirable responses amongst IDU in the Thailand study; the fact that IDU in Thailand are already stigmatized and may have not perceived any additional risk; and that social harms were not actively elicited in the AIDSVAX B/E study.

Vaccine safety concerns were important barriers in both the OECD and the non-OECD countries.  Furthermore, these were at higher rates in the STEP study compared to the AIDSVAX B/B study.  We hypothesized that this could be due to the fact that the denominator was small (only 13 men) for consideration of barriers in the STEP study (6), such that the sample could be biased; that the STEP study was a non-licensing study; and that the STEP study utilized a self-administered quetionnaire (6), as opposed to the interviewer-administered questionnaire utilized in the AIDSVAX B/B study.

In conclusion, our literature review and hypotheses regarding barriers to participation in actual HIV vaccine trials can lead to development of appropriate recruitment strategies in HIV vaccine trials, taking differences between the OECD and the non-OECD countries into account.

 

References

1. Francis DP, Heyward WL, Popovic V, Orozco-Cronin P, Orelind K, Gee C, et al 2003 Candidate HIV/AIDS vaccines: lessons learned from the world’s first phase III efficacy trials. AIDS 17:147–56.

2. Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, et al 2008 Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372(9653):1881-93.

3. Gray G, Buchbinder S, Duerr A 2010 Overview of STEP and Phambili trial results: two phase Iib test-of-concept studies investigating the efficacy of MRK adenovirus type 5 gag/pol/nef subtype B HIV vaccine. Current Opinion in HIV and AIDS 5:357–61.

4. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, et al 2009 Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. New England Journal of Medicine 361:2209-20.

5. Hammer SM, Magdalena E. Sobieszczyk, ME, Janes H, Karuna ST, Mulligan MJ, et al 2013 Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. New England Journal of Medicine 369:2083-92.

6. Newman PA, Daley A, Halpenny R, Loutfy M 2008 Community heroes or “high-risk” pariahs? Reasons for declining to enroll in an HIV vaccine trial.Vaccine 26(8): 1091-7.

 

Contact information:
Shayesta Dhalla, MD, MHSc, PhD
University of British Columbia
Home address: 214-5550 Cambie Street, Vancouver, British Columbia, CanadaV5Z 3A2.
Email: shayestadhalla@yahoo.com

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