Forecasting the future

Studies at Bangkok explore upcoming issues in trials, delivery and demand

By Emily Bass*

It is still uncertain precisely when an effective AIDS vaccine will be identified, but it’s clear that the development process will require a series of trials in different populations as well as detailed plans for manufacturing and distributing a licensed product. While some of the hallway discussions in Bangkok focused on the uncertainties of the field’s scientific endeavors, a series of posters and presentations focused attention on issues that need to be addressed, including different populations’ willingness either to participate in clinical trials or to purchase licensed vaccines.

Willingness to participate

One comprehensive multi-site cross-sectional study conducted by researchers at Johns Hopkins School of Public Health and international partners (Abstract no. ThPeC7440; go to www.iasociety.org to view abstracts) surveyed 3155 participants’ attitudes towards hypothetical vaccines and trials. Survey participants came from a variety of settings, ranging from a US university campus to a sexually transmitted infection (STI) clinic in India to members of an injection drug users seroincidence cohort in Chiang Mai, Thailand.

The study found that willingness to participate (WTP) in an AIDS vaccine trial varied widely depending on the population surveyed, ranging from 31% among college students in Baltimore to 64% among STI clinic attendees in Pune, India. The study also analyzed responders’ answers for predictors of WTP. Acceptance of a licensed AIDS vaccine was a predictor for five out of six sites, while belief in the success of an AIDS vaccine was only associated with WTP in one site. Negative predictors included fear of side-effects, belief that a partner would refuse sex, and the possibility that antibodies induced by a vaccine would result in a false-positive test for HIV infection.

Another study conducted by investigators at Emory University (ThPeC7431) looked at WTP among a predominantly black (63%), female (72%) population (n=220) of students from a small college in Georgia. The study was designed to probe participants’ understanding of and beliefs about AIDS vaccine research, and it yielded some striking findings. More than a third of those interviewed believed that an AIDS vaccine exists but is withheld from the public, and almost half agreed with the statement “in a trial I may be injected with HIV.” Overall, just 17% of those interviewed agreed with the statement “after a researcher told me about an HIV vaccine clinical trial, I would enroll in one.” The study also found that African Americans and Asians were more likely than whites to feel that it was important to have people of the same ethnic group participating in the trial (p = 0.001) or on the research team (p = 0.001).

Concerns of people in the US were also the focus of several posters presented by Project VIBE, a research study that posed an elaborate set of scenarios involving hypothetical vaccines with different characteristics (e.g., cost, level of efficacy, potential for causing a falsely positive reading in an HIV test), as well as trials with different types of designs (e.g., greater or fewer numbers of immunizations, blood samplings, etc.). These scenarios were used to explore attitudes about research participation, interest in licensed vaccines, and other issues through interviews and focus groups at sites around Los Angeles, including a gay and lesbian community center and health clinic, a needle exchange center, and a health clinic serving the city’s Latino community.

Here, too, there was heterogeneity in the responses with individuals identifying a number of barriers to uptake of an effective vaccine (TuPeD5105), including the belief that doctors experiment on patients without telling them, prior experience of being refused medical coverage, and concerns about the stigma that might be associated with seeking such a vaccine. Other abstracts from Project VIBE looked at willingness to participate in vaccine trials (ThPeC7435) and women’s concerns around uptake of a hypothetical effective vaccine (ThPeD5154).

Risk behavior/mitigation of vaccine protective effects

The benefits of an effective vaccine could be offset by other trends such as decreased condom use or increased numbers of sexual partners, which might emerge if people widely believed that an AIDS vaccine was a “magic bullet” against the virus. Since the first generation of AIDS vaccines is expected to have low or moderate levels of efficacy, many in the field feel that it’s particularly important to consider how various shifts in risk behavior might offset the benefits of a vaccine with low-, moderate-, or even high-efficacy.

In Bangkok, Peter Vickerman (London School of Hygiene and Tropical Medicine) presented a new mathematical model that attempts to address some of these questions (ThOrC1430). The model allows researchers to examine how changes in rates of unprotected sex and/or numbers of sexual partners might affect vaccines that confer different degrees of protection. The study considered two types of preventive vaccine, one which reduces the susceptibility of uninfected individuals and a second that reduces the infectiousness of infected individuals. The model was also designed to account for increased levels of STIs in vaccinees who increased their sexual risk behavior.

In a sample calculation that assumed 50% condom use prior to the vaccine’s introduction, Vickerman showed that with a vaccine that reduced the susceptibility of uninfected individuals with 40% efficacy, sexual risk must not increase by more than 70% for the vaccine to be beneficial. But if the efficacy of that vaccine is 80% then sexual risk can increase by over 300% without fully compromising the benefit.

Vickerman acknowledged the many limitations of mathematical models to predict real world outcomes but concluded that “vaccine introduction should be accompanied by increased efforts to promote reductions in risk behavior. If this is not done, and people increase their sexual risk, the benefits from a vaccination program will be reduced and transmission could increase.”

Forecasting demand

A poster (ThPeC7445) by Martha Ainsworth (World Bank) and colleagues presented a demand forecasting study conducted in Uganda in 2001-2002, using similar techniques to a study conducted in Thailand (Health Policy 57, 111, 2001). Both studies communicated concepts of vaccine efficacy and partial effectiveness and then tested respondents’ comprehension of these concepts prior to administering the questionnaire.

Participants were asked about willingness to spend from US$2.86 to US$286 on a vaccine of either 50% (n=812) or 95% (n = 803) efficacy (defined as protecting that percentage of people against infection). Controlling for household assets, efficacy and price, the study found that higher education level (upper secondary and university) correlated with willingness to purchase a vaccine. One of the striking findings in this study—and in the Thai research—was that demand for 50% and 95% effective vaccines was roughly equivalent.

The researchers also collected data on respondents’ risk factors for HIV infection in order to make rough estimates of the effect that a low- or high-efficacy vaccine would have on incidence. Twenty-five percent of men and 10% of women reported a non-spousal sexual partner in the last year, and only 51% of these individuals reported using condoms with these partners. This relatively low rate of condom use led the authors to conclude that a vaccine of low efficacy would have a limited impact on new infections in the absence of strong education and outreach campaigns for other prevention strategies.

Preparing for “the day after efficacy”

On 12 July, a satellite symposium reviewed issues that will arise once an effective vaccine candidate has been identified. Helen Rees (University of Witwatersrand, South Africa) emphasized the need to strengthen regulatory capacity in developing countries and reviewed some of the steps that the Global HIV Vaccine Enterprise might take to help facilitate this process, including sponsoring a workshop of regulators, trial sponsors and key industry partners to discuss risk-benefit evaluation and regulatory decision making as they relate to AIDS vaccine candidates. This would allow the various stakeholders to discuss how an effective candidate with a particular safety and efficacy profile might be viewed in developing versus developed countries.

Viroj Tangcharoensathien (Thai Ministry of Public Health ) reviewed a study which explored potential groups to be targeted in Thai vaccination campaigns, categorizing them in terms of the numbers of infections that would be averted and the cost of delivering the vaccine to each group. Sex workers, prisoners, conscripts and male STI patients were all described as populations that could be reached at low cost with high numbers of infections averted (based on 2002 prevalence data), whereas civil servants, police, pregnant women and military personnel could be reached at low cost but with low numbers of infections averted. Tangcharoensathien pointed out that voluntary counseling and testing is a crucial entry point for vaccine studies, and these services should be included in program cost estimates.

Other issues addressed at the symposium included the need to further explore how to deliver vaccines to adolescents and young people so that they are protected before sexual debut, and how to develop pricing structures and purchasing plans that ensure an effective vaccine is available in hard-hit resource-poor settings as soon as it is licensed.

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*Emily Bass is senior writer of the IAVI Report.