Vaccine 32 (2014) 5854–5861
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Willingness to participate in HIV vaccine trials among men who have sex with men in Chennai and Mumbai, India Peter A. Newman a,∗ , Venkatesan Chakrapani b,c , James Weaver a , Murali Shunmugam b , Clara Rubincam a a
Factor-Inwentash Faculty of Social Work, University of Toronto, 246 Bloor Street West, Toronto, ON, Canada M5S 1V4 Centre for Sexuality and Health Research and Policy, 38 Rangarajapuram Main Road, Kodambakkam, Chennai 600 024, Tamil Nadu, India c The Humsafar Trust, 3rd Floor, Manthan Plaza, Nehru Rd., Vakola, Santacruz (East), Mumbai 400055, India b
a r t i c l e
i n f o
Article history: Received 14 March 2014 Received in revised form 7 July 2014 Accepted 15 August 2014 Available online 27 August 2014 Keywords: HIV vaccine trials Willingness to participate Bioethics Posttrial services Men who have sex with men India
a b s t r a c t Introduction: Men who have sex with men (MSM) are at disproportionately high risk for HIV in India and would benefit greatly from a safe and effective HIV vaccine. We assessed willingness to participate (WTP) in HIV vaccine trials and the impact of various trial characteristics on WTP among MSM in Mumbai and Chennai. Methods: We used venue-based time-space sampling to recruit MSM at cruising sites and drop-in centers at community-based organizations. Structured survey interviews assessed sociodemographics, WTP and the impact of 10 trial characteristics on WTP. We tested for differences in WTP by sociodemographics and trial characteristics, and sociodemographic differences in the impact of trial characteristics on WTP. Results: Among 400 participants (median age = 25 years), 46.9% identified as kothi, 40.0% panthi/doubledecker, 13.0% gay/bisexual; 29.0% had primary school education or less; and 40.0% had monthly income < = 5000 INR (∼3USD/day). Overall, 48.1% reported being definitely willing to participate. Posttrial availability of an efficacious vaccine was the highest rated (90.98 on 100–point scale) trial characteristic, followed by availability of free medical treatment (90.79), life insurance (89.84) and side effects (79.81). Distance to the trial site, side effects, financial incentive, life insurance and free medical care had significant impacts on WTP, with differential importance of trial characteristics by sexual identity, education, income and living arrangement. Conclusion: The prioritization of trial-related financial and healthcare provisions, including access to an efficacious vaccine posttrial, among MSM in India indicates the importance of trials providing such services, as well as the value of formative research in identifying key concerns among participating communities in resource-limited settings. The significant impact of trial characteristics on WTP suggests that providing trial benefits deemed fair and important, addressing logistical concerns, and supporting educational interventions to mitigate vaccine fears may support recruitment of MSM in India in fairly and ethically conducted HIV vaccine trials. © 2014 Elsevier Ltd. All rights reserved.
1. Introduction India has among the highest number of persons living with HIV in the world (∼2.1 million) and 116,000 new cases per year [1]. General HIV prevalence is low (∼0.35%), but the epidemic is concentrated among men who have sex with men (MSM), with prevalence estimates from less than 1% to 15% across India [2].
∗ Corresponding author. Tel.: +1 416 946 8611; fax: +1 416 978 7072. E-mail address: [email protected] (P.A. Newman). http://dx.doi.org/10.1016/j.vaccine.2014.08.043 0264-410X/© 2014 Elsevier Ltd. All rights reserved.
In 2011, the Indian Ministry of Science and Technology partnered with the International AIDS Vaccine Initiative (IAVI) to form the HIV Vaccine Design Programme in India, demonstrating an ongoing commitment to HIV vaccine research and development [3]. Although India would greatly benefit from a safe and efficacious HIV vaccine, among nearly 200 HIV vaccine trials completed worldwide, only three have been conducted in India [4]. HIV vaccine clinical trials conducted in India, all Phase 1, include a test of an adeno-associated virus-based HIV-1 vaccine candidate among 30 healthy volunteers initiated in 2003 [5,6], a 2005 trial of a Modified Vaccinia Ankara-based (MVA) HIV-1 vaccine among 32
P.A. Newman et al. / Vaccine 32 (2014) 5854–5861
volunteers [7], and a 2009 trial of a DNA–MVA prime-boost vaccination regimen among 32 healthy volunteers [8]. The candidate vaccines were all safe and well tolerated, but did not warrant Phase 2 testing. HIV vaccine preparedness, particularly among communities at high risk of HIV exposure, is a crucial adjunct to vaccine research and development. HIV vaccine trial preparedness investigations in low-, middle- and high-income countries, synthesized in several systematic reviews, have assessed willingness to participate (WTP) in clinical trials [9–11]. Studies have focused predominantly on individual knowledge, attitudes and perceptions associated with WTP, in order to inform educational initiatives and interventions designed to engage participating communities and recruit trial volunteers. Common barriers to WTP include fear of vaccine-induced infection, and concerns about vaccine-induced seropositivity and possible side effects [10–12]. Motivators of WTP include altruism, free healthcare, and financial incentives [9,12]. Studies of WTP focused on gay and other MSM, a feasible population for HIV vaccine trials in India, have been conducted primarily in high-income countries. The few WTP studies conducted in India [13–16] provide limited information due to small samples of MSM subsumed in larger studies of vulnerable groups and lack of exploration of what may be population-specific phenomena among MSM in the Indian context. Diversity within MSM communities in India, including by socioeconomic status and sexual self-identification [17], further suggest the need to explore potential subpopulation differences in WTP and trial-related concerns. The dramatic increase in the past decade in clinical trials in resource-limited settings [18], including biomedical HIV prevention trials [4], has brought with it intensified focus on ethical and social challenges in trial implementation [19–23]. The latter have at times resulted in HIV prevention trial shutdowns due to community opposition [24,25]. Global initiatives such as UNAIDS’ Good Participatory Practices in Biomedical HIV Prevention Trials (GPP) [26] were developed in part to address these challenges, particularly in resource-limited settings. GPP guidelines may help to augment the previous focus of HIV vaccine preparedness on individual-level factors associated with WTP, with greater attention to structural features of trials that facilitate or impede the conduct of scientifically and ethically valid research. These trial features include access to medical care and HIV treatment if one is harmed or becomes HIV infected during the trial; preventing exploitation, such as enrollment of participants in HIV vaccine trials in low-income countries for the benefit of populations in high-income countries, by guaranteeing access to a free or affordable vaccine locally if proven efficacious [23,27,28]; and the extent to which trials ensure that potential volunteers have sufficient information and understanding about the trial services provided to ensure informed consent is ethically valid [27,29,30]. In the context of continuing bioethical challenges for global HIV vaccine trials and evolving efforts to address these, we assessed WTP and the influence of a range of HIV vaccine trial characteristics, that is, features of the trial itself, on WTP among diverse MSM in Chennai and Mumbai—large metropolitan areas with concentrated HIV epidemics among MSM [31] in which HIV vaccine trials could feasibly be conducted.
2. Methods 2.1. Recruitment and sampling We used venue-based time-space sampling, a method for systematic recruitment of participants from populations, such as MSM, among whom it is challenging or impossible to identify a simple random sample [32]. We identified recruitment sites in Mumbai
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and Chennai, and across two different strata with high-risk populations of MSM—cruising sites (CSs) and drop-in centers (DICs). CSs, public locations where MSM go to meet sex partners, were extensively mapped by community-based organizations (CBOs) serving MSM in each city. DICs are sites located within CBO field offices where MSM come to socialize and participate in educational events. In Chennai, Social Welfare Association for Men (SWAM) provides outreach services in 25 CSs in 4 city zones and Sahodaran provides outreach services in 29 CSs in 3 additional city zones. In Mumbai, one CBO, the Humsafar Trust (HST), provides outreach in 21 CSs in 3 zones. Peer outreach workers collected information on the estimated number of MSM that visit each CS over the course of 1 month. We calculated the sample size to be recruited from CSs in each zone to be proportional to the estimated number of MSM visiting each zone in 1 month. To efficiently meet sampling targets in potentially risky environments for project staff and MSM, the 2 or 3 busiest CSs per zone were selected for recruitment. DIC sampling events took place at 2 DICs in Chennai and 2 DICs in Mumbai. For each DIC, we recorded the number of MSM who attend on “regular” and “special event” days in order to estimate the number of MSM who attend the DIC in 1 month. We recruited MSM during activities/days during which a large number of HIV-negative and untested MSM were expected in order to target these populations, based on eligibility criteria for prophylactic HIV vaccine trials. Potential participants were screened for eligibility at each sampling event (at CSs and DICs): 18 years old or above, self-identified as kothi, panthi, double-decker, or gay, and not working at the organization. The study protocol was approved by the research ethics boards of the University of Toronto and the Humsafar Trust (Mumbai). 2.2. Data collection and measures Peer recruiters visited the venues at specified times and approached every nth person visiting the site based on the site’s client population and target recruitment number. Peer recruiters explained the study, screened for eligibility and scheduled interviews for those who were eligible and volunteered to participate. The latter were given an appointment card that they were required to show at their scheduled interview time. Cards were distributed to 480 eligible individuals, out of which 400 (83.3%) participated in interviews. Structured questionnaires were administered by trained interviewers in Tamil (Chennai) or Hindi (Mumbai) in a private room at CBO offices. Study participants were compensated 250 Indian rupees (INR) (∼$5 USD) for their time for the 45-min interview. We assessed WTP in a hypothetical HIV vaccine clinical trial using a 4-point scale: 1 = Yes, definitely willing; 2 = I am possibly willing, but I need time to think about it; 3 = I am not willing now, but I need time to think about it; and 4 = No, I am not at all willing. This was dichotomized into “Yes, definitely willing (i.e., 1)” versus “unsure or no (i.e., 2–4)” responses. Participants rated the importance of 10 trial characteristics, including distance to the trial site, financial incentive for participation, and provision of life insurance, on their WTP in an HIV vaccine trial (see Table 2). Each trial characteristic was rated on a 4-point Likert-type scale: 0 = not at all important; 1 = somewhat important; 2 = important; 3 = very important. We linearly transformed these ratings to scores on a 0–100 point scale by dividing each response by 3 and multiplying by 100. Thus, the higher the score on the 100-point scale, the higher the importance attached to that trial characteristic. Trial characteristics (i.e., distance to trial site, type of venue, financial incentive) were based on our initial qualitative research [17,33] conducted in collaboration with local CBOs, as well as systematic reviews of the literature on WTP [9–11].
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Table 1 Sociodemographic characteristics and bivariate associations with willingness to participate in HIV vaccine trials among MSM in India (n = 400). Variable Age < = 25 years >25 years Primary identity Kothi Panthi/DD/other Gay/bisexual Education Illiterate/primary/elem. school Some HS/HS diploma College degree Occupation Wage/unemployed/student Gov’t./private/volunteer org./self Sex work Income (missing = 93) < = 5000 rupees > 5000 rupees Marital status Never married Married/sep./divorced/widowed Children 0 1+ Living status Parents/wife/in-laws/partner Alone/friends
Sample n
%
Weighted prop.
95% CI
Prop. WTP
95% CI
207 193
51.75 48.25
49.73 50.27
41.23 41.75
171 164 65
42.75 41.00 16.25
46.88 40.08 13.04
99 217 84
24.75 54.25 21.00
147 219 34
p
58.25 58.77
53.10 46.90
42.42 36.51
63.49 57.58
35.92 31.37 8.15
58.16 49.47 20.20
48.68 36.70 14.63
35.31 25.86 9.42
62.23 49.07 22.02
29.30 50.16 20.54
20.50 42.63 15.57
39.98 57.69 26.59
28.80 47.64 23.56
17.11 35.92 17.87
44.23 59.63 30.39
36.75 54.75 8.50
38.60 50.43 10.98
30.82 41.96 5.52
47.01 58.87 20.64
38.49 49.15 12.36
27.21 37.94 5.31
51.16 60.45 26.17
94 213
30.62 69.38
39.97 60.03
28.90 47.83
52.17 71.10
34.01 65.99
22.89 52.79
47.21 77.11
329 71
82.25 17.75
83.97 16.03
78.89 11.98
88.02 21.11
90.23 9.77
83.11 5.45
94.55 16.89
352 48
88.00 12.00
87.81 12.19
83.38 8.81
91.19 16.62
93.11 6.89
86.47 3.39
96.61 13.53
314 86
78.50 21.50
79.00 21.00
70.07 14.19
85.81 29.93
77.81 22.19
65.61 13.43
86.57 34.39
0.308
0.455
0.503
0.818
0.040
0.007
0.023
0.666
Abbreviation: MSM, men who have sex with men; Prop., proportion; CI, confidence interval; WTP, willingness to participate; DD, double-decker; Elem., elementary; HS, high school; Gov’t, government; Org., organization; Sep., separated.
We collected sociodemographic information on age (dichotomized into less than or equal to 25 years and greater than 25 years), primary sexual self-identification (kothi, panthi/double-decker, and gay/bisexual), education (illiterate, primary/elementary school, high school/diploma/some college, and college degree), occupation (daily wage laborer/ unemployed/student, government/private sector/volunteer organization/self-employed, or sex work), income (dichotomized as less than or equal to and above 5000 INR per month), marital status (never married and married/separated/divorced/widowed), and living arrangements (with parents/wife/in-laws/partner or living alone/with friends/other).
For all analyses we used sampling weights (the inverse probability that a participant was selected for recruitment) to adjust for systematic differences in the probability of participant selection. MSM in Chennai were older, more likely to identify as kothi, less educated, more likely to be sex workers and had lower income compared to MSM in Mumbai. Differential representation in the sample was accounted for by the weighting procedures, and WTP by city was not significant (p = 0.413). We calculated standard errors using Taylor-series linearization to adjust for the time-location sampling design-effect on estimate precision using complex survey-specific procedures in Stata version 11.2 (Stata Corp., College Station, Texas).
2.3. Statistical analysis
3. Results
We characterized the sample by sociodemographic characteristics and WTP. We tested for differences in WTP by sociodemographic characteristics with Pearson chi-square tests using the Rao and Scott design-based correction [34]. We then estimated participant ratings of HIV vaccine trial characteristics and assessed the impact of each characteristic by WTP (versus not WTP or unsure) with design-adjusted t-tests using surveyspecific linear combinations of rating means. Lastly, we compared trial characteristic ratings by sociodemographics with designeffect adjusted Wald tests in survey-specific linear regression. For trial characteristic ratings that differed by sociodemographic group, we examined post-estimation linear combinations to determine which group comparison(s) were responsible for the overall rating difference. Income data were missing on 93 cases of which 49 were unemployed, 28 were students, and 15 reported employment. The 77 unemployed and students were classified as having income less than 5000 INR per month and the remaining 15 were considered valid missing. The missing cases were not included in the bivariate analysis of trial characteristic ratings by income.
From May to September 2012, we recruited 400 MSM from 24 CSs and 4 DICs in Chennai and Mumbai. Table 1 reports the sample distribution by sociodemographic characteristics, the respective weighted population proportions adjusted for sampling designeffect, and weighted population proportions of those indicating WTP. The population median age was 25 years. Almost half (46.9%) identified as kothi, 40.0% as panthi or double-decker, and 13.0% as gay/bisexual. Nearly one-third (29.0%) had primary school education or less and 40.0% had a monthly income of 5000 INR ( 5000 INR
Par/wife/family
Alone/friends
56.35 48.12 0.01 0.366
64.59
56.76 45.92
67.60
59.60 48.75 5.41 0.028
70.46
45.20 37.31
53.10
69.21
52.28 42.30
62.25
67.94
49.33 39.50
59.16
88.25
70.16 60.47
79.85
83.34
68.15 52.55
83.75
72.90
67.17 59.84
74.51
75.65
54.29 44.55
64.03
73.40
57.61 49.69
65.53
66.81
67.32 57.12
77.52
97.12
88.32 82.55
94.09
94.83
92.71 87.22
98.20
96.68
88.89 85.10
92.68
94.49
91.00 86.03
95.96
95.27
90.32 85.67
94.96
94.99
89.19 84.08
94.31
85.46
80.89 73.65
88.14
89.02
69.53 58.84
80.23
74.13
64.31 56.01
72.61
75.47
53.48 43.39
63.58
59.20 49.20 2.09 0.160 77.91 67.56 2.54 0.123 65.29 57.67 0.17 0.686
64.89 56.38 2.20 0.150 91.01 84.90 1.31 0.263 92.53 88.37 4.84 0.037 91.46 87.64 0.24 0.629
78.62 71.79 0.32 0.574 64.54 54.96 0.00 0.952
57.49 47.04 1.80 0.191 74.26 65.17 0.95 0.338 68.77 61.89 6.67 0.016
59.50 52.18 1.63 0.212 89.08 83.34 1.69 0.205 90.74 86.99 0.01 0.915 91.46 87.93 0.95 0.337
82.54 76.06 5.06 0.033 66.92 58.37 6.69 0.015
Abbreviation: MSM, men who have sex with men; DD, double-decker; Illit, illiterate; I Prim, primary; I Elem, elementary; I HS, high school; I Dipl, diploma; I Par, parents; CI, confidence interval; p, p value.
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Rating 95% CI Wald p
Income
Panthi/DD
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The vaccine trial characteristic with the greatest impact on WTP was distance to the trial site. This finding is corroborated by a systematic review of barriers to enrolment in HIV vaccine trials, which identified personal costs, including transportation, as a pervasive barrier to WTP [10]. The trial characteristic with the second greatest impact on WTP was anticipated side effects from test vaccines. Systematic reviews of WTP research [9–11] as well as studies within India [15,16] similarly identify side effects as a barrier to WTP. Concerns about side effects may have become more protracted after the unexpected increased susceptibility to HIV infection among a subsample of vaccinees in the Step Study Phase IIb HIV vaccine trial [35,36], terminated in September 2007 after most of these WTP studies were conducted. In the present study, financial incentive, life insurance and free medical treatment for trial-related harms each had significant impacts on WTP. Life insurance was similarly identified as an important determinant of WTP in an earlier study of key populations at risk in India [15]. Access to the vaccine for free if found to be efficacious in the trial was uniformly the highest rated characteristic (91/100-point scale) across participants, such that it did not differentiate by WTP. Notably, these concerns may reflect larger structural factors (e.g., poverty, lack of access to healthcare) rather than logistical challenges or vaccine-specific concerns. The constellation of financial and healthcare concerns reflect the importance to potential trial volunteers of the trial and posttrial services guaranteed to participants in a resource-limited setting. Nevertheless, an earlier systematic review of 65 pharmaceutical industry-sponsored HIV antiretroviral trials conducted from 1987 to 2006 indicate that nearly half of trial protocols did not mention posttrial services of any type [27]. Although we are not aware of a similar review of protocols for HIV vaccine trials, which are distinct in several ways from trials of medications to treat persons living with HIV, the present results underscore the importance of trial sponsors and site staff providing clear explanations about the availability or not of particular trial-related services, including medical care, life insurance, and access to products tested in the trial if they prove efficacious. If trial benefits and healthcare services are not clearly disclosed, participants cannot evaluate risk-benefit ratios, necessary for valid informed consent [23,27]. To the extent participants and local communities may not have access to an HIV vaccine if proven efficacious in the trial, questions of exploitation arise that may compromise trial ethics [22,23]. Several sociodemographic characteristics were significantly associated with the impact of HIV vaccine trial characteristics on WTP. We identified a pattern of greater importance to kothiidentified (generally lower socioeconomic status) MSM of logistical concerns (particularly distance to the trial site and whether it is in a government hospital or community venue), and financial and healthcare concerns, including trial and posttrial services (life insurance, free medical treatment). Based on our previous qualitative findings, kothis indicate a preference for trial venues at CBOs rather than hospital settings due to concerns about stigma and discrimination in the government healthcare system [33]. Sociodemographic differences in WTP among MSM suggest the importance of formative research in local communities in which HIV vaccine trials are planned; what may appear to be uniform groups (e.g., “MSM”) from an outsider’s perspective or based on behavioural definitions of MSM may reveal differences that are significant to supporting recruitment and ensuring fair and ethical conduct of HIV vaccine trials. The present results suggest that kothi-identified MSM, who tend to be at high risk for HIV infection [37,38], may be those most affected by logistical factors, and the trial and posttrial services provided by HIV vaccine trials. The lower WTP among MSM who are married (not uncommon in India due to strong cultural value placed on maintaining family
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lineage [33]), and those who have children, and the greater importance accorded to distance to the site, trial duration, side effects, and route of vaccine administration among those living with family or partner versus alone or with friends, suggests the value of addressing concerns about WTP among MSM in India from a family perspective [33]. Provision of life insurance [15] and discussion of trial-related concerns vis-a-vis ones family, may support recruitment in HIV clinical trials. After a period that has been characterized as one of deregulation of global drug trials post-2005, with less than optimal oversight [39], India’s Central Drug Standard Control Organisation (CDSCO) issued new draft guidelines for clinical trials in January 2013 following a Supreme Court decision [40]. These CDSCO guidelines specifically address compensation for trial-related injuries and life insurance “in the cases of clinical trial related serious adverse events or deaths occurring/during clinical trials” [39,40]. Based on the present study, these are issues of considerable concern to MSM communities and are significantly associated with their WTP in HIV vaccine trials. Confusion and debate have ensued over the terms of the CDSCO regulations, however, as they stipulate a requirement for compensation in the case of injuries or deaths sustained during but not related to the experimental drug being tested, as well as compensation in the case of “failure of investigational product to provide intended therapeutic effect” and “use of placebo in a placebocontrolled trial” [40]. Currently under governmental review, these regulations have been criticized within India as hasty and not engaging relevant stakeholders [40]; we would add the importance of including community stakeholders along with stakeholders from research and governmental institutions. Importantly, CDSCO’s current regulations have also resulted in U.S. and Canadian sponsors discontinuing dozens of drug trials in progress, as well as an effective cessation of new trials. It remains unclear to what extent CDSCO guidelines will be retained in their present form as well as the extent to which they will be considered applicable in the case of prevention trials, such as prophylactic HIV vaccine trials among communities at high risk of exposure. A strict reading would suggest the trial bears direct responsibility for monetary compensation and medical care for every new HIV seroconversion – including participants in the control arm as well as the experimental arm if the test vaccine is not efficacious – in addition to any other injury or death during the trial period, terms that seem likely to render global HIV vaccine trials in India untenable. As argued by clinicians and researchers in India, such an outcome serves neither investigators nor persons at risk given its stagnating effect on medical research [40]. A “middle path” has been suggested that ensures ethically and scientifically rigorous trials, including assurances from sponsors that trials conducted address health needs in India and that efficacious products would be available and affordable in India if licensed and approved [40]. Our findings suggest that ensured access to an efficacious HIV vaccine post-trial would address a key concern among MSM; combined with reasonable compensation in the event of trial-related injuries and access to HIV-related medical care, revised guidelines may help to restore the feasibility of clinical trials and address the vital need for new HIV prevention technologies in India. 4.1. Limitations The present findings should be interpreted in the context of study limitations. Although we included trial characteristics based on formative qualitative research conducted in situ, other trial characteristics also may influence WTP. Furthermore the results cannot be generalized to MSM across India and the sample size was determined by feasibility and available resources. Nevertheless, while simple random sampling of this vulnerable and underserved
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population is not feasible, we used venue-based time-space sampling to recruit MSM of diverse identities and socioeconomic statuses; thus, the results are generalizable to the considerable population of predominantly young MSM who attend CBOs and CSs, a particularly important population for HIV prevention trials [41]. Future investigations should assess WTP among transgender women, who are at disproportionately high risk for HIV in India [1], as well as among higher socioeconomic status, often gay-identified MSM, who tend to be underrepresented in Indian HIV surveillance and research; the latter may be more likely to be accessed via the Internet than in CBOs and CSs. We did not conduct HIV testing, which would present additional risks to participants due to HIV stigma and confidentiality concerns among MSM [33]; rather, we targeted populations at risk by using venue-based time-space sampling (i.e., at CSs and at DICs offering prevention education, rather than HIV clinics). However, it is possible that some respondents may have been HIV-positive and ineligible to enroll in prophylactic HIV vaccine trials. Finally, stated WTP in hypothetical HIV vaccine trials may overestimate actual participation; however, the present results indicate the value of formative research with community stakeholders to develop evidence to support recruitment for fair and ethically conducted HIV vaccine trials. 5. Conclusion
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[12]
We identified HIV vaccine trial characteristics associated with WTP among predominantly young, socioeconomically diverse MSM in India, a substantial population at high risk of HIV exposure among whom HIV vaccine trials have not been conducted. The present findings suggest the following measures may promote WTP among MSM in India in fair and ethically conducted HIV vaccine trials: (1) addressing community stakeholder concerns (i.e., side effects) through educational initiatives, perhaps informed by mental models of vaccines and clinical trials [17]; (2) supporting logistical (i.e., trial location) and financial arrangements (i.e., incentives, life insurance) deemed fair and ethical; (3) ensuring access to HIV-related medical care during and after trials; and, (4) prioritizing availability and access to the product tested if deemed efficacious.
[13]
Acknowledgements
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We offer sincere thanks to our community collaborators, The Humsafar Trust, Mumbai; Social Welfare Association for Men (SWAM), Chennai; and Sahodaran, Chennai. Special thanks to Vivek R. Anand, Sekar Balasubramaniam, Sunil Menon and Jaya for their invaluable assistance. We thank all participants and key informants for sharing their perspectives. We also wish to thank Suchon Tepjan, Joanne Daciuk and Lily Wong for administrative support. This research was supported in part by grants from the Canadian Institutes of Health Research (MOP-102512; THA-118570), the Canada Research Chairs Program and the Canada Foundation for Innovation (228382).
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Ethical and scientific implications of the globalization of clinical research. N Engl J Med 2009;360:23–816. Singh J, Mills E. The abandoned trials of pre-exposure prophylaxis for HIV: what went wrong? PLoS Med 2005;2(9):e234. Newman PA. Towards a science of community engagement. Lancet 2006;367(9507):302. UNAIDS-AVAC. Good participatory practice: guidelines for biomedical HIV prevention trials 2011. AVAC web site. UNAIDS-AVAC; 2011 (June). Available at: http://www.avac.org/sites/default/files/resource-files/Good% 20Participatory%20Practice%20guidelines June 2011.pdf [accessed 2 July 2014]. Ciaranello AL, Walensky RP, Sax PE, Chang Y, Freedberg KA, Weissman JS. Access to medications and medical care after participation in HIV clinical trials: a systematic review of trial protocols and informed consent documents. HIV Clin Trials 2009;10(1):13–24. Guenter D, Esparza J, Macklin R. 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Willingness to participate in HIV vaccine trials among men who have sex with men in Chennai and Mumbai, India Peter A. Newman a,∗ , Venkatesan Chakrapani b,c , James Weaver a , Murali Shunmugam b , Clara Rubincam a a
Factor-Inwentash Faculty of Social Work, University of Toronto, 246 Bloor Street West, Toronto, ON, Canada M5S 1V4 Centre for Sexuality and Health Research and Policy, 38 Rangarajapuram Main Road, Kodambakkam, Chennai 600 024, Tamil Nadu, India c The Humsafar Trust, 3rd Floor, Manthan Plaza, Nehru Rd., Vakola, Santacruz (East), Mumbai 400055, India b
a r t i c l e
i n f o
Article history: Received 14 March 2014 Received in revised form 7 July 2014 Accepted 15 August 2014 Available online 27 August 2014 Keywords: HIV vaccine trials Willingness to participate Bioethics Posttrial services Men who have sex with men India
a b s t r a c t Introduction: Men who have sex with men (MSM) are at disproportionately high risk for HIV in India and would benefit greatly from a safe and effective HIV vaccine. We assessed willingness to participate (WTP) in HIV vaccine trials and the impact of various trial characteristics on WTP among MSM in Mumbai and Chennai. Methods: We used venue-based time-space sampling to recruit MSM at cruising sites and drop-in centers at community-based organizations. Structured survey interviews assessed sociodemographics, WTP and the impact of 10 trial characteristics on WTP. We tested for differences in WTP by sociodemographics and trial characteristics, and sociodemographic differences in the impact of trial characteristics on WTP. Results: Among 400 participants (median age = 25 years), 46.9% identified as kothi, 40.0% panthi/doubledecker, 13.0% gay/bisexual; 29.0% had primary school education or less; and 40.0% had monthly income < = 5000 INR (∼3USD/day). Overall, 48.1% reported being definitely willing to participate. Posttrial availability of an efficacious vaccine was the highest rated (90.98 on 100–point scale) trial characteristic, followed by availability of free medical treatment (90.79), life insurance (89.84) and side effects (79.81). Distance to the trial site, side effects, financial incentive, life insurance and free medical care had significant impacts on WTP, with differential importance of trial characteristics by sexual identity, education, income and living arrangement. Conclusion: The prioritization of trial-related financial and healthcare provisions, including access to an efficacious vaccine posttrial, among MSM in India indicates the importance of trials providing such services, as well as the value of formative research in identifying key concerns among participating communities in resource-limited settings. The significant impact of trial characteristics on WTP suggests that providing trial benefits deemed fair and important, addressing logistical concerns, and supporting educational interventions to mitigate vaccine fears may support recruitment of MSM in India in fairly and ethically conducted HIV vaccine trials. © 2014 Elsevier Ltd. All rights reserved.
1. Introduction India has among the highest number of persons living with HIV in the world (∼2.1 million) and 116,000 new cases per year [1]. General HIV prevalence is low (∼0.35%), but the epidemic is concentrated among men who have sex with men (MSM), with prevalence estimates from less than 1% to 15% across India [2].
∗ Corresponding author. Tel.: +1 416 946 8611; fax: +1 416 978 7072. E-mail address: [email protected] (P.A. Newman). http://dx.doi.org/10.1016/j.vaccine.2014.08.043 0264-410X/© 2014 Elsevier Ltd. All rights reserved.
In 2011, the Indian Ministry of Science and Technology partnered with the International AIDS Vaccine Initiative (IAVI) to form the HIV Vaccine Design Programme in India, demonstrating an ongoing commitment to HIV vaccine research and development [3]. Although India would greatly benefit from a safe and efficacious HIV vaccine, among nearly 200 HIV vaccine trials completed worldwide, only three have been conducted in India [4]. HIV vaccine clinical trials conducted in India, all Phase 1, include a test of an adeno-associated virus-based HIV-1 vaccine candidate among 30 healthy volunteers initiated in 2003 [5,6], a 2005 trial of a Modified Vaccinia Ankara-based (MVA) HIV-1 vaccine among 32
P.A. Newman et al. / Vaccine 32 (2014) 5854–5861
volunteers [7], and a 2009 trial of a DNA–MVA prime-boost vaccination regimen among 32 healthy volunteers [8]. The candidate vaccines were all safe and well tolerated, but did not warrant Phase 2 testing. HIV vaccine preparedness, particularly among communities at high risk of HIV exposure, is a crucial adjunct to vaccine research and development. HIV vaccine trial preparedness investigations in low-, middle- and high-income countries, synthesized in several systematic reviews, have assessed willingness to participate (WTP) in clinical trials [9–11]. Studies have focused predominantly on individual knowledge, attitudes and perceptions associated with WTP, in order to inform educational initiatives and interventions designed to engage participating communities and recruit trial volunteers. Common barriers to WTP include fear of vaccine-induced infection, and concerns about vaccine-induced seropositivity and possible side effects [10–12]. Motivators of WTP include altruism, free healthcare, and financial incentives [9,12]. Studies of WTP focused on gay and other MSM, a feasible population for HIV vaccine trials in India, have been conducted primarily in high-income countries. The few WTP studies conducted in India [13–16] provide limited information due to small samples of MSM subsumed in larger studies of vulnerable groups and lack of exploration of what may be population-specific phenomena among MSM in the Indian context. Diversity within MSM communities in India, including by socioeconomic status and sexual self-identification [17], further suggest the need to explore potential subpopulation differences in WTP and trial-related concerns. The dramatic increase in the past decade in clinical trials in resource-limited settings [18], including biomedical HIV prevention trials [4], has brought with it intensified focus on ethical and social challenges in trial implementation [19–23]. The latter have at times resulted in HIV prevention trial shutdowns due to community opposition [24,25]. Global initiatives such as UNAIDS’ Good Participatory Practices in Biomedical HIV Prevention Trials (GPP) [26] were developed in part to address these challenges, particularly in resource-limited settings. GPP guidelines may help to augment the previous focus of HIV vaccine preparedness on individual-level factors associated with WTP, with greater attention to structural features of trials that facilitate or impede the conduct of scientifically and ethically valid research. These trial features include access to medical care and HIV treatment if one is harmed or becomes HIV infected during the trial; preventing exploitation, such as enrollment of participants in HIV vaccine trials in low-income countries for the benefit of populations in high-income countries, by guaranteeing access to a free or affordable vaccine locally if proven efficacious [23,27,28]; and the extent to which trials ensure that potential volunteers have sufficient information and understanding about the trial services provided to ensure informed consent is ethically valid [27,29,30]. In the context of continuing bioethical challenges for global HIV vaccine trials and evolving efforts to address these, we assessed WTP and the influence of a range of HIV vaccine trial characteristics, that is, features of the trial itself, on WTP among diverse MSM in Chennai and Mumbai—large metropolitan areas with concentrated HIV epidemics among MSM [31] in which HIV vaccine trials could feasibly be conducted.
2. Methods 2.1. Recruitment and sampling We used venue-based time-space sampling, a method for systematic recruitment of participants from populations, such as MSM, among whom it is challenging or impossible to identify a simple random sample [32]. We identified recruitment sites in Mumbai
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and Chennai, and across two different strata with high-risk populations of MSM—cruising sites (CSs) and drop-in centers (DICs). CSs, public locations where MSM go to meet sex partners, were extensively mapped by community-based organizations (CBOs) serving MSM in each city. DICs are sites located within CBO field offices where MSM come to socialize and participate in educational events. In Chennai, Social Welfare Association for Men (SWAM) provides outreach services in 25 CSs in 4 city zones and Sahodaran provides outreach services in 29 CSs in 3 additional city zones. In Mumbai, one CBO, the Humsafar Trust (HST), provides outreach in 21 CSs in 3 zones. Peer outreach workers collected information on the estimated number of MSM that visit each CS over the course of 1 month. We calculated the sample size to be recruited from CSs in each zone to be proportional to the estimated number of MSM visiting each zone in 1 month. To efficiently meet sampling targets in potentially risky environments for project staff and MSM, the 2 or 3 busiest CSs per zone were selected for recruitment. DIC sampling events took place at 2 DICs in Chennai and 2 DICs in Mumbai. For each DIC, we recorded the number of MSM who attend on “regular” and “special event” days in order to estimate the number of MSM who attend the DIC in 1 month. We recruited MSM during activities/days during which a large number of HIV-negative and untested MSM were expected in order to target these populations, based on eligibility criteria for prophylactic HIV vaccine trials. Potential participants were screened for eligibility at each sampling event (at CSs and DICs): 18 years old or above, self-identified as kothi, panthi, double-decker, or gay, and not working at the organization. The study protocol was approved by the research ethics boards of the University of Toronto and the Humsafar Trust (Mumbai). 2.2. Data collection and measures Peer recruiters visited the venues at specified times and approached every nth person visiting the site based on the site’s client population and target recruitment number. Peer recruiters explained the study, screened for eligibility and scheduled interviews for those who were eligible and volunteered to participate. The latter were given an appointment card that they were required to show at their scheduled interview time. Cards were distributed to 480 eligible individuals, out of which 400 (83.3%) participated in interviews. Structured questionnaires were administered by trained interviewers in Tamil (Chennai) or Hindi (Mumbai) in a private room at CBO offices. Study participants were compensated 250 Indian rupees (INR) (∼$5 USD) for their time for the 45-min interview. We assessed WTP in a hypothetical HIV vaccine clinical trial using a 4-point scale: 1 = Yes, definitely willing; 2 = I am possibly willing, but I need time to think about it; 3 = I am not willing now, but I need time to think about it; and 4 = No, I am not at all willing. This was dichotomized into “Yes, definitely willing (i.e., 1)” versus “unsure or no (i.e., 2–4)” responses. Participants rated the importance of 10 trial characteristics, including distance to the trial site, financial incentive for participation, and provision of life insurance, on their WTP in an HIV vaccine trial (see Table 2). Each trial characteristic was rated on a 4-point Likert-type scale: 0 = not at all important; 1 = somewhat important; 2 = important; 3 = very important. We linearly transformed these ratings to scores on a 0–100 point scale by dividing each response by 3 and multiplying by 100. Thus, the higher the score on the 100-point scale, the higher the importance attached to that trial characteristic. Trial characteristics (i.e., distance to trial site, type of venue, financial incentive) were based on our initial qualitative research [17,33] conducted in collaboration with local CBOs, as well as systematic reviews of the literature on WTP [9–11].
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Table 1 Sociodemographic characteristics and bivariate associations with willingness to participate in HIV vaccine trials among MSM in India (n = 400). Variable Age < = 25 years >25 years Primary identity Kothi Panthi/DD/other Gay/bisexual Education Illiterate/primary/elem. school Some HS/HS diploma College degree Occupation Wage/unemployed/student Gov’t./private/volunteer org./self Sex work Income (missing = 93) < = 5000 rupees > 5000 rupees Marital status Never married Married/sep./divorced/widowed Children 0 1+ Living status Parents/wife/in-laws/partner Alone/friends
Sample n
%
Weighted prop.
95% CI
Prop. WTP
95% CI
207 193
51.75 48.25
49.73 50.27
41.23 41.75
171 164 65
42.75 41.00 16.25
46.88 40.08 13.04
99 217 84
24.75 54.25 21.00
147 219 34
p
58.25 58.77
53.10 46.90
42.42 36.51
63.49 57.58
35.92 31.37 8.15
58.16 49.47 20.20
48.68 36.70 14.63
35.31 25.86 9.42
62.23 49.07 22.02
29.30 50.16 20.54
20.50 42.63 15.57
39.98 57.69 26.59
28.80 47.64 23.56
17.11 35.92 17.87
44.23 59.63 30.39
36.75 54.75 8.50
38.60 50.43 10.98
30.82 41.96 5.52
47.01 58.87 20.64
38.49 49.15 12.36
27.21 37.94 5.31
51.16 60.45 26.17
94 213
30.62 69.38
39.97 60.03
28.90 47.83
52.17 71.10
34.01 65.99
22.89 52.79
47.21 77.11
329 71
82.25 17.75
83.97 16.03
78.89 11.98
88.02 21.11
90.23 9.77
83.11 5.45
94.55 16.89
352 48
88.00 12.00
87.81 12.19
83.38 8.81
91.19 16.62
93.11 6.89
86.47 3.39
96.61 13.53
314 86
78.50 21.50
79.00 21.00
70.07 14.19
85.81 29.93
77.81 22.19
65.61 13.43
86.57 34.39
0.308
0.455
0.503
0.818
0.040
0.007
0.023
0.666
Abbreviation: MSM, men who have sex with men; Prop., proportion; CI, confidence interval; WTP, willingness to participate; DD, double-decker; Elem., elementary; HS, high school; Gov’t, government; Org., organization; Sep., separated.
We collected sociodemographic information on age (dichotomized into less than or equal to 25 years and greater than 25 years), primary sexual self-identification (kothi, panthi/double-decker, and gay/bisexual), education (illiterate, primary/elementary school, high school/diploma/some college, and college degree), occupation (daily wage laborer/ unemployed/student, government/private sector/volunteer organization/self-employed, or sex work), income (dichotomized as less than or equal to and above 5000 INR per month), marital status (never married and married/separated/divorced/widowed), and living arrangements (with parents/wife/in-laws/partner or living alone/with friends/other).
For all analyses we used sampling weights (the inverse probability that a participant was selected for recruitment) to adjust for systematic differences in the probability of participant selection. MSM in Chennai were older, more likely to identify as kothi, less educated, more likely to be sex workers and had lower income compared to MSM in Mumbai. Differential representation in the sample was accounted for by the weighting procedures, and WTP by city was not significant (p = 0.413). We calculated standard errors using Taylor-series linearization to adjust for the time-location sampling design-effect on estimate precision using complex survey-specific procedures in Stata version 11.2 (Stata Corp., College Station, Texas).
2.3. Statistical analysis
3. Results
We characterized the sample by sociodemographic characteristics and WTP. We tested for differences in WTP by sociodemographic characteristics with Pearson chi-square tests using the Rao and Scott design-based correction [34]. We then estimated participant ratings of HIV vaccine trial characteristics and assessed the impact of each characteristic by WTP (versus not WTP or unsure) with design-adjusted t-tests using surveyspecific linear combinations of rating means. Lastly, we compared trial characteristic ratings by sociodemographics with designeffect adjusted Wald tests in survey-specific linear regression. For trial characteristic ratings that differed by sociodemographic group, we examined post-estimation linear combinations to determine which group comparison(s) were responsible for the overall rating difference. Income data were missing on 93 cases of which 49 were unemployed, 28 were students, and 15 reported employment. The 77 unemployed and students were classified as having income less than 5000 INR per month and the remaining 15 were considered valid missing. The missing cases were not included in the bivariate analysis of trial characteristic ratings by income.
From May to September 2012, we recruited 400 MSM from 24 CSs and 4 DICs in Chennai and Mumbai. Table 1 reports the sample distribution by sociodemographic characteristics, the respective weighted population proportions adjusted for sampling designeffect, and weighted population proportions of those indicating WTP. The population median age was 25 years. Almost half (46.9%) identified as kothi, 40.0% as panthi or double-decker, and 13.0% as gay/bisexual. Nearly one-third (29.0%) had primary school education or less and 40.0% had a monthly income of 5000 INR ( 5000 INR
Par/wife/family
Alone/friends
56.35 48.12 0.01 0.366
64.59
56.76 45.92
67.60
59.60 48.75 5.41 0.028
70.46
45.20 37.31
53.10
69.21
52.28 42.30
62.25
67.94
49.33 39.50
59.16
88.25
70.16 60.47
79.85
83.34
68.15 52.55
83.75
72.90
67.17 59.84
74.51
75.65
54.29 44.55
64.03
73.40
57.61 49.69
65.53
66.81
67.32 57.12
77.52
97.12
88.32 82.55
94.09
94.83
92.71 87.22
98.20
96.68
88.89 85.10
92.68
94.49
91.00 86.03
95.96
95.27
90.32 85.67
94.96
94.99
89.19 84.08
94.31
85.46
80.89 73.65
88.14
89.02
69.53 58.84
80.23
74.13
64.31 56.01
72.61
75.47
53.48 43.39
63.58
59.20 49.20 2.09 0.160 77.91 67.56 2.54 0.123 65.29 57.67 0.17 0.686
64.89 56.38 2.20 0.150 91.01 84.90 1.31 0.263 92.53 88.37 4.84 0.037 91.46 87.64 0.24 0.629
78.62 71.79 0.32 0.574 64.54 54.96 0.00 0.952
57.49 47.04 1.80 0.191 74.26 65.17 0.95 0.338 68.77 61.89 6.67 0.016
59.50 52.18 1.63 0.212 89.08 83.34 1.69 0.205 90.74 86.99 0.01 0.915 91.46 87.93 0.95 0.337
82.54 76.06 5.06 0.033 66.92 58.37 6.69 0.015
Abbreviation: MSM, men who have sex with men; DD, double-decker; Illit, illiterate; I Prim, primary; I Elem, elementary; I HS, high school; I Dipl, diploma; I Par, parents; CI, confidence interval; p, p value.
P.A. Newman et al. / Vaccine 32 (2014) 5854–5861
Rating 95% CI Wald p
Income
Panthi/DD
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The vaccine trial characteristic with the greatest impact on WTP was distance to the trial site. This finding is corroborated by a systematic review of barriers to enrolment in HIV vaccine trials, which identified personal costs, including transportation, as a pervasive barrier to WTP [10]. The trial characteristic with the second greatest impact on WTP was anticipated side effects from test vaccines. Systematic reviews of WTP research [9–11] as well as studies within India [15,16] similarly identify side effects as a barrier to WTP. Concerns about side effects may have become more protracted after the unexpected increased susceptibility to HIV infection among a subsample of vaccinees in the Step Study Phase IIb HIV vaccine trial [35,36], terminated in September 2007 after most of these WTP studies were conducted. In the present study, financial incentive, life insurance and free medical treatment for trial-related harms each had significant impacts on WTP. Life insurance was similarly identified as an important determinant of WTP in an earlier study of key populations at risk in India [15]. Access to the vaccine for free if found to be efficacious in the trial was uniformly the highest rated characteristic (91/100-point scale) across participants, such that it did not differentiate by WTP. Notably, these concerns may reflect larger structural factors (e.g., poverty, lack of access to healthcare) rather than logistical challenges or vaccine-specific concerns. The constellation of financial and healthcare concerns reflect the importance to potential trial volunteers of the trial and posttrial services guaranteed to participants in a resource-limited setting. Nevertheless, an earlier systematic review of 65 pharmaceutical industry-sponsored HIV antiretroviral trials conducted from 1987 to 2006 indicate that nearly half of trial protocols did not mention posttrial services of any type [27]. Although we are not aware of a similar review of protocols for HIV vaccine trials, which are distinct in several ways from trials of medications to treat persons living with HIV, the present results underscore the importance of trial sponsors and site staff providing clear explanations about the availability or not of particular trial-related services, including medical care, life insurance, and access to products tested in the trial if they prove efficacious. If trial benefits and healthcare services are not clearly disclosed, participants cannot evaluate risk-benefit ratios, necessary for valid informed consent [23,27]. To the extent participants and local communities may not have access to an HIV vaccine if proven efficacious in the trial, questions of exploitation arise that may compromise trial ethics [22,23]. Several sociodemographic characteristics were significantly associated with the impact of HIV vaccine trial characteristics on WTP. We identified a pattern of greater importance to kothiidentified (generally lower socioeconomic status) MSM of logistical concerns (particularly distance to the trial site and whether it is in a government hospital or community venue), and financial and healthcare concerns, including trial and posttrial services (life insurance, free medical treatment). Based on our previous qualitative findings, kothis indicate a preference for trial venues at CBOs rather than hospital settings due to concerns about stigma and discrimination in the government healthcare system [33]. Sociodemographic differences in WTP among MSM suggest the importance of formative research in local communities in which HIV vaccine trials are planned; what may appear to be uniform groups (e.g., “MSM”) from an outsider’s perspective or based on behavioural definitions of MSM may reveal differences that are significant to supporting recruitment and ensuring fair and ethical conduct of HIV vaccine trials. The present results suggest that kothi-identified MSM, who tend to be at high risk for HIV infection [37,38], may be those most affected by logistical factors, and the trial and posttrial services provided by HIV vaccine trials. The lower WTP among MSM who are married (not uncommon in India due to strong cultural value placed on maintaining family
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lineage [33]), and those who have children, and the greater importance accorded to distance to the site, trial duration, side effects, and route of vaccine administration among those living with family or partner versus alone or with friends, suggests the value of addressing concerns about WTP among MSM in India from a family perspective [33]. Provision of life insurance [15] and discussion of trial-related concerns vis-a-vis ones family, may support recruitment in HIV clinical trials. After a period that has been characterized as one of deregulation of global drug trials post-2005, with less than optimal oversight [39], India’s Central Drug Standard Control Organisation (CDSCO) issued new draft guidelines for clinical trials in January 2013 following a Supreme Court decision [40]. These CDSCO guidelines specifically address compensation for trial-related injuries and life insurance “in the cases of clinical trial related serious adverse events or deaths occurring/during clinical trials” [39,40]. Based on the present study, these are issues of considerable concern to MSM communities and are significantly associated with their WTP in HIV vaccine trials. Confusion and debate have ensued over the terms of the CDSCO regulations, however, as they stipulate a requirement for compensation in the case of injuries or deaths sustained during but not related to the experimental drug being tested, as well as compensation in the case of “failure of investigational product to provide intended therapeutic effect” and “use of placebo in a placebocontrolled trial” [40]. Currently under governmental review, these regulations have been criticized within India as hasty and not engaging relevant stakeholders [40]; we would add the importance of including community stakeholders along with stakeholders from research and governmental institutions. Importantly, CDSCO’s current regulations have also resulted in U.S. and Canadian sponsors discontinuing dozens of drug trials in progress, as well as an effective cessation of new trials. It remains unclear to what extent CDSCO guidelines will be retained in their present form as well as the extent to which they will be considered applicable in the case of prevention trials, such as prophylactic HIV vaccine trials among communities at high risk of exposure. A strict reading would suggest the trial bears direct responsibility for monetary compensation and medical care for every new HIV seroconversion – including participants in the control arm as well as the experimental arm if the test vaccine is not efficacious – in addition to any other injury or death during the trial period, terms that seem likely to render global HIV vaccine trials in India untenable. As argued by clinicians and researchers in India, such an outcome serves neither investigators nor persons at risk given its stagnating effect on medical research [40]. A “middle path” has been suggested that ensures ethically and scientifically rigorous trials, including assurances from sponsors that trials conducted address health needs in India and that efficacious products would be available and affordable in India if licensed and approved [40]. Our findings suggest that ensured access to an efficacious HIV vaccine post-trial would address a key concern among MSM; combined with reasonable compensation in the event of trial-related injuries and access to HIV-related medical care, revised guidelines may help to restore the feasibility of clinical trials and address the vital need for new HIV prevention technologies in India. 4.1. Limitations The present findings should be interpreted in the context of study limitations. Although we included trial characteristics based on formative qualitative research conducted in situ, other trial characteristics also may influence WTP. Furthermore the results cannot be generalized to MSM across India and the sample size was determined by feasibility and available resources. Nevertheless, while simple random sampling of this vulnerable and underserved
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population is not feasible, we used venue-based time-space sampling to recruit MSM of diverse identities and socioeconomic statuses; thus, the results are generalizable to the considerable population of predominantly young MSM who attend CBOs and CSs, a particularly important population for HIV prevention trials [41]. Future investigations should assess WTP among transgender women, who are at disproportionately high risk for HIV in India [1], as well as among higher socioeconomic status, often gay-identified MSM, who tend to be underrepresented in Indian HIV surveillance and research; the latter may be more likely to be accessed via the Internet than in CBOs and CSs. We did not conduct HIV testing, which would present additional risks to participants due to HIV stigma and confidentiality concerns among MSM [33]; rather, we targeted populations at risk by using venue-based time-space sampling (i.e., at CSs and at DICs offering prevention education, rather than HIV clinics). However, it is possible that some respondents may have been HIV-positive and ineligible to enroll in prophylactic HIV vaccine trials. Finally, stated WTP in hypothetical HIV vaccine trials may overestimate actual participation; however, the present results indicate the value of formative research with community stakeholders to develop evidence to support recruitment for fair and ethically conducted HIV vaccine trials. 5. Conclusion
[4]
[5]
[6]
[7]
[8]
[9] [10] [11]
[12]
We identified HIV vaccine trial characteristics associated with WTP among predominantly young, socioeconomically diverse MSM in India, a substantial population at high risk of HIV exposure among whom HIV vaccine trials have not been conducted. The present findings suggest the following measures may promote WTP among MSM in India in fair and ethically conducted HIV vaccine trials: (1) addressing community stakeholder concerns (i.e., side effects) through educational initiatives, perhaps informed by mental models of vaccines and clinical trials [17]; (2) supporting logistical (i.e., trial location) and financial arrangements (i.e., incentives, life insurance) deemed fair and ethical; (3) ensuring access to HIV-related medical care during and after trials; and, (4) prioritizing availability and access to the product tested if deemed efficacious.
[13]
Acknowledgements
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We offer sincere thanks to our community collaborators, The Humsafar Trust, Mumbai; Social Welfare Association for Men (SWAM), Chennai; and Sahodaran, Chennai. Special thanks to Vivek R. Anand, Sekar Balasubramaniam, Sunil Menon and Jaya for their invaluable assistance. We thank all participants and key informants for sharing their perspectives. We also wish to thank Suchon Tepjan, Joanne Daciuk and Lily Wong for administrative support. This research was supported in part by grants from the Canadian Institutes of Health Research (MOP-102512; THA-118570), the Canada Research Chairs Program and the Canada Foundation for Innovation (228382).
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