Effect of race/ethnicity on participation in HIV vaccine trials and comparison to other trials of biomedical prevention

Abstract

Introduction

Racial/ethnic minorities are underrepresented in actual HIV vaccine trials in North America, and willingness to participate (WTP) and retention in an HIV vaccine trial may differ from that in Whites.

Methods

In this review, the authors identified HIV vaccine preparedness studies (VPS) in North America in high-risk populations that examined the relationship between race/ethnicity and WTP in a preventive phase 3 HIV vaccine trial, and the relationship to retention. Studies were categorized by risk group, and comparison group (Whites vs. non-Whites). Other types of trials of biomedical prevention were also identified, and WTP and retention rates were compared and contrasted to actual HIV vaccine trials.

Results

In the studies identified, WTP in a hypothetical trial HIV vaccine trial did not differ by race/ethnicity. In contrast, actual HIV vaccine trials, an HIV acquisition trial, and a phase 2B preexposure prophylaxis (PrEP) trial have enrolled a large percentage of White men. Human papilloma virus (HPV) privately-funded trials have also enrolled a large number of Whites, due to convenience sampling. Retention in the HIV acquisition trial was lower in African-Americans compared with Whites.

Conclusion

Strategies to increase WTP and enhanced retention (ER) strategies may help in recruiting and retaining minority participants in actual HIV vaccine trials and other trials of biomedical prevention.

Keywords: :

• HIV
• vaccines
• biomedical prevention
• race
• ethnicity
• willingness to participate
• retention

Introduction

Human immune deficiency virus (HIV) disproportionately affects communities of color, such as African-Americans or Blacks, and Hispanics/Latinos (Hispanics).1 In 2009, Blacks and Hispanics comprised about 12% and 16% of the US population respectively, but comprised about 44% and 20% of estimated new HIV infections.1 However, overall decreases in racial or ethnic (racial/ethnic) disparities in AIDS diagnoses occurred for these populations compared with Whites, between 2000–2009 in those aged 25–64 y. Factors fueling racial/ethnic disparities such as socioeconomic factors, demographic factors, and political factors are described in a 2008 article.2

Racial/ethnic minorities are underrepresented in actual HIV vaccine trials in the US. African-Americans accounted for a low percentage of participants in actual HIV vaccine trials.3-5 For example, the AIDSVAX B/B study, which included relatively small numbers of minority participants, suggested that vaccine efficacy rates were higher among Black and Asian participants; however, this subgroup analysis was inconclusive.6,7 The racial/ethnic disparities in the epidemiology of HIV are also a justification for increased enrollment of minorities in HIV vaccine trials, as the US Food and Drug Administration (FDA) desires adequate representation of race/ethnicity in evaluation of new products (Dr Jared Baeten, personal communication). However, in one meta-analysis of hypothetical HIV vaccine acceptiblity in the US, being Black/African-American (in reference to White) was negatively associated with HIV vaccine acceptibility.8

Facilitators/Barriers to HIV Clinical Trial Recruitment

Motivators and barriers in minorities have been examined in the US.9-13 In one study by Tello et al. in mostly African-American (79%) sexually transmitted disease (STD) clinic patients in the southern US, reimbursement for participation in HIV vaccine trials was a motivator, while HIV-seropositivity was a barrier.14 In another study in Black Americans, motivators included altruism and self-benefit. Barriers included negative side effects / safety issues such as vaccine-induced HIV infection, and social consequences.15

In one Los Angeles study, mistrust and social costs of vaccine uptake were identified as barriers.13 In another study in Spanish-speaking Latinos, motivators included: monetary incentives; convenience of study participation; sufficient study information; personal benefits; and altruism.16 Barriers included mistrust; fear of vaccine-induced HIV infection; physical side effects; stigma; and HIV-induced seropositivity.

In one US study, Blacks who had not participated in an HIV vaccine trial were compared with Blacks who had participated in ≥1 HIV vaccine trials.17 Reasons for non-participation were misinformation, such as the notion of HIV being a white, gay disease; fear/mistrust; and stigma. In another study, African-Americans were the group most likely to have conspiracy beliefs that an HIV vaccine already exists (47.1%) compared with Hispanics (26.5%), the general population (18.2%), and White MSM (13.4%).18

HIV acquisition trials

HPTN 039 examined aciclovir in herpes simplex virus-2 (HSV-2) seropositive individuals to prevent HIV acquisition.19 HPTN 039 (2005–2007) enrolled MSM in the US and Latin America, and women in sub-Saharan Africa.19 The racial/ethnic groups in the US MSM participants (overall) were: White (75.8%), Hispanic (15.9%), Black (10.2%), and Mixed/Other/Missing (13.3%). Overall retention was 85.1% at 18 mo: White (85.1%), African-American (78.8%), Hispanic (83.6%), and Mixed/Other (88.4%) at 18 mo (Dr. Jared Baeten, personal communication).

Preexposure prophylaxis (PrEP) trials

A pilot study (Project PrEPare, ATN 082) in young MSM (mean age = 19.97 y) compared a behavioral intervention (Many Men, Many Voices-3MV) alone, 3 MV combined with PrEP (tenofivir [TDF], emtricitabine [FTC]), and 3MV combined with placebo.20 The study target was 100 young men, and enrolled 68 MSM. Those enrolled were: African-American (53.5%); Other/Mixed (37.9%); White (6.9%); Native American/Alaskan Native (1.7%). In 2010 at week 24, after the positive results of the Preexposure Prophylaxis Initiative (iPrEx) study results,21 the study was unblinded. At 24 wk, retention was 98.5% overall: Whites (100%); Other/Mixed Race (99.1%); African-American (98.5%); Native American/Alaskan Native (85.7%) (personal communication, Dr Sybil Hosek). The HIV seroincidence rate in this general population is approximately 3%, although this is not study specific (personal communication, Dr Sybil Hosek).

A phase 2B proof-of-concept PrEP trial conducted between 2005–2007 in the US evaluated the clinical safety of TDF compared with placebo in MSM.22 The study enrolled 400 participants 18–60 y of age: Whites (73.3%); African-American (15%); “Other” (8.3%); and Asian / Pacific Islander (3.5%).22

Human papilloma virus (HPV) vaccine trials

These multinational phase 3 trials have included sites in North America, Europe, and Latin America. The PATRICIA (PApilloma TRIal against Cancer In young Adults) study examined the efficacy of the Cervarix vs. a Hepatitis A vaccine as a control, in over 18000 females ages 15–25 y.23 Overall, 55% of women were White.24,25

The FUTURE (Females United to Unilaterally Reduce Endo/Ectocervical Disease) I study examined Gardasil in the prevention of anogenital disease associated with HPV-6/11/16/18 in females ages 16–24 y.26 FUTURE II examined Gardasil in the prevention of high-grade cervical lesions.27 Another phase 3 trial examined Gardisil in males (3463 heterosexuals and 602 MSM) 16–26 y of age.28,29 The race distribution in females was: White (70.4%); Hispanic (12.2%); Other (8.8%); Black (4.6%); Asian 3.8%); American Indian (0.2%).30 The race distribution in males was: White (35.2%); Hispanic (20.5%); Other (14.4%); Black (19.8%); Asian (10.0%); American Indian (0.1%).30 In the MSM substudy, the race distribution was: White (60%); Hispanic (25%); Black (7%); Asian (6%); Other (3%).29

Therefore, the objective of this review is to compare and contrast hypothetical and actual WTP and retention rates in racial/ethnic minorities with respect to preventive phase 3 HIV vaccine trials in countries in North America (US and Canada). We discuss how these findings mirror or differ from literature about racial/ethnic participation and retention in other recent trials of biomedical prevention that also involve diseases with stigma and racial disparity. This would provide insights into minority participation in these trials.

Results

The authors screened 190 abstracts for eligibility through database searching and bibliographic references, and retrieved 15 HIV VPS examining WTP (Table 1), and 9 studies examining retention in North America (Table 2).

Table 1. Race/ethnicity and willingness to participate in a hypothetical HIV vaccine trial organized by risk group and comparison group (White vs. non-White)

	Risk group	Name of trial Year of trial/data collection	Race or ethnicity (Race/ethnicity)	Location	Sample size	Type of questionnaire	WTP (%)	AOR (95% CI)
Gross et al., 199643	MSM (young and older) Younger men (n = 447) Older men (n = 183)	Boston Young Men’s Study 1993–1994	White, Asian/Pacific Islander, A-A, Latino, Other	Boston, MA	Younger men: White 78.1%, Asian 8.3% Black 3.8% Latino 6.3% Other 3.6% Older men White 94.5%, Black 4.4% Latino 0.6% Other 0.6%	Self-administered	Very: 17% Somewhat: 50% Not at all: 33% (all races)	willingness did not vary by race/ethnicity***
Bartholow et al., 199733	MSM (n = 1329)	1993–1994	White, A-A, Latino, Other	Chicago, IL Denver, CO San Francisco, CA	White 81% A-A 5% Latino 10%, Asian, Native American, Other 4%	Interviewer-administered	White Definitely: 38% Probably: 38% Might be: 19% A-A Definitely: 33% Probably: 28% Might be: 27% Latino Definitely: 36% Probably: 37% Might be: 20% Other Definitely: 36% Probably: 36% Might be: 22%	willingness to participate did not differ by ethnicity***
Koblin et al., 199742	MSM (n = 698)	Project ACHIEVE 1993–1996	White, Black, Latino, Asian, Other	New York City, NY	White 67.9% Latino 18.6% Black 7.4% Asian 3.2% Other 2.9%	Interviewer-administered	Definitely: 30.3% Probably: 38.0% Might be: 23.3% Definitely not: 8.5% (all races)	willingness not associated with race/ ethnicity***
Hays and Kegeles, 199941	young MSM (ages 18–29 y) (n = 390)	Young Men’s Survey 1994	White, Asian/Pacific Islander, Latino, Native American, A-A	Eugene, OR Santa Cruz, CA Santa Barbara, CA	White 83% Asian / Pacific Islander 7% Latino 6% Native American 2% A-A 1%	Mail-back questionnaires	Extremely likely: 22% Very likely: 20% Somewhat likely: 22% Not too likely: 20% Not at all likely: 17% (all races)	willingness not associated with race/ ethnicity***
O’Connell et al., 200266	MSM (n = 474)	Vanguard 2001	White, Aboriginal, Other	Vancouver, Canada	small sample size	Self-administered	60% Aboriginal respondents	No association between WTP and ethnicity***
Strathdee et al., 200038	IDU (n = 435) 67% male 33% female MSM (n = 330)	VIDUS Vanguard 1997	White, Native*, Asian/South Asian, Other	Vancouver, Canada	IDU: White 65%, Native* 27% Other 8% MSM: White 78% Native* 5% Asian/South Asian 10% Other 8%	IDU: Interviewer-administered MSM: Self-administered	IDU: 83% (all races) MSM: Definitely: 34% Probably: 29% Unsure: 25% Probably not: 10% Would not: 2% (all races)	Willingness to participate did not differ by race/ethnicity in IDU and MSM***
Meyers et al., 199440	Methadone maintenance patients (n = 240) 70% male 30% female	Dates of data collection not given	A-A, Caucasian, Latino	North-Central Philadelphia, PA	A-A 44% Caucasian 39% Latino 17%	Self-administered	52% (all races)	minority status not significantly associated with reported WTP compared to Caucasians (AOR=1.0; 95% CI, 0.56-1.9)ucasians
Meyers et al., 199539	Female IDU In-treatment (IT) Out-of-treatment (OT) (n = 121)	Project Jumpstart 1991–1993	White, A-A, Latina, Other	North Philadelphia, PA	White 44% A-A 43% Latina 11% Other 2%	Self-administered	60% (all races)	minority status not predictive of WTP compared to Whites (AOR=1.4; (95% CI, 0.5-4.0) with Whites
Golub et al., 200536	IDU Wave 1 (n = 440) 82.7% male 17.3% female Wave 2 (n = 582) 74.7% male 25.3% female	Wave 1 ALIVE participants 1993–1994 Wave 2 2001–2002	Black, White	Baltimore, MD	Wave 1: Black 94.1% White 5.9% Wave 2: Black 95.3% White 4.7%	Interviewer-administered	Wave 1: 83% (all races) Wave 2: 86% (all races)	No differences in WTP by race***
Vlahov et al., 199467	IDU (n = 375) 83% male 17% female	Vaccine Preparedness Initiative, ALIVE 1992–1993	Black	Baltimore, MD	Black 94%	Interviewer-administered	84.5% baseline (all races)	WTP by race/ethnicity not presented
Koblin et al., 199834	66.6% MSM (n = 3257) 15.7% male IDU (n = 770) 10.4% WAHR (n = 511) 7.2% WAHR-IDU (n = 354)	HIVNET VPS 1995	White, Black, Hispanic, Other	8 US cities†	MSM: White 75% Black 7% Hispanic 13% Male IDU White 37% Black 42% Hispanic 19% WAHR-IDU White 44% Black 35% Hispanic 18% Other 2% WAHR White 18% Black 69% Hispanic 8% Other 3%	Black: (AOR =0.8; 95% CI, 0.7-1.0) Hispanic: (AOR=1.0; (95% CI, 0.8-1.3) Other: (AOR= 1.2; 95% CI, 0.8-1.7) compared to Whites	White: 76.1% Black: 76.5% Hispanic: 79.4% Other: 80.5%	Black: (AOR =0.8; 95% CI, 0.7-1.0) Hispanic: (AOR=1.0; (95% CI, 0.8-1.3) Other: (AOR= 1.2; 95% CI, 0.8-1.7) compared to Whites
Metch et al., 201337	WAHR (n = 799)	HVTN 906 2009–2010	Black Hispanic Other	Chicago, IL New York, NY Philadelphia, PA	All sites: Black 79.1% Hispanic 15.3% Other 5.6%	Interviewer- administered	All sites: Definitely: 50.7% Probably: 35.0% Probably not: 8.8% Definitely not: 5.5% (all races)	WTP not associated with race/ethnicity in Blacks compared with Hispanic/Other
Frew et al., 200735	Heterosexual GLBTQQ (n = 175) Male 30.3% Female 69.1%	HOPE clinic of Emory Vaccine Center 2007	African-Americans	Atlanta, US	175 African-Americans	Self-administered	Very likely: 25.4%** Somewhat likely: 27.2%** Not likely: 31.8%** Unsure 15.4%**	Sample consisted of only African-Americans
Tello et al., 199814	STD clinic attendees (95% heterosexual) (n = 167) 54% male 46% female	Dates of data collection not given	A-A, Caucasian, Other	Birmingham, Alabama	A-A 79% Caucasian/Other 21%	Interviewer-administered	A-A: 67% White: 66%	willingness did not vary by race/ ethnicity***
Strauss et al., 200115	Durham: Black Americans (n = 20) 60% male 40% female	Project LinCS Dates of data collection not given	White, Black, Hispanic, Other	Durham	95% Black, 5% Other	Face-to-face interviews	Durham: 40% (all races)	WTP by race /ethnicity not presented

AOR, adjusted odds ratio; WTP, willingness to participate (definitely/probably vs definitely not/probably not; very likely/somewhat likely vs. not likely); A-A, African-American; MSM, men who have sex with men; IDU, injection drug users; WAHR, women at heterosexual risk; FSW, female sex worker; CSW, commercial sex worker; NCSW, non-commercial sex worker; GLBTQQ, Gay/Lesbian, Bisexual, Transsexual/Queer/Questioning; Project LinCS, Linking Communities and Scientists; VIDUS, Vancouver Injection Drug Users’ Study; HIVNET, HIV Network for Prevention Trials (HIVNET); *Native, Aboriginal, First Nations, Inuit, or Metis; **to contact study site about trial participation (study volunteerism); ***Reference category not provided. ^†8 US cities: San Francisco, CA; Seattle, WA; Philadelphia, PA; Chicago, IL; Boston, MA; New York, NY; Denver, CO.

Table 2. Race/ethnicity and retention in an HIV vaccine preparedness study (VPS) in North America organized by risk group and White or non-White comparison group

	Risk group	Name of trial Year(s) of trial/data collection	Location	Race/ethnicity sample size	F/U visits	AOR or Crude OR (95% CI)
Buchbinder et al., 199647	Homosexual men	1993–1995 Project Jumpstart	Chicago, IL Denver, CO San Francisco, CA	Chicago White 84% Hispanic 6% A-A 8% Other** 2% Denver White 81% Hispanic 12% A-A 3% Other** 4% San Francisco White 70% Hispanic 15% A-A 7% Other** 8%	6-, 12-, 18 mo	6 mo: 90% 12 mo: 84% 18 mo: 78% Non-White race/ethnicity predicted loss to follow-up between baseline and 6 mo follow-up compared with Whites (OR = 1.6; 95% CI, 1.2–2.2)
Koblin et al., 199648	MSM	1993–1995 Project ACHIEVE	New York City, NY	White 73.2% Latino 16.2% Black 4.8% Asian 3.4% Other** 2.4%	3-, 6-, 9-,12 mo	3 mo: 87.6% 6 mo: 83.0% 9 mo: 81.0% 12 mo: 80.9% Non-White men significantly less likely to complete follow-up visits than Whites
Bartholow et al., 199733	MSM	1993–1994	San Francisco, CA Denver, CO Chicago, IL	White 81% A-A 5% Latino 10% Asian, Native, or Other** 4%	6-, 12-, 18 mo	18 mo: 70% Minorities more likely to be lost to follow-up than Whites (OR = 1.2; 95% CI, 1.1–1.3) “Other” more likely to be lost to follow-up than A-A men and Latino men (OR= 1.2; 95% CI=1.1-1.3)
Koblin et al., 200044	MSM 66.6% Male IDU 15.7% WAHR 10.4% WAHR-IDU 7.2%	HIVNET VPS 1995–1996	8 US cities*	MSM: White 75% Black 7%, Latino/Latina 13% Asian / Pacific Islander 3% Male IDU: White 37% Black 42% Latino/Latina 19% WAHR: White 18% Black 69% Latino/Latina 8% Other** 3% WAHR + IDU White 44% Black 35% Latino/Latina 18% Other** 2%	6-, 12-, 18 mo	18 mo: 85% Persons from a minority group significantly less likely to complete 18-mo visit compared with Whites
Seage et al., 200132	MSM 66.6% Male IDU 15.7% WAHR 10.4% WAHR-IDU 7.2%	HIVNET VPS 1995–1997	8 US cities*	White 61% Black 21% Hispanic 14% Other (Asians, Native Americans, and “Other**”) 4.5%	6-, 12-, 18 mo	18 mo: White: 89.7% Black 86.5% Hispanic 85.1% Other 82.8% “Other” significantly less likely to complete 18 month visit compared to Whites: (AOR=1.66; 95% CI, 1.14-2.44)
Halpern et al., 200149	Predominantly IDU Gay men	HIVNET VPS 1995–1996	Philadelphia, PA	White 45% Black 48% Hispanic 3% Other** 4%	6-, 12-, 18 mo	6 mo: 89.3% 12 mo: 88.5% 18 mo: 84.1% Those who died or lost to follow-up did not differ from those completing all 4 visits by race
Brown-Peterside et al., 200046	WAHR	Project ACHIEVE 1995–1996	New York City, NY	A-A 65% Latina 29% White 0% Other** 6%	Visits every 3 mo over a period of 18 mo	12 mo: 67% 18 mo: 62% race/ethnicity not associated with loss to follow-up
Brown-Peterside et al., 200145	WAHR	Project ACHIEVE 1998–1999	New York City, NY	A-A 85% Latina 15%	3-, 6-, 9-, 12 mo	3 mo: 98% 9 mo: 96% 12 mo: 92% no differences in race/ethnicity with regards to loss to follow-up
Koblin et al., 201350 HVTN 906	WAHR	HVTN 906 2009–2011	Chicago, IL New York City, NY Philadelphia, PA	A-A 79.1% Hispanic 15.3% Other** 5.6%	6-, 12-, 18 mo	6 mo: 85.9% 12 mo: 83.0% 18 mo: 79.5% A-A women less likely to miss their 18-month visit than Hispanic / Other (AOR=0.5; 95% CI, 0.3 to 0.7)

MSM, men who have sex with men; IDU, injection drug users, WAHR, women at heterosexual risk; FSW, female sex worker; A-A, African-American; *8 US cities: San Francisco, CA; Seattle, WA; Philadelphia, PA; Chicago, IL; Boston, MA; New York, NY; Denver, CO; **”Other” not defined in article.

Minorities examined included Blacks/African-Americans, Latinos/Latinas (Hispanics), Asians or Pacific Islanders, and “Others”. African-Americans are defined as Blacks born in the US of American parents.31 Studies at times used the terminology “African-American” and “Black, non-Hispanic” interchangeably. “Others” were classified differently or often not defined. For example, “Others” included Asians, Native Americans, and respondents who identified themselves as “Other” race/ethnicity.32,33

Hypothetical willingness to participate (WTP)

Table 1 shows hypothetical WTP in minority populations in North America organized by risk group and comparison group (White vs. non-White). The pooled WTP was 76% for Whites, 75% for Blacks/African-Americans, and 79% for Hispanics, for studies in which categories were clearly defined and stratified.14,33-35 (Table 1). From Table 1, it also appears from some studies that WTP in hypothetical HIV vaccine trials by non-Whites was higher when questions were interviewer-administered rather than self-administered, the latter including a mail-back questionnaire.

From Table 1, Whites appear to comprise the minority of the sample in most hypothetical studies conducted in the past decade (2005-present), in populations including IDU (4.7–5.9%)36; WAHR37; heterosexuals/Gay/Lesbian, Bisexual, Transsexual/Queer/Questioning (GLBTQQ) (no Whites)35 (Table 1). The sample size of Whites from earlier studies spanning from 1994–2000 was higher: IDU (37–65%)34,38-40; MSM (68–95%)33,34,38,41-43; and WAHR-IDU (44%).34 However, an exception to the results of these earlier studies was one study in WAHR in 1998, which consisted of 18% Whites.34 Thus, there has been a shift in racial distribution in hypothetical studies. However, minorities are underrepresented in actual HIV vaccine trials and related intervention trials.

Articles retrieved stated that race/ethnicity was not predictive of WTP (Table 1). In some studies, the reference category was not provided (Table 1). Furthermore, in studies where comparison groups were specified, the comparison groups differed. Some studies in MSM34 and IDU34,39,40 compared minorities to Whites. However, in the more recent HVTN 906 in WAHR, WTP was not associated with race/ethnicity in Blacks compared with those of Hispanic/Other race/ethnicity.37

Retention in HIV vaccine preparedness studies (HIV VPS)

Table 2 shows retention rates in minority populations organized by risk group and comparison group. Retention was examined up to 18 mo. In many studies, most participants were White, but other studies showed more racial diversity32,44 or did not include Whites45,46 (Table 2).

It was not always evident which minority group was being compared with Whites (Table 2). In the HIVNET VPS by Koblin et al., the authors stated that persons from a minority group collectively were significantly less likely to complete the 18-mo visit compared with Whites.44 In the same VPS, Seage et al. provided AORs showing that “Others” were significantly less likely to complete 18 mo visit compared with Whites: AOR = 1.66 (95% CI, 1.14–2.44), while other racial/ethnic minority groups were not less likely to complete their visits than Whites.32

Comparison groups also differed among studies. In the studies of retention in MSM, Whites were generally used as a comparison group, and non-White race/ethnicity was associated with loss to follow-up in minority MSM compared with Whites.32,33,44,47,48 In addition, the study by Bartholow et al. also found that MSM of “Other” ethnicities were more likely to be lost to follow-up than MSM who were African-American or Latino at 18 mo.33

In the only study in which the population was predominantly IDU, completion at 18 mo was not related to race/ethnicity.49 In studies examining retention in WAHR, 2 studies by Brown-Peterside et al., did not specify a comparison group.45,46 In addition, another study (HVTN 906) showed that African-American WAHR (AOR = 0.5; 95% CI, 0.3–0.7) were less likely to miss their 18-mo visit than Hispanic / Other WAHR50 (Table 2).

Actual HIV vaccine trials

These include the AIDSVAX B/B phase 3 HIV vaccine trial (61 sites in US, 3 sites in Canada, 1 site in the Netherlands);5 the STEP 2B Study (15 sites in the US, 3 sites in Canada, other sites in South America, Australia, and the Caribbean)4,51; and HVTN 505 (all 21 sites in the US).3 The AIDSVAX B/B trial enrolled 5108 MSM (94%) and 309 WAHR (6%).5,52 The STEP study was a study of 3000 volunteers; 62% were men (mainly MSM) and 38% were women.4,53 HVTN 505 enrolled 2500 MSM (98%) and transgender people who have sex with men (2%).3

The pooled percentages of enrolled men in AIDSVAX B/B and HVTN 505 were: 81% White, 8% Black/African-American, 7% Hispanic, 1% Asian, and 3% other.3,5 In the STEP study, the stratification was: White (51.4%), and multiracial identity (29.0%), the latter mostly from South America.4,54 The percentages of enrolled WAHR in the AIDSVAX B/B trial: were: White (29%), African-American (55%), Latino (14%), Asian/Pacific Islander (0%), and Other (2%).5

Overall retention rates have been reported for the AIDSVAX B/B study, the STEP study, and HVTN 505 (data on retention stratified by race/ethnicity was not available from the trial investigators). The overall 3-y retention rate in the AIDVAX B/B study was reported to be over 80%.55 In the STEP Study, overall retention in the study was approximately 90%.⁴ In the recently completed HVTN 505 trial of the DNA/rAd5 HIV vaccine, the yearly rate of loss to follow-up overall was 4.8% (95% confidence interval [CI], 3.8 to 6.1) in the vaccine group and 6.6% (95% CI, 5.4 to 8.0) in the placebo group (P = 0.05).3

Project PrEPare

In this pilot study, the 68 enrollees were largely young, mainly minority MSM.20 The reasons for this successful minority enrollment were multifactorial (Dr Robert M Grant, personal communication). First, the study took place in the context of provision of other healthcare services (e.g., HIV clinics), which may elicit a sense of trust. The primary author also specializes in HIV and youth and has a sophisticated knowledge of the patient population that the clinic serves. The trial also had a large community involvement with a large number of community advisory boards (Dr Robert M Grant, personal communication). The trial was also publicly-funded by the National Institutes of Health (NIH), which require representation based on race/ethnicity. However, it should be noted that in these young MSM,20 retention at 6 mo among Native American Alaskan MSM was lower (85.7%) than that of White MSM (100%) (personal communication, Dr Sybil Hosek).

Discussion

In this article, the authors examine WTP in minorities in hypothetical HIV vaccine trials, retention in minority populations in various VPS, and WTP and retention in actual HIV vaccine trials in North America. The authors also compare and contrast HIV vaccine trials compared with trials of other biomedical prevention.

Willingness to participate (WTP) was similar across racial/ethnic groups with regards to hypothetical HIV vaccine trials (Table 1) despite differences in enrollment rates in actual HIV vaccine trials. Differences in enrollment by race/ethnicity appears to be conditional on risk group; therefore, risk group should be highlighted as an important effect modifier with regards to enrollment. Furthermore, in some studies, the method of data collection (interviewer vs. self-administered questionnaire) affected reported WTP by non-Whites, and this could reflect socially desirable responses on the part of these participants.

Hypothetical WTP compared with actual WTP

Although Whites comprise the minority of the sample in most recent hypothetical WTP studies (2005–present), there continues to be an underrepresentation of minorities in actual HIV vaccine trials. Low enrollment, however, does not necessarily indicate an unwillingness to participate. Low enrollment could result from targeted recruitment of other populations, location of the venue used for recruitment, and the demographic characteristics of the catchment area. Placebo-controlled trials create a situation in which participants feel a sense of trust toward the trial investigators and sponsors, and this may preclude the participation of racial/ethnic minorities (Dr Robert Grant, personal communication). We must also consider the racial and ethnic representation among researchers and other health care workers associated with these studies, and whether this representation is at all similar to the demographics that are hoped for in vaccine studies.

Increasing enrollment of minority populations in HIV vaccine trials

Newman et al. identify several ways to increase minority recruitment in HIV vaccine trials.56,57 These were: (1) building trust through educational interventions to increase understanding and informed participation in HIV vaccine trials (2) raise awareness of individual and community risk for minorities and to combat HIV / AIDS stigma (3) using tailored approaches, recognizing differences in barriers and motivators within and between different racial/ethnic groups.

Industry-funded (privately) clinical trials vs. publicly-funded preventive clinical trials

Privately-funded trials include largely the international prophylactic HPV trials,23,26-28 although the preventive AIDSVAX B/B study was also only industry-funded (VAXGen, Inc.).58

The large-scale HPV trials did not have to strictly follow the NIH requirements for racial/ethnic minority representation in clinical trials59 (Dr Eduardo Franco, personal communication). Therefore, these HPV trials recruited largely based on convenience and enrolled large numbers of White participants including MSM, in Scandinavia, the US, and Canada. On the other hand, Project PrEPare, which was funded by the NIH, enrolled a large percentage of racial/ethnic minorities.20

Retention

Two VPS in African-American WAHR were difficult to assess due to the lack of comparison groups.45,46 On the other hand, in a VPS by Koblin et al. in WAHR, the overall 18-mo retention rate was adequate at approximately 80%.50 However, the low HIV IR in WAHR in this study (<1%) may preclude using this group for phase 3 HIV vaccine trials to assess efficacy. Typically, an HIV seroincidence below 2% is considered too low to detect an appreciable effect size in phase 3 HIV vaccine trials.60 With a low HIV IR, the sample size for an actual trial would need to be very large, beyond previous trials, other than the RV144 HIV vaccine trial in Thailand which involved over 16 000 people61 (personal communication, Dr Beryl Koblin). Therefore, women at highest risk would need to be targeted and reached and engaged over the long-term in an HIV vaccine trial, as WAHR are a critical population in the US for HIV vaccine trials.

Race/ethnicity and other clinical trials

Similar to actual HIV vaccine trials, HPTN 039 had US sites consisting mostly of White participants,19 as did a phase 2B PrEP study.22Therefore, it is possible that actual trials make even more salient issues related to trust and disenfranchisement that are experienced by members of ethnic and racial minorities.

Future HIV vaccine trials could similarly be designed as the Project PrEPare study to better address racial/ethnic disparities in participation without disrupting other trial goals. However, in these young MSM,20 retention at 6 mo among Native American/Alaskan MSM was lower than that of White MSM. Similarly, if retention among minority MSM is lower in actual HIV vaccine trials, enhanced retention strategies (ER) may improve retention rates. Furthermore, it has shown that White MSM50 and Black MSM (HPTN 061)62 including young MSM populations (personal communication, Dr Sybil Hosek) in the US have had a sufficient HIV IR (>2%) to conduct efficacy trials.

Comparison groups

The last item of importance is what the best comparison groups are for examining racial/ethnic differences in actual HIV vaccine trials. First, a phase 3 efficacy trial should have an adequate sample size and overall efficacy, prior to doing a subgroup analysis. The level of exposure to HIV and community viral load between different racial/ethnic groups such as African-Americans and Whites may also be relevant. Racial/ethnic groups such as those of African and European ancestry could also be differentiated based on genetic differences.63

Limitations

In this review, the populations examined have been limited to high-risk populations such as MSM, IDU, and WAHR. In some studies examining hypothetical WTP, the small sample sizes of minority populations limits generalizability. At times, the race/ethnicity composition was not given in full or stratified. There was some difficulty making overall conclusions because of the differences in risk groups, comparison groups, and the lack of stratification by gender with regards to racial/ethnic group. Immigrant status was hard to determine; for example, sometimes minorities were listed as Black, in other cases as African-Americans. The definition of “Other” race/ethnicity was not always specified in the VPS. Many of the VPS examining retention were older studies spanning from 1996–2001. Retention in these VPS was only examined up to 18 mo, shorter than for an actual HIV vaccine trial. The follow-up rate was worse in non-Whites, which is a topic that may be difficult to predict from hypothetical surveys. In addition, it was difficult to determine exactly which specific racial/ethnic minority groups were being compared with Whites with regards to retention.

In actual trials, there are no data on the numbers of potential participants approached for screening and the rates of refusal by race/ethnicity. Furthermore, actual vaccine and other prevention trials are not always designed with racial/ethnic comparisons of enrollment and retention in mind. Unpublished data on retention in HIV vaccine trials (AIDSVAX B/B, STEP study, and HVTN 505) with respect to racial/ethnic minorities was not available from the trial investigators. It should also be noted that the retention rates retrieved for HPTN 039 and Project PrePare were based on personal communications rather than on peer-reviewed literature. Therefore, these data depart from a systematic review and are more of a select survey, with more qualitative data provided particularly for Project PrEPare. Finally, the present review did not include studies from countries outside of North America, as the race/ethnicity dynamics may be different.

Future research

Other minority groups in North America could be further examined (e.g., Indian, Pakistani, Chinese, Arab) including immigrant populations (e.g., McDaid et al., 2012).64 Further studies on retention using standardized comparison groups (Whites) and comparing the different minorities to Whites should be conducted to better assess potential participation and retention in actual trials. For example, further preparatory studies should be conducted to capture low follow-up in non-Whites. Longitudinal studies could be performed with frequent follow-up of participants, a longer follow-up period than 18 mo, and determining changes in retention over time. Also, having a run-in period prior to the hypothetical study to assess dropouts, and ascertaining which participants are socially stable could be determined in preparatory studies. As well, research on whether racial/ethnic minorities trust privately-sponsored vs publicly sponsored trials can be conducted to understand better the issues of trust with respect to HIV vaccine trials (Dr Robert M Grant, personal communication).

Methods

In 2014, S.D. and G.P. independently searched the Cochrane database for Systematic Reviews, Medline, Pubmed, and Embase using the search terms: “HIV”, “vaccine preparedness”, “HIV vaccines”, “minority’, “race”, “willingness to participate”, and “retention”. Prominent authors in the field were used as search terms.

The authors searched the literature for HIV VPS in North America that examined WTP in a preventive phase 3 HIV vaccine trial as well as retention, both in relation to race/ethnicity. Relevant literature was also retrieved from a published HIV VPS,65 and from bibliographic references. Inclusion criteria were: (1) an HIV VPS; (2) took place in North America; (3) contained information on WTP or retention by race/ethnicity in high-risk populations (MSM, IDU, WAHR); (4) was an original article; (5) was in English.

Information on the study population, location, sample size, and the type of questionnaire used was tabulated. When available, adjusted odds ratios (AOR) for the association between race/ethnicity and the variables of WTP and retention were provided. Other trials of biomedical prevention with North American participants were retrieved through literature searching and through contacting prominent authors in the respective fields.

Conclusions

HIV vaccine preparedness studies (VPS) have examined the hypothetical relationship between race/ethnicity and WTP in a preventive phase 3 HIV vaccine trial, and a similar relationship between race/ethnicity and retention. Willingness to participate (WTP) in hypothetical trials did not differ by race/ethnicity in North American countries. However, these results on WTP and retention are not conclusive, due to the differences in risk groups, comparison groups, and the lack of stratification by gender. Actual HIV vaccine trials, an HIV acquisition trial, and a phase 2B preexposure prophylaxis (PrEP) trial have enrolled a large percentage of White men. Human papilloma virus (HPV) privately-funded trials have also enrolled a large number of Whites, due to convenience sampling. Retention in the HIV acquisition trial was lower in African-Americans compared with Whites. Because racial/ethnic disparities in the epidemiology of HIV is a justification for increased enrollment of minority populations, strategies to increase enrollment (such as in Project PrEPare) and enhanced retention (ER) strategies could be ascertained and incorporated into actual HIV vaccine trials to facilitate minority participation and retention.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

The authors would like to thank the University of British Columbia for their ongoing funding.

Acknowledgments

The authors would like to thank Dr Jared Baeten for his data on HIV acquisition trials Dr Robert M Grant for his information on preexposure prophylaxis (PrEP) trials, Dr Sybil Hosek for her data on PrEP trials, Dr Eduardo Franco for his information on human papilloma virus (HPV) trials, and also Dr Kenrad Nelson for his information on comparison groups and preparatory cohort studies.

The first author would like to acknowledge some of the retailers in Oakridge Centre in Vancouver, Canada, who have provided discounts to the first author on their merchandise. These retailers include Armani Exchange, the Bay, BCBGMAXAZRIA, Blue Lotus Art Gallery, Coach, Crate and Barrel, David’s Tea, DKNY, the Gap, Hugo Boss, Michael Kors, Safeway, and Stuart Weitzman. The views expressed in this manuscript are those of the authors and do not reflect the views of these organizations.

10.4161/hv.28870