Poster presentation at the 11th annual BC AIDS Conference in November, 1998, in Vancouver, BC. (Originally presented at the XII International Conference on AIDS in July, 1998, in Geneva, Switzerland.)

Feasibility of HIV Vaccine Trials among High-Risk Cohorts in Vancouver

Steffanie A. Strathdee, PhD; Michael V. O'Shaughnessy, PhD; Julio SG Montaner, MD, FRCP; Steve Martindale; Sue Currie; and Martin T. Schechter, OBC, MD, PhD; for the Vanguard and VIDUS Projects, the University of British Columbia and the British Columbia Centre for Excellence in HIV/AIDS.

 

ACKNOWLEDGEMENTS:

The authors gratefully acknowledge Peter GA Cornelisse, Michael L. Rekart and David M. Patrick; the staff, participants and Community Advisory Boards of the Vanguard and VIDUS Projects; and the National Health Research Development Program, Health Canada, British Columbia Ministry of Health, and Prevention and Community Action Programs, Health Canada, for project funding. Tables created by Fiona Tetlock.

 

OBJECTIVE:

Ongoing prospective studies of HIV infection among men having sex with men (MSM) and injection drug users (IDUs) in Vancouver may provide an appropriate foundation for Phase III HIV vaccine trials.

The objective of this analysis was to study feasibility and factors associated with willingness to participate in HIV vaccine trials among participants of these cohort studies.

 

BACKGROUND:

Methodologic Considerations for HIV Vaccine Trials:

Apart from ethical issues and costs, study populations must meet the following methodologic criteria in order to be considered suitable for assessing Phase III efficacy trials:

  1. High willingness to participate. High-risk individuals must not be more likely to refuse.
  2. Estimates of HIV incidence in specific target populations must be available, and must be sufficiently high to enable vaccine efficacy to be determined with a manageable sample size.
  3. High follow-up rates must be maintained. If high-risk individuals are less likely to return for follow-up, success of future HIV vaccine studies could be jeopardized.

 

Prospective Open Cohorts of Young MSM and Active IDUs in Vancouver:

Two prospective studies of HIV incidence and risk behaviours among a) young MSM and b) active IDUs have been underway in Vancouver.1,2

a) The Vanguard Project is a study of MSM aged 18 to 30 which began in May 1995.1 Participants complete self-administered questionnaires and undergo HIV tests on an annual basis.
b) VIDUS is a study of IDUs who have injected at least once in the month prior to the baseline interview. The study began in May 1996.2 Participants are followed up every 6 months, and undergo HIV testing and interviewer-administered questionnaires. Participants are reimbursed $20 at each visit.

For the purpose of this analysis, similarly worded questions were included on follow-up survey instruments in 1997, which asked individuals if they would be willing to participate in future HIV vaccine trials. A layman's definition of a vaccine was included to ensure that respondents understood what was being asked.

 

METHODS:

Statistical Analysis:

Only HIV-negative persons were included in statistical analyses.

For both cohort studies, contingency table analysis was used to compare those who said they were definitely or probably willing to participate in HIV vaccine trials, versus those who were unsure or refused. Multivariate logistic regression analysis was then used to identify independent predictors of willingness to participate, separately for both cohort studies.

For both studies, HIV incidence density and corresponding 95% confidence intervals were calculated. The latter was based on the Poisson distribution.

Persons who had not returned within two months after they were due to return were conservatively considered lost to follow-up. Using contingency table analysis, participants who were lost to follow-up by this definition were compared to persons who returned with respect to demographic and behavioural characteristics.

 

RESULTS:

Willingness to Participate among cohorts of Young HIV-negative MSM and IDUs:

A total of 330 HIV-negative MSM completed the 1997 follow-up questionnaire by February, 1998. Of these, 34% said they were "definitely willing" to participate and another 29% said they were "probably willing," for a combined total of 63%. A further 25% were unsure, 10% said they were "probably unwilling" and 2% said they would refuse.

A total of 435 HIV-negative IDUs completed the corresponding follow-up questionnaire by February 1998. A total of 83% reported that they would participate in future HIV vaccine trials, 6% said they would not and 11% were unsure.

 

Factors associated with Willingness to Participate among 330 HIV-negative young MSM:

For the MSM cohort, there were no differences between willing and unwilling with respect to demographic characteristics including age, ethnicity or education levels (Table 1). However, willing subjects reported having first had sex with a male at a significantly younger age, scored higher on a 7-item version of the Centers for Epidemiologic Studies Depression scale,3 and were significantly more likely to have a high perceived threat of becoming infected with HIV.

Men who were willing to participate were marginally more likely to have a regular male partner. There were no differences between willing and unwilling subjects with respect to any sexual or drug-using characteristics.

 

Factors associated with Willingness to Participate among 435 HIV-negative IDUs:

Similarly, among IDUs, there were no differences between willing and unwilling subjects with respect to demographic characteristics, including gender, age and ethnicity (Table 2).

Interestingly, IDUs who reported attending needle exchange programs (NEP) more than once a week were significantly more willing to participate in HIV vaccine studies.

Subjects who were willing to participate also reported first injecting at a younger age, and had a significantly higher perceived threat of HIV infection.

 

Independent Predictors of Willingness to Participate among HIV-negative MSM and IDUs:

For the MSM cohort, those with a high perceived HIV threat were nearly three times more willing to participate in HIV vaccine trials (Table 3).

Those with a high depression score were nearly twice as likely to be willing to participate.

In the corresponding analysis among IDUs (Table 4), the most important predictor of willingness to participate was frequent needle exchange program (NEP) attendance.

IDUs with a high perceived HIV threat were only marginally more willing to participate, after controlling for NEP attendance.

 

HIV Incidence:

HIV incidence for the MSM and IDU cohorts is shown in Table 5. In both studies, HIV incidence has fallen in recent months, which suggests that selective ongoing recruitment of high-risk individuals may be required if these vaccine studies are to be feasible, especially among MSM.

 

Attrition:

Among the IDU cohort, the follow-up rate was 85%. We found no evidence that higher-risk IDUs were less likely to return for follow-up. In contrast, among the MSM cohort, a lower proportion of men (80%) had returned for at least one follow-up visit (Table 5). There was also evidence of differential follow-up among MSM who reported higher-risk behaviours at baseline (Table 6).

 

CHALLENGES:

  1. There is a trade-off between recruitment of high-risk individuals into a vaccine preparedness study, and the risk of high attrition and differential follow-up. Follow-up in the MSM cohort may be more successful if a monetary incentive is provided, and if follow-up visits are scheduled more frequently, as in the IDU cohort.
  2. Large sample sizes of high-risk individuals will be needed to demonstrate HIV vaccine effectiveness. It will be necessary to pool cohorts of high-risk persons to achieve sufficient statistical power.
  3. There is a responsibility to provide adequate support for persons participating in HIV vaccine trials and to safeguard against relapse to high-risk behaviour. This necessitates comprehensive, targeted, culturally appropriate prevention programs for all target populations.

 

SUMMARY:

A satisfactory proportion of Vancouver cohort subjects were willing to participate in HIV vaccine studies. In either study, there was no indication that higher-risk individuals were more likely to refuse.

Our analysis suggests that HIV vaccine trials may be particularly promising among Vancouver's IDU population, where HIV incidence remains unacceptably high and where participants viewed such trials with enthusiasm. In our setting, needle exchange programs offer a suitable venue for recruiting high-risk IDUs.

 

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REFERENCES:

1. Strathdee SA, Hogg RS, Martindale SL, Cornelisse PGA, Craib KJP, Montaner JSG, O'Shaughnessy MV, Schechter MT. Determinants of sexual risk-taking among young HIV-negative gay men. J of Acquir Immun Defic Syndr & Hum Retrovirol 1998, 19: 61-66.
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2. Strathdee SA, Patrick DM, Currie S, Cornelisse PGA, Rekart ML, Montaner JSG, Schechter MT, O'Shaughnessy MV. Needle exchange is not enough: Lessons from the Vancouver Injection Drug Use study. AIDS 1997, 8: F59-F65.
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3. Mirowsky J, Ross CE. Age and depression. J Health Soc Behav 1992, 33: 187-205.
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