AIDS RESEARCH AND HUMAN RETROVIRUSESVolume 11, Number 10, 1995Mary Ann Liebert, Inc.

Preventing Discrimination against Volunteers in PreventiveHIV Vaccine Efficacy Trials: Conference Summary

Conference on Advances in AIDSVaccine Development—1994

AMY R. SHEON

ABSTRACT

A Workshop was held November 8,1994 to discuss actual and theoretical risks for discrimination against vol-unteers in future HIV preventive vaccine efficacy trials. A small proportion of volunteers in ongoing PhaseI/II vaccine trials have had positive HIV antibody tests due to vaccine-induced HIV antibody responses. Somevolunteers had difficulty obtaining health and life insurance, employment with the U.S. military, and with for-eign travel. Study staff were able to resolve almost all such problems. Gay men enrolled in prospective seroin-cidence studies experienced a 1.6% chance per year of undergoing required HIV antibody tests. Among sub-jects enrolled in future vaccine trials, the likelihood of such tests resulting in discrimination will depend on

the type of vaccine and antibody tests used. The Americans with Disabilities Act may be used to prevent il-legal discrimination against those actually, or erroneously thought to be HIV infected. A study is underwayto estimate the frequency with which volunteers in a study of gpl20 preventive vaccines have actually expe-rienced legal and illegal discrimination as a result of trial participation. Data and Safety Monitoring Boardscan evaluate such data and should recommend modification of trial procedures or termination of trials if vol-unteers experience severe social harm due to their participation in trials.

Participants in this workshop reviewed concerns about DISCRIMINATION BASED ON RISKdiscrimination against HIV vaccine trial volunteers and GROUP MEMBERSHIP

suggested potential solutions. Volunteers in vaccine trials riskdiscrimination from being falsely identified as HIV infected Mr. Derek Hodel, Gay Men's Health Crisis, summarized theshould the vaccine induce an antibody response reactive on conclusions of an interdisciplinary Working Group on HIVcommercial tests. Volunteers also risk discrimination if they are Preventive Vaccines. Trial volunteers who develop antibody re-

presumed, by virtue of their trial participation, to engage in il- sponses to vaccines risk discrimination that is legally permit-licit or socially proscribed high-risk behavior such as injection ted (refusal of employment in the U.S. military, denial of healthdrug use or homosexual intercourse. Speakers represented the insurance), and that is illegal (dismissal from employment).AIDS Vaccine Evaluation Group (AVEG) experience (Phase Those sponsoring vaccine trials will focus their efforts on re-

I/II trials in low and high risk volunteers1), the Vaccine ducing discrimination by differentiating true infection from an-

Preparedness Initiative (high-risk gay men and injection drug tibody-induced responses1, and by helping volunteers explainusers in prospective seroincidence and behavioral studies2-3), such test results. However, it is important to acknowledge thatthe Working Group on HIV Preventive Vaccines,4 and the discrimination against truly infected individuals, and againstCenters for Disease Control (CDC). those engaging in stigmatized behaviors is rampant. Trial spon-

Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-7620.

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1310 SHEON

sors should ensure that their efforts on behalf of uninfected vol-unteers do not tacitly condone continuing discrimination againstthose truly infected.

Ms. Sheon described a study underway among approximately200 high-risk and 100 lower-risk volunteers in AVEG Protocol201, a trial of gpl20 vaccines versus placebo. The study is mea-

suring the frequency with which trial participants experienceddiscrimination due to risk group identification and due to anti-body responses on commercial HIV tests. Results will be avail-able in 1995.

VACCINE-INDUCED SEROPOSITIVITY

Dr. Robert Belshe, St. Louis University, noted that the like-lihood a vaccinée will test HIV positive on a commercial anti-body test depends on the characteristics of the vaccine (type,number of injections, dose), the time between the vaccinationand the antibody test, and the type of antibody test used. Amongvaccines based on the viral envelope, gpl60 vaccines are more

likely to induce a positive response than gpl20 vaccines.Antibody responses diminish markedly over time.

Multivalent and more complex vaccines currently in pre-clinical development will require more sophisticated tests to dif-ferentiate vaccine response from true infection. Dr. GeraldSchochetman, CDC, noted that an efficacy trial is unlikely tobegin if scientists lack the ability to distinguish infection fromantibody response; new diagnostic tests are being developed.CDC-NIAID collaboration can help ensure transfer of suchtechnology to state, local, and reference laboratories.

Some vaccine recipients may be classified erroneously as

HIV-infected if they do mount an antibody test that is detectedon commercially available tests performed for employment,health or life insurance, hospitalization, entry into drug treat-ment, etc. Based on data from approximately 1500 gay men en-

rolled in vaccine preparedness studies in Denver, Chicago, andSan Francisco, Dr. Kathleen MacQueen, CDC, estimated thatgay men face a 1.6 per 100 person-year risk of having a re-

quired HIV antibody test. Rates of compulsory testing variedby city, and by demographic characteristics of volunteers. Menenrolled in Denver, self-employed men, and men with annualincomes >$60,000 were significantly more likely than othergroups to report required tests for health, life, or disability in-surance, while men of color were more likely than white men

to report required tests for other reasons. Other speakers notedthat with frequent incarceration, hospitalization, or entry intodrug treatment, injection drug users may face an even higherrisk of compulsory testing.

STRATEGIES TO PREVENT OR REDUCESOCIAL HARMS

A first-hand view of injection drug users' concerns aboutvaccine trials was provided by Mr. Ian Fuerman and Dr. DavidMetzger, University of Pennsylvania. These vaccine prepared-ness study investigators showed a clip from their video, "Trialson Trial," in which a studio audience of approximately 50 IDUsasked questions of an expert panel about vaccine trials. Survey

data cannot replace the richness of interpersonal contact.

Representatives from high-risk communities participate in sci-entific and protocol development meetings for vaccine trials.By listening to and addressing these concerns, investigators,trial sponsors, and government officials could increase the like-lihood of enrollment in and cooperation with vaccine trials.

Ms. Lois Wagner, Vanderbilt University, reviewed strategiesused by AVEG sites to prevent discrimination, or to mitigatesequelae. Volunteers likely to face immigration or employmentproblems are screened out, and agreements have been reachedwith insurance companies not to deny or revoke coverage basedon vaccine-induced HIV seropositivity. Identification cards andhotlines are available for volunteers, and staff are available to

explain the meaning of a positive antibody test, at a volunteer'srequest. Sheon's study will permit evaluation of the efficacy ofstrategies used at the local level in preventing or resolving dis-crimination issues.

Mr. Robert Stein, Washington, D.C., explained that theAmericans with Disabilities Act (ADA) protects individualswho are actually HIV infected, those who test HIV positive(including false positive), and those "regarded as" positive,even if due to presumed high risk behavior. Certificates ofconfidentiality should be obtained from the U.S. Departmentof Health and Human Services to protect trial site staff fromhaving to reveal trial-related data if suponaed. Trial staffshould be educated about the coverage of the ADA, andtrained to use it to intercede on behalf of volunteers facingdiscrimination. A number of states require name reporting ofall positive HIV tests to State health authorities. Some stateshave exceptions for research projects. Sites should discuss thepossibility of exempting positive results obtained during vac-

cine trials from reporting requirements. Sites working in statesthat require reporting of names of those testing HIV positivemay wish to apply for research exemptions. Mr. Stein sug-gested that trial sponsors develop a model exemption requestto facilitate this action. Community level education about vac-

cine trials, about the ADA, and about HIV testing may fur-ther mitigate the potential for discrimination against trial vol-unteers.

Ms. Carol Levine, an ethicist with the AIDS Orphan Project,recommended that vaccine trials collect data on social harmsexperienced by vaccine trial participants. Data and SafetyMonitoring Boards should monitor these data and recommendthat trials be stopped or modified should such harms be con-

sidered excessive.Some questions remain unresolved. The AVEG strategy of

screening out volunteers most likely to face compulsory test-

ing may be unfeasible for efficacy trials needing to recruit largenumbers of high-risk volunteers. A possible solution is to pro-vide in the informed consent, information about risks for com-

pulsory testing, and permit potential volunteers to weigh therisks of participating against the benefits. Risk rates could bederived from vaccine preparedness data, as shown by Dr.MacQueen, and from the anonymous survey of AVEG 201 vol-unteers described by Ms. Sheon.

Some have proposed prescreening subjects and prohibitingthose showing reactivity to any bands on Western blot testsfrom joining trials. Alternatively, blood specimens obtainedfrom volunteers prior to vaccination could be stored and then

DISCRIMINATION AGAINST VOLUNTEERS IN HIV TRIALS 1311

Table 1. Concerns about Discrimination against Trial Volunteers and Proposed Solutions

Concern Proposed solution Target of intervention

Ability to distinguish trueinfection from vaccine-induced positive tests

Discrimination due topresumption that volun-teer is HIV infecteddue to false positiveantibody test

Retain prevaccination bloodspecimens in repository for futuretesting

Modify diagnostic criteria for existingHIV tests to include HIV vaccinationstatus

Develop more specific diagnostictests; make them available to statehealth department laboratories

Prescreen volunteers for reactivityto commercial tests

Study prevalence and context fortesting; screen out individuals at high risk of compulsorytesting

Include risk of discrimination and compulsory tests in informedconsent

Provide volunteers with identification cards, and access tohotlines and staff

Negotiate agreements with insurancecompanies not to cancel/refuse coverage for trial participantsbased on false-positive HIV tests

Increase awareness of Americanswith Disabilities Act

Measure frequency of discriminationin current and future trials

Obtain exemptions from namedreporting requirements

Develop more specific HIV antibodyconfirmation test

Trial site

CDC, state healthdepartments

CDC, NIAID, state healthdepartments, industry

Trial site

NIAID, industry sponsors

Trial sites, communities

Trial sites, Data and SafetyMonitoring Board

Trial sites, CDC

State health departmentlaboratories

Discrimination due to pre-sumption that volunteeris high risk and/or amember of a stigma-tized risk group

Counsel volunteers to avoiddisclosing their participation in trials

Provide counseling/information toothers at the volunteer's request

Include low-risk volunteers in all trialsIncrease awareness of Americans

with Disabilities ActConduct media campaigns to inform people about trialsElicit support of Community Advisory Boards to inform

community about trialsObtain certificates of confidentiality

Trial sites

Trial sites, communities

NIAID

used to help resolve diagnostic difficulties among individualswith indeterminate serology tests. However, such strategiescould be prohibitively expensive and not fully effective becausesubjects may exhibit transient bands that would not be pickedup at a single screening time.

A Workshop participant, Dr. Michael Ascher, suggestedthat diagnostic criteria that call incomplete Western blot pat-terns, such as are seen in seroconversion and after vaccina-tion, positive should be reevaluated. Specificity would be im-proved by requiring evidence of progression to a more

complete pattern on a subsequent independent sample. A sec-ond sample is also recommended on all first time positives torule out specimen mixup or biologic false positivity.

Additionally, a checkbox could be added to laboratory testingforms to indicate whether those seeking antibody testing hadreceived HIV vaccines.

Concerns and proposed solutions discussed during theWorkshop are summarized in Table 1.

ACKNOWLEDGMENTS

Thanks go to the workshop co-chair, Theresa Spitz, to par-ticipants, and to Mike Ascher, Michael Gross, Jan Harrington,Patricia Fast, and Rodney Hoff for comments on the manu-

script.

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REFERENCES

1. Belshe RB, Clements ML, Keefer MC, et al: Interpreting HIVsérodiagnostic test results in the 1990s: Social risks of HIV vac-

cine studies in uninfected volunteers. Ann Intern Med1994;121:584-589.

2. Sheon AR: Overview: HIV vaccine feasibility studies. AIDS ResHum Retroviruses 1994;10(Suppl 2):S195-S196.

3. MacQueen MK, Buchbinder S, Douglas J, et al: Required HIV an-

tibody testing, social risk, and HIV vaccine efficacy trials. 1995 (sub-mitted).

SHEON

4. AIDS Action Foundation: HIV Preventive Vaccines: Social, Ethical,and Political Considerations for Domestic Efficacy Trials Report ofa Working Group Convened by the AIDS Action Foundation, 1994,Washington, DC.

Address reprint requests to:Amy R. Sheon

Division ofAIDSNational Institute of Allergy and Infectious Diseases

6003 Executive Blvd., Room 2A10Bethesda, MD 20892-7620