To test the effectiveness of new HIV-prevention methods like microbicides, late-stage trials must enroll large numbers of sexually active women. Current safety regulations require women who become pregnant to discontinue use of experimental products. However, excluding or removing pregnant women from trials raises a number of scientific and ethical concerns:

• Women at risk for HIV are also the very women most likely to become pregnant.1

• Important safety and effectiveness data on the use of new HIV prevention products in pregnancy goes uncollected—limiting potential users and access to proven products.

• High rates of pregnancy among prevention trial participants can threaten the scientific validity of a study: if too many women become pregnant, the power to detect modest effects on HIV transmission can be greatly reduced.2

A large percentage of women enrolled in past HIV-prevention trials became pregnant, which led some researchers to suggest that study participants be required to use effective non-barrier contraceptive methods. Others have questioned the morality of mandating contraceptives or restricting reproductive choice.

Methods

Conclusions

Contraception and Family Planning in HIV Prevention Trials: Current Practice and Stakeholder Perspectives

Sean Philpott¹,³, Bridget Reutener Hanes², Katherine West Slevin¹, Monica Ruiz², Amita Vyas²1Global Campaign for Microbicides; 2Prevention and Community Health, School of Public Health, The George Washington University;

3Current address: The Bioethics Program of Union Graduate College and Mount Sinai School of Medicine

To explore this issue further, we used protocol reviews, surveys, and key informant interviews to examine:

1. family planning practices in 18 completed, ongoing, or planned phase 2 and 3 clinical HIV-prevention trials; and

2. current perceptions of contraceptive services among key stakeholders, including international and local researchers, trial sponsors, community advocates, and policymakers.

•Most trials excluded women who indicated that they planned to get pregnant.

•Participants who got pregnant were required to stop product use.

•Many trials mandated some form of contraceptive use, usually a combined oral or injectable contraceptive. Even among researchers working in the HIV-prevention field, however, a majority were opposed to such contraceptive mandates.

•Policymakers, advocates, and researchers not directly involved in HIV-prevention trials were even more uniform in their opposition to mandated use of contraceptives.

Several recent trials have achieved a remarkable reduction in pregnancy rates by providing comprehensive family planning counseling without requiring women to use contraception in order to be eligible for study enrollment. Given the ethical questions raised and the attitudes we documented, trial networks and sponsors may want to reconsider the use of contraceptive mandates in favor of enhanced contraceptive provision.

Background

Results

•These studies were examined by GCM as part of its 2006 study Mapping the Standards of Care at Microbicide Clinical Trial Sites, available at http://www.global-campaign.org/clientfiles/SOC.pdf . The information presented in the table represents what the practice was at that particular site during the time of the mapping exercise and does not necessarily represent study-wide practice..

** At the time interviews were conducted, the MTN-003 VOICE study had not yet begun enrollment. The data presented in the table represents what the studies planned to do at that time, not what is current.

Survey Responses: Non-barrier contraceptive methods should be required for participants in trials

0

10

20

30

40

50

60

Disagree/ Strongly Disagree Agree/ Strongly Agree

Respondents Directly Involved in HIV Prevention Research [% (N)]

0

10

20

30

40

50

60

Disagree/ Strongly Disagree Agree/ Strongly Agree

Respondents Not Involved in HIV Prevention Research [% (N)]

Provision of Contraception and Management of Pregnancy in Select HIV Prevention Trials

DATA SAMPLEFull data set available on handout or by contacting kwest@path.org

Type of Study Study Name & Network Contraception Mandated Types of Reversible Contraceptives Allowed

Free Contraceptives Provided On-Site

Pregnancy Testing Women Allowed to Continue in

Study

Pregnancy Outcomes Collected

Microbicides

Population Council Carraguard® (Gugulethu, South Africa)*

NO Any method (except spermicide)

YESDepo, OCs

Quarterly NO YES

MDP 301 PRO 2000 (Unkhanyakude, South Africa)*

NO Any method (except spermicide; IUDs not

recommended by DoH due to high STI rates)

YESOCs, injectables, emergency contraception (referral for

tubal ligation)

Monthly YES(off product)

YES

Cervical Barrier MIRAOrtho All-Flex® diaphragm and Replens® (Harare, Zimbabwe)*

NO Any method (except spermicide)

YES(site-specific)

Quarterly YES (can choose to

continue or discontinue product

use)

YES

PrEP MTN-003 (VOICE)**Oral tenofovir and tenofovir gel

YES IUD, OCs, injectables YES(some site variability)

All visits YES(off product)

YES(via MTN-016 registry)

UW Partners PrEP Oral Truvada® and tenofovir

NO Any method (or no method)

YESOCs, injectables, implants, IUD

All visits YES(off product)

YES(and infant growth and

development)

Herpes Suppression MRC Mwanza HSV Suppression Acyclovir

NO OCs, injectables YES When suspected YES(off product)

NO

VaccineHVTN 502 (STEP) MRKAd5 trivalent vaccine

YES “Reliable” contraception NO All visits NO NO

1Gray et al. 2005; Science Daily 2008

2Ramjee et al. 2007; UNAIDS/WHO 2007.