There are six WIHS consortia, each made up of multiple clinical subsites, located in Bronx/Manhattan, NY; Brooklyn, NY; Los Angeles/Southern California/Hawaii; San Francisco/Bay Area, CA; Chicago, IL; and Washington, DC. Each consortium represents the population of HIV-infected women in its metropolitan area. An executive committee (EC) consists of investigators from each consortium, NIH program officers, and representatives of the study participants. EC members develop their specific areas of research and work with investigators outside the consortium who want to conduct research using WIHS resources. Study protocol and proposals for new research concepts for the cohort are reviewed and voted on by the EC.
Each WIHS consortium is supported by a community advisory board (CAB) comprised of study participants, and these local CAB members select representatives for the national WIHS CAB (NCAB). Participating in WIHS EC meetings and working group conference calls, NCAB members review plans and rationales for protocol changes and assist researchers in understanding what new initiatives are likely to be supported by study participants and what questions are of importance to the HIV-infected community.
Protection of Human Subjects and Informed Consent
Despite 20 years of growing awareness about HIV and AIDS, there remains a stigma associated with the diagnosis and a fear of disclosure among many infected women. HIV-negative participants worry that they will be thought to be HIV positive if identified with an HIV study. Hence, confidentiality is carefully guarded in the WIHS. A certificate of confidentiality from the U.S. Department of Health and Human Services protects study staff from being required to respond to requests for information on participants from any persons or organizations unrelated to the study. Participants are assigned study identification numbers and names are not used on any WIHS documentation except consent and locator forms and medical record requests. Forms with identifying information are maintained separately from data files in a secured file cabinet.
WIHS participants provided written informed consent, in English or Spanish, both for screening and for enrollment. For those unable to read, the consent form is read to them and this is documented on the consent form prior to obtaining signatures. WIHS consent forms include information on current study procedures and on the storage of specimens in the repository for future studies as approved by the WIHS EC. Each subsite within the WIHS consortia has consent forms approved by its institutional review board. Significant changes in the protocol and new substudies are reviewed by institutional review boards prior to initiation; women may choose whether or not to participate in new substudies without jeopardizing their status as core WIHS participants.
At the time of the original WIHS recruitment, there were few inclusion and exclusion criteria. Adult women able and willing to consent to participation in the study, complete the interview in English or Spanish, travel to the research site for an interview and physical examination every six months, and have blood drawn for laboratory testing by venous or arterial access were enrolled into one of two groups: HIV positive or HIV negative. Prior to 1996, HAART exposure was limited to early clinical trials; therefore, most enrollees were naïve to highly active therapy and many had already been diagnosed with an AIDS-defining illness. A detailed description of the original recruitment was published by Barkan et al. in 1998 (4
The goals of expansion in the period from 2001 to 2002 were to recruit a younger group with limited disease progression and to identify two groups related to treatment exposure—those who had been on HAART and those who had never been exposed to HAART—as well as a control group of HIV-negative women of similar ages and backgrounds. To obtain a representative sample of the population of HIV-infected women in the community, recruitment focused on African-American and Latina women. Eligibility criteria for the expansion cohort included the following: (i) documented results from an HIV enzyme-linked immunosorbent assay and a confirmatory Western blot for each of those who were HIV positive or documented HIV-negative results obtained within 30 days prior to enrollment for HIV-negative women; (ii) no history of clinical AIDS-related conditions, confirmed by medical record abstraction; (iii) documentation of laboratory reports of HIV RNA levels and CD4 counts surrounding the period of HAART initiation for those enrolled as HAART exposed; and (iv) consent from the woman to have her specimens stored in the WIHS national repository.
To ensure comparability with the HIV-positive women, site recruitment targeted women who engaged in high-risk behaviors for enrollment in the HIV-negative group. High-risk behaviors were defined as reporting one or more of the following criteria within the past year: (i) injection drug use; (ii) having a sexually transmitted disease; (iii) having unprotected sex with three or more men or protected sex with more than five men; or (iv) having exchanged sex for drugs, money, or shelter.
Recruitment methods used in both the original and expansion cohorts emphasized face-to-face techniques. Infectious disease, internal medicine, and obstetric and gynecology offices throughout the community were contacted for referrals. Outreach to HIV community organizations, churches and HIV ministries, and social-service organizations was conducted. Women who were part of the original cohort recruited friends and family members, women with whom they shared support groups and counseling sessions, and friends of friends.
Loss to follow-up between baseline and the first follow-up visit was 10.3% among original enrollees. For this reason, five of the six sites chose a two-step enrollment process for the period from 2001 to 2002 which required an initial screening visit and then a second baseline study visit. Due to the high loss to follow-up at some consortia among those recruited from residential drug rehabilitation centers during the 1994-to-1995 period, many sites did not recruit at drug treatment centers but did enroll women in rehabilitation who were referred by a physician or friends. These changes resulted in a loss to follow-up between baseline and first follow-up visits of only 5.3% among the expansion cohort.
After the baseline visit, the new cohort was merged into the original cohort's protocol and visit schedule. One year after the expansion recruitment was completed, the retention rate for the combined cohort was 76% for seronegative and 83% for seropositive women. One-year retention rates for new recruits were 91% among HIV-negative women and 95% among those who were HIV positive. An analysis of the successful WIHS retention efforts from 1994 through 1999 was detailed in a paper by Hessol et al. (11
The WIHS is structured with a 6-calendar-month period for visit windows. For example, visit 16 occurred between 1 April 2002 and 30 September 2002. Ideally, visits are scheduled 6 months apart plus or minus 6 weeks. Because of the importance of identifying long-term outcomes, women are never withdrawn from the study due to missed visits. Those who move out of the area may remain active by transferring to a closer WIHS site, or long-distance transportation may be provided for annual visits. Abbreviated visits may be conducted over the phone for ill or incarcerated participants, with data collection limited to the participant's medical and therapeutic history for the preceding 6 months.
At each visit, WIHS participants are asked to provide the name and contact information of a friend or family member in addition to someone in their home along with instructions regarding the limit or extent of messages that can be left. This helps to track and retain those who may have unstable living situations.