Cohort Profile: The Women’s Interagency HIV Study (WIHS)

Abstract

The National Institutes of Health established the Women’s Interagency HIV Study (WIHS) in 1993 to study the impact and progression of HIV infection among women in response to the rising number of AIDS cases and the relative paucity of clinical, behavioural and epidemiological data in this population. Women now comprise more than 50% of people with HIV (PWH) worldwide.1 The WIHS is the largest and oldest ongoing prospective cohort study of women with and at risk for HIV infection in the world, and remains the leading study to document the experience of women with HIV (WWH) in the United States. The cohort’s scope of data collection and research has expanded considerably since the two previous publications that described the methodology and profile of the study in its early years.2,3 Current areas of research include, but are not limited to: HIV-related comorbidities; epidemiological methods; genetics; frailty and ageing; behavioural and social determinants of health; pharmacology; and studies related to pursuit of an HIV cure. The purpose of this paper is to update researchers on the substantial expansion of the cohort, its methods and the available data. The six original cohort sites were in Brooklyn, NY; the Bronx/Manhattan, NY; Washington, DC; Chicago, IL; San Francisco, CA; and Los Angeles, CA. Since 1997, the WIHS Data Management and Analysis Center (WDMAC) has been located in Baltimore, MD. Four southern sites were added in 2013: Chapel Hill, NC; Atlanta, GA; Birmingham, AL/Jackson, MS; and Miami, FL. The Los Angeles site discontinued active follow-up in 2013. The cohort enrolled 4982 women who at baseline were: either HIV-seropositive (3677); or HIV-seronegative (1305; 26 of them acquired HIV during follow-up) with a history of sexually transmitted infections (STIs) or behavioural or demographic characteristics that increased their risk of acquiring HIV. Enrolment occurred during four waves: 1994-95 (2054 HIV+; 569 HIV-); 2001–02 (737 HIV+, 406 HIV-), 2011-12 (276 HIV+; 95 HIV-); and 2013-15 (610 HIV+; 235 HIV-). Eligibility criteria were similar throughout the study, but varied from wave to wave to increase representativeness of the cohort.2,3 The most recent enrolment wave during 2013–15 (Wave 4) enrolled women between the ages of 25 and 60 years. WWH were required to have documentation of a reactive HIV serology and confirmatory test. Women who used anti-retroviral therapy (ART) were eligible only if all of their regimens met criteria for highly active antiretroviral therapy (HAART), as defined by the US consensus treatment recommendations.4 Those who used non-HAART regimens were eligible only if use occurred during pregnancy or HIV pre- or post-exposure prophylaxis. Documentation of CD4+ T cell counts and HIV RNA quantification before initiation of HAART was required. HIV-seronegative women were eligible for Wave 4 if they had at least one high-risk exposure in the preceding 5 years [e.g. STI diagnosis; sex without a condom with three or more men; sex with a condom with six or more men; trading sex; sex with an HIV-seropositive man; injection drug use (IDU) or use of crack cocaine, cocaine, heroin or methamphetamine; or any partner who had any of the previously mentioned risk characteristics]. Wave 3 enrolled women between the ages of 30 and 55 years, but eligibility criteria were otherwise similar to those of Wave 2.3 During Wave 4, investigators used word of mouth and flyers to recruit participants from community-based organizations and medical, STI and family planning clinics. Since the beginning of the study in 1993, 1268 participants have died, 130 have withdrawn from the study, 806 were discontinued for administrative reasons (such as termination of a site’s participation or decreased funding that required sites to decrease enrolment), and 415 have been lost to follow-up. (Table 1) As of October 2016, the WIHS is actively following 2363 women. Disposition of participants in the Women’s Interagency HIV Study, by enrolment wave and baseline HIV statusa Dates of enrolment were: Wave 1 = 1994–95; Wave 2 = 2001–02; Wave 3 = 2011–12; Wave 4 = 2013–15. Participants were considered ‘active’ if they attended at least one visit between October 2015 and September 2016. Among active participants who were HIV-seronegative at baseline, 14 seroconverted during WIHS follow-up (11 from Wave 1, two from Wave 2 and one from Wave 3). Among deceased participants who were HIV-seronegative at baseline, eight seroconverted during WIHS follow-up (six from Wave 1 and two from Wave 2) and two seroconverted after last WIHS visit (one from Wave 1 and one from Wave 2). Examples of reasons for administrative disenrollment include termination of a site’s participation or decreased funding that required sites to decrease enrollment. Among administratively disenrolled participants who were HIV-seronegative at baseline, 1 seroconverted during WIHS follow-up (Wave 2). Among lost to follow-up participants who were HIV-seronegat