During the first WIHS recruitment phase in 1994–1995, the goal was to recruit a sample that was representative of women with HIV/AIDS in the United States. Women were enrolled into one of two groups: HIV-infected or HIV-uninfected and at-risk for acquisition of HIV infection. Almost all HIV-infected women were naive to HAART, and many had already been diagnosed with an AIDS-defining illness. The HIV-infected and HIV-uninfected women had similar demographic backgrounds and a comparable distribution of risk factors for acquisition of HIV infection. A detailed description of the original recruitment showed how similar the women in the WIHS cohort were to the U.S. HIV-infected population.10
From 1994 to 1995, 2054 HIV-infected and 569 HIV-uninfected women were enrolled into the WIHS at six locations within the United States: New York City (two sites), the Washington, DC, metropolitan area, Chicago, southern California, and northern California. Every 6 months, WIHS participants were interviewed using a structured questionnaire and received a physical and gynecological examination. Multiple gynecological and blood specimens were collected at each visit. Follow-up data for the first 24 study visits, through March 31, 2007, were included in the analyses.
For the second wave of recruitment into the WIHS, during 2001 to 2002, the goal was to recruit HIV-infected women with a younger median age and no previous AIDS diagnosis and to identify two groups related to treatment exposure: those who had been on HAART and those who had never been exposed to HAART.11
A comparison group of HIV-uninfected women of similar ages and backgrounds was also enrolled. The second recruitment phase occurred during WIHS visits 15 and 16, and after the second recruitment phase, 737 HIV-infected and 406 HIV-uninfected women were enrolled in the same six WIHS locations. The semiannual study visits for the new enrollees were essentially the same as for the original cohort participants. Follow-up data for the first 10 study visits (5 years) for the new cohort members, through March 31, 2007, were included in the analyses.
Recruitment was performed at a variety of venues for both phases. Nationally, these included HIV primary care clinics, hospital-based programs, research programs, community outreach sites, women's support groups, drug rehabilitation programs, HIV testing sites, and referrals from enrolled participants. Site-specific recruitment sources differed, however, with some sites (Brooklyn and Chicago) recruiting more heavily from primary care clinics and existing research studies.
Recruitment strategies for the original WIHS cohort have been described previously.10–12
We knew from retention analyses of the original cohort that most of the loss to follow-up occurred early, shortly after the first visit. So, for the second wave of recruitment into the WIHS, a two-step screening and enrollment process was used for both the HIV-infected and HIV-uninfected women. At the screening visit, women were asked questions to determine eligibility, and blood was drawn for HIV antibody testing. Once the results of the HIV antibody test were available and if the woman met the inclusion criteria, she was invited back for enrollment into the new WIHS cohort. The HIV-infected women gave written permission for medical record abstraction to determine if they were AIDS-free, had initiated HAART, and if on HAART, to abstract the date of HAART initiation as well as the CD4+ cell count and HIV RNA viral load just prior to HAART initiation.11
Under certain circumstances, the study personnel had the discretion of combining the screening and recruitment process into one visit.
Retention strategies for the original cohort have been described.12
In brief, retention was continually monitored at both the national and local levels. Sites frequently revisited and revised retention strategies to make them more responsive to emerging visit attendance barriers and to address changing study protocols.
Women who did not have a 6-month interview and were not known to be deceased were considered as having missed their visit. Women who moved and transferred to another WIHS site were considered to be a participant of the new site. Women who asked to be disenrolled from the study were considered lost (not retained) for all future visits. For women who were too ill to be seen for a full study visit, those in detention, and those who moved out of the study area, an abbreviated visit (usually over the telephone) was offered.
The National Death Index was searched annually for information on women not seen in the past 12 months. At some sites, local death registries, the Social Security Death Index, and calls to primary contacts were methods used to check for new death information. National death registry data was available through 2006, and local data were available through 2007.
Consent materials were reviewed and approved by the institutional review boards at each of the collaborating institutions, and informed consent was obtained from the participants.
The independent variables of interest were recruitment cohort (new vs. original), age (in decades), race/ethnicity, education, household income, employment, housing, depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D] score ≥16), cigarette smoking, alcohol use, history of injection drug use, primary care provider, healthcare insurance, crack/cocaine/heroin use, and WIHS site of enrollment. Logistic regression analyses were conducted using models with all study participants, with HIV-infected only, and with HIV-uninfected only. HIV status was included as an additional predictor in the model that included data from all women. Use of HAART, HIV RNA, and CD4 cell count were examined in the model limited to data from the HIV-infected women. Log10 was used to estimate the effect of a 10-fold change in HIV RNA, and log2 was used to estimate the effect of a 2-fold change in CD4 cell count on the outcome measure. Independent variables that changed over time were included as time varying based on data from the last completed interview.
We assessed compliance with study follow-up in two ways, by examining study retention and by evaluating semiannual visit attendance. For the retention analyses, the dependent variable was attrition, defined as having missed a study visit for more than 12 months (two successive visits) or, if deceased, for more than 12 months prior to the date of death. Retention rates were determined for each WIHS visit cycle (visits 2–24 for the original cohort and visits 2–10 for the new cohort), stratified by HIV serostatus. The retention rate was calculated as the number of women interviewed (either in person or over the phone) in the last 12 months, divided by the number of women enrolled at visit 1 minus those women who have died. Therefore, retention rates can increase from one visit to the next if either the number of women interviewed in the last 12 months has increased or the number of women who have died has increased.
For the attendance analyses, each participant study visit was defined as either attended (seen in person) or missed and analyzed as a dichotomous outcome variable. Women who died were included in the analyses up until the visit when they were reported as deceased. To compare study visit attendance in the original and new cohorts and evaluate the association between missed visits and demographic, behavioral, and clinical variables, we used repeated measures, random effects logistic regression models to account for multiple visits per woman and predictors that could differ for the same woman at different visits. A random subject effect was included to account for the dependence of multiple observations from individual participants.13
To assess our improved retention strategies for the new cohort, one of our goals was to evaluate predictors of participant attendance at earlier visits compared with later visits in the original and new cohorts. We first performed logistic regression using only study visits 2 and 3. To examine whether a previous missed visit affected attendance at a current visit, we included a predictor variable in the model that defined three categories of current and prior visit attendance (attendance at visit 3 given that visit 2 was attended, attendance at visit 3 given that visit 2 was missed, and attendance at visit 2 for which all cases attended visit 1 [the reference]). We then performed logistic regression using visits 7–10 and restricted the analyses to women who were last seen at either visit 5 or visit 6. In these analyses, we evaluated the association between attendance at two previous visits and attendance at a current visit by including a three-category predictor variable (attended previous visit but missed the visit before previous, missed previous visit but attended the visit before previous visit, and attended both previous and before previous visits [the reference]). For the missed visits, we used predictors from the previous attended visit. We excluded from the analysis visits where both previous and before previous visits were missed to avoid using predictors that were less current.
Among the 975 HIV-uninfected women enrolled at baseline, 19 women seroconverted for HIV during follow-up. Because of the small sample size, these 19 women were excluded from all analyses. Statistical analyses were performed using SAS® software version 9.1 (SAS Institute, Cary, NC) and S-PLUS® software version 8.0 (Insightful Corporation, Seattle, WA).