A total of 1331 eligible discordant couples enrolled in the prospective study after receiving CVCT services. Age, duration of union, number of deliveries, and contraceptive use were similar to those reported previously for eligible couples as a whole. The average monthly income for the male partner was 54,265 Kwacha (US $40.6) and 10,934 (US $8.2) Kwacha for the female partner (the per capita poverty line in Zambia during this time was $30.24 per month38). Self-reported literacy in English was more common in men compared with women and more common in HIV-positive men and women compared with their HIV-negative counterparts of the same gender (Table 3; P < 0.05 for each comparison). Most couples were recruited from the area around the project site and reported living an average of 3.1 years at their current address (not shown). F+M− couples were comparatively mobile, having lived at their current location for an average of 2.6 years versus 3.5 years for M+F− couples (P < 0.0001).
None of the dichotomized demographic variables or risk factors presented remained significant predictors of having no follow-up after the enrollment visit for M+F− couples in univariate analysis (see Table 3; see second set of columns in Table 2A). For F+M− couples, however, women's age ≤25 years, men's age ≤30 years, low or no alcohol intake for the woman, and the male partner reporting an outside sex partner during the past 3 months were predictive of not having follow-up in univariate analyses, and the latter 3 variables remained independently predictive in the multivariate analysis (see Table 3; see second set of columns in Table 2B).
Among couples with follow-up after the enrollment visit, women's age <17 years at first intercourse was predictive of subsequent loss to follow-up in M+F− and F+M− couples (see right-hand columns in Tables 2A, B). In M+F− couples, women's age ≤25 years and not residing close to the research site were independently predictive of loss to follow-up in multivariate analysis. No income for women and comparatively good health for men (Kigali HIV disease stage 1 or 2) were significant in univariate analysis but did not persist in multivariate analysis (see Table 2A). Among F+M− couples, the female partner reporting no income, ≤2 lifetime partners, and not having an STI in the past 5 years were significant predictors of loss to follow-up and remained so in multivariate analysis (see Table 2B).
Less than half of discordant couples identified in study-sponsored CVCT sites enrolled and returned for follow-up. Among couples with HIV-positive men, there were few differences between the 55% who enrolled with follow-up and the 45% who were ineligible, did not enroll, or had no follow-up beyond enrollment. In contrast, among couples with HIV-positive women, there was biased retention with differences in demographic and risk factor profiles between the 43% with follow-up and the 57% without.
A main barrier to HIV prevention and treatment in the African setting is traditional gender roles,21,43,44 which may also influence a woman's decision to participate in research. It is plausible that the couples enrolled here represent a subset of couples in which women have greater decision-making autonomy. Enrolled couples were older and had longer durations of union and more children than nonenrolled couples; these may also be characteristics that are associated with greater female autonomy (if autonomy develops over time as a woman's position in the family is secured through childbearing).
Among HIV-positive women, having no income and having a partner who reported recent contact with other partners was associated with loss to follow-up, and being illiterate in English was predictive of irregular attendance. The lower socioeconomic and educational status of these women,45 and the threat posed by the man's other partners,43 may have reduced their ability to negotiate participation in a research study. It is hard to establish whether the CVCT activities attract couples with greater gender equity; however, to address this, outreach activities should focus on the young, illiterate, and unemployed who were underrepresented here.
On average, women in our study had initiated sex at the age of 16 years and reported 2 premarital partners in the 4 to 5 years before entering their current union. Early sexual debut of African women is associated with early infection with HIV.46-49 Women's age <17 years at first intercourse was independently predictive of loss to follow-up in HIV-positive and HIV-negative women. Other measures related to retention and adherence included high alcohol intake in HIV-positive women, which was rare (6%) and associated with a paradoxically increased likelihood of enrollment but also with a greater likelihood of missing appointments. High alcohol intake was much more common among men50 but was not associated with enrollment or follow-up. Early sexual debut and alcohol consumption, both nonnormative behaviors for women in the cohort, are clearly associated with enrollment and retention, although in differing ways. Although these may be reflections of the socioeconomic status of the women,51-53 they may also reflect variations in familial background or psychological functioning. Further research is warranted to elucidate clearly the reasons behind these relations and to ensure that services are tailored toward the unique needs of these women.
HIV-positive women who reported a history of STI were significantly more likely to remain in follow-up, in all likelihood because they valued the STI screening and treatment provided to study participants. Free health care is much appreciated as a benefit of research participation,54 and it ensures good documentation of manifestations of HIV disease and potential cofactors for HIV transmission. The increased enrollment among modern contraceptive users suggests that family planning services were also appreciated.31,32,55 Discordant couples are advised to use condoms to prevent HIV transmission and an additional user-independent method to ensure added protection against unplanned pregnancy.56,57 Younger couples were less likely to enroll and remain in the study, possibly because they had not achieved their desired family size and were reluctant to participate in a study that placed a heavy emphasis on condom use. Fertility intentions should be discussed during counseling, and couples should be reassured that researchers are not negatively judging study participants.
Enrolled couples were reimbursed for transport, and childcare services were provided at the research site. Although this helped to reduce logistic obstacles,16,36,37,58 residing far from the clinic remained a significant predictor of attrition. Participants could walk to the clinic if they lived nearby, but bus fares were expensive. Couples needed enough money to travel, often with small children, to the clinic. Mechanisms that facilitate travel, such as vouchers or satellite clinics, should be considered in settings where distance inhibits study participation. Few participants had telephones or mailing addresses, and reminders were delivered to the home. With the increasing availability of low-cost mobile phones, telephone cards may be a useful addition to retention efforts in similar areas.36,37
The research activities described here have demonstrated the feasibility of enrolling and retaining large cohorts of serodiscordant couples; however, there were a number of issues unique to couples that must be considered. First, couples' testing was not widely available; thus, there were limited sites through which to identify discordant couples.34,59 The success of the enrollment and retention activities described here rested on the presence of a couple-focused clinical service (CVCT) from which to recruit. With the availability of more and simpler HIV rapid tests, novel strategies such as home-based HIV testing may be explored as a mechanism to expand access HIV testing.60
To remain active in a discordant couples' cohort, both partners had to be cohabiting in a sexual union. Consent procedures required individual consent from both partners, and enrollment was not limited by a need for the male partner to consent on behalf of the couple61 (although a woman would not be able to enroll if her partner refused his own participation, a man's participation would be similarly limited by his partner's refusal to consent to enrollment). Retention was also a challenge; studies of high-risk groups, particularly women, in HIV vaccine preparedness and other clinical trial programs have yielded retention rates as low as 44% to 66%.62-65 Focusing on couples adds new challenges, because the loss of either partner as a result of death or seroconversion or dissolution of the union results in loss of the couple. Separation of couples was uncommon, reported in only 4% of eligible discordant couples, a similar rate to that found in a clinical trial of VCT that took place in Kenya, Tanzania, and Trinidad and Tobago.42 In our experience, as in other reports,37 most couples were lost between screening (CVCT) and enrollment and immediately after the baseline visit. In such circumstances, clinical trials may benefit from a “run-in” design that begins with several visits before randomization. Additionally, couples-focused clinical trials may have additional exclusion criteria, such as pregnancy or highly active antiretroviral therapy (HAART) use, that further reduce the screen-to-enroll ratio. Any couples-focused research must recognize the competing social, economic, and reproductive forces that may influence continued participation. Interventions that allow couples to discuss and manage these factors are likely to encourage greater rates of enrollment and retention.
The authors thank the study participants, staff, interns, and Project Management Group members of the Zambia-Emory HIV Research Project in Lusaka, Zambia. They also thank Martha Conkling, PhD, for her editorial review and comments.
Dr. Mirjam-Colette Kempf participated in the preparation of the manuscript and coordinated the analysis, Robert Stephenson coordinated the revision in response to reviewer comments, and Ilene Brill served as the statistician for the paper. Susan Allen is the Principal Investigator for the Rwanda Zambia HIV Research Group and was responsible for securing funding, supervising data collection, and finalizing the revised manuscript. Isaac Zulu and Nzali Kancheya oversaw all recruitment and retention efforts in the field and were an active part of the paper revision process while completing their Master of Public Health degrees in the United States. Elwyn Chomba is the Senior Co-Investigator of the Zambia Emory HIV Research Project. Amanda Tichacek participated in all aspects of the study from study design to creation of instruments and data analysis and reviewed the manuscript. Alan Haworth assisted with manuscript preparation and revision.
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