Evaluation of Recruitment Approaches for the HPTN 052 Clinical Trial of HIV Serodiscordant Couples in Rural Western Kenya

Recruitment of couples is important for study success. The multi-centered HPTN 052 clinical trial was designed to evaluate whether immediate versus delayed use of ART by HIV-infected individuals would reduce transmission of HIV to their HIV-uninfected partners. The objective of this study was to retrospectively compare several approaches for community recruitment at our site in Kisumu, Kenya based on a) feedback from recruitment staff, b) associated cost, and c) number of eligible couples enrolled. A secondary objective was to assess the discordant couples’ acceptability of the community recruitment approaches relative to the a) main recruitment venues, b) educational materials, and c) local language best suited for explaining the trial. 241 couples were screened for eligibility using nine recruitment approaches. We compared the approaches used for the 60 couples found to be eligible to those used for the 56 ineligible couples for whom that information was available. Analyses for association were carried out. In-depth interviews were conducted with 20 staff and 29 discordant couples. Records were kept of the costs associated with each approach. Overall, staff interviews revealed that acceptability of the approaches was high. Challenges were present with all approaches ranging from one member of the couple not wanting to reveal their positive HIV status to their partner (Patient Support Center or PSC approach), to not finding people at home (home based counseling and testing or HBCT approach). The PSC and the HBCT recruitment approaches were the most effective in terms of recruiting eligible participants. There was an overall significant difference between the proportion of eligible and ineligible participants among the 9 approaches (χ (8) =33.5; p<0.0001). Analyses for association showed that the PSC approach resulted in attracting a greater proportion of couples who were eligible than ineligible (χ (1) =6.6; p=0.016). The cost for the PSC approach was less than one-third that of the HBCT approach. All discordant couples interviewed found the two main recruitment venues (PSC and their home) acceptable. Among couples who saw the educational materials, the majority found them useful (poster 72.7%; pamphlet 90.9%; flyer 88.9%). All couples found the language they were told about the study acceptable. The evaluation of recruitment approaches indicated that working with local partners, specifically the PSC staff and HBCT staff, was the most effective way to recruit eligible discordant couples. A focus on collaborations and partnerships between research and clinical organizations will help study recruitment efforts. DOI : 10.14302/issn.2324-7339.jcrhap-13-211 Correspondence: D.A. Gust, Epidemiology Branch, Division of HIV/AIDS Prevention, CDC 1600 Clifton Rd. Mail-Stop E-45, Atlanta GA 30333; phone 1-404-639-8841; fax 1-404-639-6127; e-mail dgust@cdc.gov; HPTN 052 ClinicalTrials.gov number, NCT00074581 Running head: Evaluation of recruitment approaches


Introduction
Enrolling qualified individuals in any clinical trial is an essential component of the success of the trial. HIV sero-discordant couples are frequently enrolled in HIV prevention intervention studies because these couples represent an important opportunity to prevent transmission. In Kenya, 5.9% of married or cohabiting couples (344,000 couples nationwide) are discordant [1]. Identification and recruitment of individuals as well as discordant couples for such studies can be particularly challenging, as there is a paucity of evidence on successful approaches. One major barrier is the low rate of both members of the couple being tested together [2] which may result from the reluctance of men in many parts of Africa to be tested [3]. Hospitals and clinics have often been cited as useful places to recruit women because the women are likely to have a history of trust with the staff, with subsequent identification of a woman's partner or spouse through further contact [4][5][6]. Active approaches such as using trained community members as recruiters [7] have been used as well as passive approaches (brochures, media) [8;9]. Training staff or community members to recruit women or couples in conjunction with more passive outreach such as posters, radio and pamphlets has been reported to be successful [3;10-13]. Respondent driven sampling where persons refer others they know to a study has been used to recruit discordant couples with some success likely due to the already established trusting relationship between referer and referee [7;14-16].

Participant Screening and Recruitment
The HPTN 052 study was conducted in Kisumu, Nyanza Province, Kenya which has a population of approximately 500,000 residents (Central Bureau of Statistics, 2000). Most residents are of Luo ethnicity [18] and speak Dholuo and often Kiswahili and English.
HIV prevalence in Nyanza Province is the highest among the eight provinces of Kenya, at 14.9% [1].
Couples were screened for HPTN 052 eligibility using the following criteria: couples reported having had vaginal or anal sex with one another at least three times in the three months prior to enrollment, the index participant had a positive HIV serology within 60 days prior to enrollment, the partner was HIV-seronegative, the couple planned to maintain a sexual relationship with each other, and intended to remain in the study area for the duration of the projected study follow-up. Other eligibility criteria included: resided in the study areas (Asembo and Karemo), and that the index participant was ARV naïve and in good health with normal laboratory parameters.
During recruitment for the HPTN 052 main study, potential participants were given explanations about the study, told that the information they provided would be kept confidential, and informed that their participation was voluntary and they could refuse to answer any questions. Potential participants were also asked to

Chart Reviews
Data for each recruitment approach were abstracted from the chart notes this was conducted retrospectively after the recruitment period was over and was available for all 60 eligible couples and for 56/181 ineligible couples.
Couples for which recruitment approach information was unavailable were potential participants who had come to the clinic site and been assigned study IDs, but did not complete the screening consent procedure or were declared ineligible due to not meeting the eligibility criteria. These couples did not proceed to the nurse counselor for the next procedure where the details of the recruitment approach were charted.  (1) =0.17; p=0.68).

Feedback from recruitment staff
Staff reported on the six approaches with which they were familiar (Table 1). They did not report on three of

Number of eligible couples enrolled by recruitment method
Among the 9 recruitment approaches used, there was an overall significant difference between the proportion of eligible and ineligible participants (χ 2 (8) =33.5; p<0.0001) the approaches yielded. The PSC approach resulted in attracting a greater proportion of couples who were eligible than ineligible (χ 2 (1) = 6.6; p=0.016).
In contrast, the peer educator approach resulted in attracting a greater proportion of ineligible than eligible couples (χ 2 (1) =24.3; p=<0.0001) ( General Community Mobilizationinformational talks at barazas or meetings of the community called by a chief, or at markets and women's groups.

Home Based Counseling and Testing:
nurses and counselors visit persons in their homes to conduct HIV counseling and testing. They use hand-held computers to enter data about the family's health, HIV test results, and the physical location of the household to allow follow-up. Persons who are found to be HIVpositive during this activity are immediately given a referral for follow-up clinical care. All persons tested are asked whether they are willing to receive a future follow-up visit.

Health and Demographic Surveillance
System -KEMRI/CDC staff who carry out a population registration system that monitors health and demographic dynamics in a geographically defined population in the areas of Asembo, Gem, and Karemo.

3(38)
"Some (at beach area) were like we don't want to hear."

Home Based
Counseling and Testing (HBCT) staff N=9 9(100) "To some, it pleased them, yet to some that was not the case; it was bad but generally very few people did not like it." 9(100) "Walking was not easy, timing of the potential clients was also not an easy task for us since we could go to homes and find that everybody else had left for the farms."

Domains of Inquiry Proportion (%) Representative Quote
Venue-Acceptability Patient Support Centers 10/10 (100) "It was good because we were together and all that happened we saw and we were told how we can help ourselves even though one of us is having it and the other does not." Home Based Counseling and Testing 19/19 (100) "That was good for me because he came and got us in the house, we did not pursue or look for him, he came by himself and we welcomed him." Language heard about study-Acceptability "..let them clarify how people infected with the virus will continue living." Pamphlet c 10/11 (90.9) "I thought it was good, when one is tested then both should." Flyer 8/9 (88.9) "I saw it and realized that it was a program for "Sir Jaodi" so I take another look at it once more." Table 3: Discordant couple interview responses (N=29) regarding acceptability of the two most frequently used recruitment venues, language used for HPTN 052 recruitment, and for those who saw educational materials, their opinions about the usefulness of the materials, Kisumu, Kenya, 2010.
Note: Information was always provided in Dholuo and sometimes in Kiswahili and English. All couples listed Dholuo as acceptable to receive study information. a Two persons were not asked about language acceptability so the denominator is less than 29. b Not all couples saw the educational materials so the denominator is less than 29. c One couple did not have an absolute opinion about the poster and pamphlet, they thought in some ways they were useful and in some ways not useful.   where fewer programs already exist. Finally, there was the possibility that participants were exposed to more than one recruitment approach as this was not an experimental study. However, we asked the participants to report the main recruitment approach that brought them to the clinic. The strength of this site specific analysis is that it provides a quantitative and qualitative evaluation of the recruitment approaches used for a clinical trial and can also be applied to programmatic work, which is increasingly focused on HIV serodiscordant couples, an important population in the multifaceted fight against the HIV scourge.
Our successful recruitment of discordant couples to participate in the HPTN 052 trial used a combination of active and passive approaches. Our evaluation of these recruitment approaches indicated that working with local HIV programs, specifically the PSC and HBCT, was the most effective approach to recruit eligible couples with the PSC approach being the less costly of the two.
Collaborations and partnerships have been highlighted as being effective in other areas of health and research [27][28]. Future research and evaluations should consider the benefits of community, health facility/ provider and research organization partnerships.