Comparison of Sexual Behavior and HIV Risk between Two HIV-1 Serodiscordant Couple Cohorts: The CHAVI 002 Study Adam J. Ritchie 1 *, Kristin Kuldanek 2 , Zoe Moodie 3 , Z. Maggie Wang 3 , Julie Fox 4 , Rebecca N. Nsubuga 5 , Kenneth Legg 2 , Esther F. Birabwa 5¤b , Pontiano Kaleebu 5 , Andrew J. McMichael 1 , Christine Watera 5¤a , Nilu Goonetilleke 1 , Sarah Fidler 2 1 Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom, 2 HIV Clinical Trials Centre, Imperial College, St Mary’s Hospital, London, United Kingdom, 3 Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 4 Department of HIV, Faculty of Medicine, King’s College, Guy and St Thomas’ Hospital, London, United Kingdom, 5 MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda Abstract Background: The CHAVI002 study was designed to characterize immune responses, particularly HIV-specific T-cell responses, amongst 2 cohorts of HIV-exposed seronegative (HESN) individuals. The absence of a clear definition of HESNs has impaired comparison of research within and between such cohorts. This report describes two distinct HESN cohorts and attempts to quantify HIV exposure using a ‘HIV risk index’ (RI) model. Methods: HIV serodiscordant couples (UK; 24, Uganda; 72) and HIV unexposed seronegative (HUSN) controls (UK; 14, Uganda; 26 couples, 3 individuals) completed sexual behavior questionnaires every 3 months over a 9 month period. The two cohorts were heterogeneous, with most HESNs in the UK men who have sex with men (MSM), while all HESNs in Uganda were in heterosexual relationships. Concordance of responses between partners was determined. Each participant’s sexual behavior score (SBS) was estimated based on the number and type of unprotected sex acts carried out in defined time periods. Independent HIV acquisition risk factors (partner plasma viral load, STIs, male circumcision, pregnancy) were integrated with the SBS, generating a RI for each HESN. Results: 96 HIV serodiscordant couples completed 929 SBQs. SBSs remained relatively stable amongst the UK cohort, whilst decreasing from Visit 1 to 2 in the Ugandan cohort. Compared to the Ugandan cohort, SBSs and RIs in the UK cohort were lower at visit 1, and generally higher at later visits. Differences between the cohorts, with lower rates of ART use in Uganda and higher risk per-act sex in the UK, had major impacts on the SBSs and RIs of each cohort. There was one HIV transmission event in the UK cohort. Conclusions: Employment of a risk quantification model facilitated quantification and comparison of HIV acquisition risk across two disparate HIV serodiscordant couple cohorts. Citation: Ritchie AJ, Kuldanek K, Moodie Z, Wang ZM, Fox J, et al. (2012) Comparison of Sexual Behavior and HIV Risk between Two HIV-1 Serodiscordant Couple Cohorts: The CHAVI 002 Study. PLoS ONE 7(5): e37727. doi:10.1371/journal.pone.0037727 Editor: Jianming Tang, University of Alabama at Birmingham, United States of America Received December 28, 2011; Accepted April 23, 2012; Published May 22, 2012 Copyright: ß 2012 Ritchie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the Center for HIV/AIDS Vaccine Immunology (National Institute of Allergy and Infectious Diseases grant A1067854). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: adam.ritchie@imm.ox.ac.uk ¤a Current address: Uganda Virus Research Institute, Entebbe, Uganda ¤b Current address: Infectious Disease Institute, Kampala, Uganda Introduction The overall risk of sexual HIV transmission reflects the frequency and nature of exposure to virus with different sex acts confer varying risks of transmission [1–10]. In addition the susceptibility of an HIV uninfected individual, and the infectious- ness of their HIV seropositive partner contribute to transmission risk [2]. The concept that certain rare individuals remain HIV uninfected despite repeated sexual exposure to an HIV infected partner has long been described [11–18]. Whilst HIV exposed seronegative (HESN) individuals have provided extensive infor- mation on the biology of HIV transmission, the relative and specific contributions of host and viral factors underlying HIV ‘resistance’ remain unclear. The absence of a consistent definition of HESNs and inclusion of well-defined control groups has complicated comparisons both between and within studies [19]. Unanswered questions remain about the frequency, type of sex, and duration of exposure required to define a HESNs phenotype. Many studies of sexual behavior have focused on either men who have sex with men (MSM) or heterosexual populations, and it is PLoS ONE | www.plosone.org 1 May 2012 | Volume 7 | Issue 5 | e37727