Effect of Baseline HIV Disease Parameters on CD4+ T Cell Recovery After Antiretroviral Therapy Initiation in Kenyan Women Lyle R. McKinnon1,2*, Makobu Kimani2, Charles Wachihi2, Nico J. Nagelkerke3, Festus K. Muriuki2, Anthony Kariri2, Richard T. Lester2,4¤, Lawrence Gelmon2,4, T. Blake Ball4,5,6, Francis A. Plummer2,4,7, Rupert Kaul1,2, Joshua Kimani2,4 1 Department of Medicine, University of Toronto, Toronto, Canada, 2 Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya, 3 Department of Community Medicine, United Arab Emirates University, Al Ain, United Arab Emirates, 4 Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada, 5 Department of Immunology, University of Manitoba, Winnipeg, Canada, 6 Laboratory of HIV Immunology, Public Health Agency of Canada, Winnipeg, Canada, 7 National Microbiology Lab, Public Health Agency of Canada, Winnipeg, Canada Abstract Background: Antiretroviral therapy (ART) for HIV infection reconstitutes the immune system and improves survival. However, the rate and extent of CD4+ T cell recovery varies widely. We assessed the impact of several factors on immune reconstitution in a large Kenyan cohort. Methodology/Principal Findings: HIV-infected female sex workers from a longitudinal cohort, with at least 1 year of pre- ART and 6 months of post-ART follow-up (n = 79), were enrolled in the current study. The median pre-ART follow-up was 4,040 days. CD4 counts were measured biannually and viral loads where available. The median CD4 count at ART initiation was 180 cells/ul, which increased to 339 cells/ul at the most recent study visit. The rate of CD4+ T cell increase on ART was 7.91 cells/month (mean = 13, range 225.92 to 169.4). LTNP status prior to ART initiation did not associate with the rate of CD4 recovery on ART. In univariate analyses, associations were observed for CD4 recovery rate and duration of pre-ART immunosuppression (r = 20.326, p = 0.004) and CD4 nadir (r = 0.284, p = 0.012). In multivariate analysis including age, CD4 nadir, duration of HIV infection, duration of pre-ART immunosuppression, and baseline viral load, only CD4 nadir (p = 0.007) and not duration of immunosupression (p = 0.87) remained significantly associated with the rate of CD4 recovery. Conclusions/Significance: These data suggest that prior duration of immune suppression does not predict subsequent recovery once ART is initiated and confirm the previous observation that the degree of CD4 depletion prior to ART initiation is the most important determinant of subsequent immune reconstitution. Citation: McKinnon LR, Kimani M, Wachihi C, Nagelkerke NJ, Muriuki FK, et al. (2010) Effect of Baseline HIV Disease Parameters on CD4+ T Cell Recovery After Antiretroviral Therapy Initiation in Kenyan Women. PLoS ONE 5(7): e11434. doi:10.1371/journal.pone.0011434 Editor: Douglas F. Nixon, University of California San Francisco, United States of America Received March 17, 2010; Accepted June 8, 2010; Published July 2, 2010 Copyright: 2010 McKinnon 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: Funding for these studies was provided by the United States President’s Plan for AIDS Relief (PEPFAR) Grant no. U62/CCU024510-05, as well as grants from the National Institutes of Health (R01 AI56980 A1), the Canadian Institutes of Health Research (HOP-43135), the Bill and Melinda Gates Foundation, and the Canadian Institutes of Health Research (CIHR) through the Grand Challenges in Global Health Initiative to FP, and Canadian Institutes of Health Research (CIHR) (MOP-89983) to RK. Salary support for FP and RK is provided by the Canada Research Chair program, and for LM by a CIHR Biomedical/Clinical HIV/AIDS Research Fellowship and the International Infectious Diseases and Global Health Training Program. 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: sijuisijali@gmail.com ¤ Current address: Division of STI/HIV Control, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada Introduction Since access to ART to treat HIV-1 infection has increased, life expectancy for people living with HIV has increased dramatically, from 5–10 years in the absence of treatment, to more than 25 years following HIV infection if treated appropriately [1]. ART decreases the risk of opportunistic infections following suppression of HIV replication, in conjunction with reconstitution of blood CD4+ T cell counts, partially reversing the hallmark immunode- ficiency that develops during AIDS [2,3]. This immune recovery means that co-infection prophylaxis can be safely discontinued in most successfully treated individuals [4]. However, not all individuals on ART reconstitute CD4+ T cells at the same rate, or to the same extent. As such, as many as 30% of patients who start ART are classified as immunological non- responders [5]. Factors that predict of poor immune reconstitution include a lower CD4 nadir [6,7], older age [8], increased immune activation [9,10], altered T cell homeostasis [7,11,12], markers of microbial translocation [13], and HIV co-receptor usage [14]. One US-based study demonstrated that individuals with a lower baseline CD4 count at the time of ART initiation achieved less immune reconstitution than those in the higher CD4 strata, and this was associated with reduced na¨ıve:memory CD4 cell and CD4:CD8 cell ratios [15]. To date, of many factors associated with PLoS ONE | www.plosone.org 1 July 2010 | Volume 5 | Issue 7 | e11434