Increased mortality among HIV-positive men on antiretroviral therapy: survival differences between sexes explained by late initiation in Uganda

Abstract

Steve Kanters,1,3 Margaret Nansubuga,2 Daniel Mwehire,2 Mary Odiit,2 Margaret Kasirye,2 William Musoke,2 Eric Druyts,3 Sanni Yaya,3 Anna Funk,3 Nathan Ford,4,5 Edward J Mills3,61Faculty of Health Science, Simon Fraser University, Burnaby, BC, Canada, 2Mildmay Uganda, Kampala, Uganda; 3Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada; 4Médecins Sans Frontières, Geneva, Switzerland; 5Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa; 6Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USABackground: We aimed to assess the relationship between gender and survival among adult patients newly enrolled on antiretroviral therapy (ART) in Uganda. We also specifically examined the role of antenatal services in favoring women's access to HIV care.Methods: From an observational cohort study, we assessed survival and used logistic regression and differences in means to compare men and women who did not access care through antenatal services. Differences were assessed on measures of disease progression (WHO stage and CD4 count) and demographic (age, marital status, and education), behavioral (sexual activity, disclosure to partner, and testing), and clinical variables (hepatitis B and C, syphilis, malaria, and anemia). A mediational analysis that considered gender as the initial variable, time to death as the outcome, initial CD4 count as the mediator, and age as a covariate was performed using an accelerated failure time model with a Weibull distribution.Results: Between 2004 and 2011, a total of 4775 patients initiated ART, and after exclusions 4537 (93.2%) were included in analysis. Men initiating ART were more likely to have a WHO disease stage III or IV (odds ratio: 1.46, 95% confidence interval [CI]: 1.29–1.66), and lower CD4 cell counts compared to women (median baseline CD4 124 cells/mm3, interquartile range [IQR]: 43–205 versus 147 cells/mm3, IQR: 68–212, P-value < 0.0001). Men were at an increased risk of death compared to women (hazard ratio: 1.38, 95% CI: 1.03–1.83). Baseline CD4 cell counts accounted for 43% of the increased risk of death in men (95% CI: 22%–113%). Access to care via antenatal services did not explain differences in outcomes.Conclusion: In this cohort there is a marked increase in risk of mortality for men and approximately half of it can be attributed to their later engagement in care. More effort is required to engage men in care in a timely manner.Keywords: HIV, antiretroviral therapy, gender, Uganda, antenatal care, mortality