Hormonal Contraceptive Use and HIV Disease Progression Among Women in Uganda and Zimbabwe

Abstract

Background HIV-infected women need highly effective contraception to reduce unintended pregnancies and mother-to-child HIV transmission. Previous studies report conflicting results regarding the effect of hormonal contraception (HC) on HIV disease progression. Methods HIV-infected women in Uganda and Zimbabwe were recruited immediately after seroconversion; CD4 testing and clinical exams were conducted quarterly. The study endpoint was time to AIDS (two successive CD4 ≤200 cells/mm3 or WHO advanced stage 3 or stage 4 disease). We used marginal structural Cox survival models to estimate the effect of cumulative exposure to depot-medroxyprogesterone acetate (DMPA) and oral contraceptives (OC) on time to AIDS. Results 303 HIV-infected women contributed 1,408 person-years (py). 111 women (37%) developed AIDS. Cumulative probability of AIDS was 50% at 7 years and did not vary by country. AIDS incidence was 6.6, 9.3 and 8.8 per 100py for DMPA, OC and non-hormonal users. Neither DMPA (adjusted hazard ratio (AHR) = 0.90; 95% CI 0.76-1.08) nor OCs (AHR =1.07; 95% CI 0.89-1.29) were associated with HIV disease progression. Alternative exposure definitions of HC use during the year prior to AIDS or at time of HIV infection produced similar results. STI symptoms were associated with faster progression while young age at HIV infection (18-24 years) was associated with slower progression. Adding baseline CD4 level and setpoint viral load to models did not change the HC results but subtype D infection became associated with disease progression. Conclusion Hormonal contraceptive use was not associated with more rapid HIV disease progression but older age, STI symptoms and subtype D infection were.

Infecting HIV-1 Subtype Predicts Disease Progression in Women of Sub-Saharan Africa

“…A complete description of the Ugandan and Zimbabwean participants is previously described (Morrison et al, 2011, Lemonovich et al, 2015). Women who became HIV infected while participating in the Hormonal Contraception and Risk of HIV Acquisition Study in Uganda and Zimbabwe (Morrison et al, 2007) were enrolled upon primary HIV-1 infection into a subsequent study, the Hormonal Contraception and HIV-1 Genital Shedding and Disease Progression among Women with Primary HIV Infection (GS) Study (Morrison et al, 2010, Morrison et al, 2011, Lemonovich et al, 2015).…”

“…Women who became HIV infected while participating in the Hormonal Contraception and Risk of HIV Acquisition Study in Uganda and Zimbabwe (Morrison et al, 2007) were enrolled upon primary HIV-1 infection into a subsequent study, the Hormonal Contraception and HIV-1 Genital Shedding and Disease Progression among Women with Primary HIV Infection (GS) Study (Morrison et al, 2010, Morrison et al, 2011, Lemonovich et al, 2015). Ethical approval was obtained from the Institutional Review boards (IRBs) from the Joint Clinical Research Centre and UNST in Uganda, from University of Zimbabwe, from the University Hospitals of Cleveland, and recently, from Western University.…”

“…From 1999 to 2003, over 4400 HIV-negative women in Uganda and Zimbabwe were enrolled in the Hormonal Contraception and the Risk of HIV Acquisition (HC-HIV) Study (Morrison et al, 2007), during which 303 women were identified with incident HIV infection and participated in the Hormonal Contraception and HIV-1 Genital Shedding and Disease Progression among Women with Primary HIV Infection (GS) Study (Morrison et al, 2010, Morrison et al, 2011, Lemonovich et al, 2015). The 76 subtype A, 177 subtype C, 31 subtype D and two URF HIV infected women (286 of 303 women) were followed for an average of 5 years, currently the largest natural history cohort of non-subtype B infections.…”

Comparison of Antibody Responses to HIV Infection in Ugandan Women Infected with HIV Subtypes A and D

“…17 We analyzed samples from a subgroup of Ugandan women in this study, aged 18-45 who were infected with HIV subtype A (N = 82) or subtype D (N = 32). These women were followed for at least 1 year after HIV seroconversion and had samples available from three or more study visits after HIV seroconversion (2,614 samples; median: 23 samples per woman; range: 3-41 samples; years of sample collection: 2001-2009, see Table 1).…”

“…18 HIV subtypes were determined previously based on phylogenetic analysis of the gp120 C2-V3 region of the HIV env gene. 17 The estimated date of seroconversion for each woman was defined as the midpoint between the last negative HIV antibody test and the first positive HIV antibody test, or 15 days after a visit documenting acute (HIV RNA-positive/antibody-negative) HIV infection. 17 …”