Vaginal microbiome, antiretroviral concentrations, and HIV genital shedding in the setting of hormonal contraception initiation in Malawi

Abstract

Objective: The aim of this study was to understand how vaginal microbiota composition affects antiretroviral concentrations in the setting of hormonal contraception initiation.

Methods: Cervicovaginal fluid (CVF) concentrations of tenofovir, lamivudine, and efavirenz from 73 Malawian women with HIV were compared before and after initiation of depot-medroxyprogesterone acetate (DMPA) or levonorgestrel implant. We evaluated antiretroviral concentrations and vaginal microbiota composition/structure in the context of contraception initiation and predicted genital shedding using multivariable repeated measurements models fit by generalized estimating equations.

Results: Mean lamivudine CVF concentrations decreased 37% 1 month after contraception initiation. Subgroup analyses revealed a 41% decrease in women 1 month after initiating levonorgestrel implant, but no significant difference was observed in DMPA group alone. Tenofovir, lamivudine, and efavirenz CVF concentrations were positively correlated with anaerobic bacteria associated with nonoptimal vaginal microbiota. Risk of genital HIV shedding was not significantly associated with tenofovir or lamivudine CVF concentrations [tenofovir relative risk (RR): 0.098, P = 0.75; lamivudine RR: 0.142, P = 0.54]. Lack of association between genital HIV shedding and efavirenz CVF concentrations did not change when adjusting for vaginal microbiota composition and lamivudine/tenofovir CVF concentrations (RR: 1.33, P = 0.531).

Conclusion: No effect of hormone initiation on genital shedding provides confidence that women with HIV on either DMPA or levonorgestrel implant contraception will not have compromised ART efficacy. The unexpected positive correlation between antiretroviral CVF concentrations and certain bacterial taxa relative abundance requires further work to understand the mechanism and clinical relevance.

Figure 1.. Antiretroviral concentrations affected by Progestin contraception initiation.

Cervicovaginal fluid concentrations of tenofovir, lamivudine and efavirenz were measured from Wek-Cel sponges using LC-MS/MS. The log transformed tenofovir (A), lamivudine (B), and efavirenz (C) concentrations were compared before, 3 days after, and 4 weeks after contraception initiation using general estimating equations. Concentrations between women on depot medroxyprogesterone acetate injectable (red) and levonorgestrel implant (teal) were compared at each visit. There were no significant statistical differences for tenofovir or efavirenz. Mean lamivudine concentrations significantly decreased 37% 1 month after contraception initiation. Mean lamivudine CVF concentrations decreased 41% in women on the levonorgestrel implant post-contraception initiation compared to pre-contraception initiation, but no significant difference for DMPA. Antiretroviral concentrations in the cervicovaginal fluid before, 3 days after, and 1 month after contraceptive hormone initiation for A) tenofovir, B) lamivudine, and C) efavirenz.

Figure 1.. Antiretroviral concentrations affected by Progestin contraception initiation.

Cervicovaginal fluid concentrations of tenofovir, lamivudine and efavirenz were measured from Wek-Cel sponges using LC-MS/MS. The log transformed tenofovir (A), lamivudine (B), and efavirenz (C) concentrations were compared before, 3 days after, and 4 weeks after contraception initiation using general estimating equations. Concentrations between women on depot medroxyprogesterone acetate injectable (red) and levonorgestrel implant (teal) were compared at each visit. There were no significant statistical differences for tenofovir or efavirenz. Mean lamivudine concentrations significantly decreased 37% 1 month after contraception initiation. Mean lamivudine CVF concentrations decreased 41% in women on the levonorgestrel implant post-contraception initiation compared to pre-contraception initiation, but no significant difference for DMPA. Antiretroviral concentrations in the cervicovaginal fluid before, 3 days after, and 1 month after contraceptive hormone initiation for A) tenofovir, B) lamivudine, and C) efavirenz.