Adherence to daily, oral TDF/FTC PrEP during periconception among HIV-exposed South African women

Abstract

Background: Daily, oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP) reduces HIV acquisition for African women. Adherence is key to efficacy and patterns of adherence can be highly variable in real-world settings. Using group-based trajectory modeling (GBTM), we sought to identify distinct patterns of periconception PrEP adherence and evaluate potential baseline predictors of such adherence trajectories.

Methods: We conducted a single-arm longitudinal study for women aged 18-35 years living in Durban, South Africa with personal or partner plans for pregnancy with a partner with HIV or of unknown serostatus. Participants were offered safer conception counseling, including daily oral PrEP; women who initiated PrEP were given a bottle with an electronic pillcap that recorded when device opens. Weekly adherence to daily PrEP was modeled using GBTM with a censored normal outcome distribution as a function of weeks since PrEP initiation. The number and functional form of the adherence trajectory groups were primarily selected based on Bayesian information criteria (BIC) and confirmed by mean estimated probabilities of group membership. A multivariable version of the selected model assessed baseline predictors of membership in adherence trajectory groups.

Results: Overall mean (95% CI) adherence to PrEP was 63% (60%, 67%). We identified four groups of women with distinct patterns of adherence: (1) high (i.e., ≥6 doses per week) steady adherence throughout follow-up (22% of PrEP initiators); (2) moderate (i.e., 4-5 doses per week), but steady adherence (31%); (3) initially high, but consistently declining adherence (21%); and (4) initially moderate adherence, followed by a rapid decline and subsequent rebound (26%). In multivariable-adjusted analyses, older age was associated with membership in the high, steady adherence group as compared to the group identified with an adherence trajectory of initially high, then decline, and finally a rebound.

Conclusions: GBTM is useful for exploring potential heterogeneity in longitudinal patterns of medication adherence. Although a large proportion of women in this study achieved high levels of adherence by electronic pillcap initially, far fewer women maintained these levels consistently. Knowledge of different adherence trajectories could be used to develop targeted strategies for optimizing HIV prevention during periconception.

Keywords: HIV prevention; adherence; group-based trajectory modeling (GBTM); oral pre-exposure prophylaxis (PrEP); periconception; women.

Figure 1

Summary of enrollment, eligibility, and retention of cohort included in trajectory analysis.

Figure 2

Observed (solid lines) and predicted (dashed lines) weekly adherence to PrEP over 39 months of follow-up assuming 2, 3, 4, and 5 trajectory groups and third-order polynomial terms for time since PrEP initiation.

Figure 3

Observed (solid lines) and predicted (dashed lines) weekly adherence to PrEP over 39 months of follow-up assuming four trajectory groups and up to second-order polynomial terms for time since PrEP initiation.