# Oral preexposure prophylaxis use and the risk of bacterial sexually transmitted infections and HIV among African women: A prospective observational cohort study

## TL;DR

This study found that using HIV preexposure prophylaxis (PrEP) among African women did not increase the risk of bacterial STIs, and HIV incidence was low among consistent PrEP users.

## Contribution

The study provides novel evidence on PrEP use and STI risk in African women, showing no increased STI risk and highlighting missed HIV prevention opportunities.

## Key findings

- PrEP use was not associated with increased STI risk compared to non-users.
- Chlamydia accounted for 87.7% of STI diagnoses during follow-up.
- No HIV infections occurred among consistent PrEP users despite high condomless sex rates.

## Abstract

Oral preexposure prophylaxis (PrEP) effectively reduces HIV incidence when used with sufficient adherence, but does not protect against bacterial sexually transmitted infections (STIs). Several studies have documented high rates of bacterial STIs among individuals initiating and using PrEP. We evaluated the association between PrEP use and the risk of STI among African women accessing family planning clinics.

We conducted a prospective cohort study nested within a large pragmatic stepped-wedge cluster randomized trial of PrEP delivery in Kenyan family planning clinics, with participant enrollment from June 18, 2021, to May 18, 2023, and follow-up through February 02, 2024 (ClinicalTrials.gov: NCT04666792). The study population included sexually active HIV–negative women aged ≥15 years at elevated HIV risk per Kenyan PrEP guidelines. Participants were offered standard-of-care oral PrEP with the option to decline and followed quarterly for 12 months with assessments of HIV status, sexual behavior, and PrEP use. Urine samples were batch tested for Neisseria gonorrhoeae and Chlamydia trachomatis using the GeneXpert CT/NG real-time polymerase chain reaction nucleic acid amplification test assay. The primary exposure was self-reported PrEP initiation and PrEP use consistency through 6 months, categorized as never used PrEP, inconsistently on PrEP, or consistently on PrEP. Multivariable modified Poisson generalized estimating equation (GEE) models with robust standard errors were used to estimate associations between PrEP use and incident STI; clinic-level intracluster correlation coefficients were negligible. The secondary outcomes were incident HIV infection and sexual behaviors, which included condomless sex at last sex, sex with any new partners in the past 3 months, and multiple sex partners. HIV testing was performed at each scheduled visit, at enrollment, and 1, 3, 6, 9, and 12 months following the Kenya national HIV testing algorithm, using Determine HIV-1/2 and Fast Response test kits. All models for the primary outcome were adjusted for baseline covariates determined apriori as potential confounders, which included age, STI diagnosis at enrollment, any contraceptive use, number of sexual partners (categorized as any more than one sexual partner), education status, marital status, last partner HIV status, any transactional sex in 3 months pre-enrollment, and clinic site.

Among 650 women enrolled, 60.0% (389) initiated PrEP at baseline and 14.6% (38/261) initiated post-enrollment. Median age was 26 years (IQR 23–30), 40% (262/650) were aged ≤24 years, and 67% (436/648) did not know their primary partner’s HIV status. At baseline, 11% (74/650) had an STI, including 9.9% (23/232) of consistent PrEP users, 9.2% (13/141) of inconsistent users, and 14.0% (38/277) of women who declined PrEP. During follow-up, 19.1% (114/597) had at least one STI diagnosis, with similar risk among women who initiated PrEP at baseline compared with those who declined (19.2% [68/354] versus 18.9% [46/244]; aRR 1.11, 95% CI 0.76–1.61; p = 0.580). Compared with non-PrEP users (12.7% [25/195]), STI risk was 6.0% (12/200) among consistent PrEP users (aRR 0.56, 95% CI 0.27–1.19; p = 0.130) and 16.5% (17/103) among inconsistent users (aRR 1.43, 95% CI 0.73–2.77; p = 0.290). Chlamydia accounted for 87.7% (100/114) of STI diagnoses. STI risk was higher among women aged ≤24 years (aRR 1.47, 95% CI 1.04–2.07; p = 0.029) and those with a baseline STI (aRR 2.96, 95% CI 2.12–4.14; p < 0.001). Four HIV infections occurred over 594 person-years (incidence 0.67, 95% CI 0.18–1.72 per 100 person-years), including three among women who declined PrEP (incidence 1.25, 95% CI 0.26–3.66 per 100 person-years). The main study limitation was oral PrEP use was assessed based on client self-report and not objectively through drug levels testing.

In this prospective cohort study among African women at elevated risk for HIV, 60% initiated PrEP at baseline and 14.6% (38/261) post-enrollment. PrEP use was not associated with increased risk for STI diagnosis through one year of follow-up. HIV incidence was low overall, consistent with expanded PrEP availability in similar populations.

Oral preexposure prophylaxis (PrEP) effectively reduces the risk of HIV infection when used with sufficient adherence but does not protect against other STIs.

Several studies have documented high rates of bacterial STIs among individuals initiating and using PrEP.

The role of PrEP in driving the increased risk for STI acquisition among individuals using PrEP has been a source of substantial scientific and public health debate.

While bacterial STI incidence among men using PrEP is well documented, data on bacterial STI incidence among women using PrEP remain limited.

We conducted an observational cohort study among 650 HIV–negative Kenyan women aged ≥15 years at substantial risk for HIV who were eligible for PrEP and enrolled between June 2021 and February 2024 at five public-sector family planning clinics.

Participants were offered standard-of-care oral PrEP and followed quarterly for 12 months with HIV testing, batched urine-based testing for Chlamydia trachomatis (C. trachomatis) and Neisseria gonorrhoeae (N. gonorrhoeae) using NAAT (GeneXpert CT/NG), and assessments of sexual behavior, PrEP use, and HIV risk according to Kenya national PrEP guidelines.

Approximately 20% of women were diagnosed with C. trachomatis or N. gonorrhoeae during follow-up, with chlamydia accounting for >87% of infections; rates of bacterial STI diagnosis for these two common curable STIs did not meaningfully differ by PrEP use status.

About 60% of women offered PrEP initiated use; no HIV infections occurred among women reporting consistent PrEP use, despite high levels of condomless sex and >78% of participants not knowing their primary partner’s HIV status. Seventy-five percent of all HIV infections (3/4) occurred among women who declined PrEP through 12 months of follow-up

Women who used PrEP did not have a higher risk of getting an STI over the year compared with women who did not use PrEP.

The frequency of curable STIs among African women eligible for PrEP was high through one year of follow-up and was similar for different categories of PrEP use.

No HIV infection occurred in women reporting consistent PrEP use, but 75% of all new HIV infections occurred in women who declined to initiate PrEP, representing a missed opportunity for HIV prevention.

The major study limitations are oral PrEP use was assessed based on client self-report and not objectively through drug levels testing, and data are from family planning clinics which may not be generalizable to women accessing other health service delivery settings.

In an observational cohort study of women at risk of acquiring HIV, David Mukasa and colleagues report that initiating HIV preexposure prophylaxis did not associate with an increased incidence of sexually transmitted infections.