Globally, new HIV infections are concentrated in eastern and southern Africa and are
largely acquired by women outside of known key populations. Identifying African women at
highest risk for HIV acquisition and successfully engaging them in HIV prevention
services, particularly pre-exposure prophylaxis (PrEP) programs, is an urgent global
health priority. The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) programs in
Africa typically rely on self-reported risk screening tools (SRST) to target HIV testing
and refer individuals for PrEP. However, these tools often perform poorly in validation
studies, missing many women at high-risk for HIV acquisition. This is partly due to
underreporting of risk factors, but also because many African women are at heightened HIV
risk solely through monogamous relationships with high-risk male partners (i.e.,
network-based risk). Moreover, even among those African women referred and enrolled into
PrEP programs, the vast majority stop using PrEP within several months of initiation.
While PrEP discontinuation has been linked to various factors, lack of self-perceived HIV
risk has been identified as a major barrier to PrEP use among cis-gender African women.
Here, the investigators hypothesize that compared to SRST alone, SRST integrated with
diagnostic testing for curable sexually transmitted infections (cSTI) will increase PrEP
use (uptake, adherence, and persistence) among cis-gender African women. The
investigators further hypothesize that this increased PrEP use will occur through two
primary mechanisms: (1) improved identification of women at high risk for HIV via
objective biomarker screening, and (2) enhanced self-perceived HIV susceptibility among
women with cSTIs. Decades of research has shown strong and consistent links between cSTIs
and female HIV acquisition risk, but cSTI testing and treatment has been largely omitted
from African HIV programs, partly due to lack of affordable cSTI diagnostics and
laboratory capacity. In addition to being risk factors for HIV acquisition, cSTIs are
also a significant cause of female reproductive morbidity, still birth, and neonatal
morbidity and mortality. With the advent of lower cost multiplex cSTI testing and point
of care diagnostics, there is new opportunity to determine whether integrated female cSTI
testing can improve HIV epidemic control.
To test the central hypothesis, the investigators will conduct an individually randomized
effectiveness implementation trial of SRST plus cSTI diagnostic testing for chlamydia,
gonorrhea, trichomonas, and syphilis compared to SRST alone to increase PrEP use among
cis-gender African women aged 15 to 39 years. The investigators preliminary observational
data suggest that there is a high burden of undiagnosed cSTIs among African women at high
risk for HIV and that adding cSTI diagnostic testing to existing PrEP eligibility
screening efforts would nearly double the number of PrEP eligible women. Preliminary data
also show women with cSTI symptoms are more likely to perceive themselves as being at
high HIV risk, and that women diagnosed with cSTIs are more likely to use PrEP. The trial
will be nested within the Rakai Community Cohort Study (RCCS), a population-based HIV
surveillance cohort in the Lake Victoria basin of Uganda in Eastern Africa, a region with
among the highest female HIV case burdens worldwide. Using a population-based design, the
investigators will be able to determine what groups and in what programmatic settings
cSTI testing would yield the greatest benefit for HIV epidemic control and overall
population health. Specific aims are:
To conduct an individually randomized effectiveness implementation trial of SRST
plus cSTI testing to increase PrEP use among African women at high HIV risk. ~4,500
HIV-negative women will be randomized 1:1 to PrEP eligibility screening based on
SRST plus cSTI testing (intervention) versus screening based on SRST alone (control
arm). Primary outcomes will be PrEP uptake after screening and adherence and
persistence at 6 months assessed through survey, clinical records, and drug level
testing.
To perform a mixed-methods, implementation science evaluation of female cSTI testing
for improving PrEP use for HIV prevention. Guided by the Reach, Effectiveness,
Adoption, Implementation, and Maintenance (RE-AIM) framework, the investigators will
use qualitative and quantitative methods to assess the mechanisms, barriers, and
facilitators to improving PrEP outcomes through cSTI testing and how this varies by
cSTI pathogen, SRST outcomes, and demographic profiles. Implementation
science-focused modules will be added to the RCCS. In-depth qualitative interviews
will be conducted at 1 and 6 months on a sample of participants after screening in
both study arms.
To determine the most efficient, population-level female cSTI testing strategies to
reduce HIV incidence in African settings. The investigators will use data and
results from Aims 1 and 2 to inform mathematical models which will evaluate
different cSTI testing approaches to reduce HIV incidence at a population level by
considering what cSTIs to screen for, in what health care settings, and at what cost
thresholds.
IMPACT: The proposed research will provide a novel and rigorous understanding of whether
integrated cSTI diagnostic testing can facilitate female PrEP use in order to reduce HIV
incidence through the identification of underserved women at high risk for HIV
acquisition and enhancement of their self-perceived HIV susceptibility. Study results
will provide actionable, Randomized Controlled Trial (RCT) level, and population-level
information to inform strategic delivery of high impact HIV prevention interventions
through integrated HIV and cSTI programming.
