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PrEP in Africa CROI 2024
Supporting PrEP Initiation and Adherence in Africa: Insights From CROI 2024

Released: April 05, 2024

Expiration: April 04, 2025

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Key Takeaways
  • A better understanding of the assays used to measure PrEP adherence, such as intracellular tenofovir-diphosphate concentrations in dried blood spots and urine tenofovir assays, is key to improving PrEP outcomes in high-risk populations.
  • Tailoring PrEP support to key populations, such as using an intensive phone call follow-up schedule, and individualizing PrEP initiation by offering individuals structured choices are important strategies for improving PrEP uptake and adherence.
  • Oral PrEP and the dapivirine vaginal ring appear to be safe for HIV prevention during the second trimester of pregnancy.

CROI 2024 had many impactful presentations. Here, I summarize 5 novel HIV prevention studies that took place in Africa.  

Novel Methods for Assessing PrEP Adherence
Dried blood spot (DBS) testing by capillary puncture is increasingly popular for HIV and HIV-1 RNA testing in Africa, as it can be performed outside of the care setting and safely transported by mail. There is interest in using DBS testing to inform pre-exposure prophylaxis (PrEP) adherence to enhance counseling and promote adherence, but reference points must first be established. These benchmarks have been established for men who have sex with men, but not African cisgender women.

A study presented by Mugwanya and colleagues aimed to establish benchmarks for intracellular tenofovir-diphosphate (TFV-DP) concentrations in DBS from oral emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) PrEP among Kenyan women aged 18-30 years without HIV. The study included 54 nonpregnant and 18 pregnant women.

Nonpregnant women were randomized to receive FTC/TDF 2, 4, or 7 times per week, whereas pregnant women received daily dosing. In nonpregnant women, TFV-DP concentrations in DBS increased with higher dosing frequency. Median TFV-DP concentrations in DBS at Week 8 were 359, 749, and 1389 fmol/punch for 2, 4, and 7 doses per week, respectively.

Pregnant women who received 7 doses per week had lower concentrations compared with nonpregnant women receiving the same dosing frequency. However, steady-state median concentrations in peripheral blood mononuclear cells were similar between pregnant and nonpregnant women (49 fmol/106 vs 50 fmol/106), but lower than observed in US populations.

These novel findings provide important benchmarks for understanding the concentration-efficacy relationship of FTC/TDF PrEP in African women, aiding in the interpretation of HIV prevention trials and optimizing PrEP dosing strategies.

In a similar vein, a substudy from the INSIGHT cohort evaluated a novel point-of-care urine tenofovir (TFV) assay using antibody-based technology to compare measured adherence with self-reported adherence among adolescent girls and young women at high risk of HIV infection. Although PrEP uptake among this population is high in Africa, early discontinuation is common. This open-label PrEP cohort consisted of 3087 sexually active adolescent girls and young women aged 16-30 years from 20 sites across South Africa, Eswatini, Kenya, Malawi, Uganda, and Zambia.

Results indicated high PrEP uptake (>95%), with nearly 90% refilling PrEP at Month 6. At various timepoints, most participants (64%-80%) showed evidence of recent PrEP use based on the novel urine TFV assay, indicating higher adherence compared with previous studies. The findings suggest that oral PrEP is effective for African adolescent girls and young women who can persist and adhere to oral PrEP and that real-time drug feedback using the urine TFV assay is acceptable in this population.

Tailoring PrEP Support Strategies on the Community and Individual Level
In reproductive health settings in sub-Saharan Africa, where young women face both HIV and unintended pregnancy, PrEP initiation and persistence are low. To address this issue, a PrEP delivery initiative was implemented in 15 postabortal clinics in Kenya, at which 8362 women sought care. Data were collected for 6 months after the clinics began delivering PrEP, during which 55% of women received information about PrEP, 73% were tested for HIV, and 36% of those who tested negative for HIV initiated PrEP. 

Following 6 months of data collection, investigators launched a cluster randomized trial, where clinics were randomized to either an intensive phone call follow-up program or standard of care (SoC) to support PrEP persistence and adherence. During the cluster randomized trial, 4112 women sought postabortal care, and 655 (15.9%) initiated PrEP. However, PrEP persistence and adherence remained low, with only 11.8%, 4.9%, and 1.8% of individuals receiving a refill at 1, 3, and 6 months post initiation, respectively.

Facilities using the phone call program saw numerically higher rates of PrEP refills at Month 1 compared with SoC facilities (15.4% vs 5.7%, respectively), with an adjusted relative risk (RR) of 2.7 (95% CI: 0.9-8.2). A subset of women tested for TFV detection via urine assay showed numerically higher TFV detection rates in the phone call arm compared with SoC at Month 1 (11.8% vs 4.9%, respectively), with an adjusted RR of 2.4 (95% CI: 0.7-8.0).

Overall, gaps in PrEP information provision and low uptake were observed. Although persistence and adherence remained a challenge, intensive phone call follow-up showed promise in improving short-term PrEP adherence, quantified as the rate of prescription refills. These observations highlight the importance of tailored interventions to support PrEP continuation and adherence among young women in reproductive health settings in sub-Saharan Africa. 

PrEP Choice
One strategy to improve PrEP persistence in addition to these tailored interventions for PrEP support is providing individuals with the agency to choose the best PrEP option for themselves according to their individual needs. This was leveraged by Kamya and colleagues in the first randomized study of a person-centered model offering individuals a structured choice between HIV prevention options. Individuals could choose between long-acting cabotegravir (LA CAB), oral PrEP, and postexposure prophylaxis (PEP), with the option to switch over time. This study enrolled both women and men at risk of HIV in rural Uganda and Kenya. 

Investigators recruited individuals from 3 randomized studies comparing the SEARCH dynamic choice HIV prevention (DCP) intervention vs SoC in outpatient departments, antenatal clinics, and the community. In total, 984 participants (487 DCP, 497 SoC) were enrolled. The SEARCH DCP intervention increased biomedical covered time (proportion of follow-up covered by LA CAB/oral PrEP/PEP) by more than 5-fold to 69.7% vs 13.3% in the SoC arm and reduced HIV incidence to 0% vs 1.8% in the SoC arm.

These data suggest that models incorporating opportunities to switch should be considered for similar populations and settings. 

Safety of Dapivirine Vaginal Ring and Oral PrEP for HIV Prevention in the Second Trimester
Another PrEP choice in development is the dapivirine vaginal ring (DVR). Epidemiologic studies have reported that pregnant people are at up to 3 times higher risk of HIV than nonpregnant people. MTN-042/DELIVER was a phase IIIb study assessing safety, adherence, and acceptability of the DVR and oral FTC/TDF during pregnancy. Results from the first 2 cohorts in this study, who received the DVR in the first trimester of pregnancy, were presented previously; however, data were presented at CROI 2024 from the third cohort, who wore the ring for up to 30 weeks of pregnancy.

This is the first study to report findings of women who initiated the DVR during the second trimester of pregnancy. Healthy pregnant people without HIV aged 18-40 years from South Africa, Uganda, Zimbabwe, and Malawi were included. Overall, 251 participants were enrolled, with 202 randomized to receive the DVR and 49 randomized to receive FTC/TDF.

Adverse pregnancy outcomes, namely stillbirth or miscarriage, related to DVR and FTC/TDF use were rare during the second trimester of pregnancy, comparable to the rates observed among communities where this study was conducted. These data, in addition to the data from the first 2 cohorts of this study and the safety data from women using the DVR at conception, provide important evidence to support the DVR and FTC/TDF for HIV prevention in pregnant people who are at risk of HIV.

Altogether, I think the landmark studies presented at CROI 2024 illustrate that PrEP is effective, safe, and feasible among many distinct populations in Africa, including women who are pregnant or who may get pregnant. These data also highlight the importance of tailoring PrEP interventions to key populations, as well as how critical individual choice is to PrEP uptake and adherence.

Your Thoughts?
How do you think the results of these studies will affect your own practice? What do you think we can learn from these studies in Africa? Leave a comment to join the discussion.