PrEP adherence stayed low despite SMS and peer support in Johannesburg
Daily oral PrEP remains one of the most effective biomedical tools for preventing HIV acquisition, but its protection depends on a simple and unforgiving condition: consistent use. In young African women, that condition is often difficult to sustain. Social pressures, privacy concerns, shifting relationships, pill fatigue, and the realities of living in resource-constrained settings can all erode adherence long before the medication itself becomes the central issue.
A sequential multiple-assignment randomized trial in Johannesburg tested whether two scalable support approaches could improve adherence among women aged 18 to 25 years who were newly starting PrEP. The design was intentionally pragmatic. Women were first assigned to either weekly two-way SMS communication or a WhatsApp peer-support group, then those with low adherence at month 3 were re-randomized to receive either monthly issue-focused counseling or drug-level feedback counseling. The trial focused on a clinically meaningful endpoint: high adherence at month 9, defined by a tenofovir diphosphate concentration of 700 fmol per punch or more on dried blood samples.
The result was blunt. Neither layer of support moved the needle in a measurable way.
Why the trial tested layered support rather than a single intervention
The study enrolled 360 participants after screening 401 women between May 16, 2019, and Jan 29, 2021. Half were assigned to weekly SMS support and half to WhatsApp groups, with approximately 25 participants per group. Both interventions were built around a common behavioral premise. Regular contact might reinforce medication-taking habits, while peer discussion could normalize the challenges of PrEP use and reduce the sense of isolation that often surrounds HIV prevention in young women.
The WhatsApp approach had a social component that was hard to ignore in a population where daily pill-taking can feel highly visible and highly personal. Facilitators prompted participants to discuss challenges with PrEP use and other life events, an attempt to connect medication behavior to the broader context in which it lives. SMS, by contrast, offered a lighter-touch option with less social exposure and potentially easier scalability. In theory, one of these models might have created enough structure to improve adherence without demanding intensive clinic resources.
The biology behind the endpoint makes the stakes plain. Tenofovir diphosphate levels in dried blood reflect cumulative exposure, not just a participant’s stated intention to take medication. Self-report can sound reassuring while pharmacology tells a different story. That makes biomarker-based adherence outcomes especially important in prevention trials, where the clinical consequence of missed doses is silent until risk becomes infection.
Drug-level feedback did not rescue low adherence at month 3
The adaptive second stage was designed for participants already showing low adherence. At month 3, those women were randomized again to either issue-focused counseling once per month or counseling based on PrEP drug concentrations measured at months 3 and 6. This type of strategy is attractive because it tries to respond to the specific reason adherence is failing rather than assuming one size fits all.
In practice, the intensified step also failed to separate from the comparator. At month 9, four of 76 participants in the drug-level feedback arm had tenofovir diphosphate concentrations at or above the threshold, compared with three of 76 in the monthly counseling arm. The relative risk was 1.33, with a wide confidence interval and no statistical significance. The sample was small at this stage, but the direction of effect offered little reason to expect a clinically meaningful advantage from the more biomarker-driven intervention.
This matters because drug-level feedback has intuitive appeal. Telling a participant that drug concentrations are low may seem more concrete than generic counseling about adherence barriers. Yet biomarker feedback can only work if the barrier is modifiable, visible, and amenable to behavioral correction. When the challenge is linked to unstable routines, privacy concerns, partner dynamics, or competing life demands, information alone may not be enough to change day-to-day medication behavior.
The adherence signal was weak across both initial strategies
At month 9, 34 of 174 participants in the two-way SMS arm had tenofovir diphosphate levels at or above 700 fmol per punch, compared with 32 of 174 in the WhatsApp arm. The relative risk was 1.06, with a 95% confidence interval spanning 0.69 to 1.64 and a p value of 0.78. Those figures point to no detectable difference between a direct messaging strategy and a peer-group model for this population.
In a prevention setting, the lack of separation across interventions is not a minor statistical footnote. It means neither design overcame the basic adherence problem at a population level. The trial was built around interventions that were both potentially scalable and relatively low-cost, but scalability is only valuable if the intervention changes behavior enough to matter biologically. Here, the blood-based endpoint suggests that weekly contact and group support were insufficient on their own.
Twenty-two serious adverse events occurred during the trial, and none were considered related to the interventions or PrEP. Safety was not the issue. The central problem was efficacy of adherence support.
What the findings imply for PrEP delivery in resource-limited settings
The trial leaves prevention programs with an uncomfortable but important message. Young women in Johannesburg can be reached, enrolled, and followed, yet the kind of support that is easiest to deliver may not be strong enough to alter PrEP adherence in a sustained way. That has implications for clinics already operating with limited staff, limited bandwidth, and a constant need to choose interventions that can be delivered at scale.
The findings also argue against assuming that digital engagement alone can solve adherence. Weekly SMS and peer-support groups may still have value for some patients, but this trial did not show a clear pharmacologic benefit. Likewise, drug-level feedback counseling did not outperform monthly issue-focused counseling once low adherence had already been identified. For implementation programs, the likely next step is not simply more messaging, but a better understanding of what kind of support addresses the real-world barriers young women face when taking PrEP every day.
The trial was registered at ClinicalTrials.gov and is complete, which strengthens confidence in the prespecified design and endpoint. Even so, the narrow adherence gains across both phases suggest that future work will need to test more intensive, more tailored, or differently timed strategies if PrEP uptake is to translate into reliable protection for young women in high-incidence settings.