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PrEP Implementation in Africa
Towards Accessible and Equitable PrEP Implementation in Africa

Released: March 16, 2026

Andrew Mujugira
Andrew Mujugira, MBChB, MSc, MPH, PhD
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Key Takeaways
  • The rarity of breakthrough infections in PURPOSE 1 and 2 suggests that LEN remains a safe and effective HIV prevention method.
  • Extended LA CAB dosing intervals, yearly LEN, and a once-monthly oral PrEP pill suggest a future with simplified HIV prevention.
  • Implementation of PrEP must focus more intently on equity and accessibility, as scale-up has been greatly limited in African regions where HIV is most prevalent.

The promise of long-acting (LA) antiretroviral drugs for HIV pre-exposure prophylaxis (PrEP) featured prominently at CROI 2026, while highlighting the very limited access to these transformative technologies in sub-Saharan Africa and the need to significantly scale up PrEP use to help end the HIV epidemic.

Resistance Analyses from PURPOSE 1 and 2
Stephanie Cox presented lenacapavir (LEN) resistance analyses from the PURPOSE 1 and 2 trials evaluating LA LEN as HIV PrEP, focusing on participants who were followed through the end of the randomized, blinded phase (abstract 130). PURPOSE 1 is being done in South Africa and Uganda in adolescent girls and young women, a key population at risk of HIV acquisition and a group needing new PrEP modalities. PURPOSE 2 is a global study that enrolled people in North and South America, South Africa, and Thailand who have sex with male partners and are at risk for HIV infection. Of participants receiving LEN in these studies, there were 3 additional HIV acquisitions: 2 in PURPOSE 1 and 1 in PURPOSE 2. The capsid resistance mutation N74D was identified in 3 participants who acquired HIV while on LEN, including 2 from PURPOSE 2 (previously presented) and 1 from PURPOSE 1 (newly identified).

The participant with the N74D resistance mutation from PURPOSE 1 was diagnosed at their Week 52 visit, after receiving 2 on-time LEN injections. The other participant in PURPOSE 1 acquired HIV during the pharmacokinetic tail phase, testing positive 487 days after their last LEN dose, but had no resistance mutations. The participant from PURPOSE 2 who acquired HIV was also diagnosed at Week 52, after 2 on-time LEN injections. The reasons for breakthrough infection are being investigated; however, to date, only 5 HIV acquisitions have occurred among 5338 participants in PURPOSE 1 and 3265 in PURPOSE 2. N74D resistance requires surveillance but does not diminish the transformative potential of twice-yearly PrEP.

I think the rarity of breakthrough infections in PURPOSE 1 and 2 suggests that LEN remains a safe and effective HIV prevention method. Its implementation in Africa outside of clinical trials has recently begun, providing another LA option, in addition to cabotegravir (CAB) and the dapivirine vaginal ring.  

New Innovations in LA PrEP
Other studies presented at CROI 2026—of yearly LEN (abstract 996), every-4-month LA CAB (abstract 495), and a once-monthly oral PrEP pill (abstract 126)—suggest a future with further simplified HIV prevention. These options may one day be used to help increase PrEP continuation and ultimately reduce the rate of HIV transmission across Africa.

Limitations on Global Implementation of LA Antiretroviral Therapy
However, enthusiasm for LA PrEP and the potential for even longer-acting options at CROI was tempered by data about the limited global scale-up. Andrew Hill presented an analysis of PrEP-to-Need ratios (PnRs) across 122 countries, with 2,302,200 people initiating PrEP in 2024 (abstract 162). He estimated that approximately 40 people needed to take PrEP to prevent 1 person from acquiring HIV, yielding a PnR of 40:1. Only 4 countries (4%) achieved the target PnR: Australia, Denmark, Norway, and the United Kingdom. In contrast, all the African countries surveyed reported medium to low or very low PnRs, indicating that, at most, 1 person is taking PrEP for each new HIV acquisition.

Of note, 69% of the low- and middle-income countries evaluated had a PnR of ≤1, indicating that fewer than 1 person is taking PrEP per HIV acquisition. These included Uganda, Mozambique, and the Democratic Republic of the Congo. In fact, PrEP coverage in Africa has decreased since 2024 in many countries, most acutely in Nigeria and Uganda, where there are now more new HIV acquisitions per year than people on PrEP.

Furthermore, LA CAB and LEN accounted for only 2.9% and 0.9% of global PrEP use, respectively, underscoring the work still needed to scale up long-acting PrEP, particularly in African countries affected by USAID/PEPFAR funding cuts. 

Final Thoughts
The data from CROI 2026 suggest a future with simplified HIV prevention: 12 pills or 1 injection each year for PrEP. However, excitement for the future must be tempered by the fact that PrEP is still not reaching the people who need it the most.

Your Thoughts
How is PrEP implementation progressing in your region? Leave a comment to join the discussion!

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