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IAS 2023 Africa
The Wait Is On: Anticipating the Uses of Long-Acting ART and PrEP in Africa

Released: September 06, 2023

Linda-Gail Bekker
Linda-Gail Bekker, MBChB, DTMH, DCH, FCP(SA), PhD
Activity Information

Activity

Progress
1
Course Completed
Key Takeaways
  • The use of LA antiretrovirals for both treatment and prevention of HIV is anticipated in many parts of Africa.
  • Four key reports from IAS 2023 provided useful insights on clinical and operational considerations for offering LA ART to adolescents, PrEP preferences among women in the open-label phase of the HPTN 084 trial of LA CAB for PrEP, monitoring strategies during PrEP in HPTN 084, and acceptability of the dapivirine vaginal ring among adolescent girls and young women in Southern Africa.

The implementation of longer-acting and less frequently dosed antiretrovirals was a prominent theme for both prevention and treatment of HIV at IAS 2023 in Brisbane, Australia. These reports were of particular interest to me in my practice in South Africa. Eagerly awaited, more extensive rollout in Africa of injectable pre-exposure prophylaxis (PrEP) and treatment outside of small pilots has not yet commenced, and rollout of vaginal rings is just beginning.

LA CAB + RPV for Treatment of Adolescents
Dr Natella Rakhmanina delivered in her plenary an in-depth account of some of the clinical and operational considerations of offering injectable long-acting (LA) treatment to adolescents and youths in her clinic in Washington, DC. LA cabotegravir (CAB) + rilpivirine (RPV) has been available in the United States as maintenance treatment for people living with virologically suppressed HIV since 2021 for adults and 2022 for individuals 12 years of age and older. Dr Rakhmanina offered as part of her presentation actual patient trajectories and feedback. She emphasized that although we find ourselves in the early stages of clinical practice and many questions and challenges remain regarding implementation, acceptability, and sustainability, LA antiretroviral therapy (ART) provides a unique opportunity to optimize care and treatment for adolescents. In Cape Town, we have a small implementation pilot underway; not unexpectedly, the group of people who are most difficult to switch to injectable ART are young people who are struggling to adhere to daily therapy and are therefore not suppressed. The current requirement for switch only in individuals who are virally suppressed means that these young people—even though they could benefit most—will be left behind.

Lessons Learned From HPTN 084, Part I: Opting for LA PrEP
In considering LA CAB for prevention, Dr Sinead Delany-Moretlwe presented HPTN 084 study findings that focused on PrEP preferences among women in the open-label phase of the study. Among individuals born female, HPTN 084 demonstrated that injectable LA CAB administered every 2 months was superior to daily oral emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) for HIV prevention. In 2022, following a protocol amendment, participants in HPTN 084 were offered enrollment in an open-label extension with a choice of LA CAB or daily FTC/TDF as PrEP. Of the 3028 eligible participants, 81% elected to enroll, and the majority (78%) chose LA CAB for PrEP. Among those who chose LA CAB, only 15% opted to begin with a daily oral CAB lead-in step, which is optional in the prescribing information. Individuals who opted for LA CAB vs daily FTC/TDF were more likely to not live with partners, to have experienced recent physical intimate partner violence, and to have been paid for sex. As we go forward, PrEP programs will need to adopt approaches to support PrEP choices that align with user values and preferences to enhance effective PrEP use and adherence.

Lessons Learned From HPTN 084, Part II: Monitoring for HIV Infection During PrEP
A second report from HPTN 084 presented by Dr Mina Hosseinipour addressed monitoring for HIV infection during PrEP use. Both false-negative and false-positive test results have important consequences for the PrEP user: False-positive HIV diagnoses may result in PrEP discontinuation, unnecessary initiation of ART, and complex counseling. On the other hand, false-negative diagnoses can delay ART initiation and lead to the emergence of drug resistance. Across the 20 clinical trial sites in HPTN 084, there were 67,314 visits for HIV testing among 3180 individuals, of whom 5% had an initial reactive HIV test. The study demonstrated that 2 positive serologic tests had a high positive predictive value and that HIV antigen/antibody assays were frequently false positive but detected all infections. Two reactive rapid tests were sufficient to confirm HIV diagnosis and recommend treatment initiation. Given the high frequency of false-positive testing, PrEP programs must consider the need for further testing, counseling about false positivity, and plans to resume PrEP after excluding HIV. The FDA prescribing information requires HIV-1 RNA confirmation of negativity, and US guidance requires antigen testing before initiation of LA CAB as PrEP to reduce the risk of false negatives and increase detection of potential acute HIV infection. However, the WHO, although suggesting nucleic acid testing—if feasible, before use of LA CAB—recognizes that this may be a barrier for those in lower- and middle-income countries, where there is concern for serious barriers in logistics, accessibility, and affordability.

Choice Between Oral PrEP and Dapivirine Vaginal Ring
In Southern Africa, females who use PrEP already can make a choice between oral PrEP and the dapivirine vaginal ring (DVR). The monthly vaginal ring diffuses dapivirine in the vagina with limited systemic absorption and was shown to provide modest protection overall, with improved efficacy among women who used the ring more consistently throughout the month. Malvern Munjoma presented data from a 2-arm prospective cohort study examining the acceptability of DVR among adolescent girls and young women. DVR was preferred over oral PrEP with a higher continuation rate, and low rates of seroconversion and adverse events were reported. Munjoma explained that adolescents in rural areas in Zimbabwe preferred DVR vs oral PrEP because it is easier to hide from family members.  

Your Thoughts?
Have you had experience in prescribing LA ART or LA PrEP? Are you still waiting for LA antiretrovirals to be available in your region? Leave a comment and join the conversation.