From CROI 2022: Implications of Long-Acting ARVs for Africa

Prevention of primary HIV acquisition remains a significant global health priority, particularly in Africa. Sub-Saharan Africa continues to bear a disproportionate burden of HIV, with the long-term sequelae of morbidity and mortality from HIV-associated cancers and comorbidities, as well as the ongoing burden of mother-to-child HIV transmission. Clinical trials have demonstrated the role of antiretrovirals (ARVs) in reducing transmission of HIV, particularly in serodiscordant relationships. This commentary highlights exciting data presented at the 2022 Conference on Retroviruses and Opportunistic Infection (CROI) with relevance for Africa.

Long-Acting (LA) Pre-exposure Prophylaxis (PrEP)
The search for innovative strategies for PrEP is a high priority in Africa, where HIV stigma is an ongoing barrier to HIV elimination efforts. For this reason, the evolving data on LA PrEP options are exciting. Updated data from the HPTN-083 trial presented by Landowitz and colleagues demonstrated the superiority of every-2-month injectable LA cabotegravir (CAB) vs daily oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for PrEP. In the combined efficacy analysis (blinded plus unblinded phases), participants receiving LA CAB had 25 incident HIV infections vs 72 in the TDF/FTC group (HR: 0.34; 95% CI: 0.22-0.54), meaning that LA CAB for PrEP reduced the risk of new HIV infections by 66% compared with daily oral TDF/FTC. Although LA CAB is not approved for use in Africa, I am excited about the potential benefits of increased PrEP adherence with this LA option.

LA Dual Prevention on the Horizon
HIV infections and unsafe abortions are major contributors to global morbidity and mortality and illuminate the unmet need for effective contraception and sexual health interventions. Medical innovations that provide dual protection against HIV acquisition and unwanted pregnancy are of great public health significance in African settings, where access to adolescent-friendly HIV and contraceptive services is limited by stigma. Young and colleagues presented promising animal data on the use of an LA in situ–forming biodegradable implant containing an ARV (dolutegravir or CAB) and contraceptive medication (medroxyprogesterone acetate or etonogestrel) for the prevention of HIV and unwanted pregnancy. If proven safe and efficacious in humans, this innovative intervention has the potential to reduce the burden of HIV and unwanted pregnancies, which disproportionately affect adolescent girls in Africa.

LA Treatment for HIV
Although acceptance of HIV testing is increasing in Nigeria and other African countries, persistent HIV stigma remains a barrier to seeking care and receiving ARVs at HIV treatment centers. In Nigeria, patients who are newly diagnosed with HIV may purchase ARVs at private medicine stores, bypassing HIV care and treatment centers for fear of meeting acquaintances. Consequently, LA injectable ARVs with the potential to reduce unintended disclosures may improve both medication adherence and retention in care.

Results presented by Overton and colleagues from the phase IIIb ATLAS-2M trial revealed that every-2-month injectable LA CAB plus LA rilpivirine was noninferior to the every-1-month regimen in terms of virologic success (HIV-1 RNA ≤50 copies/mL) and incidence of virological nonresponse (HIV-1 RNA ≥50 copies/mL) in the intention-to-treat and per-protocol analyses at 152 weeks. Similar rates of adverse events were reported in the 2 groups, with the most common being injection site reactions―99% of which were mild to moderate in severity and lasted approximately 3 days. Overall treatment satisfaction scores favored every-2-month injections through all treatment time points. These long-term data support the efficacy, safety, and durability of every-2-month injectable LA CAB plus LA rilpivirine for maintenance of virologic suppression.

Another potential use of LA therapy is for multidrug-resistant (MDR) HIV. This is particularly relevant for Africa, where drug-resistant HIV has been reported in 1 in 6 people with HIV who are not receiving treatment, and resistance to ≥1 ARV has been reported in >50% of people with HIV who are receiving treatment.

At CROI 2022, Ogbuagu and colleagues reported encouraging results from the phase II/III CAPELLA study of LA lenacapavir (LEN) for people with MDR HIV-1. Data demonstrated significant virologic suppression and improvement in CD4+ cell count in patients with baseline HIV-1 RNA ≥400 copies/mL and resistance to ≥2 agents from 3 of 4 main ARV classes. At 52 weeks in a randomized cohort of 36 patients, 83% of patients attained HIV-1 RNA <50 copies/mL and 86% attained HIV-RNA <200 copies/mL with the addition of LEN to an optimized background regimen. These results are encouraging and support the potential utility of LEN in combination with other ARVs for management of MDR HIV-1 in Africa.

Your Thoughts?
How does stigma affect prevention and care of HIV in your country? Will LA ARVs help alleviate the impacts of stigma? Join the discussion by posting a comment. For more details on this and other key HIV issues from CROI 2022, review more CCO Conference Coverage, including Capsule Summary slidesets and other ClinicalThought commentaries highlighting US and global perspectives.