By Nelly Mugo

Long-acting (LA) antiretroviral therapy (ART) holds promise for people in Africa as it improves indicators for the treatment and prevention of HIV. Could this advance help people living in low-to-middle-income countries (LMICs), including in Africa, get close to achieving the 2025 UNAIDS HIV 95-95-95 goals for HIV testing, treatment, and viral suppression?

Treatment interruption is one of the greatest threats to the HIV treatment program. A presentation at IDWeek 2024 showed that there are an estimated 20.5 million people on the President’s Emergency Plan for AIDS Relief (PEPFAR) program receiving HIV treatment and approximately 12% experience treatment interruption. These are mostly young men aged 20 to 39 years and young women aged 15 to 34 years. In South Africa, most cases of  HIV transmission arise from people living with HIV who drop out of care and experience treatment interruption. In addition, treatment interruptions increase the risk for ART drug resistance.

Can LA treatment minimize treatment interruption? We already know about the efficacy of LA injectable cabotegravir and rilpivirine (LA CAB + RPV) from studies like FLAIR and ATLAS. The FLAIR study enrolled treatment-naive people and the ATLAS study enrolled ART-experienced people. They found viral suppression with LA CAB + RPV was noninferior to oral combinations of ART. Increased patient satisfaction was found with the use of injectable therapy compared to previous oral therapy. Among patients with virologic failure and challenging vulnerabilities, LA ART achieved 94% viral suppression within 3 months of therapy initiation.

In HIV prevention, subcutaneous (SC) lenacapavir (LEN) and LA CAB and have both been shown to be highly effective in the prevention of incident HIV infections. LEN, a capsid inhibitor, demonstrated very high efficacy in HIV prevention. PURPOSE 1 and 2, summarized by Colleen Kelley at IDWeek 2024, compared SC LEN every 6 months to FTC/TAF and FTC/TDF.

PURPOSE 1 was conducted among adolescent girls and young women in South Africa and Uganda and found no incident infection among the LEN arm, with 100% efficacy. PURPOSE 1 was the first phase III clinical trial to intentionally include pregnancies and lactating women; pregnancies were common, and the outcomes were similar across both intervention arms. These findings will hopefully reduce the time required for pregnant women and breastfeeding mothers to access this highly effective HIV prevention intervention.

PURPOSE 2 compared SC LEN  every 26 weeks to emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) among cis, gay, bisexual men who have sex with men, transgender women, transgender men, and gay and bisexual men in South Africa, the US, Peru, Brazil, Mexico, Argentina, and Thailand. Two incident infections occurred among participants receiving LEN, with 96% efficacy. Both cohorts had high rates of incident sexually transmitted infections.

To me, these results are consistent with the results of the HPTN 083 (men who have sex with men/transgender women) and 084 (cisgender women) studies, which evaluated the efficacy of LA CAB for HIV prevention and demonstrated very high prevention efficacy with its use. The few incident infections with LA CAB presented with low or undetectable RNA/DNA with delayed antibody production, making routine testing inadequate for detection. These studies show that LA CAB can be a viable option for HIV prevention for persons in Africa.

Long-acting Potential

Because of these studies in treatment and prevention, I believe LA ART has great potential in increasing population HIV suppression in LMICs, including in Africa, further driving down incident infections and getting closer to the UNAIDS 95-95-95 treatment goals.

The high effectiveness of LA ART on HIV prevention and its potential for use in populations such as adolescent girls and young women, who have typically experienced challenges with adherence to oral medication, has great potential for changing the HIV epidemic trends.

Ongoing research is also evaluating weekly oral LA ART regimens, GS-1720 (a combination pill, weekly or monthly) MK-8527 (an oral nucleoside reverse transcriptase translocation inhibitor [NRTTI]), and VH4524184 (an integrase strand transfer inhibitor [INSTI]) as treatment options.

LMICs, including countries in Africa, should advocate strongly for access to LA ART, as they have the potential to close the last gap in adherence to both HIV treatment and prevention. LMICs are presently dependent on the PEPFAR program, which has steadily reduced funding. A modeling study presented at IDWeek by Aditya Gandhi et al evaluated the potential impact of reduced/withdrawal of PEPFAR funding. They found that the risk of increased incident infections and deaths would outstrip any savings from reductions in funding this HIV care program.

To me, this shows how the existence of LA ART is not enough. To realize its potential, we need more certain funding and access.

The writer is a globally renown Kenyan Scientist