Nadia Sam-Agudu

The session covers the latest on feasibility and implementation of long-acting injectable (LAI) antiretrovirals for HIV prevention and treatment in different populations drawing on experiences from a high-income country (HIC) in North America (USA), a low- and-middle income country (LMIC) in Asia (Thailand), and a LMIC in Africa (Uganda).

Monica Gandhi covers real world data and practical clinical considerations for LAI in HIV treatment. She briefly describes the FLAIR, ATLAS, and ATLAS 2M studies, citing their 1.4% virological failure rate, largely due to integrase inhibitor and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. She then describes the use of LAI (Cabotegravir/Rilpivirine) for HIV treatment in a demonstration project among hardly-reached populations in California, USA. Patients are adherence-challenged and experience poverty, mental illness, marginal housing, and/or substance addiction. Unlike the FLAIR/ATLAS studies, the demonstration project doesn't require suppression for inclusion, but excludes patients with CAB/RPV mutations. Data from 133 patients shows a 1.5% virological failure rate, on par with described studies. Jakkrapatara Boonruang is not present for their presentation on LAI feasibility and expectations in low- and middle-income countries. Andrew Mujugira discusses future LAI implementation in the context of differentiated service delivery (DSD) for HIV. He notes that LAI expands the “when” yet shrinks the options for “where” and “who” in DSD. He notes the critical need for LAI among mobile and vulnerable people such as migrants. He calls for large implementation science studies to examine LAI delivery within the product cycle to avoid shortages, and to include cost- effectiveness studies.

LAI use is expanding to more HICs, yet not so in most LMICs. This session presents experiences from LAI implementation in an HIC while providing considerations for future implementation in HIV programs in LMICs. The California demonstration study provides hope for viremic patients, for whom LAI is contraindicated in most treatment programs. Discussion is limited regarding insights into potential approaches to LAI implementation or equitable scale-up in LMICs and addressing LAI affordability globally. Key take-home points: 1) LAI implementation should be equity-based, and 2) Both qualitative and quantitative pre-implementation and implementation studies should be conducted to optimize implementation success.

Sulggi Lee

This session discussed and questioned challenges in providing long-acting therapies to “hard-to-reach” populations. Dr. Gandhi presented data demonstrating high virologic suppression rates with long-acting ART among viremic people living with HIV, while Dr. Mujugira described differentiated service delivery approaches, such as pharmacy-led PrEP, as future options for providing injectable therapies.

The session began with Dr. Gandhi emphasizing the critical need to study “hardly reached” populations, including the “10% of people living with HIV holding 90% of virus.” While registrational trials of long-acting cabotegravir/rilpivirine (FLAIR, ATLAS, ATLAS-2) have demonstrated high efficacy (1.4% virologic failure rate overall), they have excluded viremic participants. San Francisco’s Ward 86 Demonstration Project recently showed that among 57 viremic people living with HIV without prior major RPV mutations, a similar virologic rate was achieved as in the registrational trials (1.5%; the two participants with virologic failure were later found to have minor RPV mutations). The second talk by Dr. Mujugira emphasized the need for innovative differentiated service delivery approaches to provide long-acting injectables given current limitations in where and by whom these therapies are delivered (by healthcare providers, at hospitals/clinics). Pharmacy-led programs have shown promise with oral PrEP in Kenya (CROI 2023 #978). Two injectable PrEP pharmacy-led studies are now being performed in South Africa (AXIS study) and Seattle, Washington, U.S. (Kelly Ross Pharmacy), which may provide insight. Finally, the success of delivering long-acting injectables will greatly depend on the rapidity of regulatory approvals, national programs for delivering therapies, cost, insurance barriers, supply chain limitations, health equity.

While high rates of virologic suppression have now been shown with long-acting injectables, the ability to achieve 95-95-95 by 2030 will depend on the ability to reach populations who are most in need of these therapies. Ongoing efficacy studies need to include "hard-to-reach” populations such as viremic people living with HIV. Furthermore, to make long-acting injectables available to low- and middle-income countries, large implementation studies are needed to determine optimal means of delivering these therapies at scale and should be performed earlier in the product cycle.