Table 1 Policy summary and key outcomes

• Background

Use of antiretroviral treatment in people with HIV (PWH) to suppress viral replication has been critical for helping to reduce HIV incidence as well as deaths from HIV. Although viral suppression is attained for most adults living with diagnosed HIV in East, Central, Southern and West Africa (ECSWA), challenges remain with sustained adherence to daily oral pill taking for some in the population. Long-acting injectable treatment could offer an effective alternative in such people, with lenacapavir + cabotegravir being a possible regimen option. In order to explore this, we used an existing individual-based model of HIV in the ECSWA context to assess potential effectiveness and cost-effectiveness of a policy of introduction of lenacapavir + cabotegravir with the aim of increasing levels of sustained viral suppression in PWH. We assume that the policy would involve active offer of lenacapavir + cabotegravir in people with sustained viral load measured >1000 copies/mL (despite enhanced adherence counselling) on oral drugs, and to people living with diagnosed HIV who are not currently engaged in treatment.

• Main findings and limitations

Our modelling analysis suggests that there are substantial potential health benefits from introducing lenacapavir + cabotegravir long-acting treatment in ECSWA settings. Across all setting scenarios, our assumptions on uptake led to a median 15% of people on ART being on lenacapavir + cabotegravir over the first 10 years from its introduction. Given this, there was a decrease in median percentage of diagnosed PWH with viral load >1000 copies/mL from 8.3% to 6.9% over the first 10 years (a 17% reduction). This was predicted to lead to a median 19% reduction in HIV deaths and a 18% reduction in mother to child transmission of HIV. Implementation costs are uncertain, but at an average total annual cost per person of $ 140 we found that introduction of lenacapavir + cabotegravir in settings with percentage of diagnosed PWH with viral load <1000 copies/mL below 93% is likely to be cost-effective in the context of a cost-effectiveness threshold of $ 500/DALY averted. If the cost could be $ 100 per year then lenacapavir + cabotegravir introduction is likely to be cost-effective in almost all settings. If targeted at women aged 15−39 or young people aged 15−24 the introduction of lenacapavir + cabotegravir is predicted to be cost-effective even in the context of a cost-effectiveness threshold of $ 150.

• Policy implications

We suggest that pilot implementation studies be conducted to confirm the viability of implementation. Such studies are needed to further understand whether introduction of lenacapavir + cabotegravir has potential. It is important that there is community engagement at every stage, especially since this might help to manage and address some of the equity issues but also prepare, raise awareness and incentivize targeted PWH eligible to access long acting injectable treatment. Implementation studies might initially recruit people who are attending clinic but self-report poor adherence to oral medication and have unsuppressed viral load. As more experience is gained and if and when it becomes clear that the injections can be consistently delivered in clinics and viral suppression attained in such PWH then this would provide evidence to support roll out of offer of lenacapavir + cabotegravir in this group. Implementation studies might then move on to studies which seek out people who have dropped out of care to offer them the option of lenacapavir + cabotegravir. This would initially be in people who are unlikely to be mobile who could likely be found if they did not return to care after their first injection in order to ascertain reasons. It may be possible to explore community-based delivery of injections. Frequent viral load monitoring, ideally at point of care, and resistance testing will be important in such studies to check that the regimen is leading to sustained viral suppression and not associated with development of drug resistance mutations. While implementation studies are needed before a recommendation can be made to introduce long acting treatment in the way proposed, policy-makers should begin to consider how they might make the proposed regimen available, including consideration of whether this might be done in community settings.