Long-acting therapies are promising alternatives to the daily oral medication paradigm

Dr. Gandhi identified current issues in the state of antiretroviral therapy for HIV including cost, weight gain, daily oral dosing, and pregnancy. He reviewed the current landscape of long-acting drugs including the two-monthly long-acting cabotegravir/rilpivrine antiretroviral combination delivered via intramuscular injection (ATLAS, ATLAS-2M, FLAIR), as well as islatravir which is being studied as an implant and broadly neutralising antibodies as infusions. He insightfully compared these developments with long-acting contraceptive and depot antipsychotics in patients who struggle with daily oral dosing.

Key Learning Points

Ultimately, the emphasis has to be on patient autonomy. As for any chronic disease, people living with HIV need to be involved in decision-making regarding treatment options, especially where relative valuation of cost, adverse effects, and pregnancy planning may be highly individualised. Decreasing dosing interval is generally preferable; however, weighed against a more invasive treatment delivery system it may not be desirable for every patient.

Combining treatment of HIV with other preventative measures, for example contraception in a woman of childbearing age, may limit the impetus for research into drug safety during pregnancy. This is at the cost of limiting the application of newer treatments to non-pregnant patients. The cost of developing newer drugs inevitably limits the criteria for recruitment of people living with HIV into trials, but where practicable we must be inclusive in our research to better reflect the worldwide population living with HIV.

While injections, implants, and patches are exciting prospects for patients with difficulty in adhering to daily oral medication, we must still consider social determinants of health when determining their utility. The requirement for cold chain for injectable drug may not be achievable in the most remote settings. The higher barrier to resistance of newer longer-acting drugs may be an opportunity but also risk developing further resistance-associated mutations in treatment-experienced patients if there is an unexpectedly “long tail” due to a missed injection. Dr Gandhi notes to date that most studies are in people already virologically suppressed. If we hope to eradicate HIV, we must advocate for studies inclusive of the real-world patients from marginalised and difficult-to-engage populations who may have the most to benefit.