Injectable drugs are superior in preventing regimen failure among people living with HIV (PLHIV) who have struggled with medication adherence.
This is according to a study — “Cabotegravir plus Rilpivirine for Persons with HIV and Adherence Challenges” by Aadia I. Rana, Lu Zheng, Jose Castillo-Mancilla, et al — that appeared in the New England Journal of Medicine.
WHERE WE’RE AT
Antiretroviral therapy (ART) lowers mortality and slows the progression of disease among PLHIVs and prevents the transmission of HIV. And yet, according to the researchers, “although modern ART is composed mostly of fixed-dose, combination daily oral tablets, which have an established safety profile, the estimated percentage of viral suppression among persons with HIV is only 67%.”
This is because “many persons with HIV face challenges in adhering to ART, such as social and structural barriers, side effects, stigma, and competing priorities. Long-acting injectable ART offers a less-frequent dosing alternative that is directly observed by health care providers, which could facilitate durable virologic suppression in this population.”
STUDY FOCUS
In this study, the researchers conducted an open-label, randomized trial involving PLHIVs who had inadequate adherence to ART (a persistent HIV-1 RNA level of >200 copies per milliliter or loss to follow-up). Participants received up to 24 weeks of adherence support, conditional economic incentives, and standard care with oral ART (step 1). Participants who had an HIV-1 RNA level of 200 copies per milliliter or lower in step 1 were randomly assigned in a 1:1 ratio to either continue standard care or switch to monthly injections of long-acting cabotegravir plus rilpivirine with or without oral lead-in therapy (step 2).
The primary outcome was regimen failure, defined as confirmed virologic failure (two consecutive HIV-1 RNA measurements of >200 copies per milliliter) or treatment discontinuation during step 2.
“The oral ART group was almost twice as likely to have regimen failure, at 41.2%, compared to the injectable group, which had a failure rate of 22.8%,” said co-author Carl Fichtenbaum. “This is a paradigm-shifting study. It has impacted not only the direction of research but also treatment guidelines around the world.”
FINDING ALTERNATIVES
For Fichtenbaum, “A significant number of people with HIV struggle taking antiretroviral pills every day. As a result, they have uncontrolled HIV, which contributes to their decline in health and leads to further spread of HIV in the community,” said Fichtenbaum, a faculty member in the Division of Infectious Diseases in the Department of Internal Medicine. “Developing an intermittent treatment relieves the need for daily pills and, given that no medicine is needed at home, directly addresses the stigma that many people with HIV face.”
In infectious diseases such as HIV — in addition to impacting a patient’s personal health — reduced medication adherence results in ongoing transmission of the virus and can have a significant impact on public health.
“This will likely lead to an increase in the number of people with well-controlled HIV in the community,” said Fichtenbaum.
For co-author Rana, this emphasizes the importance of clinical trials including populations representative of the HIV epidemic. “This study enrolled participants from 33 sites across the US who face challenges with consistent engagement in care, including those with active substance use, mental health issues and unstable housing. This is exactly the population we need to target when testing interventions to end the HIV epidemic.”
