Long-Acting Injectable HIV Therapy: Addressing Adherence Challenges
Elizabeth Hastie, MD discussed the LATITUDE trial results, highlighting the need for wider access to this treatment, especially for those not virally suppressed, and could help shape future healthcare guidelines.
Long-acting injectable antiretroviral therapy using cabotegravir and rilpivirine (LAI CAB/RPV) has shown superior outcomes compared to daily oral ART for people with HIV facing adherence challenges, as evidenced in the LATITUDE study. Although, the trial's incorporation of conditional economic incentives (CEI) and compensation raises questions about the generalizability of its results. To address this, researchers aimed to evaluate the real-world outcomes of LAI CAB/RPV in a similar population at a Ryan White-funded primary care HIV clinic.
A total of 63 participants with HIV met the inclusion criteria for this observational study. Among them, 71% were male, 27% female, and 2% non-binary, with a median age of 43 years. The ethnic breakdown revealed that 46% were white, 16% black, and 38% Hispanic. Notably, 41% reported current or prior injection drug use, 40% had active substance use, and 57% had a psychiatric diagnosis. At the onset of treatment with LAI CAB/RPV, 43% had a viral load (VL) ≥ 50 copies/mL, while 11% had a VL > 10,000 copies/mL. Additionally, 14 participants (22%), all of whom had a detectable VL at baseline, were prescribed additional antiretroviral therapy (ART) during the 48-week period. Among the 50 participants providing virologic data, 10 (20%) discontinued LAI CAB/RPV: 4 (8%) due to virologic failure (VL ≥ 200 copies/mL) with resistance-associated mutations (RAMs), and six (12%) for other reasons, including participant preference and one death.
Elizabeth Hastie, a fellow at UCSD, highlighted the adherence challenges faced in Southern California that can impact the effectiveness of long-acting injectable HIV treatments. “On average across the United States, the percent of people who have adherence issues with ARTs is about 45%, and that's about the same in Southern California. So you know, when we talk about adherence, it's really to oral antiretroviral therapies, and Southern California has some unique adherence challenges. Particularly, we have a lot of substance use disorder and higher rates of methamphetamine use disorder. In particular, we also have a lot of other issues, including mental health insurance and just mistrust with the medical system. So I'd say that overall, Southern California, while it has some unique aspects of adherence issues, it's a really good representation of the entire country.”
Adherence challenges were defined as having at least one HIV viral load (VL) > 200 copies/mL in the past 12 months, alongside either a poor response to oral ART (two VLs > 200 copies/mL, separated by at least four weeks within the previous 18 months) or being lost to clinical follow-up (no contact with an HIV provider for six months or more and non-adherence to ART for at least seven days). The primary outcome was the discontinuation of LAI CAB/RPV or a VL ≥ 200 copies/mL within 48 weeks, while the secondary outcome focused on confirmed virologic failure with resistance-associated mutations (RAMs).
Hastie discussed the implications of real-world outcomes for future HIV therapies, stating, “The idea of being able to approve long-acting injectables for individuals who are not virally suppressed, that's really the dream. And so this study provides support that we should, as providers, be able to offer this intervention for individuals who are not virally suppressed, and the dream, and I think we'll get there, because there's a lot of studies going on, is that the FDA will approve it for individuals who are not virally suppressed.”
The findings of this observational study revealed that individuals facing adherence challenges achieved outcomes comparable to those in clinical trials with CEI, with 20% experiencing either a viral load (VL) ≥ 200 copies/mL or discontinuation of LAI CAB/RPV, compared to 24.1% in the LATITUDE trial at 48 weeks. The lower primary outcome rate in this study may be attributed to a higher-risk population referred to LATITUDE to benefit from CEI and compensation.
Hastie concluded, “the evidence from the study and other similar studies could potentially change guidelines for clinics across the nation. We looked at some patient demographics to see if anything was particularly associated with regimen failure. We looked at race, insurance, BMI, if they have substance use disorder or mental health disorders, and we only found two things associated with long-acting injectable failure, and one was having a low CD4, and the other was active substance use disorder, so everything else wasn't associated with it. We feel that this should potentially encourage physicians to consider long-acting injectables for people with adherence challenges, even if they have mental health disorders and even if they have a history of injection drug use, because those weren't associated with failure.”
