Once-Monthly 2-Drug HIV Regimen Found Noninferior to Daily Oral Treatment

Recent data from 2 major phase 3 studies showed that a once-monthly injection of rilpivirine (Janssen) and cabotegravir (ViiV Healthcare) have similar efficacy in maintaining viral suppression in adults with HIV compared with the standard-of-care oral, 3-drug regimen.

The results from the Antiretroviral Therapy as Long-Acting Suppression (ATLAS) and the First-Long-Acting Injectable Regimen (FLAIR) trials were presented at the 2019 Conference on Retroviruses and Opportunistic Infections.

The novel 2-drug, long-acting (LA) injectable therapy regimen could significantly improve the treatment landscape for individuals with HIV. If approved, the regimen would be the first monthly dosing option for the management of HIV.

In the ATLAS trial, 616 patients with HIV received either the once-monthly injection of rilpivirine and cabotegravir or continuation of current antiretroviral therapy of 2 nucleoside reverse transcriptase inhibitors plus an integrase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI), or protease inhibitor. The findings demonstrated the once-monthly regimen’s noninferiority to an oral 3-drug regimen.¹

Key findings from the ATLAS trial include¹:

• Virologic suppression rates (HIV-1 RNA <50 c/mL) at week 48 were similar between treatment arms [LA regimen: 285/308 (92.5%), CAR: 294/308 (95.5%), adjusted difference: -3%, 95% confidence interval: -6.7, 0.7].
• Patients who switched to the LA regimen from the previous oral therapy reported a significant improvement in satisfaction compared with those who remained on the oral therapy at week 44.
• Treatment with the LA regimen was generally well-tolerated, with low rates of serious adverse events and drug- or injection-related withdrawals.

One percent of the patients who received the LA regimen developed confirmed virologic failure (CVF) with subsequent identification of resistance mutations to 1 or both agents, according to the study. Two of these patients had pre-existing NNRTI resistance.¹

The FLAIR study evaluated the antiviral activity and safety of the LA regimen in virologically-suppressed adults with HIV, following 20 weeks of induction therapy with abacavir/dolutegravir/lamivudine.²

Key findings form the FLAIR trial include²:

• Virologic suppression rates at week 48 were similar between treatment arms [LA regimen: 264/283 (93.3%), adjusted difference: 0.4%. 95% confidence interval: -3.7, 4.5].
• Patient treatment satisfaction significantly improved after switching to the LA regimen from the previous oral therapy compared to remaining on oral therapy at week 48.
• Treatment with the LA regimen was generally well-tolerated, with low rates of serious adverse events [18/283 (6.4%)] and adverse events leading to withdrawals [9/283 (3.2%)].

Of those who received the LA regimen, 1% of patients experienced CVF, all of whom had treatment-emergent, NNRTI and INSTI resistance.²

In addition, the ATLAS-2m study is currently investigating the LA regimen administered every 2 months.³

“This long-acting, 2-drug regimen may provide an opportunity to change the paradigm for people living with HIV by breaking the cycle of daily pill taking, which has been a defining characteristics of HIV therapy for several decades,” FLAIR principal investigator Chloe Orkin, MD, consultant physician and clinical professor at Queen Mary University of London, said in a statement.³

References

• Swindells S. Long-acting cabotegravir + rilpivirine as maintenance therapy: ATLAS week 48 results. Presented at: 2019 Conference on Retroviruses and Opportunistic Infections. Seattle, Washington. March 7, 2019.
• Orkin C. Long-acting cabotegravir + rilpivirine for HIV maintenance: FLAIR week 48 results. Presented at: 2019 Conference on Retroviruses and Opportunistic Infections. Seattle, Washington. March 7, 2019.
• Janssen Announces Results of Two Phase 3 Studies Which Showed Long-Acting Injectable HIV Treatment Regimen Of Rilpivirine and Cabotegravir Demonstrated Comparable Safety and Efficacy to Daily Oral HIV Therapy [news release]. Janssen. https://www.janssen.com/janssen-announces-results-two-phase-3-studies-which-showed-long-acting-injectable-hiv-treatment. Accessed March 7, 2019.