by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
April 7, 2020
The two-drug regimen of long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) given IM every 4 weeks was found to be highly effective and non-inferior to daily oral ART in two Phase 3 studies. These results and the known pharmacokinetics of CAB+RPV enabled the evaluation of a longer and more convenient 8-week dosing interval. The ATLAS-2M is a multicenter, open-label, Phase 3b non-inferiority (NI) study of CAB+RPV maintenance therapy given Q 8-weeks or Q 4-weeks to treatment-experienced, HIV-infected adults. The study randomized 1,045 persons who were virologically suppressed on IM CAB+RPV every 4 weeks (rolled over from the ATLAS study) or on oral therapy, to receive CAB+RPV every 8 or every 4 weeks. Sixty-three percent were naive to CAB+RPV LA while 37% transitioned from the Q 4-week arm of the ATLAS trial. The primary endpoint (at week 48) was the proportion of subjects with plasma HIV-1 RNA ≥ 50 c/mL with a NI margin of 4% and the secondary endpoint was the proportion with HIV-1 RNA < 50 c/mL based on a NI margin of 10%. For the primary endpoint CAB +RPV given Q 8 weeks was noninferior to Q 4-week dosing (1.7% vs 1.0%) and for the secondary analysis 94.3% vs 93.5% had viral loads < 50 c/mL. There were eight confirmed virologic failures (2 sequential VLs of > 200 c/mL) in the 8-week arm and two confirmed virologic failures in the Q 4-week arm. Five and 0 of the virologic failures respectively, had archived resistance-associated mutations to RPV either alone (n=4) or with a CAB mutation (n=1) at baseline. On-treatment resistance mutations to RPV, CAB, or both drugs not present at baseline were found in 5/8 of the 8-week virologic failures and both of the four-week virologic failures. The safety profiles were similar for 4-week and 8-week dosing. Injection site reactions were reported in 98% of participants but were mild or moderate and lasted a median of 3 days. Discontinuation for an adverse event occurred in only 2% of patients including 12 in the 8-week and 13 in the 4-week groups. Of those treated every 8 weeks (rolled over from ATLAS Q 4-weeks), 93% expressed a preference for Q 8-week dosing. This study concludes that Q 8-week dosing of LA CAB+RPV is non-inferior to Q 4-Week dosing and generally well tolerated, thus supporting the therapeutic effectiveness of these two antiviral agents given at 2-month intervals.
This is the follow-up data from the 48-week data recently published in the NEJM and presented as the Clinical Research Update on March 24th (ATLAS and FLAIR trials). It appears likely by the end of this year, if not sooner, long-acting IM cabotegravir + rilpivirine will be a therapeutic option for some of our patients. However, there will be logistical issues with clinical sites and reimbursement factors to work out. Overall, an 8-week option for this treatment would certainly be preferable to every 4 weeks.
Webcast Link: http://www.croiwebcasts.org/p/2020croi/croi/34
The author has no conflicts of interest to disclose.
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