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Long-Acting 4/8-Week Cabotegravir/Rilpivirine Maintains Control at 96 Weeks
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Download the PDF here Latte-2
9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris
Mark Mascolini
Long-acting cabotegravir/rilpivirine injected every 4 or 8 weeks largely maintained viral control through 96 weeks in antiretroviral-naive adults first treated with an oral regimen in the LATTE-2 trial [1]. Two phase 3 studies are evaluating the every-4-week dose.
This long-acting regimen combines the integrase inhibitor cabotegravir with the nonnucleoside rilpivirine. After 30/25-mg oral dosing (with abacavir/lamivudine) establishes safety and viral control, participants received every-4-week or ever-8-week injections of 200/300 mg/mL or continued cabotegravir plus abacavir/lamivudine. Participants were at least 18 years old, were naive to antiretroviral therapy, and had a CD4 count of 200 or more.
Researchers randomized 115 people to every-8-week dosing, 115 to every-4-week dosing, and 56 to daily oral cabotegravir plus abacavir/lamivudine. The three groups did not differ substantially in median age (35 overall), pretreatment viral load (4.4 log, or about 25,000 copies), or pretreatment CD4 count (489). Women made up 8% of the study population and African Americans 15%.
A week-48 FDA snapshot analysis determined that 92% in the 8-week group, 91% in the 4-week group, and 89% in the oral group had a viral load below 50 copies. Respective proportions at 96 weeks were 94%, 87%, and 84%. Treatment differences at week 96 were 10.0% (95% confidence interval [CI] 0.6% to 20.5%) in the 8-week group versus oral dosing and 3.0% (95% CI -8.4% to 14.4%) in the 4-week group versus oral dosing.
At 96 weeks 5 people (4%) in the 8-week arm, none in the 4-week arm, and 1 (2%) in the oral arm had virologic nonresponse. One person in the 8-week group, none in the 4-week group, and 1 in the oral group stopped treatment for lack of efficacy. Two people in the 8-week arm, none in the 4-week arm, an 1 in the oral arm had protocol-defined virologic failure. One of the two people with virologic failure in the 8-week group had detectable integrase and nonnucleoside mutations by week 48. After week 48 there were no protocol-defined virologic failures in any study arm.
Grade 3 or 4 drug-related adverse events (excluding injection site reactions) affected 2 people (2%) in the 8-week group, 5 (4%) in the 4-week group, and 1 (2%) in the oral group. Respective numbers (and percents) with serious adverse events were 11 (10%), 11 (10%), and 7 (13%). Two people (2%) in the 8-week group, 8 (7%) in the 4-week group, and 1 (2%) in the oral group discontinued treatment because of adverse events. Grade 3 or 4 lab abnormalities affected 19% in the 8-week arm, 29% in the 4-week arm, and 21% in the oral arm.
Most injection site reactions were mild (84%) or moderate (15%), and 89% resolved within 7 days. Pain was the most frequent injection site reaction, affecting 66%. Two of 230 people had an injection site reaction leading to discontinuation, both in the every-8-week arm. On a scale of 0 to 6 with 0 indicating "very dissatisfied" and 6 "very satisfied," 85% in the 8-week group, 76% in the 4-week group, and 76% in the oral group registered satisfaction levels of 6, while 14%, 21%, and 15% had satisfaction scores of 5.
These 96-week results appeared in Lancet on the day of this presentation, July 24, 2017 [2].
Reference
1. Eron J, Margolis D, Gonzalez-Garcia J, et al. Safety and efficacy of long-acting CAB and RPV as two drug IM maintenance therapy: LATTE-2 week 96 results. 9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris. Abstract MOAX0205LB.
2. Margolis DA, Gonzalez-Garcia J, Stellbrink HJ, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet. Published online July 24, 2017. DOI: http://dx.doi.org/10.1016/S0140-6736(17)31917-7.
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