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CAB LA Plus RPV Every 2 Months Controls HIV in Adolescents
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AIDS 2024, July 22-26, 2024, Munich
Mark Mascolini
Long-acting cabotegravir (CAB LA) plus rilpivirine (RPV), each injected every 2 months throughout a 48-week trial, kept HIV suppressed in a study involving 144 adolescents in Africa, the United States, and Thailand [1]. After 48 weeks all participants in IMPAACT 2017 said they preferred injected CAB LA + RPV to oral therapy.
In the United States the FDA has licensed CAB LA + RPV every 1 or 2 months for adults who maintain an undetectable viral load taking a pill-based antiretroviral regimen. Data from IMPAACT 2017 Cohort 1 (in which adolescents maintained their background regimen and added injected CAB or RPV every 4 or 8 weeks) supported FDA approval of CAB LA + RPV once a month or every 2 months at a dose similar to the adult dose in virologically suppressed adolescents at least 12 years old and weighing at least 35 kg.
IMPAACT 2017 Cohort 2 includes 144 adolescents who switched from an oral antiretroviral combination to oral CAB plus oral RPV for 4 weeks, then began injected adult doses of the drugs from week 4 through 96. The presentation at AIDS 2024 analyzed 48-week data.
Cohort 2 study participants came from 18 sites-7 in the United States, 4 in South Africa, 3 in Thailand, 2 in Botswana, and 2 in Uganda. Among 44 Cohort 1 participants who joined the Cohort 2 analysis, 43 received the week 48 injection. Cohort 2 also included 100 adolescents naive to CAB LA or RPV, and 97 of them got the week 48 injection.
These 144 IMPAACT 2017 participants had a median age of 15 years (range 12 to 17), 51% were female, 74% were black, and 92% got HIV infection vertically or perinatally. Median body mass index stood at 19.5 kg/m2 and weight at 48 kg.
About one third of participants (37%) had a drug-related adverse event, 2 of which were grade 3 or worse (injection site pain and abscess and injection site abscess). Both people continued taking CAB + RPV. Researchers tallied no drug-related serious adverse events. After week 48 a single participant had a grade 4 anaphylactic reaction later defined as a postinjection reaction not consistent with anaphylaxis. This person stopped treatment. Through study week 48, one third of participants had at least one injection site reaction, most of them (90%) grade 1 and most of which (89%) resolved in 7 days.
Proportions of participants reporting "no hurt" from CAB injections changed from 36.6% at week 4, to 33.1% at week 8, 43.3% at week 24, and 56.4% at week 48. "No hurt" response rates were similar for RPV. All 140 adolescents who answered the Preference Questionnaire at week 48 reported favoring intermittent injections over daily oral therapy.
At week 48 observed median predose concentration of CAB (2.77 ug/mL) and RPV (67.9 ng/mL) came close to predose concentrations in adults receiving injections of CAB and RPV and lay well above the protein-adjusted 90% inhibitory concentrations of CAB and RPV. CAB appeared to reach steady-state concentration by week 48; time to steady state could not yet be determined for RPV.
All 140 IMPAACT 2017 participants with viral load measured at week 48 had a load below 50 copies. An FDA snapshot analysis yielded a virologic success rate of 97.2% at that point. No one had confirmed virologic failure, defined as 2 consecutive viral loads at or above 200 copies while taking CAB LA + RPV.
Reference
1. Gaur AH, Baltrusaitis K, Capparelli EV, et al. Long-acting cabotegravir (CAB) plus rilpivirine (RPV) in the first, virologically-suppressed adolescents with HIV-1 to receive an every 8-week, all-injectable regimen in a multicenter, multinational Study: IMPAACT 2017 week 48 outcomes. AIDS 2024, July 22-26, 2024, Munich. Abstract OAB2606LB.
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