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  11th IAS Conference on HIV Science 18-21 July 2021
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Only 1 More Virologic Failure on CAB + RPV in Weeks 96 to 124 of FLAIR
  IAS 2021, 11th IAS Conference on HIV Science, July 18-21, 2021
Mark Mascolini
Once-monthly injected cabotegravir plus rilpivirine (CAB + RPV) continued to control HIV in 80% of adults switching from a suppressive pill regimen in a phase 3 trial [1]. FLAIR researchers recorded only 1 new confirmed virologic failure after week 96 and no new drug-related serious adverse events.
FLAIR, a phase 3 randomized open-label trial [2], helped establish CAB + RPV as a licensed once-monthly injectable regimen (after oral lead-in dosing) to maintain HIV suppression induced by another oral combination. At IAS 2021 FLAIR investigator updated findings from study week 96 through week 124.
The trial began with 809 antiretroviral-naive adults with a viral load at or above 1000 copies and any CD4 count who started oral single-tablet dolutegravir/abacavir/lamivudine. People who reached a confirmed viral load below 50 copies by week 20 got randomized evenly to continue the oral combination (n = 283) or switch to oral CAB + RPV for 4 days followed by injected CAB + RPV every 4 weeks (n = 283). Week-48 results determined that CAB + RPV is virologically noninferior to the continued oral dolutegravir regimen [3].
Of the 283 people randomized to CAB + RPV, median age stood at 34, 23% were women, 76% white, 17% black, and 10% Hispanic. Median body mass index measured 24 kg/m2 and median CD4 count 624. Of the 243 people who entered the extension phase of the trial at week 96, 229 remained in the protocol to this week-124 analysis.
Rates of virologic nonresponse (viral load at or above 50 copies) were 3.2% at week 96 and 4.9% at week 124. Five additional people (1.8%) had virologic nonresponse after week 96, including 1 additional person with confirmed virologic failure. Rates of virologic success (below 50 copies) were 86.6% at week 96 and 80.2% at week 124. Of the 42 people (14.8% of 283) not recorded as below 50 copies at week 124 (13 more participants than at week 96), most failed to make the grade for nonvirologic reasons.
The 1 additional person with confirmed virologic failure (2 confirmed viral loads at or above 200 copies) at week 124 was a man with HIV-1 subtype A6, no pretreatment resistance mutations, and 5 treatment-emergent nonnucleoside or integrase inhibitor mutations at failure. Low CAB and RPV concentrations earlier in treatment may have contributed to virologic failure. This man regained a viral load below 50 copies with efavirenz plus tenofovir/emtricitabine.
Among 283 people analyzed through week 124, 102 (36%) had any drug-related adverse event, 5 (2%) had any drug-related grade 3 or 4 adverse event, 15 (5%) had any adverse event leading to withdrawal from the study, 33 (12%) had any serious adverse event, and 1 had a drug-related serious adverse event (right knee arthritis at week 48). There were no serious drug-related adverse events after week 96. This adverse event analysis excluded injection site reactions.
Of 17,392 injections through week 124, 3732 (21.5%) caused injection site reactions. Most such reactions were grade 1 (89%) or grade 2 (11%), and the rate of these reactions fell over time, from about 70% at week 4 to 20% at week 124. Seven people overall (2.5% of 283) dropped out of the trial because of injection site reactions, including 1 person between weeks 96 and 124. Injection site reactions lasted for a median of 3 days.
Results indicate that in a closely observed and supported clinical trial, 4 of 5 people can maintain an established undetectable viral load through 124 weeks with once-monthly injected CAB + RPV. Throughout the study 5 people had confirmed virologic failure, including 1 between week 96 and week 124. Researchers recorded no drug-related serious adverse events after week 96.
1. Orkin C, Morell EB, Tan DHS, et al. Week 124 results of the randomized, open-label, phase 3 FLAIR study evaluating long-acting cabotegravir + rilpivirine for treatment in adults with HIV-1 infection (ITT-E population). IAS 2021, 11th IAS Conference on HIV Science, July 18-21, 2021. Abstract OAB0302.
2. ClinicalTrials.gov. Study to evaluate the efficacy, safety, and tolerability of long-acting intramuscular cabotegravir and rilpivirine for maintenance of virologic suppression following switch from an integrase inhibitor in HIV-1 infected therapy naive participants. ClinicalTrials.gov identifier NCT02938520. https://clinicaltrials.gov/ct2/show/NCT02938520
3. Orkin C, Arasteh K, Gorgolas Hernández-Mora M, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 infection. N Engl J Med. 2020;382:1124-1135. doi: 10.1056/NEJMoa1909512.



3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; CAB, cabotegravir; CAR, current antiretroviral therapy; DTG, dolutegravir; IM, intramuscular; LA, long-acting; RPV, rilpivirine.
1. U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. 2021. Available at: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/15/virologic-failure. Accessed March 25, 2021. 2. Saag MS, et al. JAMA. 2020;324(16):1651–1669. 3. ViiV Healthcare. Cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension (Cabenuva) Prescribing Information. US, January 2021. 4. ViiV Healthcare. Vocabria Summary of Product Characteristics. EU, December 2020.
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