CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

628

24-Week Viral Suppression in Patients Starting Long-Acting CAB/RPV Without HIV Viral Suppression Matt Hickey , Janet Grochowski, Francis Mayorga-Munoz, Elizabeth Imbert, John D. Szumowski, Jon Oskarsson, Mary Shiels, Samantha Dilworth, Ayesha Appa, Diane Havlir, Monica Gandhi, Katerina Christopoulos University of California San Francisco, San Francisco, CA, USA Background: We previously demonstrated that initiation of long-acting cabotegravir/rilpivirine (LA-CAB/RPV) in people with HIV (PWH) with an unsuppressed HIV viral load (VL) at the Ward 86 clinic in San Francisco can rapidly lead to viral suppression (VS). We now seek to evaluate the durability of VS in this population. Methods: We conducted a retrospective cohort study of PWH who started LA-CAB/RPV before 7/17/2023, focusing on those with HIV VL ≥50 copies/mL at initiation. Our primary outcome was VS (VL <50 copies/mL) and LA-CAB/ RPV persistence (not discontinued or late by >14 days) at 24 weeks, using the closest VL to 24+/-8 weeks. We considered missing 24-week VL as 1) unsuppressed (primary analysis); and 2) suppressed if evidence of VS before and after the outcome window (sensitivity analysis). We also describe viral failure (VF), defined as <2-log viral load decline at 4 weeks or VL ≥200 copies/ mL after initial VS with emergent CAB- or RPV-associated resistance mutations; discontinuations; and overall VS at week 24 including those who switched to oral ART. Results: Among 243 PWH initiating LA-CAB/RPV, 88 (36%) had baseline VL ≥50 copies/mL and 60 had ≥32 weeks of follow-up time to assess the primary outcome (88% cisgender men, 47% age ≥50, 40% white, 28% Latino/a, 25% Black, 47% with housing instability, 43% using stimulants). At 24 weeks, 51 (85%) had VS, 4 had VL ≥50 copies/mL and 5 had missing VL data (table). Forty-nine met the primary outcome of LA-CAB/RPV persistence and VS (82%; 95%CI 69-90%), with this estimate rising to 85% (52/60) using imputed VLs in sensitivity analysis. Of the four with VL ≥50 copies/mL at week 24, two had VF with resistance (RT E138K, INSTI R263K; RT L100I, Y181I) and two had slow viral decay without resistance. After week 24, both patients with VF later attained VS on alternative regimens (lenacapavir(LEN)+BIC/TAF/FTC and CAB+LEN). Four other patients discontinued LA-CAB/RPV before week 24: two had VS on oral ART at week 24, one had VS after switch to oral ART but missing week 24 VL, and one was off ART and lost to follow-up due to psychosis. Week 24 VS on either LA-CAB/RPV or oral ART using imputed VL data was 92% (55/60). Conclusion: In those initiating LA-CAB/RPV without viral suppression, 24-week VS estimates were at least 85%. Long-acting ART can be an important tool for improving VS among patients who face adherence challenges to oral ART.

countries (LMICs). The combination of LA lenacapavir (LEN) and CAB has not been studied in a clinical trial but poses promise for LMICs. Methods: Providers (MDs/pharmacists) at the UCSF Ward 86 Clinic, the UCSD Owen Clinic, MetroHealth in Cleveland, and the UPenn HIV Clinic used LEN subcutaneously every 6 months after oral loading in combination with CAB administered intramuscularly every 4 or 8 weeks in patients with adherence challenges to oral ART. A case series was assembled with the following data points: gender, age, housing insecurity and/or substance use, viral load (VL) prior to starting LEN/CAB, duration between CAB doses (every 4 or 8 weeks), whether RPV was maintained, viral mutations, whether VS (VL <75 copies/ml) was achieved on LEN/CAB, and if so, time to VS. Results: The Table shows patients in the case series (n=34; 76% male 24% cis/ trans female; 41% Black; 38% Latino/a; median age 47 (range 28-75) years; 71% with CAB every 8 weeks). All patients had difficulty adhering to oral ART, with 56% reporting housing insecurity, substance use, or both. The reason(s) for either adding LA LEN to CAB/RPV (68%) or using LEN/CAB without RPV (32%) were documented/suspected NNRTI mutations (n= 21, 59%), INSTI mutations (n=5, 15%), high VL when switching or starting LA ART (n=6, 18%) or continued viremia on CAB/RPV alone (n=4, 12%). One patient was started on LEN + CAB/RPV due to a high body mass index and another had LA RPV intolerance. Injection sites reactions on LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 suppressed (VL <75) after starting LEN (94%) at a median of 8 weeks (4-16), with only 16 (47%) being suppressed at baseline. Conclusion: In this case series of 34 patients started on LEN every 6 months in combination with CAB every 4 or 8 weeks (with or without RPV), high rates of VS (94%) were seen. Reasons for using this combination included adherence challenges, underlying ART resistance (mostly to NNRTIs) or low-level viremia on CAB/RPV. This data supports a clinical trial of LEN/CAB to study this combination for global use. The figure, table, or graphic for this abstract has been removed. Lenacapavir Efficacy in CAPELLA Patients With No Fully Active Agents in Optimized Background Regimen Onyema Ogbuagu 1 , Winai Ratanasuwan 2 , Anchalee Avihingsanon 3 , Ploenchan Chetchotisakd 4 , Andrew Wiznia 5 , Kimberly Workowski 6 , Chien-Ching Hung 7 , Jason Brunetta 8 , Benoit Trottier 9 , Mohammed Rassool 10 , Hui Wang 11 , Nicolas Margot 11 , Hadas Dvory-Sobol 11 , Martin S. Rhee 11 , Sorana Segal-Maurer 12 1 Yale University, New Haven, CT, USA, 2 Mahidol University, Bangkok, Thailand, 3 Thai Red Cross AIDS Research Center, Bangkok, Thailand, 4 Khon Kaen University, Khon Kaen, Thailand, 5 Albert Einstein College of Medicine, Bronx, NY, USA, 6 Emory University, Atlanta, GA, USA, 7 National Taiwan University Hospital, Taipei, Taiwan, 8 Maple Leaf Medical Clinic, Toronto, Canada, 9 Clinique Médicale du Quartier Latin, Montreal, Canada, 10 University of the Witwatersrand, Johannesburg, South Africa, 11 Gilead Sciences, Inc, Foster City, CA, USA, 12 New York Presbyterian Hospital, New York, NY, USA Background: Lenacapavir (LEN), a long-acting HIV-1 capsid inhibitor, is approved for the treatment of heavily treatment-experienced (HTE) people with HIV (PWH) with multidrug resistance (MDR) in combination with other antiretrovirals (ARVs). LEN is highly potent with no overlapping resistance with other ARVs. In CAPELLA, LEN in combination with an optimized background regimen (OBR) led to high virologic suppression: 78% (n=56/72; week [W] 52). We assessed LEN efficacy in participants whose OBR had no fully active ARVs. Methods: The Phase 2/3 CAPELLA study enrolled HTE PWH with MDR. Eligible participants had resistance to ≥2 ARVs in ≥3 of the 4 main ARV classes (NRTI, NNRTI, PI, INSTI). After oral loading, SC LEN was administered every 6 months. OBRs were selected by the clinicians; other investigational drugs were permitted. OBR overall susceptibility score was the sum of susceptibility scores for each OBR ARV; 0 (no susceptibility), 0.5 (partial susceptibility) and 1 (full susceptibility). Efficacy data (HIV-1 RNA copies/mL; FDA Snapshot algorithm) were assessed at W26, 52, and 104. LEN and OBR ARV resistance analyses were done at virologic failure (virologic rebound ≥50 copies/mL or <1 log 10 decline vs baseline). Results: Of the enrolled 72 participants, 12 (17%) had no fully active ARVs in their OBR; 6/12 and 1/12 had 1 or 2 partially active (score 0.5 each) ARVs, respectively. Median (range) number of OBR ARVs was 4 (2–6). Overall, OBR comprised NRTI (9 participants), INSTI (8), PI (7) or NNRTI (6); 5, 2, and 2 participants were on a CD4 post-attachment inhibitor (ibalizumab), CCR5 inhibitor (maraviroc), or attachment inhibitor (fostemsavir), respectively. Treatment outcomes: 8 participants had HIV-1 RNA <50 copies/mL at all 3 visits (W26, 52, and 104), including 1 participant with LEN resistance (R; M66I) at W10 and an OBR change at W25. 1 participant with missing W104 data was

Poster Abstracts

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629

Case Series Examining the Long-Acting Combination of Lenacapavir and Cabotegravir: Call for a Trial Monica Gandhi 1 , Lucas Hill 2 , Janet Grochowski 1 , Alexander Nelson 3 , Katerina Christopoulos 1 , Diane Havlir 1 , Catherine A. Koss 1 , Francis Mayorga-Munoz 1 , Jon Oskarsson 1 , John D. Szumowski 1 , Ann Avery 3 , Laura Bamford 2 , Jillian Baron 4 , William R. Short 4 , Corrilynn O. Hileman 3 1 University of California San Francisco, San Francisco, CA, USA, 2 University of California San Diego, La Jolla, CA, USA, 3 MetroHealth Medical Center, Cleveland, OH, USA, 4 University of Pennsylvania, Philadelphia, PA, USA Background: Long-acting antiretroviral therapy (LA-ART) is novel and has been used for both virologically-suppressed (VS) and viremic patients with adherence challenges. The currently-approved LA-ART combination – cabotegravir (CAB) and rilpivirine (RPV) – is limited by the relatively high prevalence (up to 10%) of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistant virus globally and is not endorsed for low-and-middle-income

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