CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

949

IMPAACT 2017 Adolescent/Parent Experiences With LA Cabotegravir Plus Rilpivirine for HIV Treatment Elizabeth D Lowenthal 1 , Jennifer C. Chapman 2 , Martina Zapata Vaca 1 , Shawn Ward 3 , Ryan Milligan 3 , Andres Camacho-Gonzalez 4 , Gaerolwe Masheto 5 , Cindy McCoig 6 , Andi Ace 3 , Rodica Van Solingen 7 , Dwight Yin 8 , Sarah Buisson 9 , Carolyn Bolton 10 , Aditya Gaur 11 , for the IMPAACT 2017 Team 1 University of Pennsylvania, Philadelphia, PA, USA, 2 Children's Hospital of Philadelphia, Philadelphia, PA, USA, 3 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 4 Emory University, Atlanta, GA, USA, 5 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 6 ViiV Healthcare, Madrid, Spain, 7 Janssen Research & Development, LLC, Pennington, NJ, USA, 8 National Institute of Allergy and Infectious Diseases, Rockville, MD, USA, 9 FHI 360 , Bangkok, Thailand, 10 University of Alabama at Birmingham–CIDRZ, Lusaka, Zambia, 11 St Jude Children's Research Hospital, Memphis, TN, USA Background: The ongoing More Options for Children and Adolescents Study (MOCHA; IMPAACT 2017; Clinicaltrials.gov NCT03497676) is the first to examine use of long-acting injectable (LAI) cabotegravir (CAB) plus rilpivirine (RPV) in virologically suppressed adolescents, 12 to <18 years of age, with HIV-1. Little is known about the acceptability of this treatment approach for adolescents, including whether it changes over time. Methods: Participants switched from pre-study antiretrovirals to adolescent/ adult dosing of CAB-LAI plus RPV-LAI after oral lead-in MOCHA Cohort 2. They were queried about their preferred choice of treatment (every 8-week LAI versus daily oral) and the reasons for this preference at 8- (n=142), 24- (n=141), and 48-weeks (n=115). Reasons for the preferred regimen were recorded verbatim and coded thematically by the study team. In-depth interviews (IDIs) were conducted by phone with 8 U.S.-based adolescents and separately with 4 parents after at least 24 weeks on study to provide insight into participants' experiences. Interview transcripts were coded and analyzed using the Consolidated Framework for Implementation Research. Results: Overall, 144 adolescents enrolled in Cohort 2 at 18 sites in 5 countries. All but 4/142 (3%) participants at week 8 and 2/141 (1%) at week 24 stated that they preferred injectable LA medicines over daily orals. The primary themes for preferring LAI were: convenience and burden reduction. The most prominent components of burden reduction were the decrease in adherence-related stress and increased privacy. IDI participants expanded on these themes. All interviewees (adolescents and parents) favored LAI and reported convenience as a driving factor for them/their child to continue the LAI regimen. Having their medical team's support and monitoring for adherence to each LAI dose was repeatedly raised as a key reducer of perceived treatment burden, as was freedom from the daily reminder of HIV diagnosis seen as inherent to oral treatment. A surprising element of the IDI data was feedback that several adolescents had not understood vital elements of the LAI process such as the location of the injections needing to be in the buttocks, despite having completed informed consent/assent counseling. Conclusion: Feedback from adolescents receiving LAI antiretrovirals for up to 48 weeks in the MOCHA study has been favorable thus far. IDIs data suggest that structured and developmentally tailored counseling may be essential to LAI implementation for adolescents. Cabotegravir PopPK Analysis of Adults & Adolescents Living With/At Risk for HIV Receiving PrEP Yu-Wei Lin 1 , S. Y. Amy Cheung 1 , Isabelle Deprez 1 , Susan Ford 1 , Jon Collins 2 , Cindy McCoig 3 , Conn M. Harrington 2 , Aditya Gaur 4 , Carolyn Bolton 5 , Lynda Stranix Chibanda 6 , Sybil Hosek 7 , Mark Marzinke 8 , Brookie Best 9 , Edmund Capparelli 9 , for the IMPAACT 2017 Team 1 GlaxoSmithKline, Collegeville, PA, USA, 2 ViiV Healthcare, Durham, NC, USA, 3 ViiV Healthcare, Madrid, Spain, 4 St Jude Children's Research Hospital, Memphis, TN, USA, 5 Centre for Infectious Disease Research in Zambia, Lusaka, Zambia, 6 University of Zimbabwe, Harare, Zimbabwe, 7 John H. Stroger Jr. Hospital of Cook County, Chicago, IL, USA, 8 The Johns Hopkins University, Baltimore, MD, USA, 9 University of California San Diego, San Diego, La Jolla, CA,USA Background: Cabotegravir (CAB) is an integrase strand transfer inhibitor approved in adults and adolescents (12 to <18 years) weighing >35kg as long acting injectable (LAI) HIV-1 prevention, and for treatment in combination with rilpivirine. An existing CAB population pharmacokinetic (PopPK) model was limited to adult PK (Han 2023). We set out to extend and optimize that existing PopPK model for adolescents (12 to <18 years) by incorporating available adolescent PK data from the IMPAACT 2017/MOCHA (NCT03497676) and HPTN 083/084-01(NCT04824131/ NCT02720094) clinical trials. Methods: PK data following oral lead-in (30mg once daily, QD for at least 4 weeks) and LAI treatment (an initial 600mg 4-week loading dose followed by

400mg Q4W or 600mg Q8W) from 147 adolescents with HIV (IMPAACT 2017) and 62 HIV-negative adolescents (HPTN 083/084-01) with weight of 35.2-168 kg, body mass index (BMI) of 15.8-51.6 kg/m 2 and 12 to 17 years were added to adult data (n=1647). The PopPK model parameters were re-estimated based on this pooled dataset using NONMEM 7.3. The updated PopPK model was used to simulate PK profiles for CAB for Q4W and Q8W regimens in adolescents and adults. Individual exposure metrics (e.g. C tau ,ss) were derived and compared between adolescents and adults. Results: A 2-compartment model with 1st-order absorption adequately described CAB PK in adolescents and adults. No new covariates were identified as compared to the adult PopPK model. Weight and smoking status were significant determinants of CL/F, and only weight was a determinant of Vc/F, Vp/F, and Q/F. Needle length, female sex, splitting of the injection, and BMI were significant determinants of KA IM (absorption rate for LAI). Adolescents had CAB LA exposure at steady state (C tau ,ss median, 5th-95th: 2.36, 0.849-4.13 µg/mL for 600mg Q8W) comparable to that of adults (C tau ,ss : 1.91, 0.786-3.33 µg/mL for Q8W), with their exposure levels falling within the same range across all dosing phases, and contained within the established efficacy and safety thresholds of 0.45 and 22.5µg/mL. Conclusion: The addition of adolescent data to the adult PopPK dataset allowed expansion of the prior PopPK model down to 35 kg and optimization of predictions in adolescents. Given the similarity of CAB PK across adolescents and adults, same dosing regimens apply for adults and adolescents.

Poster Abstracts

951

Expanded Cytotoxic T-Lymphocytes and NK Cell Subsets in Infants With Perinatal HIV Akshay Iyer 1 , Lesley de Armas 1 , Vinh B. Dinh 1 , Rajendra Pahwa 1 , Suresh Pallikkuth 1 , Paula Vaz 2 , Maria Grazia Lain 2 , Savita Pahwa 1 1 University of Miami, Miami, FL, USA, 2 Fundação Ariel Glaser Contra o SIDA Pediátrico, Maputo, Mozambique Background: The nature of immune mechanisms that are important for HIV reservoir establishment or limiting reservoir size are poorly understood and may differ in infants compared to adults. However, immunological studies in pediatric cohorts are hindered by limited blood volume for sampling. Methods: We investigated the immune landscape in infants with perinatal HIV from Maputo, Mozambique using multi-omic single cell analyses and 1 million PBMC. 4 HEI (HIV Exposed Infected), ART-naïve infants with plasma virus load (VL) between 5.2 and 7 logs were evaluated along with 3 HEU (HIV Exposed Uninfected) infants. Cryopreserved PBMC from blood samples collected at 1 mo of age were thawed and cultured with or without anti-CD3 and anti-CD28 Abs for 16-18 hr across 3 independent experiments. After culture, cells were labeled with TotalSeq-C universal cocktail Abs (Biolegend) for feature barcoding, followed by single cell capture using Chromium (10X Genomics). Libraries were generated for sequencing of 5' mRNA, surface protein, and V(D)J genes. Sequencing data was mapped and aligned to human reference genome via Cell Ranger (v3.1.2). Quality control, normalization, integration, clustering, and annotation were performed in R using dsb, Seurat, and Fastmnn. V(D)J was analyzed with scRepertoire. Results: mRNA data generated 30 cell clusters which were manually annotated using a combination of gene and protein expression. Two distinct clusters were identified only in HEI infants: an NK and CD8+ T cell populations. The unique NK subset was characterized with low expression of both CD56 and CD16 by gene and protein expression compared to 3 other NK cell clusters. Relative gene expression analysis revealed downregulation of NK receptors (KLRC2, KLRC4, KLRD1) and cytokines and cytolytic transcripts (IFNG, GNLY,

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CROI 2024 301