First Case of HIV Seroconversion With Integrase Resistance Mutations on Long-Acting Cabotegravir for Prevention in Routine Care.

Autor: Koss CA; University of California, San Francisco, San Francisco, California, USA., Gandhi M; University of California, San Francisco, San Francisco, California, USA., Halvas EK; University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Okochi H; University of California, San Francisco, San Francisco, California, USA., Chu C; University of California, San Francisco, San Francisco, California, USA., Glidden DV; University of California, San Francisco, San Francisco, California, USA., Georgetti Gomez L; University of California, San Francisco, San Francisco, California, USA., Heaps AL; University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Conroy AA; University of California, San Francisco, San Francisco, California, USA., Tran M; Men's Health Foundation, Los Angeles, California, USA., Shetler C; University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Hoeth D; University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Kuncze K; University of California, San Francisco, San Francisco, California, USA., Louie A; University of California, San Francisco, San Francisco, California, USA., Rivera Garza H; University of California, San Francisco, San Francisco, California, USA., Wafula Mugoma E; Global Programs for Research and Training, Nairobi, Kenya., Penrose KJ; University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Chohan BH; University of Washington, Seattle, Washington, USA., Ayieko JO; Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya., Mills A; Men's Health Foundation, Los Angeles, California, USA., Patel RR; Whitman Walker Health, Washington DC, USA.; Washington University, St. Louis, Missouri, USA., Mellors JW; University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Parikh UM; University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Open forum infectious diseases [Open Forum Infect Dis] 2024 Aug 26; Vol. 11 (9), pp. ofae468. Date of Electronic Publication: 2024 Aug 26 (Print Publication: 2024).
DOI: 10.1093/ofid/ofae468
Abstrakt: Background: Long-acting cabotegravir (CAB-LA) is highly effective for HIV prevention, but delayed HIV diagnoses and integrase strand transfer inhibitor (INSTI) resistance were observed in trials. We report the first case in routine clinical care of HIV infection on CAB-LA with INSTI resistance.
Methods: The SeroPrEP study enrolls individuals in the United States who acquire HIV on pre-exposure prophylaxis modalities to assess diagnostics, antiretroviral (ARV) drug levels, resistance, and treatment outcomes. Resistance mutations in full-length HIV-1 integrase were identified by single-genome sequencing (SGS). Cabotegravir concentrations in plasma and hair segments were measured by liquid chromatography-tandem mass spectrometry.
Results: A 23-year-old gender-nonbinary person, male at birth, restarted CAB-LA 6 months after discontinuation due to losing insurance. Prior to restart, HIV-1 RNA was not detected, but 20 days elapsed before CAB-LA injection. After the second CAB-LA injection, HIV antigen/antibody returned reactive (HIV-1 RNA 451 copies/mL). SGS of plasma HIV-1 RNA identified INSTI mutation Q148R in 2/24 sequences 2 days postdiagnosis; commercial genotype failed amplification. Cabotegravir hair concentration was 0.190 ng/mg 2 weeks prediagnosis; plasma cabotegravir was high (3.37 μg/mL; ∼20× PA-IC 90 ) 14 days postdiagnosis. Viral suppression was maintained for 6 months on darunavir/cobicistat/emtricitabine/tenofovir alafenamide, then switched to doravirine + emtricitabine/tenofovir alafenamide due to nausea.
Conclusions: In this first case of HIV infection on CAB-LA with INSTI resistance in routine care, cabotegravir resistance was detected only with a sensitive research assay. Accelerated pathways to minimize time between HIV testing and CAB-LA initiation are needed to optimize acute HIV detection and mitigate resistance risk. Sustained product access regardless of insurance is imperative to reduce HIV infections on CAB-LA.
Competing Interests: Potential conflicts of interest. C.A.K. reports research grant funding to institution from the NIH and Gilead Sciences. DVG reports research grant funding to institution from the NIH and receipt of consulting fees from Gilead Sciences and Merck. MT reports receipt of lunch for institution/clinic from Gilead Sciences and ViiV Healthcare and brand medication samples provided by Gilead Sciences to institution/clinic to be used as per standard of HIV prevention/care. AM reports research funding to institution from Gilead Sciences, ViiV, and Merck, and serving on advisory boards for Gilead, ViiV, and EMD Serono. JWM reports research grant funding to institution from the NIH, USAID, and Gilead Sciences; consulting fees from Gilead Sciences; travel support from the Conference on Retroviruses and Opportunistic Infections to attend the CROI meeting as a member of the CROI Scientific Program Committee; membership in the CROI Foundation (non-profit); President of the Foundation for Control of HIV Drug Resistance (non-profit); share options in Galapagos NV, Infectious Disease Connect, Inc, and MingMed Biotechnology Co., Ltd. UMP reports research grant funding to institution from the NIH; payments in the past (2021-2023) from Merck and Company for work that is now completed and unrelated to the current manuscript; and payment and one night of lodging from Thermo-Fisher for a presentation at a scientific conference. All other authors report no potential conflicts.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze: MEDLINE
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