High concordance in plasma and CSF HIV-1 drug resistance mutations despite high cases of CSF viral escape in individuals with HIV-associated cryptococcal meningitis in Botswana. (2nd November 2022)

• Record Type: Journal Article
• Authors: Kelentse, Nametso; Moyo, Sikhulile; Choga, Wonderful T; Lechiile, Kwana; Leeme, Tshepo B; Lawrence, David S; Kasvosve, Ishmael; Musonda, Rosemary; Mosepele, Mosepele; Harrison, Thomas S; Jarvis, Joseph N; Gaseitsiwe, Simani
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 78:Number 1(2023)
• Page Start: 180
• Page End: 184
• Publication Date: 2022-11-02
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkac372
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Objectives: We compared the patterns of HIV-1 drug resistance mutations between the CSF and plasma of individuals with HIV-associated cryptococcal meningitis. Methods: This is a cross-sectional study of archived CSF and plasma samples collected from ART-exposed participants recruited in the Phase 3 AmBisome Therapy Induction Optimisation randomized controlled trial (ISRCTN72509687) conducted in Botswana between 2018 and 2021. HIV-1 RT and protease genes were genotyped using next-generation sequencing and HIV-1 drug resistance mutations were compared between the CSF and plasma compartments stratified by thresholds of ≥20% and <20%. Results: Overall, 66.7% (16/24) of participants had at least one HIV-1 drug resistance mutation in the CSF and/or plasma. A total of 15/22 (68.2%) participants had HIV-1 drug resistance mutations at ≥20% threshold in the plasma and of those, 11 (73.3%) had been on ART longer than 6 months. HIV-1 drug resistance mutations were highly concordant between the CSF and plasma at ≥20% threshold despite a substantial number of individuals experiencing CSF viral escape and with only 54.5% with CSF WBC count ≥20 cells/mm 3 . Minority HIV-1 drug resistance mutations were detected in 20.8% (5/24) of participants. There were no mutations in the CSF that were not detected in the plasma. Conclusions: There was high concordance in HIV-1 drug resistance mutations in the CSF and plasma, suggesting intercompartmental mixing and possibly a lack of compartmentalization. Some individuals harboured minority HIV-1 drug resistance mutations, demonstrating the need to employ more sensitive genotyping methods such as next-generation sequencing for the detection of low-abundance mutations.