Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease. (16th September 2021)

• Record Type: Journal Article
• Authors: Bouba, Yagai; Armenia, Daniele; Forbici, Federica; Bertoli, Ada; Borghi, Vanni; Gagliardini, Roberta; Vergori, Alessandra; Cicalini, Stefania; Mazzotta, Valentina; Malagnino, Vincenzo; Lichtner, Miriam; Latini, Alessandra; Mussini, Cristina; Andreoni, Massimo; Antinori, Andrea; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca; Santoro, Maria Mercedes
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 76:Number 12(2021)
• Page Start: 3272
• Page End: 3279
• Publication Date: 2021-09-16
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkab322
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Objectives: To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options. Methods: HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm. Results: Overall, median (IQR) CD4 count (cells/mm 3 ) nadir and at last genotypic resistance test (GRT) available were 98 (33–211) and 312 (155–517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%–10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count <200 cells/mm 3, who were perinatally infected and with a long treatment history significantly increased as FPR levels decreased. Regarding resistance, 933 (67.5%) individuals accumulated at least one class resistance, with 52.7%, 48.2%, 23.5% and 13.2% of individuals showing resistance to NRTIs, NNRTIs, PIs and INIs; while 23.2%, 27.2%, 14.3% and 2.8% harboured resistance to 1, 2, 3 and 4 classes, respectively. Individuals with FPR ≤5% showed a significantly higher level of resistance to PIs, NRTIs and INIs compared with others. The proportion of individuals harbouring strains susceptible to ≤2 active drugs was only about 2%; nonetheless, this proportion doubled (4.6%) in patients infected with FPR ≤5%. Conclusions: Our findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.