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/mm3) 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/mm3, 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.

Bouba, Y., Armenia, D., Forbici, F., Bertoli, A., Borghi, V., Gagliardini, R., et al. (2021). Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 76(12), 3272-3279 [10.1093/jac/dkab322].

Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease

Armenia D.;Bertoli A;Malagnino V.;Andreoni M.;Ceccherini Silberstein F.;Santoro M
2021-09-16

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/mm3) 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/mm3, 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.
16-set-2021
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
CD4 Lymphocyte Count
Genotype
Humans
Tropism
Viral Load
Viral Tropism
HIV Infections
HIV-1
Bouba, Y., Armenia, D., Forbici, F., Bertoli, A., Borghi, V., Gagliardini, R., et al. (2021). Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 76(12), 3272-3279 [10.1093/jac/dkab322].
Bouba, Y; Armenia, D; Forbici, F; Bertoli, A; Borghi, V; Gagliardini, R; Vergori, A; Cicalini, S; Mazzotta, V; Malagnino, V; Lichtner, M; Latini, A; M...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/289645
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