OBJECTIVES: Notwithstanding the growing proportion of HIV-1 non-B subtypes in Europe, the impact of their genetic background on response to antiretroviral therapy is still unclear. The aim of this study was to compare response to protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) containing regimens in patients carrying non-B or B clades with matched resistance mutation patterns. METHODS: We analyzed HIV-1 pol sequences of 1,108 patients stored in the ARCA (Antiretroviral Resistance Cohort Analysis) database and obtained before treatment. Response to therapy was defined as viral load suppression below 50 HIV-1 RNA copies/ml at week 12. By evaluating the combination of major resistance mutations, genotype coding generated 35 and 12 different vectors for PI or NNRTI treatments. RESULTS: The proportion of subjects achieving virological suppression was comparable in patients with non-B or B variants stratified for treatment status (51.5% vs. 41.5% in naïve and 46.7% vs. 38.7% in experienced patients) and regimens including PIs (46.9% vs. 39.7%) or NNRTIs (56.7% vs. 40%). No difference in response to therapy in patients with non-B and B HIV-1 was observed in any matched genotype with respect to treatment combination. When B vs. specific non-B clades (C, F1, CRF02_AG) were compared, the only difference was a better response of CRF02_AG compared to B clade (75.0% vs. 36.7%; p=.012). CONCLUSIONS: Response to PI- and NNRTI-based therapy is comparable in patients carrying non-B or B subtype matched for HIV-1 pol genotype. Further clade-specific studies are advisable to investigate possible minor effects on response to treatment.

EVALUATION OF VIROLOGICAL RESPONSE TO ANTIRETROVIRAL THERAPY IN PATIENTS CARRYING HIV-1 NON-B SUBTYPES ACCORDING TO BASELINE MUTATIONAL PATTERNS / M. Franzetti ; tutor: C. Balotta; coordinatore: A. D'Arminio Monforte. - : . Università degli Studi di Milano, 2013 Jan 23. ((25. ciclo, Anno Accademico 2012. [10.13130/franzetti-marco_phd2013-01-23].

EVALUATION OF VIROLOGICAL RESPONSE TO ANTIRETROVIRAL THERAPY IN PATIENTS CARRYING HIV-1 NON-B SUBTYPES ACCORDING TO BASELINE MUTATIONAL PATTERNS

M. Franzetti
2013-01-23

Abstract

OBJECTIVES: Notwithstanding the growing proportion of HIV-1 non-B subtypes in Europe, the impact of their genetic background on response to antiretroviral therapy is still unclear. The aim of this study was to compare response to protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) containing regimens in patients carrying non-B or B clades with matched resistance mutation patterns. METHODS: We analyzed HIV-1 pol sequences of 1,108 patients stored in the ARCA (Antiretroviral Resistance Cohort Analysis) database and obtained before treatment. Response to therapy was defined as viral load suppression below 50 HIV-1 RNA copies/ml at week 12. By evaluating the combination of major resistance mutations, genotype coding generated 35 and 12 different vectors for PI or NNRTI treatments. RESULTS: The proportion of subjects achieving virological suppression was comparable in patients with non-B or B variants stratified for treatment status (51.5% vs. 41.5% in naïve and 46.7% vs. 38.7% in experienced patients) and regimens including PIs (46.9% vs. 39.7%) or NNRTIs (56.7% vs. 40%). No difference in response to therapy in patients with non-B and B HIV-1 was observed in any matched genotype with respect to treatment combination. When B vs. specific non-B clades (C, F1, CRF02_AG) were compared, the only difference was a better response of CRF02_AG compared to B clade (75.0% vs. 36.7%; p=.012). CONCLUSIONS: Response to PI- and NNRTI-based therapy is comparable in patients carrying non-B or B subtype matched for HIV-1 pol genotype. Further clade-specific studies are advisable to investigate possible minor effects on response to treatment.
BALOTTA, CLAUDIA
D'ARMINIO MONFORTE, ANTONELLA
Settore MED/17 - Malattie Infettive
EVALUATION OF VIROLOGICAL RESPONSE TO ANTIRETROVIRAL THERAPY IN PATIENTS CARRYING HIV-1 NON-B SUBTYPES ACCORDING TO BASELINE MUTATIONAL PATTERNS / M. Franzetti ; tutor: C. Balotta; coordinatore: A. D'Arminio Monforte. - : . Università degli Studi di Milano, 2013 Jan 23. ((25. ciclo, Anno Accademico 2012. [10.13130/franzetti-marco_phd2013-01-23].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/215588
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