Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy

C. F. Perno, A. Cozzi-Lepri, C. Balotta, F. Forbici, M. Violin, A. Bertoli, G. Facchi, P. Pezzotti, G. Cadeo, G. Tositti, S. Pasquinucci, S. Pauluzzi, A. Scalzini, B. Salassa, A. Vincenti, A. N. Phillips, F. Dianzani, A. Appice, G. Angarano, L. MonnoG. Ippolito, M. Moroni, A. D'Arminio Monforte, M. Montroni, G. Scalise, A. Costantini, M. S. Del Prete, U. Tirelli, G. Nasti, G. Pastore, L. M. Perulli, F. Suter, C. Arici, F. Chiodo, F. M. Gritti, V. Colangeli, C. Fiorini, L. Guerra, G. Carosi, G. P. Cadeo, F. Castelli, C. Minardi, D. Vangi, G. Rizzardini, G. Migliorino, P. E. Manconi, P. Piano, T. Ferraro, L. Cosco, E. Pizzigallo, F. Ricci, G. M. Vigevani, L. Pusterla, G. Carnevale, A. Pan, P. Viganò, M. Mena, F. Ghinelli, L. Sighinolfi, F. Leoncini, F. Mazzotta, S. Ambu, S. Lo Caputo, G. Angarano, B. Grisorio, S. Ferrara, P. Grima, P. Tundo, G. Pagano, N. Piersantelli, A. Alessandrini, R. Piscopo, M. Toti, S. Chigiotti, F. Soscia, L. Tacconi, A. Orani, G. Castaldo, A. Scasso, A. Vincenti, A. Scalzini, F. Alessi, M. Moroni, A. Lazzarin, A. Cargnel, F. Milazzo, L. Caggese, A. D'Arminio Monforte, S. Melzi, F. Delfanti, B. Carini, B. Adriani, S. Garavaglia, C. Moioli, R. Esposito, C. Mussini, N. Abrescia, A. Chirianni, O. Perrella

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor-containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P=.04, X2 test). Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30-3.75; P=.004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy.

Original languageEnglish
Pages (from-to)983-991
Number of pages9
JournalJournal of Infectious Diseases
Volume184
Issue number8
DOIs
Publication statusPublished - Oct 15 2001

Fingerprint

Protease Inhibitors
Peptide Hydrolases
HIV
Mutation
Pharmaceutical Preparations
Therapeutics
HIV Reverse Transcriptase
RNA-Directed DNA Polymerase
Codon
Logistic Models
Odds Ratio
Confidence Intervals

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy. / Perno, C. F.; Cozzi-Lepri, A.; Balotta, C.; Forbici, F.; Violin, M.; Bertoli, A.; Facchi, G.; Pezzotti, P.; Cadeo, G.; Tositti, G.; Pasquinucci, S.; Pauluzzi, S.; Scalzini, A.; Salassa, B.; Vincenti, A.; Phillips, A. N.; Dianzani, F.; Appice, A.; Angarano, G.; Monno, L.; Ippolito, G.; Moroni, M.; D'Arminio Monforte, A.; Montroni, M.; Scalise, G.; Costantini, A.; Del Prete, M. S.; Tirelli, U.; Nasti, G.; Pastore, G.; Perulli, L. M.; Suter, F.; Arici, C.; Chiodo, F.; Gritti, F. M.; Colangeli, V.; Fiorini, C.; Guerra, L.; Carosi, G.; Cadeo, G. P.; Castelli, F.; Minardi, C.; Vangi, D.; Rizzardini, G.; Migliorino, G.; Manconi, P. E.; Piano, P.; Ferraro, T.; Cosco, L.; Pizzigallo, E.; Ricci, F.; Vigevani, G. M.; Pusterla, L.; Carnevale, G.; Pan, A.; Viganò, P.; Mena, M.; Ghinelli, F.; Sighinolfi, L.; Leoncini, F.; Mazzotta, F.; Ambu, S.; Lo Caputo, S.; Angarano, G.; Grisorio, B.; Ferrara, S.; Grima, P.; Tundo, P.; Pagano, G.; Piersantelli, N.; Alessandrini, A.; Piscopo, R.; Toti, M.; Chigiotti, S.; Soscia, F.; Tacconi, L.; Orani, A.; Castaldo, G.; Scasso, A.; Vincenti, A.; Scalzini, A.; Alessi, F.; Moroni, M.; Lazzarin, A.; Cargnel, A.; Milazzo, F.; Caggese, L.; D'Arminio Monforte, A.; Melzi, S.; Delfanti, F.; Carini, B.; Adriani, B.; Garavaglia, S.; Moioli, C.; Esposito, R.; Mussini, C.; Abrescia, N.; Chirianni, A.; Perrella, O.

In: Journal of Infectious Diseases, Vol. 184, No. 8, 15.10.2001, p. 983-991.

Research output: Contribution to journalArticle

Perno, CF, Cozzi-Lepri, A, Balotta, C, Forbici, F, Violin, M, Bertoli, A, Facchi, G, Pezzotti, P, Cadeo, G, Tositti, G, Pasquinucci, S, Pauluzzi, S, Scalzini, A, Salassa, B, Vincenti, A, Phillips, AN, Dianzani, F, Appice, A, Angarano, G, Monno, L, Ippolito, G, Moroni, M, D'Arminio Monforte, A, Montroni, M, Scalise, G, Costantini, A, Del Prete, MS, Tirelli, U, Nasti, G, Pastore, G, Perulli, LM, Suter, F, Arici, C, Chiodo, F, Gritti, FM, Colangeli, V, Fiorini, C, Guerra, L, Carosi, G, Cadeo, GP, Castelli, F, Minardi, C, Vangi, D, Rizzardini, G, Migliorino, G, Manconi, PE, Piano, P, Ferraro, T, Cosco, L, Pizzigallo, E, Ricci, F, Vigevani, GM, Pusterla, L, Carnevale, G, Pan, A, Viganò, P, Mena, M, Ghinelli, F, Sighinolfi, L, Leoncini, F, Mazzotta, F, Ambu, S, Lo Caputo, S, Angarano, G, Grisorio, B, Ferrara, S, Grima, P, Tundo, P, Pagano, G, Piersantelli, N, Alessandrini, A, Piscopo, R, Toti, M, Chigiotti, S, Soscia, F, Tacconi, L, Orani, A, Castaldo, G, Scasso, A, Vincenti, A, Scalzini, A, Alessi, F, Moroni, M, Lazzarin, A, Cargnel, A, Milazzo, F, Caggese, L, D'Arminio Monforte, A, Melzi, S, Delfanti, F, Carini, B, Adriani, B, Garavaglia, S, Moioli, C, Esposito, R, Mussini, C, Abrescia, N, Chirianni, A & Perrella, O 2001, 'Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy', Journal of Infectious Diseases, vol. 184, no. 8, pp. 983-991. https://doi.org/10.1086/323604
Perno, C. F. ; Cozzi-Lepri, A. ; Balotta, C. ; Forbici, F. ; Violin, M. ; Bertoli, A. ; Facchi, G. ; Pezzotti, P. ; Cadeo, G. ; Tositti, G. ; Pasquinucci, S. ; Pauluzzi, S. ; Scalzini, A. ; Salassa, B. ; Vincenti, A. ; Phillips, A. N. ; Dianzani, F. ; Appice, A. ; Angarano, G. ; Monno, L. ; Ippolito, G. ; Moroni, M. ; D'Arminio Monforte, A. ; Montroni, M. ; Scalise, G. ; Costantini, A. ; Del Prete, M. S. ; Tirelli, U. ; Nasti, G. ; Pastore, G. ; Perulli, L. M. ; Suter, F. ; Arici, C. ; Chiodo, F. ; Gritti, F. M. ; Colangeli, V. ; Fiorini, C. ; Guerra, L. ; Carosi, G. ; Cadeo, G. P. ; Castelli, F. ; Minardi, C. ; Vangi, D. ; Rizzardini, G. ; Migliorino, G. ; Manconi, P. E. ; Piano, P. ; Ferraro, T. ; Cosco, L. ; Pizzigallo, E. ; Ricci, F. ; Vigevani, G. M. ; Pusterla, L. ; Carnevale, G. ; Pan, A. ; Viganò, P. ; Mena, M. ; Ghinelli, F. ; Sighinolfi, L. ; Leoncini, F. ; Mazzotta, F. ; Ambu, S. ; Lo Caputo, S. ; Angarano, G. ; Grisorio, B. ; Ferrara, S. ; Grima, P. ; Tundo, P. ; Pagano, G. ; Piersantelli, N. ; Alessandrini, A. ; Piscopo, R. ; Toti, M. ; Chigiotti, S. ; Soscia, F. ; Tacconi, L. ; Orani, A. ; Castaldo, G. ; Scasso, A. ; Vincenti, A. ; Scalzini, A. ; Alessi, F. ; Moroni, M. ; Lazzarin, A. ; Cargnel, A. ; Milazzo, F. ; Caggese, L. ; D'Arminio Monforte, A. ; Melzi, S. ; Delfanti, F. ; Carini, B. ; Adriani, B. ; Garavaglia, S. ; Moioli, C. ; Esposito, R. ; Mussini, C. ; Abrescia, N. ; Chirianni, A. ; Perrella, O. / Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy. In: Journal of Infectious Diseases. 2001 ; Vol. 184, No. 8. pp. 983-991.
@article{b453f0455f95475295eb232bb451271a,
title = "Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy",
abstract = "The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor-containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.9{\%}) had mutations in the RT, 5 (2{\%}) carried primary mutations in the PR, and 131 (52.8{\%}) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0{\%}) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P=.04, X2 test). Mutations at codons 10 and 36 of PR (present in 39.3{\%} and 40.0{\%} of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95{\%} confidence interval, 1.30-3.75; P=.004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy.",
author = "Perno, {C. F.} and A. Cozzi-Lepri and C. Balotta and F. Forbici and M. Violin and A. Bertoli and G. Facchi and P. Pezzotti and G. Cadeo and G. Tositti and S. Pasquinucci and S. Pauluzzi and A. Scalzini and B. Salassa and A. Vincenti and Phillips, {A. N.} and F. Dianzani and A. Appice and G. Angarano and L. Monno and G. Ippolito and M. Moroni and {D'Arminio Monforte}, A. and M. Montroni and G. Scalise and A. Costantini and {Del Prete}, {M. S.} and U. Tirelli and G. Nasti and G. Pastore and Perulli, {L. M.} and F. Suter and C. Arici and F. Chiodo and Gritti, {F. M.} and V. Colangeli and C. Fiorini and L. Guerra and G. Carosi and Cadeo, {G. P.} and F. Castelli and C. Minardi and D. Vangi and G. Rizzardini and G. Migliorino and Manconi, {P. E.} and P. Piano and T. Ferraro and L. Cosco and E. Pizzigallo and F. Ricci and Vigevani, {G. M.} and L. Pusterla and G. Carnevale and A. Pan and P. Vigan{\`o} and M. Mena and F. Ghinelli and L. Sighinolfi and F. Leoncini and F. Mazzotta and S. Ambu and {Lo Caputo}, S. and G. Angarano and B. Grisorio and S. Ferrara and P. Grima and P. Tundo and G. Pagano and N. Piersantelli and A. Alessandrini and R. Piscopo and M. Toti and S. Chigiotti and F. Soscia and L. Tacconi and A. Orani and G. Castaldo and A. Scasso and A. Vincenti and A. Scalzini and F. Alessi and M. Moroni and A. Lazzarin and A. Cargnel and F. Milazzo and L. Caggese and {D'Arminio Monforte}, A. and S. Melzi and F. Delfanti and B. Carini and B. Adriani and S. Garavaglia and C. Moioli and R. Esposito and C. Mussini and N. Abrescia and A. Chirianni and O. Perrella",
year = "2001",
month = "10",
day = "15",
doi = "10.1086/323604",
language = "English",
volume = "184",
pages = "983--991",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy

AU - Perno, C. F.

AU - Cozzi-Lepri, A.

AU - Balotta, C.

AU - Forbici, F.

AU - Violin, M.

AU - Bertoli, A.

AU - Facchi, G.

AU - Pezzotti, P.

AU - Cadeo, G.

AU - Tositti, G.

AU - Pasquinucci, S.

AU - Pauluzzi, S.

AU - Scalzini, A.

AU - Salassa, B.

AU - Vincenti, A.

AU - Phillips, A. N.

AU - Dianzani, F.

AU - Appice, A.

AU - Angarano, G.

AU - Monno, L.

AU - Ippolito, G.

AU - Moroni, M.

AU - D'Arminio Monforte, A.

AU - Montroni, M.

AU - Scalise, G.

AU - Costantini, A.

AU - Del Prete, M. S.

AU - Tirelli, U.

AU - Nasti, G.

AU - Pastore, G.

AU - Perulli, L. M.

AU - Suter, F.

AU - Arici, C.

AU - Chiodo, F.

AU - Gritti, F. M.

AU - Colangeli, V.

AU - Fiorini, C.

AU - Guerra, L.

AU - Carosi, G.

AU - Cadeo, G. P.

AU - Castelli, F.

AU - Minardi, C.

AU - Vangi, D.

AU - Rizzardini, G.

AU - Migliorino, G.

AU - Manconi, P. E.

AU - Piano, P.

AU - Ferraro, T.

AU - Cosco, L.

AU - Pizzigallo, E.

AU - Ricci, F.

AU - Vigevani, G. M.

AU - Pusterla, L.

AU - Carnevale, G.

AU - Pan, A.

AU - Viganò, P.

AU - Mena, M.

AU - Ghinelli, F.

AU - Sighinolfi, L.

AU - Leoncini, F.

AU - Mazzotta, F.

AU - Ambu, S.

AU - Lo Caputo, S.

AU - Angarano, G.

AU - Grisorio, B.

AU - Ferrara, S.

AU - Grima, P.

AU - Tundo, P.

AU - Pagano, G.

AU - Piersantelli, N.

AU - Alessandrini, A.

AU - Piscopo, R.

AU - Toti, M.

AU - Chigiotti, S.

AU - Soscia, F.

AU - Tacconi, L.

AU - Orani, A.

AU - Castaldo, G.

AU - Scasso, A.

AU - Vincenti, A.

AU - Scalzini, A.

AU - Alessi, F.

AU - Moroni, M.

AU - Lazzarin, A.

AU - Cargnel, A.

AU - Milazzo, F.

AU - Caggese, L.

AU - D'Arminio Monforte, A.

AU - Melzi, S.

AU - Delfanti, F.

AU - Carini, B.

AU - Adriani, B.

AU - Garavaglia, S.

AU - Moioli, C.

AU - Esposito, R.

AU - Mussini, C.

AU - Abrescia, N.

AU - Chirianni, A.

AU - Perrella, O.

PY - 2001/10/15

Y1 - 2001/10/15

N2 - The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor-containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P=.04, X2 test). Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30-3.75; P=.004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy.

AB - The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor-containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P=.04, X2 test). Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30-3.75; P=.004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy.

UR - http://www.scopus.com/inward/record.url?scp=0035887629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035887629&partnerID=8YFLogxK

U2 - 10.1086/323604

DO - 10.1086/323604

M3 - Article

C2 - 11574912

AN - SCOPUS:0035887629

VL - 184

SP - 983

EP - 991

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 8

ER -