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Low rate of virological failure and maintenance of susceptibility to HIV‐1 protease inhibitors with first‐line lopinavir/ritonavir‐based antiretroviral treatment in clinical practice
Author(s) -
Prosperi Mattia C.F.,
Zazzi Maurizio,
Punzi Grazia,
Monno Laura,
Colao Grazia,
Corsi Paola,
Di Giambenedetto Simona,
Meini Genny,
Ghisetti Valeria,
Bonora Stefano,
Pecorari Monica,
Gismondo Maria Rita,
Bagnarelli Patrizia,
Carli Tiziana,
De Luca Andrea
Publication year - 2010
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.21927
Subject(s) - lopinavir , viral load , lopinavir/ritonavir , ritonavir , emtricitabine , virology , medicine , drug resistance , resistance mutation , hazard ratio , proportional hazards model , human immunodeficiency virus (hiv) , biology , confidence interval , antiretroviral therapy , rna , microbiology and biotechnology , reverse transcriptase , biochemistry , gene
Abstract Protease inhibitor (PI)‐resistant HIV‐1 has hardly ever been detected at failed boosted PI‐based first‐line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first‐line lopinavir/ritonavir (LPV/rtv)‐based therapy with available baseline HIV‐1 RNA load, a viral genotype and follow‐up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV‐1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV‐1 RNA (RH 1.79, 95%CI 1.10–2.92 per 1 − log 10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02–1.06 per 10‐point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV‐1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50‐copy and/or 500‐copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow‐up HIV‐1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996–2003, 2010. © 2010 Wiley‐Liss, Inc.