title: 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.
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.
authors.affiliation: Clinic of Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy. ahnven@yahoo.it
authors.forename: Mattia C F
authors.initials: MC
authors.lastname: Prosperi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zazzi
authors.forename: Grazia
authors.initials: G
authors.lastname: Punzi
authors.forename: Laura
authors.initials: L
authors.lastname: Monno
authors.forename: Grazia
authors.initials: G
authors.lastname: Colao
authors.forename: Paola
authors.initials: P
authors.lastname: Corsi
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.forename: Genny
authors.initials: G
authors.lastname: Meini
authors.forename: Valeria
authors.initials: V
authors.lastname: Ghisetti
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.forename: Monica
authors.initials: M
authors.lastname: Pecorari
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Gismondo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bagnarelli
authors.forename: Tiziana
authors.initials: T
authors.lastname: Carli
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D006801:Humans; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019438:Ritonavir