title: The role of baseline HIV-1 RNA, drug resistance, and regimen type as determinants of response to first-line antiretroviral therapy.
abstract: The factors influencing virological response to first-line combined antiretroviral therapy (cART) in an Italian cohort of HIV-1-infected patients were examined. Eligible patients were those enrolled in a national prospective observational cohort (Antiretroviral Resistance Cohort Analysis), starting first-line cART between 2001 and 2011 and who had at least one follow-up of HIV-1 RNA. The primary endpoint was virological success, defined as the first viral load <50  copies/ml. Time to events were analyzed by Kaplan-Meier analysis and Cox proportional hazard model. One thousand three hundred five patients met the study inclusion criteria. In a multivariable model adjusting for transmission mode, presence of transmitted drug resistance, baseline CD4(+) cell count, viral subtype, and type of NRTI backbone employed, independent predictors of virological success were higher baseline viral load (≥500,000 vs. <100,000 HR 0.52; P < 0.001), a weighted genotypic susceptibility score (wGSS) <3 (HR 0.58; P = 0.003), male sex (HR 0.76 P = 0.001), and type of initial third drug employed (integrase inhibitor vs. boosted protease inhibitors HR 3.23; P < 0.001). In the subset with HIV-1 RNA >100,000  copies/ml, virologic success was only associated with the use of integrase inhibitors in the first cART regimen. Independent predictors of immunological success were baseline CD4(+) cell count and wGSS <3. High baseline HIV-1 RNA, predicted activity of the first-line regimen based on genotypic resistance testing, gender, and use of new agents were found to predict time to achieve virological success. The type of initial nucleoside analog backbone was not found to predict virological response.
authors.affiliation: Clinic of Infectious Diseases, IRCCS San Martino-IST, National Institute of Cancer, Genoa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Biagio
authors.forename: Stefano
authors.initials: S
authors.lastname: Rusconi
authors.forename: Angela
authors.initials: A
authors.lastname: Marzocchetti
authors.forename: Alessio
authors.initials: A
authors.lastname: Signori
authors.forename: Irene
authors.initials: I
authors.lastname: Schiavetti
authors.forename: Bianca
authors.initials: B
authors.lastname: Bruzzone
authors.forename: Laura
authors.initials: L
authors.lastname: Monno
authors.forename: Grazia
authors.initials: G
authors.lastname: Punzi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Colao
authors.forename: Giovanni
authors.initials: G
authors.lastname: Penco
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zazzi
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007558:Italy; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D012189:Retrospective Studies; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral
keywords: CD4; HIV-1 RNA; N(n)RTI backbone; drug regimen; drug resistance; wGSS