title: Early virological failure after tenofovir + didanosine + efavirenz combination in HIV-positive patients upon starting antiretroviral therapy.
abstract: A prospective, randomized pilot trial was conducted in naive patients comparing three different combinations: zidovudine+lamivudine+lopinavir/ritonavir (arm A) versus tenofovir+lamivudine+efavirenz (arm B) versus tenofovir+didanosine+efavirenz (arm C). HIV-RNA slope (days 1, 3, 7, 14 and 28) was slower in arm C with respect to arm B (P < 0.0001). Seven out of eight patients (87.5%) reached undetectable HIV-RNA by week 28 in arm A, 10/10 (100%) in arm B and 6/10 (60%) in arm C. Among arm C patients who failed at week 4, one HIV isolate showed 67N and 219Q, and another one showed 210F and 215D substitutions in the HIV reverse transcriptase gene at baseline, respectively. Non-nucleoside reverse transcriptase inhibitor resistance-related mutations appeared first, followed by 65R mutations in all cases. Efavirenz AUC(0-24) values were lower in arm C with respect to arm B, especially in patients who failed early. A high virological failure rate after tenofovir+didanosine+efavirenz correlated with a slower HIV-RNA decrease and a peculiar accumulation of resistance mutations. A constellation of factors could be correlated with early failure events in patients receiving this combination such as resistance mutations or polymorphisms present at baseline, low CD4+ T-cell count or advanced disease and unexpectedly low efavirenz plasma levels.
authors.affiliation: Institute for Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. torti.carlo@libero.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Eugenia
authors.initials: E
authors.lastname: Quiros-Roldan
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Andrea
authors.initials: A
authors.lastname: Patroni
authors.forename: Paola
authors.initials: P
authors.lastname: Villani
authors.forename: Valeria
authors.initials: V
authors.lastname: Tirelli
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cologni
authors.forename: Daniela
authors.initials: D
authors.lastname: Zinzi
authors.forename: Sergio
authors.initials: S
authors.lastname: Lo Caputo
authors.forename: Paolo
authors.initials: P
authors.lastname: Perini
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010349:Patient Compliance
chemical_list: D019380:Anti-HIV Agents