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Early Virological Failure after Tenofovir + Didanosine + Efavirenz Combination in HIV-Positive Patients upon Starting Antiretroviral Therapy

2005; SAGE Publishing; Volume: 10; Issue: 4 Linguagem: Inglês

10.1177/135965350501000405

2040-2058

Carlo Torti, Eugenia Quirós-Roldán, Mario Regazzi, Andrea Antinori, Andrea Patroni, P. Villani, Valeria Tirelli, Giuliana Cologni, Daniela Zinzi, Sergio Lo Caputo, Paolo Perini, Giampiero Carosi, Carlo Torti, Eugenia Quirós-Roldán, A. Patroni, Valeria Tirelli, Giuliana Cologni, Giuseppe Lapadula, Filippo Castelnuovo, Giuseppe Paraninfo, Salvatore Casari, Francesca Moretti, Silvia Costarelli, Giampiero Carosi, Daniela Zinzi, Mauro Zaccarelli, P Marconi, Andrea Antinori, Sergio Lo Caputo, Piera Pierotti, Francesco Mazzotta, P. Perini, AM Orani, P. Villani, Maria Cusato, Mario Regazzi, Franco Gargiulo, N. Manca, Carmine Tinelli,

Pneumocystis jirovecii pneumonia detection and treatment

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.