Antiviral efficacy and genotypic resistance patterns of combination therapy with stavudine/tenofovir in highly active antiretroviral therapy experienced patients

Andrea Antinori, Maria Paola Trotta, Paola Nasta, Teresa Bini, Stefano Bonora, Antonella Castagna, Mauro Zaccarelli, Tiziana Quirino, Simona Londonio, Stefania Merli, Valerio Tozzi, Giovanni Di Perri, Massimo Andreoni, Carlo Federico Perno, Giampiero Carosi

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: To evaluate antiviral efficacy of stavudine/tenofovir (d4T/TDF) backbone combination in late-line antiretroviral therapy, and to assess clinical and virological determinants of treatment success. Design: Multicentric retrospective analysis on patients starting d4T/TDF after highly active antiretroviral therapy (HAART) failure. Methods: The primary endpoint was the change in plasma HIV-1 RNA from the baseline (time of d4T/TDF initiation) to 6 months of therapy; secondary endpoint was the risk of virological failure. Results: Among 172 patients included, a mean change in HIV-1 RNA of -1.69 (+1.23) and -1.53 (+1.43) log 10 cp/ml was observed respectively at weeks 24 and 48 after starting d4T/TDF combination. Any single type-1 thymidine analogue mutation (TAM; M41L, L210W, T215Y) had a negative effort on the change in HIV RNA at 6 months, whereas among type-2 TAMs (D67N, K70R, K219Q), only D67N showed a trend for a negative effect. Presence of M184V mutation was related with a greater reduction in HIV RNA during d4T/TDF exposure. The risk of virological failure at 6 months after d4T/TDF starting was 22%. Type-1 TAMs were associated with a greater risk of failure (adjusted hazard ratio [HR]=1.65; 95% confidence interval [CI] 1.19-2.29). Conversely, M184V showed a protective effect. In 17 genotypic tests available at failure, no K65R mutation was detected, whereas a trend for an increasing prevalence of d4T-associated mutations was found. Conclusions: Combining TDF with a thymidine analogue as d4T may be effective as component of antiretroviral rescue regimens in HIV-infected patients with previous exposure to nucleoside analogue reverse transcriptase inhibitor. Previous selection of type-1 TAMs induces a detrimental effect over virological response.

Original languageEnglish
Pages (from-to)233-243
Number of pages11
JournalAntiviral Therapy
Volume11
Issue number2
Publication statusPublished - 2006

ASJC Scopus subject areas

  • Pharmacology

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