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

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) log10 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.