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


METHODS
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.
Antinori
Andrea
A
National Institute for Infectious Diseases L. Spallanzani IRCCS, Roma. antinori@inmi.it
Trotta
Maria Paola
MP
Nasta
Paola
P
Bini
Teresa
T
Bonora
Stefano
S
Castagna
Antonella
A
Zaccarelli
Mauro
M
Quirino
Tiziana
T
Landonio
Simona
S
Merli
Stefania
S
Tozzi
Valerio
V
Di Perri
Giovanni
G
Andreoni
Massimo
M
Perno
Carlo Federico
CF
Carosi
Giampiero
G
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D005075:Biological Evolution; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018119:Stavudine / Q000494:pharmacology* / Q000627:therapeutic use; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine