title: Antiviral efficacy and genotypic resistance patterns of combination therapy with stavudine/tenofovir in highly active antiretroviral therapy experienced patients.
abstract: 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.
authors.affiliation: National Institute for Infectious Diseases L. Spallanzani IRCCS, Roma. antinori@inmi.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Trotta
authors.forename: Paola
authors.initials: P
authors.lastname: Nasta
authors.forename: Teresa
authors.initials: T
authors.lastname: Bini
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.forename: Mauro
authors.initials: M
authors.lastname: Zaccarelli
authors.forename: Tiziana
authors.initials: T
authors.lastname: Quirino
authors.forename: Simona
authors.initials: S
authors.lastname: Landonio
authors.forename: Stefania
authors.initials: S
authors.lastname: Merli
authors.forename: Valerio
authors.initials: V
authors.lastname: Tozzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine