The 118I reverse transcriptase mutation is the only independent genotypic predictor of virologic failure to a stavudine-containing salvage therapy in HIV-1-infected patients.
Patients infected with HIV-1 with more than 1000 HIV-1 RNA copies/mL, who were genotyped within 3 months before starting stavudine and treated for at least 3 months with a stable stavudine-containing highly active antiretroviral therapy, were selected from our database to identify the determinants of response to stavudine. Nonresponse was defined as a failure to achieve HIV-1 RNA level of less than 400 copies/mL or a reduction of more than 2 log10 by week 12. Univariate logistic analysis was used to elicit the failure-associated reverse transcriptase mutations (scored 1 to develop a genotype score). Eighty-one patients were eligible for the analysis, including 75 (93%) who previously received zidovudine. Thirty-five (43%) were nonresponders. Univariate logistic analysis revealed the following failure-associated mutations: 41L (P = 0.0001), 44D (P = 0.02), 118I (P = 0.0006), 184V (P = 0.04), 210W (P = 0.0004), and 215Y (P = 0.002) for a median stavudine score of 2. Failure was observed in 7 (18.9%) of 37 patients with a score less than 2, compared with 28 (63.6%) of 44 patients with a score of 2 or greater (P < 0.0001). The multivariable analysis showed that the 118I mutation (P = 0.04) was the only independent genotypic predictor of failing on a stavudine- containing highly active antiretroviral therapy.
Gianotti
Nicola
N
Clinic of Infectious Diseases, Vita-Salute San Raffaele University, Italy. gianotti@hsr.it
Galli
Laura
L
Boeri
Enzo
E
De Bona
Anna
A
Guffanti
Monica
M
Danise
Anna
A
Salpietro
Stefania
S
Lazzarin
Adriano
A
Castagna
Antonella
A
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015751:Genes, pol; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012367:RNA, Viral / Q000097:blood; D016879:Salvage Therapy / Q000379:methods; D017422:Sequence Analysis, DNA; D013223:Statistics as Topic; D018119:Stavudine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018119:Stavudine; D054303:HIV Reverse Transcriptase