Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group.

AIDS. 1999 Sep 10;13(13):1705-9. Unique Identifier : AIDSLINE MED/99437271
Pellegrin I; Izopet J; Reynes J; Denayrolles M; Montes B; Pellegrin JL; Massip P; Puel J; Fleury H; Segondy M; Department of Virology, Bordeaux University Hospital, France.

Abstract: OBJECTIVE: Assessment of genotypic changes in the reverse transcriptase gene of HIV-1 occurring in antiretroviral naive patients treated by stavudine plus didanosine combination therapy. METHODS: Sequence analysis (codons 1-230) was performed after amplification of the reverse transcriptase gene from plasma samples collected at baseline and at the end of treatment from 39 previously treatment-naive patients treated for 24-48 weeks. RESULTS: At baseline, mutations associated with zidovudine resistance were detected in plasma from two patients: Asp67Asn/Lys219Gln and Leu210Trp. Among the 39 subjects, 18 (46%) developed mutations: one developed the Val75Thr/Ala mutation, four (10%) developed a Gln151Met multidrug-resistance mutation (MDR), associated in one of them with the Phe77Leu and the Phe116Tyr MDR mutations and 14 (36%) developed one or more zidovudine-specific mutations (Met41Leu, Asp67Asn, Lys70Arg, Leu210Trp, Thr215Tyr/Phe). The development of a Met41Leu zidovudine-specific mutation was associated with the development of a Gln151Met mutation in one patient. Other reverse transcriptase mutations known to confer resistance to nucleoside analogues were not detected. At inclusion, there was no statistical difference in HIV-1 load between patients who developed resistance mutations and those who did not. RNA HIV-1 load decrease was higher (P = 0.05) in patients who maintained a wild-type reverse transcriptase genotype (-2.22 log10 copies/ml) than in patients who developed resistance mutations (-1.14 log10 copies/ml). CONCLUSION: Stavudine/didanosine combination therapy is associated with emergence of zidovudine-related resistance or MDR mutations in naive patients. These findings should be considered when optimizing salvage therapy for patients who have received a treatment including stavudine/didanosine combination.

Keywords: JOURNAL ARTICLE Adult Anti-HIV Agents/*ADMINISTRATION & DOSAGE Didanosine/*ADMINISTRATION & DOSAGE Drug Resistance, Multiple/*GENETICS Drug Therapy, Combination Human HIV Infections/*DRUG THERAPY/VIROLOGY HIV-1 Reverse Transcriptase/*GENETICS *Mutation Reverse Transcriptase Inhibitors/*ADMINISTRATION & DOSAGE Stavudine/*ADMINISTRATION & DOSAGE Support, Non-U.S. Gov't Viral Load Zidovudine/*ADMINISTRATION & DOSAGE

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