3rd International Workshop on HIV Drug Resistance 2-5 August 1994, Kauai, Hawaii, USA

IN VITRO AND IN VIVO CORRELATES OF ZDV/ddI/NEVIRAPINE THERAPY OF HIV-1 INFECTION

Int Wkshop HIV Drug Res 1994 Aug 2-5;3:43 (abstract no. 42)

John L. Sullivan¹, Frank Brewster¹, Mohan Somasundaran¹, Thomas Greenough¹, Dan Pauletti², Cheng-Kon Shih², Johanna Griffm², Maureen Myers², Katherine Luzuriaga^1
1Dept. of Pediatrics, Univ. of Mass. Med. School, Worcester, MA and ²Boehringer-Ingelheim Pharmaceuticals, Ridgefield, CT

Replication of laboratory and primary isolates in the presence of ZDV/ddI/Nevirapine (NVP) therapy has been examined in vitro and in vivo. Laboratory (IIIB) and primary isolates resistant to ZDV/NVP were cultured in vitro with ZDV (1 µM), NVP (1 µM) and increasing (2, 10, 20 µM) concentrations of ddI. ddI dose-dependent reduction of viral replication without complete suppression was observed. Outgrowth of virus resistant to all three drugs was observed. Genotypic analysis of the triple resistant virus demonstrated mutations in the reverse transcriptase gene which resulted in amino acid changes consistent with decreased sensitivity to ZDV, NVP, and ddI. Two children with prior ZDV/ddI experience (Group 1) and 3 children with prior ZDV/NVP (Group 2) experience have received ZDV/ddI/NVP therapy. Both children in Group 1 experienced rapid (< 24 hours) declines in blood viral load after the addition of NVP to their regimen. More modest declines in blood viral load were observed in Group 2 after the genotypic evaluations of all viral isolates are in progress. In conclusion, reduction in viral load without complete suppression of viral replication was observed both in vitro and in vivo after the introduction of ZDV/NVP/ddI therapy; the rapidity and extent of viral load reduction appeared to be dependent on prior antiretroviral experience. Funded in part by Boehringer-Ingelheim Pharmaceuticals.

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1994-08-02
42

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