HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with Abacavir

Objective: To assess HIV-1 RNA levels and the relationship between HIV-1 re verse transcriptase (RT) genotype from plasma and cerebrospinal fluid (CSF) during treat ment with abacavir (Ziagen, ABC) or placebo in combination wi th stable background therapy (SBG) in subjects with AIDS dementia complex ( ADC) (study CNA3001). Design: One-hundred and five HIV-1 infected adults with ADC were randomized to receive either ABC (600 mg twice daily) or ABC-matched placebo (twice d aily) in addition to SBG for 12 weeks. Methods: Plasma and CSF were collected for population sequencing at baselin e and week 12 (CSF optional). Sequences were analyzed for mutations associa ted with resistance to nucleoside reverse transcriptase inhibitors (NRTI). Results: Sixty out of sixty-seven subjects with baseline plasma HIV-RT sequ ence data harbored virus with greater than or equal to1 NRTI-associated mut ations; 50 out of 67 had the M184V mutation. At week 12, more subjects in t he ABC group had plasma HIV-1 RNA less than or equal to 400 copies/ml than the SBG group (46% versus 13%, P= 0.002). Non-response to ABC was associate d with multiple baseline zidovudine (ZDV)/stavudine (d4T)-associated mutati ons. Baseline RT mutation patterns differed in 14 out of 21 (67%) paired sa mples from plasma and CSF. Four subjects experienced >1 log(10)copies/ml re ductions in CSF HIV-1 RNA, two in the absence of reductions in plasma HIV-1 RNA and two With undetectable plasma HIV-1 RNA at baseline. Conclusions: Substantial decreases in plasma and CSF HIV-1 RNA following ad dition of ABC were not precluded by baseline HIV-1 NRTI-associated mutation s, including the M184V mutation, but non-responders commonly harbored multi ple ZDV/d4T-associated mutations. HIV-1 RNA responses and RT genotype appea r to be discordant between CSF and plasma in some subjects. (C) 2001 Lippin cott Williams & Wilkins.