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

Abstract

Substantial decreases in plasma and CSF HIV-1 RNA following addition of ABC were not precluded by baseline HIV-1 NRTI-associated mutations, including the M184V mutation, but non-responders commonly harbored multiple ZDV/d4T-associated mutations. HIV-1 RNA responses and RT genotype appear to be discordant between CSF and plasma in some subjects.

HIV‐1 Chemokine Coreceptor Utilization in Paired Cerebrospinal Fluid and Plasma Samples: A Survey of Subjects with Viremia

“…Brew et al reported results similar to those of Di Stefano et al, by assessment of cytopathological effect and tropism [28]. Observations of phenotypic compartmentalization are also consistent with the CSF:plasma discordance noted in more-extensive analysis of env sequences [46,47] or pol resistance mutations [48][49][50][51][52][53] to define virus genotypes in the 2 compartments. We observed discordance in both directions, including 2 examples of the R5 phenotype in plasma and the R5+X4 phenotype in CSF.…”

Defining and Evaluating HIV-Related Neurodegenerative Disease and Its Treatment Targets: A Combinatorial Approach to Use of Cerebrospinal Fluid Molecular Biomarkers

“…In this respect, Glaxo-Wellcome should be especially commended for undertaking a study (CNAB3001) on the impact of abacavir on ADC during the early development of the drug. It was hoped that its potency and favorable CNS penetration would prove effective in treating this condition (Lanier et al 2001). Unfortunately, the study failed to show that addition of abacavir to optimized therapy made a difference in the measured outcomes.…”

Changing Patterns in the Neuropathogenesis of HIV During the HAART Era

“…A study on the effect of HAART on HIV-1 recovery from purified peripheral blood monocyte-derived macrophages showed that circulating monocytes constitute a significant source of replication-competent virus in HAART naive HIV patients and in HIV patients failing HAART (44). Moreover, a study by Lanier et al describing evolutionary relationships between the HIV-1 reverse transcriptase from multiple anatomical compartments of a patient enrolled in a phase III trial designed to assess the efficacy of ABC in subjects with HAD, reports compartmentalized evolution in the midfrontal gyrus of the brain and suggest that incomplete drug penetrance into this region may in part be responsible (47,65).…”