67. Distribution of HIV env and pol Variants in CSF and Plasma of Patients with and without Antiretroviral Therapy

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Session 15 Oral Abstract Session
Neuropathogenesis
Session Time: Tuesday, 10 am - 12:30 pm
Room 606-609

11:30 67.

Distribution of HIV env and pol Variants in CSF and Plasma of Patients with and without Antiretroviral Therapy
J. K. Wong*^1,2, S. Letendre^1,3, T. Macaranas¹, C. Ignacio¹, O. A. Daly², H. F. Guenthard⁴, M. C. Strain¹, S. D. W. Frost^1,5, S. Pillai¹, B. Good¹, M. Furtado⁷, S. Wolinsky⁶, I. Grant³, D. D. Richman^1,2, and J. A. McCutchan¹
¹Univ. of California, San Diego; ²VA San Diego Healthcare System, CA; ³HNRC, San Diego, CA; ⁴Univ. Hosp., Zurich, Switzerland; ⁵Antiviral Res. Ctr., San Diego, CA; ⁶Northwestern Univ., Chicago, IL; and ⁷Applied Biosystems, Foster City, CA

Background: Differences in characteristics of viral populations in CNS and lymphoid tissues may affect ARV treatment response. Drug therapy may also alter viral population genetics.
Method: Cell-free plasma and CSF from 6 drug-experienced and 5 drug-naïve patients with established HIV infection (median CD4 221) were studied. HIV protease and the N-terminal 2/3 of RT were population sequenced from RNA extracts using the Viroseqª system. Nested RT PCR was performed in quadruplicate for the C2-V3 region of env, cloned and 12 to 15 clones were sequenced from each source sample. Phylogenetic analysis was performed using the software suite Phylip.
Results: HIV RNA from 6/6 drug-experienced patients had drug-resistance mutations in at least 1 compartment. 2/6 patients had discordant drug resistance profiles. In 4 of 6 patients, highly resistant genotypes were identical in all aa residues. Among drug naïve patients, 4/5 demonstrated independent clustering of C2-V3 sequences while only 1 of 6 treated patients did so (FischerÕs exact test, p=0.06). The 1 patient with independent clustering of C2-V3 also demonstrated discordance of resistance genotype.
Conclusions: Consistent with previous observations, these results suggest that viral populations in CSF and plasma are frequently distinct. However, failure of drug therapy and the emergence of drug resistance appears to be associated with equilibration of viral populations in CSF and blood. Because of the neurotoxic potential attributed to specific HIV envelope types, such perturbations in the population genetics of HIV may have important clinical implications.