Evidence for late stage compartmentalization of HIV-1 resistance mutationsbetween lymph node and peripheral blood mononuclear cells

Objective: To determine the overall distribution of drug-resistance mutatio ns to nucleoside reverse transcriptase inhibitors of HIV strains recovered from the lymph nodes (LN) and peripheral blood mononuclear cell (PBMC) comp artments of four HIV-infected patients receiving zidovudine and didianosine and to compare them with antiretroviral-naive patients. Design: Molecular comparison of major and minor HIV-1 env and pol region va riants residing in LN and PBMC compartments. Materials and methods: Proviral DNA sequences were amplified by PCR from bo th PBMC and LN compartments, cloned into PGEM-T II Easy vector and sequence d. The clones were subjected to molecular and phylogenetic ananlysis. Results: Comparison of PBMC and LN-derived HIV-1 variants in the env V3 reg ion showed that nucleotide and amino acid variability was a characteristic feature of LN-derived variants. In contrast, a majority of resistance mutat ions to reverse transcriptase inhibitors were localized in the PBMC compart ment rather than in LN, which is thought to be a reservoir of HIV. Conclusions: Distinct compartmentalization or independent evolution of pol and env gene variants between LN and PBMC could be due to the differential selection pressure imposed by the combination drug regimen, hence the bimod al distribution of resistance variants between LN and PBMC compartments. (C ) 2000 Lippincott Williams & Wilkins.