In vivo HIV-1 compartmentalisation: Drug resistance-associated mutation distribution

Four patients who had received highly active antiretroviral therapy (HAART) , and had postmortem samples stored, were tested for genotypic resistance u sing consensus sequencing. One patient was further investigated using singl e-copy sequencing. Patients 1, 3, and 4 showed a relatively uniform distrib ution of resistance associated mutations, with only a small number (one to three) of protease mutations detectable. Patient 2 had a number of detectab le mutations (four to eight, depending on the tissue) with similar distribu tions between the tissues. The exception was viruses detected in the esopha gus, which were more diverse. Plasma was a moderately representative tissue of the viruses circulating in these individuals. However, some mutations d etectable in some tissues were not seen in plasma (e.g., M461 and D30N in t he protease). Single-copy sequencing revealed a wide distribution of quasi- species and a number of defective viruses in the proviral DNA and RNA. This study supports the concept that a wide variety of quasi-species circulate in each individual and that there may be viruses evolving independently in different body compartments. (C) 2002 Wiley-Liss, Inc.