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 using consensus sequencing. One patient was further investigated using single-copy sequencing. Patients 1, 3, and 4 showed a relatively uniform distribution of resistance-associated mutations, with only a small number (one to three) of protease mutations detectable. Patient 2 had a number of detectable mutations (four to eight, depending on the tissue) with similar distributions between the tissues. The exception was viruses detected in the esophagus, which were more diverse. Plasma was a moderately representative tissue of the viruses circulating in these individuals. However, some mutations detectable in some tissues were not seen in plasma (e.g., M46I and D30N in the 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.