Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen different envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4(+) CCR5(+) cells. Infectivity and cell-cell fusion assays showed that most envelopes used both CCR5 and CCR3. One brain-derived envelope used a broad range of coreceptors, while three other brain envelopes from one individual were restricted to CCR5. However, there was no correlation between tissue of origin and coreceptor use. Envelopes showed two very distinct phenotypes depending on their capacity to infect macrophages and to exploit low levels of CD4 and/or CCR5 for infection. Envelopes that were highly fusigenic and tropic for macrophages were identified in brain tissue from four of the five patients. The enhanced macrophage tropism correlated with reduced sensitivity to inhibition by Q4120, a CD4-specific antibody, but not with sensitivity to the CCR5 inhibitor, TAK779. The highly macrophage-tropic envelopes were able to infect cells expressing low levels of CD4 and/or CCR5. Comparison with several well-characterized macrophage-tropic envelopes showed that the four identified patient envelopes were at the top limit of macrophage tropism. In contrast, all four lymph node-derived envelopes exhibited a non-macrophage-tropic phenotype and required high levels of CD4 for infection. Our data support the presence of envelopes that are highly fusigenic and tropic for macrophages in the brains of patients with neurological complications. These envelopes are able to infect cells that express low levels of CD4 and/or CCR5 and may have adapted for replication in brain macrophages and microglia, which are known to express limited amounts of CD4.

Co-occurring mental illness and addiction is very common and results in worse treatment outcomes compared to singly diagnosed addicted individuals. Integrated treatment for co-occurring disorders is associated with better treatment outcomes; however there is a wide range of what is included in integrated treatment. Due to patient and staff interests, integrated treatment often includes complementary and alternative therapies, including music and art therapy. There is a need to study how these approaches effect treatment engagement, retention, and outcome. This study was a prospective naturalistic non-randomized pilot study without a control group that sought to evaluate how participation in a music therapy program affected treatment outcomes for individuals with co-occurring mental illness and addiction. In summary, music therapy appears to be a novel motivational tool in a severely impaired inpatient sample of patients with co-occurring disorders. Future studies of music therapy in integrated co-occurring disorder setting should include a control group.