Dissociation of immunologic and virologic responses to highly active antiretroviral therapy

Objective: Immunologic markers, levels of HIV DNA, and infectious HIV were compared in partial responders (PR) to HAART who had high plasma HIV RNA le vels but stable or increasing levels of CD4(+) peripheral blood mononuclear cells (PBMC), and patients with complete failure (CF) who had very low or decreasing levels of CD4(+) PBMC and high plasma HIV RNA levels. Design and Methods: CD4 and CD8 levels were monitored by flow cytometry. be ta(2)-microglobulin (beta(2)M) and neopterin levels were measured by quanti tative enzyme immunoassays. Plasma and PBMC from 11 PR and 13 CF were analy zed for infectious HIV levels in limiting dilution cultures. Polymerase cha in reaction (PCR) assays were used to quantify cellular HIV DNA and plasma HIV RNA. Results: In comparison with CF, PR had little or no CD4(+) cell loss, a sub stantial increase in CD8(+) cells, significantly fewer positive plasma HIV cultures (p = .03), lower frequencies of infectious HIV in total PBMC (p = .005) and in CD4(+) PBMC (p < .001), and lower frequencies of HIV DNA in CD 4(+) PBMC (p = .007). Conclusions: Lower levels of infectious HIV and a lower frequency of CD4(+) PBMC that contain "productive" HN DNA in PR as compared with CF may contri bute to the stable or increasing CD4(+) PBMC levels of the PR. However, HAA RT may also have effects on lymphocyte homeostasis independent of its antiv iral activity.