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 levels 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.


METHODS
CD4 and CD8 levels were monitored by flow cytometry. Beta2-microglobulin (beta2M) and neopterin levels were measured by quantitative enzyme immunoassays. Plasma and PBMC from 11 PR and 13 CF were analyzed for infectious HIV levels in limiting dilution cultures. Polymerase chain 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 substantial 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 CD4+ PBMC (p = .007).


CONCLUSIONS
Lower levels of infectious HIV and a lower frequency of CD4+ PBMC that contain "productive" HIV DNA in PR as compared with CF may contribute to the stable or increasing CD4+ PBMC levels of the PR. However, HAART may also have effects on lymphocyte homeostasis independent of its antiviral activity.
Fessel
W J
WJ
Kaiser Permanente Medical Center, San Francisco, California 94115, USA.
Krowka
J F
JF
Sheppard
H W
HW
Gesner
M
M
Tongson
S
S
Weinstein
S
S
Ascher
M
M
Kwok
S
S
Christopherson
C
C
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019798:Neopterin / Q000097:blood; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D001613:beta 2-Microglobulin / Q000097:blood
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D001613:beta 2-Microglobulin; D019798:Neopterin