Peripheral blood mononuclear cell human immunodeficiency virus type 1 proviral DNA quantification by polymerase chain reaction: relationship to immunodeficiency and drug effect.
Human immunodeficiency virus type 1 (HIV-1) proviral DNA from peripheral blood mononuclear cells (PBMCs) was quantitated in 61 HIV-1-seropositive individuals by a nonisotopic polymerase chain reaction assay. Primers from the gag region (SK38, SK39) were used to determine the log10 HIV-1 proviral copy number per 10(6) CD4+ T lymphocytes (peripheral blood proviral load). A standard curve was generated for each assay by using ACH-2 cell DNA. The peripheral blood proviral load was followed in 15 individuals in a longitudinal study and was measured in 45 individuals in a cross-sectional analysis. Three of four untreated patients who were followed for 14 months had stable PBMC proviral loads and CD4+ T lymphocyte counts; one untreated patient had a sustained increase in PBMC proviral load followed 5 months later by a significant decline in the CD4+ T lymphocyte count. Eleven previously untreated individuals were monitored for 1 year following initiation of zidovudine and/or 2',3'-dideoxyinosine therapy. The mean log10 number of proviral HIV-1 copies per 10(6) CD4+ T cells decreased from 4.3 +/- 0.4 at the baseline to 3.5 +/- 0.6 after 2 to 4 months of therapy (P < 0.01). This initial 0.8 log10 fall in the PBMC proviral load after the initiation of therapy was followed by a rise in the PBMC proviral load by the sixth month of therapy. The PBMC proviral load in 45 subjects, both treated (n = 25) and untreated (n = 20), correlated inversely with the CD4+ T lymphocyte count (P < 0.01, R = 0.49). PBMC proviral DNA quantification by a nonisotopic polymerase chain reaction assay correlates with HIV-1 disease progression and could be used to monitor the effect of antiretroviral therapy.
Montoya
J G
JG
Center for AIDS Research, Stanford University Medical Center, California 94305.
Wood
R
R
Katzenstein
D
D
Holodny
M
M
Merigan
T C
TC
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology*; D015496:CD4-Positive T-Lymphocytes; D004279:DNA, Viral / Q000032:analysis*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics*; D015215:Zidovudine / Q000494:pharmacology
D004279:DNA, Viral; D015215:Zidovudine