Decrease in HIV provirus in peripheral blood mononuclear cells during zidovudine and human rIL-2 administration.
Quantification of human immunodeficiency virus (HIV) proviral DNA in peripheral blood mononuclear cells (PBMC) was performed in 13 HIV-seropositive asymptomatic individuals during 10-24 months by polymerase chain reaction amplification of multiple half-log dilutions of cellular DNA. At enrollment, subjects had a geometric mean titer of 100 copies of HIV provirus per 10(6) PBMC (mean +/- SD, 2 +/- 0.9 log10). In four untreated individuals there was no significant change in provirus levels during a mean period of 13.3 months. In eight patients treated with zidovudine (ZDV) and human recombinant interleukin 2 (rIL-2), HIV provirus copies declined to 13 per 10(6) cells (1.1 +/- 0.8 log10) at the end of the first course of ZDV and rIL-2 at week 20 (p less than 0.01), and to 40 per 10(6) cells (1.6 +/- 0.9 log10) after 12 months of treatment (p less than 0.04). Subsequent courses, which included 12 weeks of ZDV alone or 4 weeks of IL-2 alone, did not significantly change the already depressed provirus copy numbers. Proviral copy number also remained depressed during drug-free "washout periods" between courses. Finally, we observed a return to a geometric mean of 400 copies per 10(6) cells (2.6 +/- 0.3 log10) a mean of 7.9 months after discontinuation of therapy. Measurement of changes in HIV provirus should provide a direct marker for defining antiviral activity of drugs, biologics, and combination therapy.
Clark
A G
AG
AIDS Clinical Trial Unit, Stanford University, California.
Holodniy
M
M
Schwartz
D H
DH
Katzenstein
D A
DA
Merigan
T C
TC
D004279:DNA, Viral / Q000097:blood*; D005500:Follow-Up Studies; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000382:microbiology; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use*
D004279:DNA, Viral; D007376:Interleukin-2; D011994:Recombinant Proteins; D015215:Zidovudine