Markers for HIV-disease progression in untreated patients and patients receiving AZT: evaluation of viral activity, AZT resistance, serum cholesterol, beta 2-microglobulin, CD4+ cell counts, and HIV antigen.
In order to find parameters which allow the assessment of the clinical state of HIV patients with or without antiviral therapy, viral cultures on lymphocytes and monocytes/macrophages, CD4-cell counts, HIV antigen, beta 2-microglobulin and serum cholesterol were evaluated for their predictive value. As had been shown previously for lymphocytes, the efficiency of viral isolation on macrophages also depends on the disease stage (CDC) of the patients and thus has a high predictive value. A multivariant discriminant analysis showed that the combination of beta 2-microglobulin, viral antigen, CD4+ cell count and HDL cholesterol predicted the outcome of viral cultures with 80% accuracy. While viral antigen, CD4+ cell counts and beta 2-microglobulin had been known, HDL cholesterol deserves further evaluation as prognostic parameter. The analysis of HIV derived from patients with AZT showed a 20-200-fold in vitro drug resistance after seven to 24 months of therapy. DNA sequence determination of such strains isolated from AZT patients over time showed only two of the amino acid exchanges described in the literature for resistant strains and an additional Val60-Ile transition after 32 months of therapy.
Rübsamen-Waigmann
H
H
Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus, Frankfurt am Main, Germany.
Schröder
B
B
Biesert
L
L
Bauermeister
C D
CD
von Briesen
H
H
Suhartono
H
H
Zimmermann
F
F
Brede
H D
HD
Regeniter
A
A
Gerte
S
S
D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood*; D004352:Drug Resistance, Microbial; D005069:Evaluation Studies as Topic; D006678:HIV / Q000302:isolation & purification*; D015488:HIV Antigens / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007958:Leukocyte Count; D008264:Macrophages / Q000382:microbiology; D009000:Monocytes / Q000382:microbiology; D013997:Time Factors; D015215:Zidovudine / Q000627:therapeutic use*; D001613:beta 2-Microglobulin / Q000032:analysis*
D008076:Cholesterol, HDL; D015488:HIV Antigens; D001613:beta 2-Microglobulin; D015215:Zidovudine