Resistance to AZT and ddC during long-term combination therapy in patients with advanced infection with human immunodeficiency virus

D. D. Richman, T. C. Meng, S. A. Spector, Margaret A Fischl, L. Resnick, S. Lai

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

To ascertain whether combination therapy with zidovudine (AZT) and zalcitabine (ddC) delayed the emergence of AZT resistance, isolates of human immunodeficiency virus (HIV) were evaluated from 15 previously untreated patients with advanced HIV disease who received combination therapy. Eighteen sequential viral isolates were available from 15 patients who received ≥6 months of combination therapy. Isolates from eight (73%) of 11 patients obtained between 24 and 48 weeks of therapy were AZT resistant [50% inhibitory concentration (IC50) ≥0.45 μM; range, 0.45-2.0 μM]. Four of these eight patients yielded virus isolates that were highly AZT resistant (IC50 > 1.0 μM). No changes in ddC susceptibility were discerned. The median IC50 for ddC was 0.2 μM and ranged from 0.07 to 0.5 μM. The CD4 cell counts of patients with AZT-sensitive virus tended to have higher median areas under the curve (AUC) and greater increases compared with patients who had AZT-resistant virus. They also had higher means and ranges of the average CD4 cell counts at week 36 (p = 0.01) and week 48 (p = 0.04). These data would indicate that the previously described more sustained CD4 cell responses conferred by the addition of ddC to AZT therapy cannot be ascribed to delayed emergence of AZT resistance with combination therapy.

Original languageEnglish
Pages (from-to)135-138
Number of pages4
JournalJournal of Acquired Immune Deficiency Syndromes
Volume7
Issue number2
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

HIV
Inhibitory Concentration 50
Infection
CD4 Lymphocyte Count
Viruses
Therapeutics
Zalcitabine
Zidovudine
Virus Diseases
Area Under Curve

Keywords

  • Antiviral chemotherapy
  • Drug resistance
  • Human immunodeficiency virus (HIV)
  • Zalcitabine (ddC)
  • Zidovudine (AZT, ZDV)

ASJC Scopus subject areas

  • Virology
  • Immunology and Allergy

Cite this

Resistance to AZT and ddC during long-term combination therapy in patients with advanced infection with human immunodeficiency virus. / Richman, D. D.; Meng, T. C.; Spector, S. A.; Fischl, Margaret A; Resnick, L.; Lai, S.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 7, No. 2, 01.01.1994, p. 135-138.

Research output: Contribution to journalArticle

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