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Updated: Aug 13, 2026

Amplifying and Quantifying HIV-1 RNA in HIV Infected Individuals with Viral Loads Below the Limit of Detection by Standard Clinical Assays
13:58

Amplifying and Quantifying HIV-1 RNA in HIV Infected Individuals with Viral Loads Below the Limit of Detection by Standard Clinical Assays

Published on: September 26, 2011

Infectious amplification of wild-type human immunodeficiency virus from patients' lymphocytes and modulation by

D Mathez1, R F Schinazi, D C Liotta

  • 1Hôpital Raymond Poincaré, Unité d'Immunovirologie, Garches, France.

Antimicrobial Agents and Chemotherapy
|October 1, 1993
PubMed

Insights

The novel oxathiolane analog (-)-FTC shows superior in vitro potency against HIV-1 compared to other drugs like AZT. Combinations of AZT with FTC or DDC demonstrate synergistic effects, even against resistant strains.

Area of Science:

  • Virology
  • Pharmacology
  • Infectious Diseases

Background:

  • Human immunodeficiency virus (HIV) type 1 reverse transcriptase inhibitors are crucial for treatment.
  • Evaluating the in vitro potency of novel and existing drugs is essential for optimizing HIV therapy.
  • Understanding drug resistance and cross-resistance patterns informs combination therapy strategies.

Purpose of the Study:

  • To determine the relative in vitro potency of nine HIV-1 reverse transcriptase inhibitors.
  • To assess the efficacy of drug combinations, including synergistic interactions.
  • To compare drug concentrations from a cell-to-cell transmission assay with in vivo requirements.

Main Methods:

  • A coculture assay using limiting dilution technique to measure infectious primary cells from HIV-positive patients.
  • Evaluation of drug reduction under increasing concentrations of nine HIV-1 reverse transcriptase inhibitors.
  • Multiple-drug effect analysis to determine synergistic interactions between drugs.

Main Results:

  • The (-)-L-enantiomer of 2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC] demonstrated the highest potency (EC90 = 55 nM), outperforming DDC, 3TC, AZT, TIBO R82913, and DDI.
  • HIV from AZT-naive patients was more sensitive to (-)-FTC, 3TC, and DDC than AZT-resistant HIV, indicating partial cross-resistance.
  • Synergistic interactions were observed with combinations of AZT plus (-)-FTC or AZT plus DDC, even in cells with AZT-resistant HIV.

Conclusions:

  • (-)-FTC is a potent HIV-1 reverse transcriptase inhibitor with superior in vitro activity.
  • Combination therapy, particularly AZT with (-)-FTC or DDC, shows synergistic effects and potential against resistant HIV strains.
  • The cell-to-cell virus transmission assay provides inhibitory concentrations closer to in vivo requirements than conventional assays.

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