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Updated: Jul 16, 2026
19:57
An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings
Published on: March 30, 2014
Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase
M H St Clair1, J L Martin, G Tudor-Williams
1Division of Virology, Burroughs Wellcome Co., Research Triangle Park, NC 27709.
Science (New York, N.Y.)
|September 27, 1991
Summary
Switching HIV-1 therapy from zidovudine (AZT) to didanosine (ddI) led to decreased ddI sensitivity and increased AZT sensitivity. A specific mutation emerged, conferring resistance to ddI and suppressing AZT resistance, highlighting the importance of combination therapy.
Area of Science:
- Virology
- Molecular Biology
- Pharmacology
Background:
- Human immunodeficiency virus type-1 (HIV-1) treatment often involves sequential antiretroviral therapies.
- Zidovudine (AZT) was a primary treatment, but drug resistance is a significant clinical challenge.
- Switching to alternative nucleoside reverse transcriptase inhibitors like didanosine (ddI) is a common strategy.
Purpose of the Study:
- To investigate the in vitro drug sensitivity of HIV-1 isolates after switching from AZT to ddI therapy.
- To identify genetic mutations in HIV-1 reverse transcriptase associated with altered drug sensitivity.
- To evaluate the impact of specific mutations on resistance profiles to both ddI and AZT.
Main Methods:
- Serial HIV-1 isolates were collected from five patients with acquired immunodeficiency syndrome (AIDS) undergoing therapy changes.
- In vitro drug sensitivity assays were performed for ddI and AZT.
- The reverse transcriptase coding region of HIV-1 was sequenced to identify mutations.
Main Results:
- HIV-1 isolates showed decreased sensitivity to ddI and increased sensitivity to AZT over 12 months post-ddI initiation.
- A novel mutation in the reverse transcriptase gene was identified, correlating with reduced ddI sensitivity.
- This mutation, when present with the AZT resistance mutation, resulted in increased AZT sensitivity and conferred resistance to ddI and ddC, while suppressing AZT resistance effects.
Conclusions:
- The emergence of specific HIV-1 mutations can alter drug resistance profiles during sequential therapy.
- A single mutation can confer resistance to multiple drugs and modulate the effects of other resistance mutations.
- Combination therapy for HIV-1 may be crucial in preventing the emergence of drug-resistant viral variants.
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