Abstract
Object: The S69-X-X (X indicates one amino acid) insertion, conferring drug-resistance to multiple nucleoside reverse transcriptase (RT) inhibitors, has been identified in the RT of human immunodeficiency virus type 1 (HIV-1). We now report 4 kinds of insertion mutations which were identified in viruses isolated from 3 HIV-1 infected patients.
Patients and Methods: Fifteen HIV-1 infected hemophiliacs who receive d RT inhibitors for more than 3 years were examined. HIV-1 RNA was extracted from the plasma virus, and the RT regions were sequenced.
Results: The S69-X -X insertion mutations were found in 3 out of 15 patients. These mutations emerged under conditions where the patients were receiving ZDV+3TC, ddI+d4T or ZDV+ddI. In one case, the pattern of insertion changed from S69-S-S to S69-S-G during ZDV+ddI treatment. After insertion mutations were detected, treatment of these three cases was switched to one protease inhibitor plus two RT inhibitors combination therapies, and their HIV-1 RNA levels decreased to below the detection limit. In two patients, the HIV-1 RNA levels were maintained below the detection limit for more than one year after the protease inhibitors were added in the course of treatment. In the other patient, no pattern indicative of the insertion was found in the HIV-1 RNA appearing at the time of relapse.
Conclusion: The results revealed that the insertion mutations were not particularly harmful from the clinical point of view. To determine the influence of these insertions on the clinical course, further investigation is needed.
