Occurrence of HIV-1 reverse transcriptase gene mutation at codon 215 in HIV-infected infants

Background: The nucleoside reverse transcriptase inhibitor Zidovudine (ZDV) decreases mother to child transmission of HIV infection. Nevertheless, sig nificant proportions of mothers who are treated during pregnancy with ZDV s till transmit the virus. Along with other factors, failure of ZDV prophylax is may be due to maternal infection with ZDV-resistant strains and their co nsequent vertical transmission. Objectives: The purpose of the study was to investigate the occurrence of mutations at codon 215 in HIV-1 infected inf ants and its association with clinical status and virological parameters. S tudy design: The cohort consisted of 49 HIV-1 infected infants. Mononuclear cell DNA was isolated from whole blood and served as the input DNA for bot h a qualitative DNA PCR and the codon 215 assay (nested PCR). HIV-1 viral l oad (RNA PCR) was measured in plasma by the Roche Amplicor (TM) Monitor ass ay. Results: Twelve of the 49 (24.5%) demonstrated viral strains with mutat ion at codon 215. A significant difference was found in infants born betwee n 1992 and 1994 (6.3%) compared to those born in 1998-1999 (33.3%). Further more, in those infants born in 1998-1999, there was a trend toward an incre ase in the frequency of zidovudine resistant mutations at codon 215 corresp onding to an increase in maternal zidovudine treatment. The mixture of wild and mutant HIV-1 strains was detected in two of 14 infants (14.3%) with a low viral load ( < 750 000 c/ml) compared to nine of 19 (47.4%) infants wit h extremely high levels of HIV-1 RNA concentration ( > 750 000 c/ml). Only two of 33 tested infants were HIV symptomatic and in both, a mixture of wil d and mutant HIV-I strains was detected. In both infants, the viral load wa s > 750000 c/ml. Conclusions: This study showed that the overall frequency of ZDV resistant strains in infants born in 1998-1999 was significantly hig her than that found in infant samples from 1992 to 1994. By 1998, the stand ard of care for mothers known to be infected with HIV was treatment with ei ther monotherapy using ZDV or combined therapy using a variety of antiretro viral agents including ZDV. Although the exact role of ZDV resistance in li miting the effectiveness of therapies aimed at blocking vertical transmissi on of HIV remains to be defined, it is clear that drug resistant strains of HIV are occurring more frequently in all types of HIV infection, including infants. (C) 2001 Elsevier Science B.V. All rights reserved.