Hlv Korea

Genotypic Resistance of Anti-retroviral Drugs in Koreans

The decreases in incidence of AIDS-related opportunistic illnesses and declining mortality among HIV-infected persons have been largely attributed to the availability of HAART. However, our ability to sustain these advances among HIV-positive persons is threatened by the emergence of antiretroviral drug resistance.

Genotypic resistance of anti-retroviral drugs in Koreans was investigated in a cross-sectional study conducted with 41 HIV-infected Koreans (29 naïve and 12 HAART-experienced for a mean duration of 11.3 months) from October 1999 to September 2000 in an outpatient clinic of a university hospital and the Korean National Institute of Health. The entire protease gene and 250 amino acids of the reverse transcriptase (RT) gene were amplified and sequenced. Analysis was done by DNASTAR and the program was supported by HIV RT and Protease Sequence Stanford Database (HRP-ASAP). Primary resistance to nucleoside analogue reverse transcriptase inhibitors (NRTIs) was observed in 4 out of 29(14%) naïve individuals, whereas primary resistance to protease inhibitors (PIs) was found in none of naïve individuals. The frequently involved codons in NRTI resistance were at positions 41(50%), 69 (50%), and 215(50%). In HAART-experienced individuals, the prevalence for primary resistant genotypes was 42% for NRTIs and 25% for PIs. The most frequent NRTI mutations occurred at codons 184(42%) and 41(17%), whereas the most common PI resistance mutation was at codons 82(17%) and 48(8%). Some atypical amino acid changes such as M41I, D67G, T69A, M184I/R, G190K, L210M of the RT and L10M, K20I, G48R, L63A/I/T, G73S, V82I of the protease gene were detected in HIV-infected Koreans. Codon 63 may not be associated with resistance in Koreans but only a typical characteristic of the Korean isolates since L63A/I/T mutation in the protease gene was detected in 93% of naïve and HAART-experienced Koreans. Resistance was detected 3 times more frequently in the RT gene and more frequently in the protease gene in the HAART-experienced compared to the naïve Koreans. Genotypic resistance may be useful prior to the introduction of HAART in Korea. Since Korean isolates have some unique characteristics in genotypic resistance, phenotypic resistance and clinical correlation are to be considered for the evaluation of the effects of specific drugs.

Several studies have demonstrated that resistance testing improves virologic response to second-line HAART regimens among HIV-infected persons who have failed initial empiric therapy, and the prevalence of resistance mutations or resistance phenotypes among drug-naïve persons is generally low21). However, eventual recommendations regarding resistance screening to inform the choice of initial HAART regimen depend largely on the prevalence of resistance among HAART-naïve persons, so ongoing surveillance of resistance in treatment-naïve populations is critical.