High prevalence of genotypic resistance to nucleoside reverse transcriptase inhibitors among therapy-naive individuals from the Warsaw cohort.
BACKGROUND
The purpose of this study was to recognize nucleoside reverse transcriptase inhibitor (NRTI)-resistant HIV-1 strains among a group of therapy-naive patients, and subsequently to guide the choice of antiretroviral therapy.


METHODS
HIV strains present in sera of 128 antiretroviral therapy-naive patients were tested for NRTI resistance-associated mutations. The RT-PCR amplified HIV rt regions were analyzed with an INNI-LiPA-HIV-1 RT assay. The number and pattern of resistance-associated mutated codons were determined and interpreted as resistance to particular drugs.


RESULTS
Mutated codons were detected in 66 (51.5%) out of 128 tested samples. In 54 (81.8%) out of 66 samples, a K70R mutation was identified, which was followed by an M184V mutation in 22 cases (33.3%). For a majority of these samples, mixed wild/mutant populations were recognized in 44 (66.6%) cases. The interpretation of hybridization data revealed drug-resistant strains in 37 (28.9%) out of all samples tested. The determined resistance to particular drugs was as follows: 20 strains were resistant to zidovudine (ZDV), ten to lamivudine (3TC) and six to didanosine (ddI)/zalcitabine (ddC)/abacavir (ABC). In one case, a ZDV/3TC-resistant HIV strain was found.


CONCLUSIONS
The prevalence of mutations associated with NRTI resistance was high in the tested cohort. The key reasons for that were most probably needle and drug sharing within the group of intravenous drug users (IVDUs) and the use of ZDV in monotherapeutic regimes in the early 1990s.
Horban
A
A
Molecular Diagnostic Laboratory, AIDS Diagnosis and Therapy Center, Hospital for Infectious Diseases, 37 Wolska Str., PL-01-201 Warsaw, Poland.
Stanczak
J J
JJ
Bakowska
E
E
Tobolewska
E J
EJ
Przybylska-Stengiel
K J
KJ
Stanczak
G P
GP
Burkacka
E
E
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005838:Genotype; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D054303:HIV Reverse Transcriptase