Prevalence of genotypic resistance to nucleoside analogues in antiretroviral-naive and antiretroviral-experienced HIV-infected patients in Spain.
OBJECTIVE
To determine the prevalence of genotypic resistance to nucleoside analogues (NA) in a large group of HIV-infected individuals in Spain, some of whom had no previous treatment with antiretroviral drugs (antiretroviral-naive) and some of whom had such experience (antiretroviral-experienced).


METHODS
Cross-sectional study in out-patient clinics in three reference hospitals for HIV/AIDS located in Barcelona, Madrid and Seville, Spain.


METHODS
Primary mutant genotypes were examined in plasma HIV RNA collected from 150 antiretroviral-naive subjects, half in 1993 and the other half in 1997. Furthermore, drug resistance mutations were analysed in plasma collected from another 150 antiretroviral-experienced patients who had received 2 NA for longer than 1 year, either in sequence as monotherapy or as combination therapy. A line probe assay was used for recognizing mutations conferring resistance to zidovudine (ZDV), didanosine (ddI), zalcitabine (ddC), and lamivudine (3TC). A point-mutation nested-PCR assay was used for examining a codon 151 mutation associated with multiple drug resistance.


RESULTS
One or more mutations associated with primary resistance to NA were seen in 10 antiretroviral-naive (13.3%) patients in 1993 and in nine (12%) in 1997. In all but two cases, they were associated with ZDV resistance. In contrast, all but six (96%) of the antiretroviral-experienced subjects harboured drug-resistant mutant viruses. The codon 184 mutation (associated with resistance to 3TC) was detected in 92% of patients treated with 3TC, but also in 18% of those treated with only ddI or ddC. The codon 215 mutation was found in 67.3% of patients who had been exposed to ZDV; the codon 69 mutation was found in 15% of patients treated with ddC; and the codon 74 mutation was found in only 7.2% of patients treated with ddI. Finally, the codon 151 multidrug resistant mutation was found in four (2.7%) of 150 patients with a long-term exposure to NA.


CONCLUSIONS
Overall, the prevalence of drug-resistant HIV-1 genotypes was 12.7% in antiretroviral-naive patients, most of whom had ZDV-resistant mutants. There is no evidence of an increase during the last 5 years. However, multidrug-resistant HIV genotypes are currently circulating in Spain.
Gómez-Cano
M
M
Infectious Diseases Department, Instituto de Salud Carlos III, Madrid, Spain.
Rubio
A
A
Puig
T
T
Pérez-Olmeda
M
M
Ruiz
L
L
Soriano
V
V
Pineda
J A
JA
Zamora
L
L
Xaus
N
N
Clotet
B
B
Leal
M
M
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D016049:Didanosine / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013030:Spain / Q000453:epidemiology; D016047:Zalcitabine / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D016047:Zalcitabine; D054303:HIV Reverse Transcriptase; D016049:Didanosine