Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients.
Surveillance of drug resistance mutations in antiretroviral-experienced HIV(+) patients may provide useful information regarding options available for rescue interventions. All resistance tests performed from 1999 to 2005 on antiretroviral-experienced individuals at one reference laboratory in Madrid were examined. Only mutations associated with drug resistance recorded at the September 2006 IAS-USA list were considered. A total of 2137 specimens were analyzed. Overall, 71.1% showed resistance mutations to at least one drug class, 56.1% to at least two, and 21% to all three drug families. Resistance mutations were 65% for NRTI, 44.4% for NNRTI, and 42.5% for PI. Mutations T215Y/F, M184V, and M41L were the most frequent for NRTI. Their rate significantly declined since 1999. K65R significantly increased since 1999 (0.8%) to 2003 (7.3%) but declined up to 3.3% in 2005. For NNRTI, K103N significantly increased from 21.8% in 1999 to 29.5% in 2005 (p < 0.01). The most frequent PI resistance mutations were L90M (24.3%), V82X (19.9%), M46I/L (19.5%), and I54V (17.1%). The presence of five or more was 58.8% in 1999 but declined to 22.2% in 2005. The rate of drug resistance mutations causing NRTI and PI resistance has steadily declined in antiretroviral-experienced patients since 1999. The availability of a large number and/or more convenient NRTI as well as the wide use of ritonavir-boosted PI could explain these observations. However, broad PI cross-resistance was seen in nearly 25% of antiretroviral-experienced patients in 2005. Therefore, there is a still need for new antiretrovirals with different resistance profiles.
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Carmen
C
de Mendoza
Carolina
C
Garrido
Angelica
A
Corral
German
G
Ramírez-Olivencia
Inmaculada
I
Jiménez-Nacher
Natalia
N
Zahonero
Juan
J
Gonzalez-Lahoz
Vincent
V
Soriano
D000328:Adult; D004252:DNA Mutational Analysis; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D015995:Prevalence; D011480:Protease Inhibitors / Q000494:pharmacology; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013030:Spain / Q000453:epidemiology
D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors