Geographic and temporal trends of transmitted HIV-1 drug resistance among antiretroviral-naïve subjects screening for two clinical trials in North America and Western Europe.
OBJECTIVE
To determine the prevalence of transmitted drug resistance (TDR) in antiretroviral (ARV)-naïve HIV-1-infected subjects who were screened for two clinical trials by geographic region and time.


METHODS
Studies M03-613 and M05-730 screened ARV-naïve subjects in 2004 and 2005-2006, respectively. Screening drug resistance genotype assays were performed using population sequencing, and prevalence of drug resistance mutations (DRMs) was assessed at 39 amino acid positions in HIV-1 protease and reverse transcriptase (RT) and compared between geographic regions and calendar years.


RESULTS
In 913 subjects, the prevalence of DRMs was higher in North America than in Western Europe, including any DRM (13.6% vs. 6.8%, p < .001), non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs (7.3% vs. 3.2%, p = .006), protease inhibitor (PI) DRMs (3.6% vs. 0.8%, p = .004), and nucleoside reverse transcriptase inhibitor (NRTI) DRMs (6.1% vs. 3.8%, p = ns). The prevalence of TDR to NNRTIs was higher compared to PIs within each region (p = .031 for North America, and p = .011 for Western Europe). Logistic regression analysis suggested a higher prevalence of DRMs in 2005-2006 compared to 2004 for NNRTIs (p = .03) and, to a lesser extent, for PIs (p = .07).


CONCLUSIONS
TDR to NNRTIs was more frequent than to PIs in both geographic regions, increased over time, and was highest in North America.
Rahim
Sibtain
S
Abbott Laboratories, Abbott Park, IL, USA. rahim@abbott.com
Fredrick
Linda M
LM
da Silva
Barbara A
BA
Bernstein
Barry
B
King
Martin S
MS
D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D024882:Drug Resistance, Viral / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005838:Genotype; D005843:Geography; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D015995:Prevalence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D055815:Young Adult
D044966:Anti-Retroviral Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1