Antiretroviral-drug resistance among patients recently infected with HIV.
BACKGROUND
Among persons in North America who are newly infected with the human immunodeficiency virus (HIV), the prevalence of transmitted resistance to antiretroviral drugs has been estimated at 1 to 11 percent.


METHODS
We performed a retrospective analysis of susceptibility to antiretroviral drugs before treatment and drug-resistance mutations in HIV in plasma samples from 377 subjects with primary HIV infection who had not yet received treatment and who were identified between May 1995 and June 2000 in 10 North American cities. Responses to treatment could be evaluated in 202 subjects.


RESULTS
Over the five-year period, the frequency of transmitted drug resistance increased significantly. The frequency of high-level resistance to one or more drugs (indicated by a value of more than 10 for the ratio of the 50 percent inhibitory concentration [IC50] for the subject's virus to the IC50 for a drug-sensitive reference virus) increased from 3.4 percent during the period from 1995 to 1998 to 12.4 percent during the period from 1999 to 2000 (P=0.002), and the frequency of multidrug resistance increased from 1.1 percent to 6.2 percent (P=0.01). The frequency of resistance mutations detected by sequence analysis increased from 8.0 percent to 22.7 percent (P<0.001), and the frequency of multidrug resistance detected by sequence analysis increased from 3.8 percent to 10.2 percent (P=0.05). Among subjects infected with drug-resistant virus, the time to viral suppression after the initiation of antiretroviral therapy was longer (P=0.05), and the time to virologic failure was shorter (P=0.05).


CONCLUSIONS
The proportion of new HIV infections that involve drug-resistant virus is increasing in North America. Initial antiretroviral therapy is more likely to fail in patients who are infected with drug-resistant virus. Testing for resistance to drugs before therapy begins is now indicated even for recently infected patients.
Little
Susan J
SJ
Antiviral Research Center, Department of Medicine, University of California-San Diego, San Diego 92103, USA. slittle@ucsd.edu
Holte
Sarah
S
Routy
Jean-Pierre
JP
Daar
Eric S
ES
Markowitz
Marty
M
Collier
Ann C
AC
Koup
Richard A
RA
Mellors
John W
JW
Connick
Elizabeth
E
Conway
Brian
B
Kilby
Michael
M
Wang
Lei
L
Whitcomb
Jeannette M
JM
Hellmann
Nicholas S
NS
Richman
Douglas D
DD
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009656:North America; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects; D012189:Retrospective Studies
D019380:Anti-HIV Agents; D012367:RNA, Viral