August 8, 2002
Among persons in North America who are newly infected with HIV, the prevalence of transmitted resistance to antiretroviral drugs has been estimated at 1 to 11 percent. In the current study, researchers determined the prevalence of such resistance in a retrospective analysis of susceptibility to antiretroviral drugs before treatment and drug-resistance mutations in HIV plasma samples from 337 subjects with primary HIV infection who had not yet received treatment between May 1995 and June 2000 in 10 North American cities. Responses to treatment could be evaluated in 202 subjects.
Time to viral suppression was defined by the first of two consecutive plasma values of less than 500 HIV RNA copies/ml in plasma samples collected at least 14 days apart. Treatment interruption for more than 14 days was considered a discontinuation of therapy. The time to virologic failure was defined as the time from the first achievement of viral suppression to the first value for plasma RNA > 500 copies/ml while the subject received potent antiretroviral therapy (ART).
Baseline plasma samples were analyzed for susceptibility, measured by determining the ratio of the concentration required for 50 percent inhibition [IC50] of the subject's virus to the IC50 for a drug-sensitive control virus (NL4-3) for each antiretroviral drug tested.
The frequency of resistance mutations detected by sequence analysis increased from 8.0 percent during 1995-1998 to 22.7 percent during 1999-2000, and the frequency of multidrug resistance detected by genotypic analysis increased from 3.8 percent during 1995-1998 to 10.2 percent during 1999-2000. Seventy-four percent of subjects received a regimen containing a protease inhibitor; 20 percent containing a nonnucleoside reverse transcriptase inhibitor; and 6 percent a regimen containing both.
Among subjects infected with drug-resistant virus, the time to viral suppression after initiating antiretroviral therapy was longer, and the time to virologic failure was shorter. According to a comparison between subjects receiving two or fewer active drugs (drugs with an IC50 for the subject's virus no more than 10 times that for the control virus) and those receiving three or more active drugs, the number of active drugs in the treatment regimen did not significantly affect time to viral suppression.
Researchers concluded that 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, they write, is now indicated even for recently infected patients.
New England Journal of Medicine
08.08.02; Vol. 347; No. 6:385-394; Susan J. Little, M.D.; Sarah Holte, Ph.D.; Jean-Pierre Routy, M.D.; Eric S. Daar, M.D.; Marty Markowitz, M.D.; Ann C. Collier, M.D.; Richard A. Koup, M.D.; John W. Mellors, M.D.; Elizabeth Connick, M.D.; Brian Conway, M.D.; Michael Kilby, M.D.; Lei Wang, Ph.D.; Jeannette M. Whitcomb, Ph.D.; Nicholas S. Hellmann, M.D.; Douglas D. Richman, M.D.