Little SJ, Holte S, Routy JP, et al. N Engl J Med. 2002;347:385–394
Purpose of the Study.
Highly active antiretroviral therapy (HAART) has dramatically reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) in Western countries. A consequence of the widespread availability of these agents is the potential for transmission from an individual carrying resistant virus to uninfected contacts. The purpose of this study was to evaluate the prevalence of HAART-resistant HIV in newly identified and untreated HIV-infected subjects.
The plasma of 377 adult subjects from 10 North American cities with primary HIV infection who had not been treated and who are identified between May 1995 and June 2000 was evaluated for phenotypic resistance to available antiretroviral agents and the presence of mutations in viral reverse transcriptase and protease genes that would be predictive of drug resistance to various antiretroviral agents (genotypic analysis). Responses to initial treatment was also evaluated in 202 of the subjects.
Over the 5-year study period, the frequency of transmitted drug resistance increased significantly. Phenotypic resistance increased from 3.4% to 12.4% and the frequency of multidrug resistance increased from 1.1% to 6.2%. Resistance mutations by sequence analysis increased from 8% to 22.7% and the frequency of multidrug resistance by sequence analysis increased 3.8% to 10.2%. All of these changes were statistically significant (P < .05). In subjects infected with drug-resistant virus, the time to viral suppression after initiation of treatment was longer and the time to virologic failure was shorter (P = .05).
The proportion of new HIV infections with drug-resistant virus is increasing. Initial antiretroviral therapy is more likely to fail in subjects in patients with drug-resistant virus. Testing for resistance to drugs before therapy initiation is now suggested even for recently infected patients.
Although the study population was primarily adult males, a similar prevalence of drug-resistant virus is likely to be present in infected women of childbearing age. This has direct implications for the initiation of treatment during pregnancy and interventions to prevent maternal-infant HIV transmission. A further concern is the tendency of wild type virus to replace drug-resistant virus in the plasma when the virus is no longer under the pressure of drug therapy. Therefore, even if it is no longer detectable in plasma, a drug-resistant variant may persist in the reservoir of latently infective CD4+ T cells. It is currently recommended that all newly identified adult subjects with HIV have resistance testing performed to optimize their initial antiretroviral regimen. Similar approaches should be considered in HIV-infected pregnant women and newly identified HIV-positive infants and children.