HIV Drug Resistance -- A Chink in the Armor

"In the resource-rich countries, a remarkable success story has emerged during the past decade in the treatment of human immunodeficiency virus (HIV) infections. ... This success, however, has not been without consequences, the most serious of which are toxic effects associated with current regimens and development of resistance to antiretroviral drugs. In this issue of the Journal, Little et al. ("Antiretroviral-Drug Resistance Among Patients Recently Infected With HIV") report that in North America, the proportion of new HIV infections with some degree of drug resistance is increasing. [Editor's note: The article was summarized in the PNU on 08.08.02.]

" ... The report is cause for concern but not alarm. Although the study found that the prevalence of resistance increased significantly between the period from 1995 through 1998 and the period from 1999 through 2000, the overall prevalence of high-level multidrug resistance remained low (6.2 percent, according to phenotypic testing). Moreover ... suppression was still achieved by 24 weeks in all but one patient regardless of the patterns of susceptibility.

"The study involved predominantly urban, white, non-Hispanic men whose risk factor for HIV was sex with men. Other studies suggest that drug-resistant variants of HIV are increasingly being transmitted in certain parts of the world but not in others. Although many factors may account for regional differences, the rate of transmission of drug-resistant viruses appears to be inversely associated with the availability of optimal antiretroviral regimens and the rate of adherence to them. ... It is encouraging that the World Health Organization, in collaboration with the International AIDS Society, is developing a global program of surveillance for resistance to anti-HIV drugs to help guide national and international treatment efforts.

"Different types of assays for susceptibility to anti-HIV drugs are available in resource-rich countries such as the United States. ... Phenotypic assays may be particularly useful in complex situations in which multiple mutations are present, since mutations may interact to make a virus more or less susceptible to individual drugs.

"Most, though not all, randomized clinical trials support the use of drug-resistance testing to help guide treatment after regimens have failed. ... The best results are often seen when resistance testing is combined with the use of expert advice. ... Testing for antiretroviral-drug resistance should now be incorporated into the treatment of all patients in whom antiretroviral drugs are used. ... Resistance testing is also recommended for all pregnant women with detectable plasma viremia. ... However, to prevent mother-to-infant transmission and to treat patients with an acute primary HIV-infection syndrome, antiretroviral therapy should be instituted promptly, before the results of resistance testing are available.

" ...Our goals should include worldwide access to the most potent antiretroviral regimens, appropriate education about adherence to these complex treatment programs, monitoring of all treated patients for viral suppression and emergence of resistance, and development of long-term strategies to prevent resistance or to treat resistant virus effectively when it develops. Only by achieving these goals can we minimize viral drug resistance and thereby maximize therapeutic options for patients' lifelong battle against HIV."

The author is affiliated with Massachusetts General Hospital.

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