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Scaling Up Treatment for the Global AIDS Pandemic: Challenges and Opportunities
drug-resistant variants, as well as the lower viral load in partially treated patients (compared with untreated patients), may contribute to a lower rate of transmission of drug-resistant virus (Leigh Brown et al., 2003). Nevertheless, public health efforts should be focused on trying to minimize the rate of acquiring resistance (i.e., by treating drug-sensitive cases appropriately), rather than on trying to prevent the transmission of drug-resistant strains.
Thus resistance to HIV drugs can be acquired, and HIV-resistant viruses can be transmitted. And most HIV-infected individuals with drug-resistant virus are initially infected with a drug-sensitive virus that acquires resistance during ART (Deeks, 2003).
The prevalence of drug resistance among HIV strains in the United States may be as high as 50 percent, based on the results of a large cohort study of HIV-infected adults receiving HAART (Richman et al., 2004). Drug resistance has been found for each class of drugs available for ART, and resistance may be present for more than one drug or class—a phenomenon known as multidrug resistance (Richman et al., 2004).
Acquired resistance is dependent upon several factors, including patient adherence to therapy, the mutation rate of the virus, and the efficacy of the ART regimen (Blower et al., 2003a; Deeks, 2003; Leigh Brown et al., 2003; Hirsch et al., 1998, 2000, 2003) (see Box 3-1). Adherence rates of less than 90 percent and less than 80 percent have been shown to result in drug resistance and virological failure (Hirsch et al., 1998, 2000, 2003; Paterson et al., 2000; Sethi et al., 2003). As discussed above, ineffective regimens that do not completely suppress viral replication will lead to resistant virus, and the use of sequential mono or dual therapy is no longer recommended because of its now-recognized association with the development of a high rate of drug resistance (Deeks, 2003; Hirsch et al., 1998, 2000, 2003; Leigh Brown et al., 2003).
Transmitted resistance occurs when a person is infected with a virus that has previously acquired resistance. Cases of drug-resistant virus in the United States were first documented in the mid-1990s, and several recent reports have suggested that the percentage of new infections demonstrating some form of drug resistance has risen significantly since then (Grant et al., 2002; Little et al., 2002; Simon et al., 2002). If transmitted drug-resistant virus is not faced with the continuous selection pressure of ART, it can revert back to the drug-sensitive, wild type of virus (Hirsch et al., 2003). Hence, the drug-resistant virus may not be measured at a particular point in time. However, the first documented case of a resistant virus that was stably transmitted from one person to a another, who then passed it on to a third person, was reported in 2003 (Taylor et al., 2003). See Appendix B for a more-detailed discussion of resistance.