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HIV Therapy: Consider Compliance When Choosing Drugs

Katherine M. Bennett

Given the many possible combinations of HIV-fighting drugs, the decision about which mix will banish the infection may boil down to issues of compliance and specialized care.

AIDS researcher Nathan Clumeck, M.D., commenting on two research articles in the Dec. 16 issue of the New England Journal of Medicine, suggested that patient compliance, testing of drug susceptibility, and monitoring serum drug concentrations might be the critical factors in long-term success. The two studies compared commonly used multiple-drug regimens with ones containing efavirenz, a nonnucleoside reverse-transcriptase inhibitor, for the treatment of HIV infection. 

One study compared the efficacy of efavirenz and indinavir, both in combination with two nucleoside reverse-transcriptase inhibitors, in adults infected with HIV. Patients assigned to the efavirenz-containing regimen had to swallow fewer tablets and capsules a day than patients in the other group. 

Analysis of all the patients who started the study showed no statistical difference between the two regimens in their ability to decrease the viral load in plasma. When counting dropouts from the study as patients for whom the therapy was ineffective, however, the researchers found that the regimen of efavirenz, zidovudine, and lamivudine had greater antiviral activity than the standard regimen of indinavir, zidovudine, and lamivudine. 

In the other study, 57 children with HIV infection took efavirenz for 48 weeks in combination with nelfinavir and one or more nucleoside reverse-transcriptase inhibitors. The children, all younger than 16 years, had previously taken a nucleoside reverse-transcriptase inhibitor but not a nonnucleoside reverse-transcriptase inhibitor or protease inhibitor. 

Researchers found that the regimen quickly decreased the viral load in the children's plasma and sustained that decrease for the remainder of the study. Only 11 percent of the children had a severe or life-threatening adverse reaction. 

In contrast to the pharmacokinetics of protease inhibitors, nonnucleoside reverse-transcriptase inhibitors are well absorbed after an oral dose and remain in the body a fairly long time. Clumeck noted in his editorial that the "superior results of efavirenz therapy could therefore be due to better compliance and better acceptance of the regimen by the patients." 

HIV can render itself resistant to all nonnucleoside reverse-transcriptase inhibitors after just one mutation in the gene encoding reverse transcriptase. Clumeck warned practitioners of "the possibility that resistance [to efavirenz and similar drugs] may emerge with widespread use while we await the results of long-term studies of efficacy."