COMBINATION ANTIRETROVIRAL THERAPY

Excellent guidelines for treatment of HIV with antiretroviral drugs have been published recently. There are currently three classes of antiretroviral drugs: nucleoside-analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors. The goal of antiretroviral therapy is to inhibit replication of HIV completely and for as long as possible. While single antiretroviral agents can decrease the amount of virus in plasma by 10- to 100-fold (1-2 logs), the effect is temporary. The replication process for HIV is so prone to error that a wide variety of strains that vary genetically ("quasi-species") are present at all times. The biological pressure exerted by a single antiviral agent simply selects for the survival of the quasi-species that is most resistant to that drug. Using at least two drugs increases the probability that the existing quasi-species will not be able to resist all the drugs in the regimen simultaneously. In the ideal situation, no quasi-species that is resistant to all the drugs in the antiretroviral combination will be present, thereby assuring little or no replication of HIV. When there is so little replication of virus, few mutational events that might lead to a resistant virus can occur and it may be possible to sustain the antiretroviral effect for years.