Is It Time To Proactively Switch Successful Antiretroviral Therapy? Carefully Check Your SWATCH

The routine use of triple-drug antiretroviral therapy in the mid-1990s heralded the beginning of the highly active antiretroviral therapy (HAART) era in HIV therapeutics. With these potent regimens, viral replication in lymphatic tissue could be reduced almost completely, leading to levels of virus in plasma below assay detection limits (<50 copies/mL). This resulted in steady increases in CD4 cell counts, reductions in opportunistic infections, and a dramatic reduction in HIV-related mortality rates.

Yet HAART is not always successful. Many patients have trouble tolerating some of the short-term (for example, gastrointestinal) side effects, while others develop longer-term complications, such as hyperlipidemia, insulin resistance, lactic acidosis, or peripheral fat wasting. Other patients experience virologic failure, defined as the inability to achieve HIV RNA levels less than 50 copies/mL or failure to sustain this level of suppression once it has been achieved, a phenomena referred to as viral load rebound. In many instances, viral load rebound is associated with the emergence of resistance-conferring mutations within the viral genome, resulting in virus with reduced susceptibility to one or more of the drugs in the failing regimen. Although there are 17 antiretroviral agents within four drug classes currently approved by the U.S. Food and Drug Administration, many of the resistance-conferring mutations lead to cross-resistance to some or all drugs within the same class, thereby limiting treatment options.

Published guidelines regarding the use of antiretroviral therapy are founded on the fundamental principles of HIV virology: Ongoing replication in the presence of selective drug pressure is a recipe for the development of resistance (1-3). Therefore, the primary goal of the initial therapeutic regimen is to suppress viral replication to the maximum degree possible and sustain this level of suppression for as long as possible. In current clinical …