New developments in HIV therapeutics

Although there are currently 21 individual drugs and several combinations thereof that have been approved by the Food and Drug Administration (FDA) for marketing in the US for the treatment of HIV/AIDS, there remains a pressing need for new therapeutics in this area. Until recently, all AIDS drugs inhibited either of the viral enzymes reverse transcriptase (RT) or protease. RT inhibitors are further classified as either nucleoside (NRTIs) or non-nucleoside (NNRTIs). The majority of treatment regimens use a variety of combinations of at least two, and as many as five, of these drugs. Nonetheless, current therapy is plagued by the emergence of viral populations that are often resistant to other drugs in the same class. This often severely limits treatment options for patients who have experienced treatment failure. It is now common for newly infected individuals to be infected with HIV that contains mutations that compromise the efficacy of more than one of the approved drugs [1]. A second major limitation of current therapy is related to convenience and tolerability. Many drugs have sub-optimal dosing requirements including high pill burden, food and drug interactions, and the requirement for dosing up to three times daily. Poor tolerability is also problematic for many patients, and can include variations in lipid and glucose levels, liver enzyme elevations, gastrointestinal disturbances, neurological effects, and effects on renal function [2]. These complications can have a negative impact on patient compliance - a key to the successful management of HIV. Poor compliance is directly related to the development of resistance and therapeutic failure. All of the issues mentioned above highlight the need for the introduction of new drugs for the treatment of HIV/AIDS. Optimally, these new drugs should be directed at new viral or cellular targets that have not yet been compromised by clinical resistance. The ideal drug should also have a low pill burden, be taken no more than once daily, and should be free of significant drug interactions, food effects, and side effects. Additionally, the optimal drug should have a high barrier to the development of resistance. © 2005 Elsevier Inc. All rights reserved.