The most significant advance in the medical management of HIV-1 infection has been the treatment of patients with antiviral drugs, which can suppress HIV-1 replication to undetectable levels. The discovery of HIV-1 as the causative agent of AIDS together with an ever-increasing understanding of the virus replication cycle have been instrumental in this effort by providing researchers with the knowledge and tools required to prosecute drug discovery efforts focused on targeted inhibition with specific pharmacological agents. To date, an arsenal of 24 Food and Drug Administration (FDA)-approved drugs are available for treatment of HIV-1 infections. These drugs are distributed into six distinct classes based on their molecular mechanism and resistance profiles: nucleoside-analogy reverse transcriptase inhibitors (NNRTIs), non–nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors, protease inhibitors (PIs), fusion inhibitors, and coreceptor antagonists. In this article, we will review the basic principles of antiretroviral drug therapy, the mode of drug action, and the factors leading to treatment failure (i.e., drug resistance).
Standard antiretroviral therapy (ART) consists of the combination of at least three antiretroviral (ARV) drugs to greatly suppress the HIV virus and stop the progression of HIV disease. These drugs do not kill or cure the virus but, prevent the growth of the virus. The aim of antiretroviral treatment is to keep the amount of HIV in the body at a low level. This stops any weakening of the immune system and allows it to recover from any damage that HIV might have caused.