Treatment regimens containing combinations of antiretroviral inhibitors, commonly known as highly active antiretroviral therapy (HAART), revolutionized the treatment of people living with HIV by markedly lowering viral load and decreasing the incidence of AIDS-associated opportunistic infections. Despite the success of HAART, these regimens are insufficient to cure HIV-positive individuals of their infection. Additionally, patients receiving HAART suffer metabolic abnormalities, drug toxicities, have difficulty adhering to the complex drug regimens, and develop strains of HIV that are resistant to therapy.
Novel therapeutic approaches are needed to improve treatment outcomes in people infected with HIV. The identification of viral and cellular drug targets is essential for fueling the drug and vaccine development pipeline. Early drug discovery efforts concentrated on a relatively small number of viral targets, for example, viral enzymes (reverse transcriptase, protease, integrase), and used traditional drug discovery tools such as high throughput screening of small molecule libraries. More recently, efforts by pharmaceutical companies have focused on improving the characteristics of existing antiretroviral drugs to reduce pill burden and toxicity, and prolong half-life in the body.
While small molecule inhibitors are still being sought, new targets among host proteins and pathways critical to HIV replication and persistence are being discovered and exploited. Next generation modalities such as cell and gene therapies, vaccines for infected persons, monoclonal antibodies, and nucleic acid based inhibitors are also being actively explored.
Last Updated July 21, 2015