%0 Journal Article
%T The Continuing Evolution of HIV-1 Therapy: Identification and Development of Novel Antiretroviral Agents Targeting Viral and Cellular Targets
%A Tracy L. Hartman
%A Robert W. Buckheit Jr.
%J Molecular Biology International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/401965
%X During the past three decades, over thirty-five anti-HIV-1 therapies have been developed for use in humans and the progression from monotherapeutic treatment regimens to today¡¯s highly active combination antiretroviral therapies has had a dramatic impact on disease progression in HIV-1-infected individuals. In spite of the success of AIDS therapies and the existence of inhibitors of HIV-1 reverse transcriptase, protease, entry and fusion, and integrase, HIV-1 therapies still have a variety of problems which require continued development efforts to improve efficacy and reduce toxicity, while making drugs that can be used throughout both the developed and developing world, in pediatric populations, and in pregnant women. Highly active antiretroviral therapies (HAARTs) have significantly delayed the progression to AIDS, and in the developed world HIV-1-infected individuals might be expected to live normal life spans while on lifelong therapies. However, the difficult treatment regimens, the presence of class-specific drug toxicities, and the emergence of drug-resistant virus isolates highlight the fact that improvements in our therapeutic regimens and the identification of new and novel viral and cellular targets for therapy are still necessary. Antiretroviral therapeutic strategies and targets continue to be explored, and the development of increasingly potent molecules within existing classes of drugs and the development of novel strategies are ongoing. 1. Introduction Since the approval of AZT for the treatment of HIV-1 infection, twenty-three additional therapeutic agents have been approved for use in humans [1]. The first drugs approved in the United States to treat HIV-1 infection inhibit the specific activity of the virally encoded reverse transcriptase, the viral enzyme essential for conversion of the viral RNA genome into a DNA provirus that integrates itself into the host genome. Two classes of reverse transcriptase inhibitors are currently marketed¡ªnonnucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) [2]. Another approved and marketed class of HIV-1 antiviral therapeutics inhibits the HIV-1 protease, a viral enzyme required to process newly synthesized viral polyproteins into the mature viral gene products, enabling the virus to assemble itself into new infectious virus particles [3]. A third class of HIV-1 therapeutics inhibits viral infection by preventing virus attachment to the host cell CCR5 chemokine receptor or prevents the fusion of the viral and cellular membranes
%U http://www.hindawi.com/journals/mbi/2012/401965/