History of Acquired Immunodeficiency Syndrome (AIDS)

Introduction

Acquired Immunodeficiency Syndrome (AIDS) made its first appearance in 1981. Two years later, in 1983, HIV (human immunodeficiency virus) was found to be the cause of the syndrome and after that commenced an immense search towards finding appropriate therapy for this fatal disease. The first drug that was apporoved and licensed by FDA was the former created 3’-azido-2’,3’-dideoxythymidine (also called zidovudine, or AZT) after it demonstrated in vitro inhibitory effect on HIV. However, there was a predecessor of AZT that inhibited in vitro HIV, a substance called suramin, which was used in the treatment of african trypanosomiasis and oncochersiasis, although it was abonded due to its severe toxicity. As said above, zidovudine was on older drug, developed in 1964 as a potential anticancer agent, however it was of low interest as it showed only modest effects. AZT falls into the category of NRTIs (nucleoside reverse transcriptase inhibitors). After it enters into the cell, this nucleoside analogue is phosphorylated into nucleotide which interferes with the viral reverse transcriptase, thus leading to early termination of the viral DNA chain so that enzymes from the cell can eliminate this compounds.

After AZT several other NRTIs were produced and approved for use. In spite of the enthusiasm from the results of AZT, it was soon made clear that monotherapy does not supresses effectively HIV, leading to the emerge of mutation that were resistant to the drug. Later, in 1995-1997, the approval of the sanquinavir, the first protease inhibitor(PI) and nevirapine, the first non-nucleoside reverse transcriptase inhibitor (NNRTI) opened the path towards what would be called later highly active antiretroviral therapy (or...

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...s the Atripla described above and it is predicted that FDCs will play a constantly increasing role in the HIV therapy. The use of FDCs also provides the ability to incorporate new classes of antiretroviral agents, thus enhancing the therapeutic results.

Several issues that have emerged lately regarding anti-HIV therapy are the selection of first line regimen in treatment-naïve patients consisting of two NRTIs, while the third agent could be a NNRTI or a ritonavir-boosted PI, even the lately approved integrase inhibitor raltegavir. Also, severe toxicity remains an important problem, as it can interfere with the well being of patients. Moreover, the use of monotherapy as maintance agents using boosted protease inhibitors has been under research, however their ability to supress the HIV load for a long time is limited. Another major issue is the dissemination of