Abstract
The history of the human immunodeficiency virus (HIV)/AIDS therapy, which spans over 30 years, is one of the most dramatic stories of science and medicine leading to the treatment of a disease. Since the advent of the first AIDS drug, AZT or zidovudine, a number of agents acting on different drug targets, such as HIV enzymes (e.g. reverse transcriptase, protease, and integrase) and host cell factors critical for HIV infection (e.g. CD4 and CCR5), have been added to our armamentarium to combat HIV/AIDS. In this review article, we first discuss the history of the development of anti-HIV drugs, during which several problems such as drug-induced side effects and the emergence of drug-resistant viruses became apparent and had to be overcome. Nowadays, the success of Combination Antiretroviral Therapy (cART), combined with recently-developed powerful but nonetheless less toxic drugs has transformed HIV/AIDS from an inevitably fatal disease into a manageable chronic infection. However, even with such potent cART, it is impossible to eradicate HIV because none of the currently available HIV drugs are effective in eliminating occult “dormant” HIV cell reservoirs. A number of novel unique treatment approaches that should drastically improve the quality of life (QOL) of patients or might actually be able to eliminate HIV altogether have also been discussed later in the review.
Highlights
Since the identification of the first acquired immunodeficiency syndrome (AIDS) patient in the US in 1981, the progress of antiretroviral therapy for human immunodeficiency virus (HIV)-1 infection and AIDS has been very rapid, making it unique in the history of medicine [1, 2]
The history of the human immunodeficiency virus (HIV)/AIDS therapy, which spans over 30 years, is one of the most dramatic stories of science and medicine leading to the treatment of a disease
These observations indicate that the HIV-1 CA is a highly attractive druggable target and this is expected to lead to the development of therapies to block or enhance these virus-host interactions in order to cause premature or delayed uncoating and potentially add to the combination antiretroviral therapy (cART) armamentarium for HIV-1 patients
Summary
Since the identification of the first acquired immunodeficiency syndrome (AIDS) patient in the US in 1981, the progress of antiretroviral therapy for HIV-1 infection and AIDS has been very rapid, making it unique in the history of medicine [1, 2]. In the mid1990s, treatment of HIV-1 infection/AIDS was revolutionized by the development of HIV-1 protease inhibitors and the introduction of combination antiretroviral therapy (cART). This new therapy strongly suppressed viral replica-. A number of obstacles were encountered when conducting cART in the early days, such as drug-related toxicities and the emergence of drug resistance against all the -existing antiretroviral regimens To overcome these problems, attempts have been made to develop more potent and safer anti-HIV-1 drugs effective against any existing drug-resistant HIV-1 strains and as a result, some new generation RTIs (e.g. tenofovir disoproxil fumarate) and protease inhibitors (PIs) (e.g. darunavir) were developed [13, 14]. REVERSE TRANSCRIPTASE INHIBITORS (RTIS): DISCOVERY OF THE FIRST HIV-1/AIDS DRUGS
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