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Antiviral therapy and, particularly, anti-HIV therapy has definitely come of age [1]. There are now more than 30 compounds that have been formally approved for the therapy of virus infections. The nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine, didanosine, zalcitabine, stavudine, lamivudine and abacavir are used in the treatment of human immunodeficiency virus (HIV) infections and...
The history of HIV treatment is characterised by a rapid development. In 1987, 6 years after the discovery of AIDS, the US Food and Drug administration approved the first drug against HIV. Since then three different classes of antiretroviral drugs including 16 drugs are currently available, others have reached phase III studies and immunotherapy and vaccines are in development.
The use of antiretroviral combinations in HIV-1 infection has led to a dramatic improvement in the morbidity and mortality associated with HIV/AIDS [1]. The concept of combining therapeutic agents is not unique to HIV infection and has proven successful in a variety of medical areas, most notably cancer. For example, the most significant successes in the fight against childhood leukemias were seen...
Current antiretroviral therapy guidelines [1] recommend the combination of at least two nucleoside retrotranscriptase inhibitors (NRTI) plus at least one protease inhibitor (PI) and/or at least one nonnucleoside retrotranscriptase inhibitor (NNRTI) for the treatment of HIV infection. Different specific drugs are chosen to comply with this general scheme considering the stage of the disease, the occurrence...
The presently employed components of HAART are derived from a variety of chemically and pharmacologically different drug classes. The first compounds, which possessed antiretroviral activity were designed as nucleoside analogues in order to inhibit the reverse transcriptase. The first drug zidovudine (AZT) became available in 1987 and was followed soon by several compounds, which were directed at...
Signs and symptoms associated with the acute illness, also referred to as acute retroviral syndrome (ARS), are observed in approximately two-thirds of HIV-infected patients [1, 2]. Similar symptoms have been reported in patients infected through sexual intercourse and through the intravenous route except for mucosal lesions in the genital tract which are more frequently observed in patients contaminated...
Substantial declines in the rates of AIDS-related illness, hospitalization, and death in people with HIV infection have been achieved in the current era of highly active antiretroviral therapy (HAART) [1–3]. Sustained suppression of viral load below the level of detectability is required to achieve optimal impact on immunologic function and clinical outcomes [4, 5]. If plasma viral load is inadequately...
Since the anecdotal case reports from the Franco Lori and Douglas Nixon groups [1, 2] the concept of interrupting therapy as a therapeutic strategy in HIV infection has gained interest both in research and in clinical practice [3]. Structured therapy interruption (STI) could be considered as the simplest method of active immuno-mediated therapy [3]. This strategy may be interpreted as an auto-vaccination...
The course of the human immunodeficiency virus (HIV) infection has dramatically changed since the immune reconstitution induced by new antiretroviral therapeutic regimens, or highly active antiretroviral therapy (HAART) combining inhibitors of the HIV reverse transcriptase (RTI) and protease (PI). Indeed, by blocking virus production these agents allow the immune system to reconstitute the CD4 cell...
Implementing successful HAART of HIV-1-infected children poses several unique challenges. Children appear to have less virologic success from HAART than adults. However, careful consideration of multiple factors may assist in maximizing the virologic efficacy of HAART, including its duration [1]. Obstacles to successful HAART of children include: difficulties in administering drugs; difficulties adhering...
Currently, there is no consensus on the definition of HIV treatment failure. Current guidelines [1–3] suggest considering virologie, immunologic and clinical responses in assessing treatment failure (Tab. 1). Virologic failure may be defined as a lack of an initial HIV RNA response to therapy or an increase or rebound in HIV RNA levels following an initial response. Immunologic failure may be defined...
Currently, there are two methodologies for assessing the sensitivity of HIV-1 to antiretroviral (ARV) medications: genotyping and phenotyping. Genotyping is generally done either by direct sequencing or with line-probe assays that look for specific mutations in the reverse transcriptase (RT), protease (PR) and other domains that might be associated with viral resistance to medications. Phenotyping...
Progress in the treatment of HIV infection over the past decade has resulted in dramatic reductions in morbidity, mortality and health care utilization as more effective treatment regimens have been developed and simpler schedules of drug administration have been devised [1, 2]. As more effective regimens have provided durable suppression of viral replication, it has become clear that reversal of...
The spreading epidemic of human immunodeficiency virus type 1 (HIV-1) infection and acquired immunodeficiency syndrome (AIDS) is poised to become the greatest scourge of humankind in recorded history. As efforts to control HIV-1 continue globally, attitudes about this formidable opponent have changed from pathos of initial despair, and after a brief heady euphoria, have settled into modern-day cautious...
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