Pharmacology Of Antiretroviral Agents

Infection with the human immunodeficiency virus (HIV) is now recognized as a chronic disease. Although the success of highly active antiretroviral therapy is indisputable, several problems persist. Since drugs cannot uproot the microorganism, cure is not yet possible and patients must maintain lifelong adherence with the risk of toxic effects, drug interactions and pill resistance. A clear understanding of viral replication and its interaction with host cell factors has led to the development of a large number of effective antiretroviral drugs (ARVs). New drugs from the existing class such as apricitabine, elvucitabine and etravirine have shown promising results against HIV isolates resistant to first-line drugs. These drugs have offered a new choice to patients with drug-resistant disease. However, the impact of their long-term use on safety remains to be assessed. New drugs with a unique mechanism of action, such as inhibitors of CD4 receptor attachment, maturation inhibitors, pharmacokinetic activators, capsid assembly inhibitors and growth factor-derived inhibitors of the lens epithelium are still under development. Currently, ARVs, particularly tenofovir and emtricitabine, are also being evaluated for the prevention of sexual transmission of HIV-1. Initial results from a network of HIV prevention trials are encouraging and have recommended the use of ARVs for pre-exposure prophylaxis. Thus, ARVs are the key element of the HIV prevention and treatment strategy. This article discusses the challenges associated with HIV-1 treatment and highlights several major advances in the development of ARVs.

Significant progress in understanding HIV replication and its pathogenesis has helped identify different pharmacological targets. This has resulted in the availability of a large number of antiretroviral drugs (ARVs). Antiretroviral therapy (ART) has moved from azidothymidine monotherapy (AZT) to the combination of 2 ARVs from nucleoside reverse transcriptase inhibitors (NRTIs) to highly active antiretroviral therapy (HAART)