A Concise Review of Existing Therapies and Recent Advances in the Management of HIV Infection

Abstract

Human immunodeficiency virus (HIV) is an RNA retrovirus capable of replicating its genome by the DNA dependent RNA polymerase (DdRp). The virus infects the lymphocytes with the help of viral glycoproteins like Gp 120 and Gp 41. The entry of virus leads to the release of viral RNA inside the host cell, which is further replicated, and assembly of virion particles leads to the release of viral particles that further infect the other host cells. Established therapies include those that inhibit the entry of virus in the host cell, those inhibiting the integrase activity, those acting as protease inhibitors and also we have Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside reverse transcriptase inhibitors (NNRTIs) with NRTIS being the competitive inhibitors of DdRp also show mitochondrial toxicity. Protease inhibitors are known for their adverse effect profile and several drug interactions due to their enzyme inhibitory property. The most effective approach in the management is the highly active antiretroviral therapy containing the combined use of drugs having varied mechanisms of action. Still, long term use of these agents can end up in resistance against these agents. Well documented adverse effect profile along with various drug interactions associated with anti-HIV drugs mandates the need for the development of newer drugs against HIV. Newer molecules provide a better safety profile and better alternatives for drug-resistant cases. Therefore, this review focuses on existing therapies along with various newer pipeline drugs with their mechanisms and advantages over the existing therapies.

Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions

“…Since the identification of HIV as the causative agent of the acquired immunodeficiency syndrome (AIDS) [1,2], we have assisted in an impressive drug discovery rush. In less than 30 years this incredible scientific effort has led to the identification of a complex and variegated new armamentarium of antiviral agents, that specifically target HIV [3][4][5][6]. Nowadays, we have several classes of antiviral agents, targeting specific phases of the HIV 1 replication cycle.…”

“…The current treatment of infected patients always consists of a combination of two or more drugs, according to the presence of viral coinfections and therapy response to the different agents [4,13]. The combination of diverse agents with different targets within the viral replication cycle steps is mandatory, due to the likely selection of resistant mutants [5]. However, it should be considered that, although very efficient in managing the infection, the current therapeutic strategies are not capable of eradicating the virus from the host.…”