Pp. 3-22 (20)
Sarah Nanzigu, Francis Xavier Kasujja and Immaculate Nankya
Over thirty antiretroviral agents have been developed since the beginning of
the fight against the human immunodeficiency virus (HIV). This breakthrough was
fostered by the enormous leaps made in understanding viral replication, a cycle that
begins with the interaction between the virus and the host cell, usually a CD4-bearing
T-lymphocyte. This results into the fusion of the viral membrane with the cellular
plasma membrane and the transfer of viral material, including RNA, into the cytoplasm
of the host cell. Then, using viral DNA-dependent RNA reverse transcriptase, viral
DNA is formed from RNA. Viral DNA is soon translocated to the host cell nucleus
where it is integrated into the host DNA in a reaction catalyzed by integrase enzyme.
The proviral DNA formed at this stage is used to produce immature viral polypeptides
that are eventually cleaved and packaged into mature virions by protease enzyme.
Drugs have been developed that target each of these steps; they include entry inhibitors,
reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors. The reverse
transcriptase inhibitor, Zidovudine, a nucleoside analogue, was the first antiretroviral
agent to be approved in 1987. It was followed by many other nucleotide, nucleoside and
non-nucleoside reverse transcriptase inhibitors, and eventually, by protease inhibitors,
integrase inhibitors and entry inhibitors. Other viral targets are still under research.
HIV drugs, HIV Treatment, Antiretroviral drugs, Antiretroviral
therapy, Retroviral treatment, Reverse transcriptase inhibitors, Protease inhibitors,
Integrase inhibitors, HIV entry inhibitors, HIV vaccines, ART.
Department of Pharmacology and Therapeutics, Makerere University College of Health Sciences, Kampala, Uganda.