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HIV and drug therapy


The human immunodeficiency virus (HIV) is a topic of intensive contemporary research. Hallmarks of the virus include sexual transmission, progressive immune failure, and subsequent deadly infections/cancer. HIV operates by infecting immune system cells, particularly macrophages and T lymphocytes.
The HIV virus is spherical, and contains reverse transcriptase, integrase, and single-stranded RNA+. It is contained by a viral envelope, which is embedded with proteins from the host cell and a particular glycoprotein referred to as gp120. The gp120 molecules allow the viral cells to adhere to its target receptors located on the exterior of immune cells.
HIV infects macrophages by first binding its gp120 proteins to two proteins located on macrophages: the CD4 receptor, which is important in immune recognition, and the CCR5 co-receptor, the function of which is not fully understood beyond HIV. The membranes then fuse together, causing the viral RNA to be released into the cell along with key enzymes. Reverse transcriptase creates HIV DNA, which is then integrated into the host’s DNA via integrase. The host, now referred to as a provirus, continues to replicate the integrated DNA until protease cleaves the viral protein out. It is then transcribed into RNA, viral components collectively aggregate, and the new HIV cell buds off as a mature virion. While viruses that undergo a lysogenic or lytic cycle destroy the host cell, HIV does not. For this reason, its life cycle is classified as productive.
Because gp120 is critical to the primary step of the HIV life cycle, it is a highly conserved protein in the otherwise mutation-prone virus. Scientists have attempted to exploit this conservation in immunotherapy, developing gp120 specific treatments. Maraviroc is a current therapeutic drug that binds to the CCR5 receptor, blocking the binding of gp120 to the macrophage cell. In a clinical study of Maraviroc, over 600 patients were separated into two groups. Group 1 received a placebo drug and Group 2 received 150mg of Maraviroc twice a day.
Table 1: The results of the clinical study, including decrease in HIV RNA levels.
PlaceboMaraviroc given twice daily
# Subjects209426
Baseline plasma HIV RNA (log10 copies/mL)4.864.85
Plasma HIV RNA (logstart subscript, 10, end subscript copies/mL) at Week 484.08*3.01*
< 400 copies/mL at Week 4822%56%
< 50 copies/mL at Week 4817%46%
Adverse events5%4
There were no additional adverse events such as illness or death associated with the experimental group.
Source: ViiV Healthcare (2014). Trial in Treatment-Naive Subjects. Pfizer Manufacturing Deutschland GmbH. Research Triangle Park, NC 27709.
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