HIV, for human immunodeficiency virus, is a virus that attacks the immune system,
weakening the body’s ability to fight infections. Progressive destruction of the immune system
eventually leads to its failures, a state known as “acquired immunodeficiency syndrome”,
or AIDS, when the body is incapable of defending itself from common infections.
HIV targets a specific group of cells called CD4+ cells. CD4 is a receptor expressed on
the surface of many immune cells, including T helper cells, macrophages and dendritic cells,
where it is essential for cell communication and hence normal function of the immune system. HIV
hijacks this receptor to gain access to the cells. Apart from CD4 receptor, another factor, called
a co-receptor, is also required for HIV entry and infection. Several co-receptors have been
identified in different cell types, with CXCR4 and CCR5 being the most common. CXCR4 is expressed on
many T-cells, but usually not on macrophages, and is used by T-tropic strains of HIV. CCR5 is
expressed on macrophages, some T-cells, and is used by M-tropic strains. Some HIV strains use
CCR5 to infect initially but evolve to use CXCR4 later during disease progression. Viruses that
can use both co-receptors are call dual-tropic. Some people are born with a deletion in CCR5 and
are substantially resistant to HIV infection. HIV life cycle starts with attachment of a
HIV envelope protein, gp120, to CD4 receptor and co-receptor, followed by fusion of HIV with host
cell. The virus then injects its content, HIV RNA and several enzymes, into the cell. One of these
enzymes, known as “reverse transcriptase”, is used to convert HIV RNA into DNA,
an important step that would allow the virus to integrate into host cell DNA. Once in the
nucleus, HIV enzyme integrase inserts the viral DNA into the host DNA. At this point the virus
may adopt either LATENT or ACTIVE infection. In active infection, HIV uses the host machinery
to produce multiple copies of its RNA and proteins, which are then assembled into new
virus particles, ready to infect more CD4 cells. In latent infection, the virus remains integrated
in host DNA, and may lie dormant for years, forming a latent HIV reservoir, which can
reactivate and infect again at a later time. HIV is transmitted through infected body fluids,
most commonly via sexual contacts, shared contaminated needles, and mother to child
during childbirth or through breastfeeding. It is not transmitted through air or casual contacts.
Diagnosis is by detection of viral protein, RNA, proviral DNA, or antibody produced against HIV.
There are three stages of HIV infection: The acute stage generally develops within
a couple of weeks after a person is infected with HIV. During this time,
patients may experience flu-like symptoms. HIV multiplies rapidly resulting in high viral load
in the blood and increased risks of transmission. The chronic stage, also called clinical latency,
is usually asymptomatic. HIV continues to multiply but at much slower speeds. Patients may not have
any symptoms, but they can still spread HIV to others. Without treatment, the disease usually
progresses to AIDS within 2 to 10 years. AIDS is the final stage of HIV infection.
As the immune system is failing, the body can’t fight off common diseases, and opportunistic
infections take hold. AIDS is diagnosed when CD4 cell count is lower than 200 per microliter, or if
certain opportunistic infections are present. There is currently no cure but treatment
with anti-retroviral therapy can slow down progression to AIDS and reduce transmission
risks. Anti-retroviral drugs are classified based on their ability to interfere with certain stage
of HIV life cycle. Accordingly, there are: entry and fusion inhibitors, reverse transcriptase
inhibitors, integrase inhibitors, and protease inhibitors. These drugs, however, cannot reach
the latent virus, which hides out safely in healthy T-cells but may reactivate and infect
again. This is the major reason why HIV infection is not curable with current available treatments.