Human immunodeficiency virus
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HIV is a spherical, enveloped RNA virus. It is a retrovirus, using
reverse transcriptase to produce a DNA copy from viral RNA that
is incorporated into the host nucleus to become the template for
further viral RNA. Three genes are required for viral replication:
gag, pol and env. HIV is classified as a lentivirus. There are two
types that are pathogenic for humans: HIV-1, which is most
common; and HIV-2, which is found mainly in West Africa and
appears to be less virulent.
Infection with HIV has spread worldwide, transmitted by the
parenteral and sexual routes. Infection is most common in individuals
at high risk of sexually transmitted diseases, especially
those where genital ulceration is common. In developed countries,
the main risk groups are intravenous drug users and men who have
sex with men; heterosexual transmission is less common but does
In developing countries, HIV spreads mainly by heterosexual
transmission and through unscreened transfusions or use of
contaminated medical equipment. Infection can be transmitted
from mother to fetus.
The virus principally infects cells with a CD4 receptor (e.g. T cells
and macrophages). Viral replication results in progressive T-cell
depletion and diminished cell-mediated immunity. Different virus
strains display varying affinities for cells that express particular
chemokine receptors. Lacking T-cell help, B-cell function is also
reduced. HIV causes damage to neural cells and stimulates cytokine
release that may also cause neurological damage. Many of the
clinical signs of AIDS are caused by secondary infections, which
occur when the CD4 count falls.
A few weeks after infection, a mononucleosis-like syndrome may
develop with rash, fever and lymphadenopathy. There is a primary
viraemia after which the viral load reduces to a steady state, the
concentration ('set-point') being related to outcome. The CD4
count declines and, if untreated, reaches a point (<0.2 � 109/L)
where CD4 function is sufficiently compromised for secondary
infections and malignancies to develop, a condition known as
acquired immune deficiency syndrome (AIDS). Use of highly
active antiretroviral therapy (HAART) delays this development.
Bacteria Mycobacterium tuberculosis, Mycobacterium avium-
intracellulare (see Pathogenic mycobacteria
, Streptococcus pneumoniae
Protozoa Toxoplasma gondii
, Cryptosporidium parvum
Fungi Candida spp
., Cryptococcus neoformans
Viruses Varicella zoster
virus (VZV), human papovavirus.
sarcoma (HHV-8), non-Hodgkin's
Children with HIV infection are especially vulnerable to childhood
viral infections (e.g. measles) and recurrent bacterial infections
Diagnosis is by detection of HIV-specific antibody using two different
immunoassay methods. As seroconversion may take up to
3 months, an initial negative result should be repeated.
HIV viral load and CD4 count are tested on presentation and
regularly during care. Resistance should be tested initially and
if a change of therapy is necessary. HLA B5701 and tropism
are tested if treatment with abacavir or CCR5 antagonist is
Antiretroviral drugs are described in Virus structure, classification and antiviral therapy
. Therapy aims to
maintain the virus at fewer than 50 copies, prevent the emergence
of resistance, restore immunological function and prevent transmission.
Treatment is initiated for any patient with opportunistic
infection or when the CD4 count is <0.350 � 109/L, although
patients with higher counts may benefit. It is also recommended
for pregnant women who do not meet these criteria (see Congenital and perinatal infections
). Patients must be aware of the lifelong commitment. Because
RNA viruses lack efficient mechanisms for genetic proof-reading,
mutations arise rapidly and patients develop drug resistance
Regimens must be adapted to an individual patient's medical
and social condition. Patients infected with resistant virus require
tailored regimens. Regimens may include an NNRTI and two
NRTI, or a combination that includes a protease or integrase
inhibitor. As the immune system starts to recover with treatment,
known as immune reconstitution, symptoms from opportunistic
infection can worsen due to the effects of the enhanced immune
- Avoidance of partners who have a high-risk factor and unprotected
intercourse (e.g. by using barrier contraception).
- Screening of blood products.
- Health education and free needle-exchange programmes for
intravenous drug users.
- Antigenic diversity has frustrated vaccine development.
- Antiretroviral prophylaxis should be given for infected needlestick
- Transmission from mother to child can occur (see Congenital and perinatal infections