Transmission:

Trans -mission occurs mainly by one of three routes: 1) sexually (it is present in both semen and
vaginal secretions), 2) with blood or blood products (whole blood, plasma, clotting factors, and
cellular fractions of blood by transfusion, or by inoculation with HIV-contaminated needles), and
3) perinatally (either transplacentally, during passage through the birth canal, or in breast
feeding).

Pathogenesis:

Once the HIV virion is in the bloodstream, its gp 160 (composed at gp 120 and gp 41)
glycoproteins bind to the CD4 receptor on target cells. This CD4 receptor is present in high
concentration on T-helper lymphocytes. These cells are actually referred to as CD4+ T-helper
cells. Other cells that possess CD4 receptors in lower concentrations and which can become
infected are macrophages, monocytes, and central nervous system dendritic cells. Following HIV
binding to the CD4 receptor, the viral envelope fuses with the infected host cell, allowing capsid
entry.

Following initial infection, HIV can begin replication immediately, resulting in rapid progression
to AIDS, or there can be a chronic latent course. The former, most common pattern occurs in 3
stages 1) starting with initial infection, marked by an acute mononucleosis-like viral illness 2)
progresses for a variable number of years (median 8 but range of less than 1 to greater than 20)
of disease-free latency 3) after AIDS develops most patients die within 2 years if they do not
receive effective antiretroviral therapy.

1) An acute viral illness like mononucleosis (fever, malaise, lymphadenopathy, pharyngitis,

etc.) develops in 80% about 1 month after initial exposure. There are high levels of blood-borne
HIV (viremia) at this stage, and the viruses spread to infect lymph nodes and macrophages. An
HIV-specific immune response arises, resulting in decreased viremia and resolution of the above
symptoms. However, HIV replication continues in lymph nodes and peripheral blood.

2) A clinical latency follows for a median of 8 years during which there are no symptoms of
AIDS, although some patients develop a dramatic generalized lymphadenopathy (possibly
secondary to an aggressive immune attack against HIV harbored in the lymph nodes). This is not
a true viral latency without viral replication; HIV continues to replicate in the lymphoid tissue
and there is a steady gradual destruction of CD4 T-lymphocytes (helper) cells. CD4+ T-
helper cells are the number one target of HIV. The virus reproduces in these cells and destroys
them. Toward the end of the 8 years, patients are more susceptible to bacterial and skin
infections, and can develop constitutional (systemic) symptoms such as fever, weight loss, night
sweats, and adenopathy.

3) AIDS develops for a median of 2 years followed by death. AIDS is now defined as having a
CD4 T-lymphocyte count of less than 200 (with serologic evidence of HIV infection such as a
positive ELISA or western blot test) and/or one of many AIDS-defining opportunistic infections,
which are infections that usually only patients with AIDS develop. These include Candida
esophagitis, Pneumocystis carinii pneumonia, the malignancy Kaposi's sarcoma, and many
others. Normal CD4+ T-cell counts are 1000 cells/μl blood. In HIV-infected persons the count
declines by about 60 cells/ml blood/year.

Diagnosis of HIV

Following infection with HIV, viral RNA or antigens (such as p24) can be detected in the blood
within weeks. Three to 6 weeks later antibodies against HIV antigens appear. The enzyme-linked
immunosorbent assay (ELISA) test detects antibodies. Any positive results must be confirmed
using the Western blot technique.

Viral Load and CD4 count

CD4 counts are used to determine severity of HIV infection, risk of opportunistic infection,
prognosis, and response to anti-viral therapy. We can now measure plasma HIV RNA by the
polymerase chain reaction (PCR) orbranched chain DNA assay. There is mounting evidence that
higher plasma HIV RNA levels (viral load) correlate with a greater risk of opportunistic
infection, progression to AIDS, and risk of death. CD4 counts are still the best predictor of a
patient's current risk for particular opportunistic infections. David Ho has popularized the train
analogy to explain the predictive values of HIV viral load and CD4 counts. Viral load tells you
the speed at which the train is heading for the cliff (low CD4, development of opportunistic
infections and death) while the CD4 count tells you where the train currently is! For example, if
a patient has a CD4 count of 450 cells/mL and a viral load of >106 copies/μL that patient is at
low risk for developing Pneumocystis carinii pneumonia today (CD4>200 cells/micL ) but is at
great risk in the future for rapid CD4 count decline, opportunistic infection and death if not
treated.