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HIV
/ AIDS
A
Clinician's Guide
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| Preface |
Although it is about
20 years since HIV infection and AIDS gained prominence,
HIV therapeutics is an evolving science. Rapid strides
made in our understanding of HIV pathogenesis have translated
into important clinical benefits for people living with
HIV. The introduction of new drugs that potently inhibit
HIV replication have successfully reduced morbidity and
mortality and improved the quality of life for HIV-positive
patients.
India is believed to be the country with the second largest
number of people living with HIV. Currently, it is estimated
that about 4 million Indians are living with HIV. In the
years to come, these individuals will definitely place
a larger burden on the healthcare services.
Treatment of HIV patients requires a detailed knowledge
of the disease, as well as advances in therapeutics. The
aim of this booklet is to equip clinicians with current
concepts on HIV infection and enable them to treat patients,
using both anti-HIV drugs, as well as drugs for treating
opportunistic infections. |
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| Why is AIDS such a burning
issue today? |
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The grim statistics
Figure 1: The number of adults and children estimated
to be living with HIV/AIDS at the end of 2000
- At the end of 2000, there were 36.1 million adults
and children living with HIV/AIDS
- During 2000, 5.3 million children and adults were
infected with HIV, and 3 million people died
- The total number of AIDS deaths since the beginning
of the epidemic is estimated to be 21.8 million
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| What is the magnitude
of the problem in India? |
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Today, South Africa is the country
with the greatest number of HIV-infected individuals
in the world, followed by India. Official Indian estimates
range from 3.5 to 5 million, and perhaps the actual
number may be far more. Moreover, given the similarities
between Africa and India, the holocaust that is currently
sweeping Africa may well repeat itself in India.
In fact, a recent study concluded that there has been
an increase in the number of deaths due to AIDS in Mumbai
city (Lancet 1999;354:1175-6).
No longer is HIV infection diagnosed exclusively in
individuals from the high-risk groups (e.g. commercial
sex workers-CSWs, intravenous drug users). It is increasingly
being diagnosed in housewives and pregnant women. This
is an ominous sign, and indicates the extent to which
HIV has spread in the community.
Routes of infection of HIV in
India (%)
- In Tamil Nadu, almost half a million people are
infected with HIV, and the infection rate is 3 times
higher in villages than in the cities
- In 5 years, the infection rate among CSWs has increased
from 1% to 51% in Mumbai
- Among injecting drug users in Manipur the infection
rate has risen from 1% to 55.8%
- Among patients attending sexually transmitted diseases
clinics, the infection rate has shot up from 23% to
36% in 1 year in Mumbai
Ref: Lancet 1999;353:48
These statistics clearly reveal the magnitude of
the problem in India.
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| How is HIV transmitted? |
HIV is transmitted by
the following routes:
1. Sexual transmission: This
is the commonest route of transmission worldwide as well
as in India. The presence of sexually transmitted diseases
further increases the risk of transmission of HIV.
2. Transfusion of infected blood
and blood products: HIV may be acquired through
blood transfusion. The probability of acquiring HIV infection
after receiving HIV-infected blood is 95%. Haemophiliacs
and thalassaemics are at particular risk for acquiring
HIV infection.
3. Maternal transmission:
HIV may be transmitted from an infected mother to her
infant during pregnancy, during delivery or after delivery
through breast-feeding.
4. HIV-contaminated instruments:
Use of HIV-contaminated instruments, e.g. needle sharing
among injecting drug users, can transmit HIV. Acupuncture
and tattoos may also transmit HIV. Re-usable needles may
transmit HIV infection if proper sterilisation techniques
are not used.
Occupational exposure to HIV may occur. Percutaneous exposure
involves needles carrying HIV-infected blood, which accidentally
prick the healthcare professional. However, the risk of
acquiring HIV via a percutaneous exposure is 0.3%, whereas
after a mucocutaneous exposure, the risk is believed to
be even lower i.e. about 0.09%. |
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| How does HIV replicate? |
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HIV is a virus, and needs a living cell within which
it can multiply. Once HIV enters the human body, it
specifically seeks out a particular type of T-lymphocyte
in the blood, called the CD4 T-lymphocyte. The various
stages of HIV replication are explained below.
Stages of HIV reproduction
1. HIV enters a CD4 cell.
2. HIV is a retrovirus, meaning that its genetic information
is stored on single-stranded RNA instead of the double-stranded
DNA found in most organisms. To replicate, HIV uses
an enzyme known as reverse transcriptase to convert
its RNA into DNA.
3. HIV DNA enters the nucleus of the CD4 cell and inserts
itself into the cell's DNA. HIV DNA then instructs the
cell to make many copies of the original virus.
4. With the help of the protease enzyme, new virus particles
are assembled. These newly formed viruses leave the
cell, ready to infect other CD4 cells.
Characteristics of HIV replication
Rapid replication of HIV, with concomitant destruction
of CD4 cells, occurs continuously throughout the course
of HIV infection, including the initial clinically asymptomatic
phase of infection. It is estimated that the turnover
of the virus is very high - up to 109 virus particles
every 1.5 to 2 days.
In patients with advanced HIV disease, as many as 109
new HIV virions are produced each day and as many as
2 x 109 CD4 cells turn over per day.
Sanctuaries of HIV in the body
HIV not only infects the CD4 cells, but also establishes
infection in certain sanctuary sites such as the central
nervous system, lymphoid tissue and testes. During the
early stages of HIV infection, a virus reservoir is
established in resting memory CD4+ lymphocytes. Since
these cells have a very long half-life, the possibility
of a cure for HIV infection with antiretroviral therapy
is unlikely.
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| Which tests are used
to diagnose HIV infection? |
Tests which are commonly
used to diagnose HIV infection are:
1. ELISA: This is
the initial, or screening, test for HIV infection. It
tests for the presence of antibodies against HIV in the
blood. A positive result is usually obtained within 3
months of acquiring the infection.
2. Western Blot: This
is a confirmatory test. It detects antibodies against
antigens coded by 3 different viral genes.
As per NACO (National AIDS Control Organisation) guidelines,
HIV infection is diagnosed on the basis of blood tests
using three different ELISA/Rapid simple tests using different
antigen preparations. Cases of AIDS are diagnosed on the
basis of two different ELISA/Rapid tests on different
antigens and the presence of AIDS-related opportunistic
infections. The Western Blot test is used for confirmation
of diagnosis when ELISA tests are indeterminate.
3. Polymerase chain reaction
(PCR) assays: The PCR technique is used
to assay for both HIV RNA and HIV DNA.
HIV infection can be diagnosed in the window period (i.e.
when antibodies to HIV have not yet developed and ELISA
is negative) by the HIV DNA PCR assay or the p24 antigen
test.
The HIV RNA PCR test can measure the amount of HIV RNA
in the blood (also referred to as the "viral load").
The viral load indicates the rate of disease progression,
with higher viral loads predictive of faster disease progression.
HIV RNA PCR is also used to assess the response to anti-HIV
therapy.
The viral load may also be measured using another technique
known as the branched DNA (bDNA) technique. |
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| What is "Primary
HIV Infection"? |
The term "primary
HIV infection" (also called "acute HIV infection")
refers to the illness which occurs when HIV first infects
an individual. This stage is characterized by non-specific
flu-like symptoms such as fever, lethargy, sore throat,
malaise, rash, lymphadenopathy, arthralgias, myalgias,
headaches and rarely asymptomatic meningitis. These symptoms
usually occur within 2 to 6 weeks after acquiring the
virus. Most symptoms usually resolve within 2 to 3 weeks.
Within 2 to 4 weeks after the initial infection, high
levels of virus are present in the blood. The immune system
now begins to recognise the virus and produce antibodies.
HIV antibodies can be detected in the blood usually within
1 to 3 weeks after symptoms appear.
The time period during which the individual is infected
with HIV, but has no antibodies in his blood, is called
the "window period". During the window period,
the HIV-infected person is capable of transmitting the
virus to others, and is infectious.
This phase of primary HIV infection is also called the
"acute seroconversion syndrome". The term "seroconversion"
refers to the appearance of HIV antibodies in the blood.
During the window period, the ELISA test will give a negative
result; the only tests for detecting HIV infection at
this stage are the PCR test or the p24 antigen test. |
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| What is the natural history
of HIV infection? |
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HIV attacks the CD4 T-lymphocytes
HIV has a special affinity for the CD4 T-lymphocyte.
It multiplies rapidly and continuously within these
cells. Although the body does replace the lost CD4 cells,
the rate of destruction of the CD4 cells far exceeds
the body's ability to replace them.
Thus, as HIV infection progresses, there is a progressive
decline in the number of CD4 T-lymphocytes. The CD4
count may drop to as low as 50 cells/µ l or even
lower, from the normal level of about 1000 cells/µl.
HIV infection leads to immunodeficiency
HIV destroys the CD4 cells, which play a vital role
in immune function. The loss of CD4 cells leads to immunodeficiency
in HIV-infected patients. In other words, these patients
become susceptible to a variety of "opportunistic
infections".
Opportunistic infections are commonly encountered when
the CD4 count is less than 200 cells/µ l. The
lower the number of CD4 cells, the more advanced is
the stage of the disease.
Thus, HIV causes a progressive and irreversible destruction
of the immune system.
Immunodeficiency causes opportunistic
infections
As the immune function declines, the HIV-positive patient
is plagued by a variety of opportunistic infections.
Virtually no system or organ is spared. Moreover, as
immunodeficiency increases, these infections become
more difficult to treat, and have a greater tendency
to relapse.
Immunodeficiency leads to death
If an HIV-positive patient is left untreated, over the
years, his CD4 cells will continue to decline progressively,
immune function will deteriorate, and ultimately, he
would die because of the opportunistic infections that
ravage his body.
Schematic representation
of HIV disease progression,
including symptoms that may occur at each stage of HIV
infection
Common opportunistic
infections in India
1. Tuberculosis, both pulmonary as well as extrapulmonary.
This is one of the commonest presentations. Atypical
mycobacteria such as Mycobacterium avium complex (MAC)
may also cause infection.
2. Oral candidiasis
3. Oesophageal candidiasis
4. Herpes zoster
5. Diarrhoea, which may be due to a variety of pathogens:
Protozoal - Amoeba, Giardia, Isospora belli, Cryptosporidium
Helminths -Strongyloides
Viral - Cytomegalovirus
6. Bacterial pneumonia and Pneumocystis carinii pneumonia
7. Toxoplasma encephalitis
8. Cryptococcal meningitis
9. Cytomegalovirus (CMV) retinitis
Cancers such as Kaposi's sarcoma and non-Hodgkin's lymphoma
are also seen in these patients.
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