SYNDROME / AIDS
WHAT IS AIDS?
Disease caused by the retrovirus human immunodeficiency
virus(HIV) and characterized by profound immunosuppression that
leads to opportunistic infections, secondary neoplasm and neurologic
HIV is transmitted primarily via unprotected sexual intercourse,
contaminated blood transfusions, hypodermic needles, and during
pregnancy, delivery, or breastfeeding. Some bodily fluids, such as
saliva and tears, do not transmit HIV
EPIDEMIOLOGY & STATISTICS
Since its discovery in 1981, AIDS has increased to epidemic
According to the National Centers for Disease Control and
Prevention (CDC), 42 million people are estimated to be
living with HIV/AIDS. Of these, 38.6 million are adults,
19.2 million are women, and 3.2 million are children under
Genetic research indicates that HIV originated in west-
central Africa during the late nineteenth or early twentieth
century HIV/AIDS has had a great impact on society, both as
an illness and as a source of discrimination.
HIV AND LIFE CYCLE
There is 2 main variant HIV-1
It is a retrovirus with two copies
of single stranded RNA genome
Genome contains gag (core
protein), pol (reverse
transcriptase, protease, integrase
enzymes) and env (envelope
Virus encodes 6 regulatory and
It uses reverse
transcriptase to transform
its ss-RNA genome into a
ds-DNA for integration into
its host genome
It has marker proteins
(gp120) in the protein coat
that allow it to recognize
specific cells in the human
The protein coat also
contains MHC-I and MHC-
COMPLETE ACTIVATION OF HIV
While CD4 is recognized by the virus, it is not sufficient for viral
attack; it needs a costimulatory signal.
T cells: coreceptor is CXCR4, which also acts as a receptor for the
chemokine SDF-1; there is competitive inhibition between chemokine
and HIV for binding; the HIV strain is called T-tropic
INFECTION OF HUMAN CELL WITH HIV
HIV gp120 surface protein
binds CD4 on target cell
component, gp41, binds
coreceptor CXCR4 to
Viral genome and other
proteins are able to enter
the cell via nucleocapsid
RT transcribes the ssRNA
The next DNA strand is
made, making a double
stranded DNA molecule
called a provirus
The dsDNA is transferred
to the nucleus to be
added to the host genome
via the viral integrase
protein at HIV LTR sites
Co receptor facilitate the tight binding of the virus to the cell
membrane and induce conformational change in the viral
envelope glycoproteins .
Mostly helper T cells ( TH cells) and sometimes monocytes
macrophages ,Nk cells, certain B cells and glial cells are
target for HIV
During infection , the virus infects TH cells within local
mucosal surfaces infecting local lymphoid tissues.
The virus quickly disseminates systemically infecting remote
lymphoid tissues as well as the glial cells . Then the virus
quickly appears in genital secretions.
Within weeks of initial infection , virus specific cytotoxic T
cells appear in the peripheral blood and lymphoid tissues.
After short period , neutralizing antibodies may be detected
in the plasma and virus replication process is initiated in this
Hosts develop an adequate immune response to the virus .
However reverse transcriptase makes very high replication
error ( 1 in 10000 bases copied) .
So that HIV progeny virus mutates in each replication cycle
,thus HIV infected cells persists in lymph nodes.
Infected cells can be killed directly by virus replication or
indirectly by virus specific effector mechanisms.
After several months of infection , a balance is established
among virus replication , immune effector mechanisms and
cells available for virus replication , and the infection enters
its chronic phase during which the patient is generally
Rapid viral replication is accompanied by a marked drop in
the number of circulating CD4+ T cells
99 % virus replication occurs in CD4+ T cells in lymphoid
organs and 1% virus replication occurs in monocytes and
resting CD4+ T cells.
When CD4+ T cells decline below 200 cells/µl ,infections
with variety of opportunistic microbes occur.
The risk of opportunistic infections ( OIs) and malignancies
are high when CD4 T cells is below 50 cells/µl .
The rate of immunologic and clinical progression is directly
related to the extent of virus replication and varies
considerably from individual to individual
SIGN AND SYMPTOMS
Brief flu-like illness two to four weeks after becoming infected.
Signs and symptoms may include:
Fever, Headache, Sore throat, Swollen lymph glands, Rash,
Diarrhea , Weight loss
The development of an opportunistic infection — an infection
that occurs when your immune system is impaired — such
as Pneumocystis carinii pneumonia (PCP)
A CD4 lymphocyte count of 200 or less — a normal count
ranges from 800 to 1,200 which causes
Soaking night sweats , Dry cough and shortness of breath
Shaking chills or fever higher than 100 F (38 C) for several
Persistent white spots or unusual lesions on tongue or in
Persistent headaches, Blurred and distorted vision
,Persistent fatigue , Swelling of lymph nodes for more than
There is more likely to develop certain cancers, especially
Kaposi's sarcoma, cervical cancer and lymphoma
Symptoms of HIV in children :
Children who are HIV-positive may experience:
Difficulty gaining weight
Difficulty growing normally
Problems walking ,Delayed mental development
Severe forms of common childhood illnesses such as ear
infections (otitis media), pneumonia and tonsillitis
TESTING FOR HIV
Enzyme-linked immunosorbent assay (ELISA). This
screening test is usually the first test used to detect infection
with HIV. If antibodies to HIV are present (positive result), the
test is usually repeated.
Western blot. This test requires high technical skills. It is
more difficult than the ELISA to perform and interpret
accurately, but it is less likely to give a false-positive result
because it can distinguish HIV antibodies from other
antibodies that may react to the ELISA. A Western blot is
usually done to confirm the results of two positive ELISA
Indirect fluorescent antibody (IFA). This test also detects
antibodies made to fight an HIV infection. Like a Western
blot test, it is used to confirm the results of an ELISA.
Polymerase Chain Reaction (PCR). This test detects the
RNA of HIV, rather than detecting antibodies to HIV.
Therefore, PCR can reveal an HIV infection before
antibodies can be detected. PCR can also accurately
determine whether a baby born to an infected mother has
HAART: Highly Affective Anti-Retro Viral Therapy: Physicians
consider 200 to 350 CD4 cells/mm3 as the range to consider .
HAART combines two types of antiretroviral drugs
RTI’s (Reverse Transcriptase Inhibitors):
Type 1: NRTI’s – nucleoside drugs provide faulty DNA
building blocks, stopping the DNA chain the virus uses to
make copies of itself.
Type 2: NNRTI’s- non-nucleoside RT inhibitors bind RT
so the virus cannot carry out its copying function
NNRTI’s (Non-Nucleoside RTI’S) : Delavirdine, Nevirapine,
Protease Inhibitors: Indinavir, Ritonavir
WHAT DOES THE FUTURE HOLD?
Scientists are working on more potent protease
inhibitors, less toxic RT inhibitors, as well as 2 new
classes of drugs:
*Fusion Inhibitors- Drugs which act to block HIV before it
enters the human immune cell. This class of drugs works to
stop HIV replication at an earlier stage.
*Integrase Inhibitors- Aim to block the integration of the
virus’s DNA into the cell’s chromosome. 2 different integrase
inhibitors are currently in human trials.