HIV infection (AIDS)

AIDSAIDS
Acquired Immuno deficiency syndrome or
AIDS, is a collection of symptoms due to
underlying infections and malignancies
resulting from specific damage to immune
system caused by human immunodeficiency
virus (HIV).
04/19/14 2Biochemistry for medics

IncidenceIncidence
• HIV (human immunodeficiency
virus) infection has now spread to
every country in the world.
• Approximately 40 million people
are currently living with HIV
infection, and
• An estimated 25 million have died
from this disease.
• In the United States,
approximately 1 million people are
currently infected.

A Global view of HIV InfectionA Global view of HIV Infection
04/19/14 Biochemistry for medics 4

AIDSAIDS
• The first indication of this new syndrome came in 1981
in homosexual drug addict males;
• they had two things in
common- Pneumocystis pneumonia and Kaposi’s
sarcoma.
• Both these are markers of collapsed immune system,
• The affected patients appeared to have lost their
immune competence, rendering them vulnerable to
overwhelming and fatal infections with relatively
avirulent micro-organisms, as well as to lymphoid and
other malignancies.
• This condition was given the name Acquired Immuno
deficiency Syndrome (AIDS).

AIDS MarkersAIDS Markers
Pneumocystis pneumonia and Kaposi’s
sarcoma are considered AIDS markers,
since they reflect the underlying collapsed
immune system04/19/14 Biochemistry for medics 6

Human Immunodeficiency VirusHuman Immunodeficiency Virus
• In 1986, The International
Committee on virus Nomenclature
decided on the generic name of the
causative virus as the Human
Immunodeficiency Virus.
• HIV, the etiological agent of AIDS,
belongs to lentivirus subgroup of
the retroviridae family.
• This family of viruses is known for
latency, persistent viremia, infection
of the nervous system, and weak
host immune responses.

Human Immunodeficiency VirusHuman Immunodeficiency Virus
• HIV has high affinity for CD4 T
lymphocytes and monocytes.
• HIV binds to CD4 cells and
becomes internalized. The
virus replicates itself by
generating a DNA copy by
reverse transcriptase.
• Viral DNA becomes
incorporated into the host
DNA, enabling further
replication.

Structural Characteristics of HIVStructural Characteristics of HIV
• HIV is a spherical enveloped virus of about 90-
120 nm in diameter
• There is a lipoprotein envelop, which consists
of lipids derived from the host cell membrane
and glycoproteins which are viral coded.
• The major virus coded envelop proteins are the
projecting knob like spikes on the surface and
the anchoring transmembrane pedicles.

• The spikes, gp 120 constitute the major surface
component of the virus which binds to the cell
CD4 receptors on susceptible host cells.
• These specific receptors, known as cluster of
differentiation- CD4 are present on certain
cells in the body, the cells possessing these
receptors are called CD 4 +
cells and these are -
T helper cells, B lymphocytes ,macrophages,
monocytes and dendritic cells.
• Transmembrane pedicles gp 41 cause cell to
cell fusion.

A cross sectional schematic diagram of HIV virion, showing lipid bilayer
in the form of viral envelop , Nucleocapsid core, which includes a layer of
a protein called p17 and an inner layer of a protein called p24.

• Interior to the envelope is an
outer icosahedral nuclear capsid shell and
an inner cone-shaped core containing
ribonucleoproteins.
• The enzymes integrase p32, protease p10,
reverse transcriptase p55/66 and 2 copies of
single stranded genomic RNA are present
inside the core.
• (The proteins and glycoproteins are indicated
by their mass expressed as kilo Daltons)

Genome of HIVGenome of HIV
There are two types of genes analyzed-
a) Structural genes encode for products which
participate in formation of functional structure of
virus
1) gag gene
• encodes for core and shell of virus.
• The gene product is a precursor protein p55, which
is cleaved into p17, p24 and p15.
• The p24 antigen (major core antigen) can be
detected in serum during the early stages of
infection till the appearance of the antibodies.

Genome of HIV (Structural genes)Genome of HIV (Structural genes)
2) pol gene
• Encodes for the polymerase reverse
transcriptase and other viral enzymes such as
protease and integrase.
• It is expressed as a precursor protein, which is
cleaved in to components like p64 which has
reverse transcriptase and RNAse
activity: p51 which has only reverse
transcriptase activity: p10 is a protease that
cleaves gag precursor and p32 is an integrase.

Genome of HIV (Structural genes)Genome of HIV (Structural genes)
3) env gene - determines the synthesis of
envelop glycoprotein gp 160 which is
cleaved into gp 120 and gp41 .
Glycosylation occurs after cleavage. The
antibodies to gp 120 are the first to appear
after HIV infection and are present in
circulation till the terminal stage of
infection.

b) Non structural and Regulatoryb) Non structural and Regulatory
genesgenes
1) vif - (Viral infectivity factor gene) influences
infectivity of viral particles.
2) vpr-stimulates promoter region of the virus
3) vpu (in HIV-1 ) and vpx (in HIV-2) enhance
maturation and release of progeny virus from
cells.
Detection of the type specific
sequences vpu and vpx is useful in
distinguishing between infection by HIV type 1
and 2.04/19/14 16Biochemistry for medics

genesgenes
4) tat –( trans activating gene) – (2 copies)
having stimulatory effect on synthesis of all
viral proteins .
5) rev - (Regulator of viral genes) –(2 copies )–
required for expression of structural genes.
6) nef ( negative factor gene) down regulates
viral replication. It may be responsible for the
regulation of latent state of virus.

genesgenes
7) LTR - (long terminal repeat) sequences
flanking on both sides giving promoter,
enhancer and integration signals.
Schematic representation of HIV genome

Antigenic variations in HIVAntigenic variations in HIV
• Based on molecular and antigenic differences, two
types of HIV have been recognized.
• The original isolates of HIV and the related strains
present all over the world belong to HIV type 1.
• The HIV strains, first isolated from West Africa,
which react with HIV type I antiserum very weakly
or not at all have been termed as HIV type 2.
• It has 40 % genetic similarity and is more closely
related to Simian immunodeficiency virus than to
HIV-1.
• It can cause AIDS but is less pathogenic and is less
common.

• HIV is a highly mutable virus and exhibits
frequent antigenic variations as well as differences
in other features such as nucleotide sequences,
cell tropism, growth characteristics and
cytopathology.
• Not only are there differences between isolates of
HIV from different races or persons but also
between sequential isolates from the same person,
and even between those obtained from different
sites of the same person at the same time.
• This great variability is believed to be due to error
prone nature of reverse transcription.

• HIV-1 strains have been classified in to at least ten
subtypes based on sequence analysis of
their gag and env genes.
• These subtypes have been designated as A to J and
constitute the Group M (For major), which cause
the large majority of HIV-1 infections worldwide.
• A few HIV-1 strains isolated from West Africa do not
fall within the major group and have been
designated as group O ( For Outlier).
• Some later isolates of HIV-1 distinct from M and O
groups have been called Group N (for new)

Mode of transmissionMode of transmission
• HIV is transmitted when the virus enters the
body, usually by injecting infected cells or
semen.
• There are several possible ways in which
the virus can enter.
• Sexual contact- In 75 % cases ,
transmission is by sexual contact.
o Most commonly, HIV infection is spread by
having sex with an infected partner.

o The virus can enter the body through the
lining of the vagina, vulva, penis, rectum, or
mouth during sex.
o People who already have a sexually
transmitted disease, such as syphilis,
genital herpes, chlamydial infection,
gonorrhea, or bacterial vaginitis, are
more likely to acquire HIV infection
during sex with an infected partner.

• Parenteral- In 15 % cases, it is by blood transfusion
or blood product transfusion.
o Sharing of unsterilized needles or syringes in drug
addicts contaminated with blood from an infected
person can spread virus.
o HIV can be spread in health-care settings
through accidental needle sticks or contact with
contaminated fluids.
o HIV can also spread through organ
transplantation.
o Donors are now tested for HIV to minimize this risk.

• From mother to child
o Women can transmit HIV to their babies
during pregnancy or birth, when infected
maternal cells enter the baby's circulation.
o 30% of children born to infected mothers
have the acquired infection unless virus is
treated by antiviral drugs before
pregnancy.
o In nursing mothers transmission can occur
through breast milk.

Mortality/Morbidity in HIV InfectionMortality/Morbidity in HIV Infection
• The course of HIV infection is
characterized primarily by latency.
• Profound immune suppression
eventually develops and the illness
appears to be almost uniformly lethal.
• Progression from HIV infection to AIDS
occurs 8-10 years after infection
without antiretroviral treatment.

Mortality/Morbidity in HIVMortality/Morbidity in HIV
InfectionInfection
• Since the introduction of highly active
antiretroviral therapy (HAART) and
prophylaxis against opportunistic
pathogens, death rates from AIDS have
declined significantly.
• An HIV-positive patient older than 50 years
with a nearly undetectable viral load and a
CD4 count more than 350 now has less than
a 5% chance of dying or progressing to full
blown AIDS within 3 years.04/19/14 Biochemistry for medics 28

Age for HIV InfectionAge for HIV Infection
• Most AIDS cases occur in adults aged 25-49
years (70% of cases).
• Adolescents and young adults (aged 13-24
y) represent 25% of new cases.
• Young children represent fewer than 1% of
AIDS cases in the United States.
• Internationally, children younger than 15
years are estimated to account for close to
10% of all HIV cases.

PathogenesisPathogenesis
• Infection is transmitted when virus enters
the blood or tissues of a person and comes
in to contact with a suitable host cell,
principally the CD4 lymphocytes.
• The virus may infect any cell bearing the
CD4 antigen on the surface.
• Primarily these are the CD4 + helper T
lymphocytes.

PathogenesisPathogenesis
• Some other immune cells possessing CD4
antigens are also susceptible to infection,
like B lymphocytes, monocytes and
macrophages including specialized
macrophages such as Alveolar macrophages
in the lungs and Langerhans cells in the
dermis.
• Glial cells and microglia cells are also
susceptible.

Steps of viral entry in to the host cellSteps of viral entry in to the host cell
• Attachment of virus into the host cell –
Specific binding of the virus to the CD4
receptors is by the envelop glycoprotein
gp120.
• Cell to cell fusion – For infection to take place
the cell fusion is essential.
o This is brought about by the transmembrane
glycoprotein gp 41. HIV-1 utilizes two major
co-receptors along with CD4 to bind to, fuse
with, and enter target cells; these co-receptors
are CCR5 and CXCR4, which are also receptors
for certain endogenous chemokines.

Steps of viral entry in to the hostSteps of viral entry in to the host
cellcell
o Strains of HIV that utilize
CCR5 as a co-receptor are
referred to as macrophage
tropic viruses (M –tropic
viruses)
o Strains of HIV that utilize
CXCR4 are referred to as T -
tropic viruses.
o Many virus strains are dual
tropic in that they utilize
both CCR5 and CXCR4.

• Uncoating of the viral envelope and
entry of nuclear capsid core into the cell
o After fusion of virus with the host cell
membrane, HIV genome is uncoated and
internalized in to cell.
o Viral RNA is released into the core
cytoplasm

• Viral transcription
o viral reverse transcriptase mediates
transcription of its RNA;
o RNA-DNA hybrid is formed.
o Original RNA strand is degraded by
ribonuclease H, followed by
o synthesis of second strand of DNA to yield
double strand HIV DNA

• Integration into the host DNA as provirus
o The double stranded DNA is integrated in to the genome
of the infected host cell through the action of the viral
integrase enzyme, causing a latent infection.
• Fate of provirus
o From time to time, lytic infection is initiated releasing
progeny virions, which infect other cells.
o The long and variable incubation period of HIV is
because of the latency.
o In an infected individual the virus can be isolated from
the blood, lymphocytes, cell free plasma, semen, cervical
secretions, saliva, urine and breast milk

Steps of viral entry in to the hostSteps of viral entry in to the host
cellcell

Steps of viral exit from host cellSteps of viral exit from host cell
• Transcription back into RNA
o The viral DNA is transcribed into RNA and
multiple copies of viral RNA are produced.
o There are only nine genes in HIV RNA, and
these code for the production of structural
proteins, accessory proteins, and enzymes
essential for the virus's replicative cycle.

Steps of viral exit from host cellSteps of viral exit from host cell
• Virion assembly - With the help of viral
protease, the new virions are assembled
into the polypeptide sequences needed for
HIV virion formation and infectivity.
• Cell lysis. The infected cell is made to burst
open, presumably by the action of cellular
proteins.

Causes of immune deficiencyCauses of immune deficiency
• The primary pathogenic mechanism in HIV infection is the
damage caused to the CD4+
T lymphocytes
o The T4 cells decrease in numbers and the T4:T8 cell ratio is
reversed.
o The infected cells do not release cytokines.
o This has a marked damping effect in the cell mediated immune
response.
o Though the major damage is to cellular immunity, the humoral
mechanisms are also affected. AIDS patients are unable to
respond to new antigens.
o There is polyclonal activation of B lymphocytes leading to
hypergammaglobulinemia.
o These are non specific antibodies and are irrelevant to antigens.

Causes of immune deficiencyCauses of immune deficiency
• Monocyte, macrophage system is also affected
apparently due to the lack of the activating
factors by the T4 lymphocytes.
• The activity of NK cells and Tc (T Cytotoxic)
cells are also affected.
• The clinical manifestations are due to failure of
the immune responses.
• This renders the patient susceptible to life
threatening opportunistic infections and
malignancies.

Immune deficiency in HIV InfectionImmune deficiency in HIV Infection

Clinical ManifestationsClinical Manifestations
• AIDS is only the last stage in the wide spectrum of
clinical features in HIV infection.
• The center for disease control (USA) has classified
the clinical course of HIV infection under various
groups.
• Acute HIV infection
• Asymptomatic or Latent infection
• Persistent generalized lymphadenopathy (PGL)
• AIDS related complex
• Full blown AIDS (Last stage)

1. Acute HIV infection1. Acute HIV infection
• A flu-like illness with fever, sore throat,
headache, tiredness, skin rashes and
enlarged lymph nodes in the neck within
several days to weeks after exposure to virus.
• These symptoms usually disappear of their
own within a few weeks.
• The test for HIV antibodies appears negative
while HIV antigenemia (p24 antigen) and viral
nucleic acids can be demonstrated at the
beginning of the phase.

1. Acute HIV infection1. Acute HIV infection
• This phase is also
called window
period or phase of
Sero conversion.
• Some patients do
not develop
symptoms after they
first get infected
with HIV.

2. Asymptomatic or2. Asymptomatic or  Latent infectionLatent infection
• All persons infected with HIV, pass through a phase
of symptomless infection (Clinical latency), which
may last up to several years.
• The progression of disease varies widely among
individuals.
• This state may last from a few months to more than
10 years.
• During this period, the virus continues to multiply
actively and infects and kills the cells of the immune
system.
• The virus destroys the CD4 cells that are the
primary infection fighters.

2. Asymptomatic or2. Asymptomatic or Latent infectionLatent infection
• The patients show positive antibody tests
during this phase.
• Even though the person has no symptoms, he
or she is contagious and can pass HIV to others.
• The median time between primary HIV
infection and development of AIDS has been
stated as approximately 10 years.
• About 5-10 % percent of the infected appear to
escape clinical AIDS for 15 years or more.
• They have been ‘long term survivors” or
“long term non progressors”.

33.. Persistent generalized lymphadenopathy Persistent generalized lymphadenopathy
(PGL)(PGL)
• This has been defined by presence of
enlarged lymph nodes, at least I cm in
diameter, in two or more non contiguous
extra inguinal sites, that persist for at least
three months, in the absence of any current
illness or medication that may cause
lymphadenopathy.
• These are diagnostic of HIV when blood
tests are positive for antibodies.

4. AIDS related complex4. AIDS related complex
• The patients present with weight loss – of
more than 10% of body weight, persistent
fever, diarrhea, generalized fatigue and
signs of other opportunistic infections may
be apparent.
• The opportunistic infections are oral
candidiasis, herpes zoster, salmonellosis or
Tuberculosis and hairy cell leucoplakia.

Opportunistic infections in AIDSOpportunistic infections in AIDS

4. AIDS related complex4. AIDS related complex
• The patients are usually severely ill and many
of them progress to AIDS in few months.
• The CD4 cell count decreases steadily when the
count falls to 200, or less, clinical AIDS usually
sets in.
• For this reason the case definition by CDC
includes all HIV infected cases with CD4 + T
cell counts of 200 or less, irrespective of
clinical condition.

5.5. Full blown AIDSFull blown AIDS
• This is the end stage disease representing the
irreversible break down of immune defense
mechanisms.
• In addition to the opportunistic infections the
patient may develop primary CNS lymphomas
and progressive multifocal
leukoencephalopathy, dementia and other
neurological abnormalities.
• Kaposi sarcoma and Pneumocystis pneumonia
are almost always observed in a majority of
patients.

Kaposi’s sarcomaKaposi’s sarcoma
• Kaposi’s sarcoma- is an indolent, multifocal
non metastasizing mucosal or cutaneous tumor
probably of endothelial origin, represented in
the form of purple spots in the skin.

Disease progression through different Disease progression through different
phases in HIV infected casesphases in HIV infected cases
CD4 count comes down while the viral count
goes high with the passage of time

Laboratory Diagnosis of HIV infectionLaboratory Diagnosis of HIV infection
1) Non Specific Tests- The following tests help to establish
the immunodeficiency in HIV infection.
a) Total Leukocyte and lymphocyte count- to
demonstrate leucopenia and lymphopenia. The
lymphocytic count is usually below 2000/mm3
b) T cell subset Assays- Absolute CD4+ cell count is less
than 200 /L.T4 T8 ratio is reversed.. The decrease in CD4
is the hall mark for AIDS.
c) Platelet count-
shows Thrombocytopenia.
d) IgA and Ig G levels are raised
e) Diminished cell mediated Immunity as indicated by
skin tests
f) Lymph node biopsy shows profound abnormalities.

2.Specific Tests for HIV infection- These
include demonstration of -
• HIV antigen,
• Antibodies,
• Viral nucleic acids or other components and
• Isolation of virus

i) Detection of antigen
o Following a contact, as by blood transfusion,
the viral antigen may be detectable in blood
after about 2 weeks.
o If the infecting dose is small, as following a
needle stick injury, the process may be
considerably delayed.
o The major core antigen p24 is the earliest
virus marker to appear in blood.

• i) Detection of antigen (contd.)
• Free p24 antigen disappears from circulation and
remains absent during the long asymptomatic phase
to reappear only when severe clinical disease sets
in.
• The p24 Capture ELISA assay, which uses anti p24
antibody as the solid phase can be used for this.
• This test is positive in about 30% of the infected
persons.
• In the first few weeks after infection and in the
terminal phase, the test is uniformly positive.

• Detection of antibodies
o It takes 2-8 weeks to months for the
antibodies to appear in circulation
o IgM antibodies appear first, to be followed
by IgG antibodies
o Once antibodies appear they increase in
titer for the next several months
o IgM antibodies disappear in 8-10weeks
while IgG antibodies remain through out.

• Detection of antibodies (contd.)
• There are two types of serological
tests- Screening tests and supplemental
tests.
i) Screening tests include-
o ELISA- ELISA is the most frequently used
method for screening of blood samples for
HIV antibody.

ELISA
1) First generation - whole viral lysates
2) Second generation - recombinant antigen
3) Third generation - synthetic peptide
4) Fourth generation - antigen + antibody
(Simultaneous detection of HIV antigen and
antibody) - HIV duo

Laboratory Diagnosis of HIV Laboratory Diagnosis of HIV
infectioninfection
Significance of ELISA
• Antibody can be detected in a majority of
individuals within 6-12 weeks after infection using
the earlier generation of assays.
• But it can be detected within 3-4 weeks when
using the newer third generation ELISA.
• Due to their ability to detect p24 antigen, the
fourth-generation ELISA can be of value in
detecting early infection.
• The window period can be shortened to two
weeks using p24-antigen assay.04/19/14 63Biochemistry for medics

infectioninfection
• p24 Capture ELISA assay with HIV ELISA
is currently used for screening blood
donors.

infectioninfection
ii) Supplemental Tests
a)Western Blot Test
b) Indirect Immunoflorescence test
c)Radio ImmunoPrecipitaion Assay
iii) Rapid Tests
a) Dot Blot assay
b) Particle Agglutination tests
c) HIV spot and comb test
d)Fluorimetric micro particle technologies04/19/14 65Biochemistry for medics

infectioninfection
Western blotting
• Western blots are regarded as the gold
standard and seropositivity is diagnosed
when antibodies against both the env and
the gag proteins are detected.
• The sensitivity of the test systems are
currently being improved by the use of
recombinant antigens.

Laboratory Diagnosis of HIVLaboratory Diagnosis of HIV
infectioninfection
3. Demonstration of viral Nucleic acid
• This can be accomplished by probes or by PCR techniques.
• The latter may be useful because of its extremely high
sensitivity.
• Cases of HIV are occasionally missed because individuals
can have negative antibody tests during the early stages of
infection.
• Also, a few people with long-term HIV infection may have
false negative antibody tests or may be chronic carriers
who are clinically asymptomatic.

infectioninfection
• PCR -In this the target HIV
RNA or proviral DNA is
amplified enzymatically in
vitro by chemical reaction.
• It is an extremely sensitive
assay because a single copy
of proviral DNA can be
amplified.
• Qualitative PCR is useful for
diagnostic purposes.

infectioninfection
• Three different
techniques namely RT-
PCR, nucleic acid
sequence based
amplification (NASBA)
and branched-DNA (b-
DNA) assay have been
employed to develop
commercial kits.

infectioninfection
4. Virus isolation
• virus isolation is accomplished by the co cultivation of the
patient's lymphocytes with fresh peripheral blood cells of
healthy donors or with suitable culture lines such as T-
lymphomas.
• The presence of the virus can be confirmed by reverse
transcriptase assays, serological tests, or by changes in
growth pattern of the indicator cells.
• Virus isolation is tedious and time-consuming (weeks) and
is successful in only 70 to 90% of cases.
• Therefore virus isolation is mainly used for the
characterization of the virus.

infectioninfection
5. Alternative to classical tests
a) Oral fluid (saliva) HIV tests
b) Urine tests

Treatment of HIV InfectionTreatment of HIV Infection
• All treatment for HIV infection and AIDS
today focuses on arresting the progression
of the disease within the body as measured
by T cell counts and tests for viral load.
• There are two principal approaches to
treatment: immunotherapy and anti-HIV
drug treatments

a)Immunotherapy
• Immunotherapy is transfusion based treatment designed
to replace lost immunoglobulins needed to fight HIV
infection (passive immunotherapy), to provide cellular
factors such as interleukins (IL-2) or to introduce selected
or altered immune cells to attack cells harboring the virus
(adoptive immunotherapy).
• The results of trials using this latter approach, however,
have been inconclusive, and no group has yet shown a
survival benefit.

b) Anti-HIV drug treatment
• Treatment with anti-HIV drugs attempts to
reduce viral load by blocking new infection
in the host cell.
• The drugs used target two major enzymes
of HIV which are needed for the infection
cycle: reverse transcriptase and protease.

I) Reverse transcriptase inhibitors
• Reverse transcriptase inhibitors act at the pre-integration
stage - before the viral RNA has been converted to DNA
and enters the host cell nucleus to integrate into the cell
chromosome.
• These drugs block the reverse transcription of viral RNA
into viral DNA.
• There are two types of reverse transcriptase inhibitors,
both of which accomplish the same objective: nucleoside
and nucleotide analogues, and non-nucleoside reverse
transcriptase inhibitors.

i) Nucleoside analogues
• Constitute the most effective family of
antiretroviral drugs
• Operate by mimicking nucleic acids normally
incorporated into viral DNA.
• They interfere with reverse transcriptase and thus
prevent infection.
• Nucleotide analogues have the same action but
are based around a different sugar.

ii) Non-nucleoside reverse transcriptase
inhibitors
• Directly inhibit reverse transcription and, unlike
nucleoside analogues,
• Do not have to go through chemical changes in the
infected cell before beginning their action.
• The two main non-nucleoside reverse
transcriptase inhibitors are Nivirapine, and
Delavirdine.

2) Protease inhibitors
• Protease inhibitors block HIV replication after
integration.
• These drugs inhibit the function of the protease
needed to process the ‘gag-pol’ polypeptide into
proteins.
• As a result, no infectious virus can be produced.
• Since protease inhibitors act after integration, they
can obstruct infectious HIV production in both acutely
and chronically infected T cells and macrophages.
• Saquinavir, Ritonavir, Indinavir, and Nelfinavir are the
licensed protease inhibitors used in the clinical
practice04/19/14 78Biochemistry for medics

3) Combination treatment
• Since reverse transcriptase inhibitors and protease
inhibitors address different stages of viral replication,
using both families of drugs in combination has been
shown to be more effective than monotherapy in impeding
the spread of HIV in the body and reducing viral loads.
• This combination of two reverse transcriptase inhibitors,
one of which is a thymidine analogue, and a protease
inhibitor, blocks infection both before and after integration
and in both activated and resting T cells.
• This combinational therapy is termed as highly active anti-
retroviral therapy (HAART).

4) The future
• In addition to the positive results shown by
combination therapy trials, a number of
developments may hold promise for the near
future.
• These include genetically engineered killer T cells
which attack HIV before it reproduces, and
research into genetically deactivating the CXCR4
and CCR5 T cell co-receptors, which are a path for
HIV entry into cells.

PreventionPrevention
• The risk of contracting HIV increases with the
number of sexual partners.
• A change in the lifestyle can reduce the risk.
• HIV-infected mothers are not recommended to
have children at present and pregnancy itself can
to be a risk factor for seropositive mothers.
• A recent clinical trial demonstrated the efficacy of
AZT in preventing transmission of HIV from the
mother to the fetus.

PreventionPrevention
• The spread of HIV through blood
transfusion had virtually been eliminated
since the introduction of blood donor
screening in many countries.
• Blood products such as factor VIII now
undergo routine treatment which appears
to inactivate any HIV present effectively.

Development of vaccineDevelopment of vaccine
Development of vaccine is fraught with several problems
unique to this virus. These include-
1) HIV can mutate rapidly, thus, it is not possible to design
antibodies against all antigens.
2) Antibody alone is not sufficient, cell mediated immunity
may also be necessary.
3) Virus enters the body not as free virions but also as
infected cells, in which the virus or the provirus is
protected against antibody or cell mediated lysis.
4) Virus readily establishes life long latent infection hiding
from antibodies.

Approaches to an AIDS vaccineApproaches to an AIDS vaccine
The main types of approaches to an AIDS vaccine are as
follows:
• Live attenuated virus
• Inactivated virus
• Live recombinant viruses
• Synthetic peptides
• Recombinant DNA products (gp120, gp160)
• Native envelope and/or core proteins
• Anti-idiotypes antibodies
• Passive immunization
• To-date, the best hope lies in an inactivated vaccine

Cause of death in HIV infectionCause of death in HIV infection
• Despite progress in dealing directly with HIV, however, the
virus, by impairing the immune system, exposes the
infected person to a range of opportunistic viral, bacterial,
and parasitic infections and malignancies.
• It is these which are the actual cause of death in most
patients with AIDS and, notwithstanding the success of
anti-HIV drug treatment in reducing viral load, it is still
unclear whether HIV induced damage to the immune
system can be reversed.
• New strains of HIV undetectable by current screening
methods and resistant to the best antiretroviral drugs
currently available have also now been discovered.

SummarySummary
• Acquired immunodeficiency syndrome, is a disease caused
by Human Immuno deficiency Virus and is characterized
by marked Immunosuppression.
• The mode of transmission is by sexual contact, blood
transfusions, needle prick injury or from mother to child.
• About 5-10 % percent of the infected appear to escape
clinical AIDS for 15 years or more. They have been ‘long
term survivors” or “ long term non progressors”.
• ELISA is the method most commonly employed for the
screening purpose and western Blotting is used for the
confirmation of the diagnosis.
• Treatment is imparted simply to check the progression of
the disease, there is no cure of AIDS and there is no vaccine
available for prophylaxis of this disease.04/19/14 87Biochemistry for medics

HIV infection (AIDS)

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