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HIV infection

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r Ãcquired Immune Deficiency Syndrome
r HIV: human immunodeficiency virus
r Lymphocyte and neurons mainly affected
r Mainly transmitted through sexuality/blood
r Pathogenesis: CD4+ T cells are severely
destroyed, immunodeficiency comes and then
opportunistic infections and malignant tumors
2
 HIV infection

rSummaries:
r Clinical features: The syndrome is
defined by the development of serious
opportunistic infections, neoplasms, or
other life-threatening manifestations
resulting from progressive HIV-induced
immunosuppression.

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 ¦  

rHIV(human immunodeficiency virus):

HIV-1
HIV-2

4
 ¦  

r HIV-1 is a retrovirus that probably

originated in Ãfrica. The earliest evidence of
infection has been obtained from a blood
sample obtained in the Congo in 19÷9.
r In North Ãmerica, the epidemic of
clinical disease caused by HIV-1 infection
was first recognized in New York City and
Los Ãngeles in the late 1970s.

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 ¦  

r HIV-1 has been detected almost all

parts of the world.
r There are many variants of clades of
HIV-1 worldwide.

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 ¦  

r HIV-2 is sufficiently different

genetically from HIV-1 to be classified
as a separate virus. It is found almost
exclusively in Western Ãfrica.
r The biologic behavior of HIV-2 in
terms of transmission and clinical
manifestations is similar to that of HIV-1

7
 ¦  

r HIV-1 and HIV-2 are retroviruses,

enveloped, containing positive-sense,
single-stranded RNÃ that is reverse
transcribed to DNÃ and integrated into
the host cell genome.
r HIV virions contain a number of viral
proteins. The most common one that is
directly assayed is the core antigen(p24).

¦  -Structure of HIV-1

Viral RNÃ

gp120

gp41 9
 ¦
 

r ÃIDS was first recognized in 191,

when unusual clusters of Pneumocystis
carinii pneumonia and Kaposi's sarcoma
were reported in young, previously
healthy homosexual men in New York
City, Los Ãngeles, and San Francisco.

10
 ¦
 

rSource of infection¬
r Patients and HIV carriers :
r Mainly in blood, sperm, secretion of vagina
r Ãlso in saliva, tear, milk

11
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r Sexual contact (70 D ~0 D of
HIV/ÃIDS)
r ¦xposure to blood, largely through
injecting drug use and transfusion
r Perinatal transmission from infected
mothers to their infants
12
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r Sexual contact is the predominant mode
of HIV transmission throughout the world.
However, the geographic distribution of
cases attributable to homosexual and
heterosexual transmission varies markedly.

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r Heterosexual transmission is the major
mode of spread of HIV infection in Ãfrica, most
of South Ãmerica, and the Caribbean(70D~0
D in the world)
r Male-to-male sexual transmission
continues to account for a major proportion in
North Ãmerica and ¦urope (÷D~10D in the
world) (but the proportion of heterosexual
transmission is growing rapidly) 14
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r Ãnal sex (infection rate is about 1%)
has been consistently found to be more
risky than vaginal sex (infection rate is
about 0.0[%~0.1÷%).

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r ¦xposure to blood:
r Largely through injecting drug use
and transfusion is another major mode of
spread of HIV infection.

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r   

 the risk of
transmitting hepatitis B from a patient who is
hepatitis B e antigen-positive by needlestick
is about [0%, the risk of transmitting hepatitis
C from a patient who has circulating hepatitis
C virus is about [%; and the risk of
transmitting HIV from a patient with HIV
infection is about 0.[%
17
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 from
infected mothers to their infants is the
major mode of spread of HIV infection in
children.
r c , during delivery, or
postpartum 
 


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Infection rate of different behaviour

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r ¦verybody is susceptible to HIV
rGroups with high risks:
r Male homosexual
r Injecting drugs users
r Hemophilia patients etc.

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r People newly infected in 2002: ÷ Million
r ÃIDS deaths in 2002: [ Million
r People with HIV/ÃIDS in 2002: 42 Million
r Total No. of ÃIDS deaths since the beginning
of the epidemic until the end of 2001:
22 Million
r Total No. of ÃIDS orphans since the beginning
of the epidemic until the end of 2001:
14 Million 22
 ¦
 

r ¦very ÷ seconds, a new HIV infection

occur in the world.
r World over at present, every [ ± 4
minutes, one person dies of HIV
r ¦very 14 seconds, ÃIDS create another
orphan.

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rSub Saharan Ãfrica [.÷ Million

rÃsia and the Pacific 970,000
r¦astern ¦urope & Central Ãsia 2÷0,000
rLatin Ãmerica and the Carribean 210,000
rThe Middle ¦ast and North Ãfrica [,000
rHigh-income countries 7÷,÷00

24
  

r HIV subverts the immune system

by infecting CD4+ T cells(T-cell
lymphotropic) that normally orchestrate
immune responses and by activating the
immune system and inducing a cytokine
`milieu that the virus uses to its own
`replicative advantage.

2÷
  

r HIV destroys CD4+¼CD+¼NK

etc. and causes damage of the CNS.

2½
  

r Viremia and p24 levels decrease in

association with the emergence of host
immune responses, although viral RNÃ
remains detectable by RT-PCR in the majority
of patients.
r During the asymptomatic period of HIV
infection, p24 antigen is generally undetectable
and plasma cultures are usually negative.
r P24 and viremia again rise to detectable
levels with the onset of clinical ÃIDS.
27
 

2
  

r Ãntibody responses to a number of

viral proteins can be detected, including
products of the viral genes env (gpl20,
gp41), gag (p24), and pol (p[2) etc.

29
  

r Ãntibodies to HIV do not develop

until after the initial decline in HIV
viremia and can first be detected within
2 to  weeks after infection.

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r The major target of HIV infection is the

CD4+ T cell, although HIV can also infect
other cell types such as macrophages.
r Ãfter fusion of the virion with the cell
membrane, uncoating and reverse transcription
of the viral RNÃ `genome occur. The reverse-
transcribed double-stranded DNÃ genome is
then transported to the nucleus, where it is
integrated into the host cell genome.
[2
  

r During acute infection, p24 antigen is

also detectable in plasma.
r Ãntibodies to core and envelope proteins
can be demonstrated within 2 to ½ weeks
after the onset of symptoms and generally
persist throughout the course of infection.

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r Neurotropic

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r The clinical features of HIV infection

may vary according to the individual¶s
age, sex, race, geographic location,
treatment status, and behavioral history.
r Onset of ÃIDS may be gradual or
abrupt.

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r a
 






 
includes:
r Primary(acute) infection (days to weeks)
r Ãsymptomatic infection (years)
r Persistent generalized lymphadenopathy
(months)
r Symptomatic infection (months)

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Ãcute stage Ãsymptomatic stage PGL symptomatic stage

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r 


 
 
  
r à majority of patients infected with
HIV develop an acute mononucleosis-like
illness characterized by fever, headache,
lymphodenopathy, pharyngitis, macular
rash, and malaise within one to several
weeks of exposure.

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r 


 
 
  
r Ãseptic meningitis, hepatosplenomegaly,
extreme fatigue, weakness, arthralgias, and
myalgias are also frequently associated
with this syndrome.
r Syndrome usually resolve within 2 to 4
weeks.

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r 
 
 
r 2 to 10 years asymptomatic stage

40
  
  



 

r 
 



 

r Lymphadenopathy, defined here as
enlargment of the lymph nodes in at least two
extrainguinal sites for a minimum of [ months
in the absence of any illness or drug known to
cause lymphadenopathy, is usually present and
results from the massive viral replication and
immunologic response (lymphocyte
recruitment and proliferation).
41
  
  



 

r 
 



 

r Biopsy reveals reactive hyperplasia and
expansion of germinal centers.
r The presence of persistent lymphadenopathy
does not influence prognosis; however, a
decrease in the size of the involved nodes
correlates with the onset of ÃIDS and portends a
poor prognosis.

42
  
  



 

r P
 
 
r Nonspecific complaints of fever,
weight loss, diarrhea, and malaise;
lymphadenopathy; and oral thrush are
frequently noted in patients who have
been infected with HIV for more than ÷
years and whose CD4 counts are
generally dropping toward 200/mm[ or
below.
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r Nowadays, once the CD4 count
reaches 200/mm[, patients are classified
as having ÃIDS.

44
  
  



 

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r Ãs the HIV patient becomes
immunodeficient, the infections tend to
be severe, widespread, chronic, indolent,
recurrent, atypical and difficult to treat
and eradicate.

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r Diseases suggestive of immune deficiency,
such as PCP, varicella zoster infection, chronic
herpes simplex lesions, cutaneous fungal
infections, and oral leukoplakia portend
progression to ÃIDS-defining infections.
r The risk of reactivating tuberculosis is
increased to >[0%.
4½
  
  



 

r P
 
 


×

  


r The Centers for Disease Control and
Prevention has identified certain cancers as
ÃIDS-defining diseases: Kaposi's sarcoma,
(primary encephalopathy ), lymphoma
(especially non-Hodgkin's lymphoma and
primary central nervous system lymphoma,
anal cancer and cancer of the cervix that has
spread to neighboring tissue).
47
  
  



 

r P
 
 


×

  


r Many other kinds of cancer may be
more likely to develop in people with HIV
infection. Of course, people without HIV or
ÃIDS can also have these types of cancer.
r Ãbout four people out of 10 who have
ÃIDS will develop a cancer at some time
during their illness.
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WBC, PLT, RBC and Hb decrease at
different levels
r     

Ãnti-HIV; p24; PCR for DNÃ; RT-PCR
for HIV RNÃ; HIV isolation from blood etc.
r      
CD4+ T cells decreased (<0.÷~1.÷109/L)
CD4/CD 1.0 (1.÷~1.7:1)
49
  

r ¦pidemiologic data: groups at risks

r Clinical manifestations:
Ãcute HIV infection should be suspected
in any person at risk who has an unexplained
febrile viral-like illness. When the patient has
obvious manifestations such as Kaposi's
sarcoma or P. carinii pneumonia, the
diagnosis of ÃIDS is readily established.
r Laboratory tests: positive anti-HIV
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r zidovudine/-etrovir (Ã
T,
DV)
r didanosine/ëidex, ëidex EC (ddI)
r zalcitabine/6 ë
(ddC)
r stavudine/]erit (d4T)
r lamivudine/Epivir ([TC)
r abacavir/]iagen (ÃBC) ÷1
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r nevirapine/ëiramune (NVP)
r delavirdine/-escriptor (DLV)
r efavirenz× ustiva (¦FV)

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r indinavir/Crixivan
r ritonavir/Gorvir
r saquinavir/ nvirase, Fortovase
r nelfinavir/ëiracept
r amprenavir/Ãgenerase
r lopinavir/ritonavir, [aletra

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r HÃÃRT is the therapy, composed of multiple

anti-HIV drugs, that is prescribed to many HIV-
positive people, even before they develop
symptoms of ÃIDS. The therapy usually
includes one nucleoside analog (DNÃ chain
terminator), one protease inhibitor and either a
second nucleoside analog (³nuke´) or a non-
nucleoside reverse transcription inhibitor
(NNRTI).
÷4
   


 


r P. carinii was originally considered a

protozoan, but is now considered to be
more closely related to fungi.
r It is thought that infection is
transmitted from human to human or from
environmental reservoirs to humans.
r Ãbout 0% who have ÃIDS will
develop PCP at some time during their
illness.
÷÷
   


 


r Typically, patient presents with cough

with or without scanty expectoration(most
often PCP is associated with dry cough),
breathlessness, chest pain and fever.
r Usually the tempo of development
and progression of these symptoms is sub-
acute spanning over a month or more.

÷½
   


 


r Chest examination is mostly

normal. However, diffuse rales may
be encountered.

÷7
   


 


r The chest X-ray may provide a clue

to the diagnosis of PCP. Classically,
PCP presents with diffuse bilateral,
symmetrical reticular or granular
opacities.

÷
   


 


r ¦xcept pleural effusions and

intrathoracic adenopathy, all
radiographic patterns of lung
involvement have been described with
PCP, including focal infiltrates,
lobar/segmental consolidation, nodular
shadows and cavitation.

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r Diagnosis of PCP relies on

demonstrating the organism in sputum
or bronchoalveolar lavage (BÃL)
specimens.

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r For initial treatment of PCP,

Trimethoprim-Sulphamethoxazole
(TMP-SMX) is the drug of choice. 2
tablets t.i.d for [ weeks.

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r Ãfter recovery from an initial

episode of PCP, life long secondary
prophylaxis with TMP-SMX is
indicated.

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r à sarcoma is a cancer that develops

in connective tissues such as cartilage,
bone, fat, muscle, blood vessels, or
fibrous tissues (related to tendons or
ligaments). Kaposi's sarcoma (KS) was
named for Dr. Moritz Kaposi who first
described it in 172.

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r In most cases, KS causes

widespread lesions that erupt at many
places on the body soon after ÃIDS
develops. Lesions may arise on the skin
and the mouth and may affect the
lymph nodes and other organs, usually
the gastrointestinal tract, lung, liver, and
spleen.
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r ¦ventually, in almost all cases, KS

spreads throughout the body. ¦xtensive
lung involvement by KS can be fatal.
More often, however, patients die of other
ÃIDS-related complications such as
infections.
r In contrast, classic KS usually
involves only one or a few areas of skin,
most often the lower legs.
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rTreatment:
r Systemic chemotherapy with
vincristine, vinblastine, etoposide,
bleomycin, paclitaxel, liposomal
daunorubicin, or doxorubicin may be
helpful.
r Radiotherapy may provide palliation if
patients refuse or are intolerant of
chemotherapy.
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