Gu Junsheng

HIV infection

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

 Summaries:
 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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 Etiology

 HIV(human immunodeficiency virus):

HIV-1
HIV-2

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 Etiology

 HIV-1 is a retrovirus that probably

originated in Africa. The earliest evidence of
infection has been obtained from a blood
sample obtained in the Congo in 1959.
 In North America, the epidemic of
clinical disease caused by HIV-1 infection
was first recognized in New York City and
Los Angeles in the late 1970s.

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 Etiology

 HIV-1 has been detected almost all

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

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 Etiology

 HIV-2 is sufficiently different

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

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 Etiology

 HIV-1 and HIV-2 are retroviruses,

enveloped, containing positive-sense,
single-stranded RNA that is reverse
transcribed to DNA and integrated into
the host cell genome.
 HIV virions contain a number of viral
proteins. The most common one that is
directly assayed is the core antigen(p24).
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Etiology-Structure of HIV-1

Viral RNA

gp120

gp41
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 Epidemiology

 AIDS was first recognized in 1981,

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

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 Epidemiology

 Source of infection ：
 Patients and HIV carriers :
 Mainly in blood, sperm, secretion of vagina
 Also in saliva, tear, milk

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 Epidemiology

 Modes of transmission ：
 The primary modes of transmission:
 Sexual contact (70 ％ ~80 ％ of
HIV/AIDS)
 Exposure to blood, largely through
injecting drug use and transfusion
 Perinatal transmission from infected
mothers to their infants
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 Epidemiology

 Modes of transmission
 Sexual transmission:
 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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 Epidemiology
 Modes of transmission
 Sexual transmission:
 Heterosexual transmission is the major
mode of spread of HIV infection in Africa, most
of South America, and the
Caribbean(70 ％ ~80 ％ in the world)
 Male-to-male sexual transmission continues
to account for a major proportion in North
America and Europe (5 ％ ~10 ％ in the world)
(but the proportion of heterosexual transmission
is growing rapidly)
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 Epidemiology

 Modes of transmission ：
 Sexual transmission:
 Anal sex (infection rate is about 1%)
has been consistently found to be more
risky than vaginal sex (infection rate is
about 0.03%~0.15%).

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 Epidemiology

 Modes of transmission ：
 Exposure to blood:
 Largely through injecting drug use
and transfusion is another major mode of
spread of HIV infection.

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 Epidemiology
 Modes of transmission ：
 Exposure to blood:
 Needlestick injury: the risk of
transmitting hepatitis B from a patient who is
hepatitis B e antigen-positive by needlestick
is about 30%, the risk of transmitting hepatitis
C from a patient who has circulating hepatitis
C virus is about 3%; and the risk of
transmitting HIV from a patient with HIV
infection is about 0.3%
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 Epidemiology

 Modes of transmission ：
 Perinatal transmission from infected
mothers to their infants is the major mode
of spread of HIV infection in children.
 Gestation, during delivery, or
postpartum breast feeding

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Infection rate of different behaviour

Routes of transmission Infection rate

IDU 0.67%
Through
transfusion 90%-100%
blood
nosocomial 0.3%-0.5%
homosexual 5%-10%
Sexual
Male to female 0.1%-0.2%
contact
Female to male 0.03%-0.1%
Mother to baby 30%
 Epidemiology

 Susceptible groups:
 Everybody is susceptible to HIV
 Groups with high risks:
 Male homosexual
 Injecting drugs users
 Hemophilia patients etc.

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艾滋病流行已成为人类第四位死亡原因

死因顺位 疾病 占总死因百分比 死亡数 ( 百万 /

年)
1 缺血性心脏病 12.67 7.089
2 脑血管疾病 9.91 5.544
3 急性呼吸道感染 7.08 3.963

4 HIV/AIDS 4.78 2.673

5 COPD 4.75 2.660
6 腹泻病 4.21 2.356
7 围产期疾病 3.95 2.213
8 结核病 2.98 1.669
9 呼吸道肿瘤 2.20 1.230
10 交通事故 2.13 1.193
 Global Estimates of the HIV/AIDS
as of end 2002
 People newly infected in 2002: 5 Million
 AIDS deaths in 2002: 3 Million
 People with HIV/AIDS in 2002: 42 Million
 Total No. of AIDS deaths since the beginning
of the epidemic until the end of 2001:
22 Million
 Total No. of AIDS orphans since the beginning
of the epidemic until the end of 2001:
14 Million 22
 Epidemiology

 Every 5 seconds, a new HIV infection

occur in the world.
 World over at present, every 3 – 4
minutes, one person dies of HIV
 Every 14 seconds, AIDS create another
orphan.

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 The number of newly infected
with HIV during 2002

 Sub Saharan Africa 3.5 Million

 Asia and the Pacific 970,000
 Eastern Europe & Central Asia 250,000
 Latin America and the Carribean 210,000
 The Middle East and North Africa 83,000
 High-income countries 75,500

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 Pathogenesis

 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.

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 Pathogenesis

 HIV destroys
CD4+ ， CD8+ ， NK etc. and causes
damage of the CNS.

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

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 Pathogenesis

 Antibody responses to a number of

viral proteins can be detected, including
products of the viral genes env (gpl20,
gp41), gag (p24), and pol (p32) etc.

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 Pathogenesis

 Antibodies to HIV do not develop

until after the initial decline in HIV
viremia and can first be detected within
2 to 8 weeks after infection.

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Pathogenesis

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 Pathogenesis

 The major target of HIV infection is the

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

 During acute infection, p24 antigen is

also detectable in plasma.
 Antibodies to core and envelope
proteins can be demonstrated within 2 to 6
weeks after the onset of symptoms and
generally persist throughout the course of
infection.

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 Pathogenesis

 Neurotropic

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 Clinical manifestations of HIV infection

 The clinical features of HIV infection

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

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 Clinical manifestations of HIV infection

 The clinical spectrum of HIV infection

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

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 Natural history of HIV infection

Acute stage Asymptomatic stage PGL symptomatic stage

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 Clinical manifestations of HIV infection

 Primary infection (Acute infection):

 A 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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 Clinical manifestations of HIV infection

 Primary infection (Acute infection):

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

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 Clinical manifestations of HIV infection

 Asymptomatic infection:
 2 to 10 years asymptomatic stage

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 Clinical manifestations of HIV infection

 Persistent generalized lymphadenopathy:

 Lymphadenopathy, defined here as
enlargment of the lymph nodes in at least two
extrainguinal sites for a minimum of 3 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).
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 Clinical manifestations of HIV infection

 Persistent generalized lymphadenopathy:

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

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 Clinical manifestations of HIV infection

 Symptomatic infection:
 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 5
years and whose CD4 counts are
generally dropping toward 200/mm3 or
below.
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 Clinical manifestations of HIV infection

 Symptomatic infection:
 Nowadays, once the CD4 count
reaches 200/mm3, patients are classified
as having AIDS.

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 Clinical manifestations of HIV infection

 Symptomatic infection of HIV /

opportunistic infection:
 As 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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 Clinical manifestations of HIV infection

 Symptomatic infection of HIV /

opportunistic infection:
 Diseases suggestive of immune deficiency,
such as PCP, varicella zoster infection, chronic
herpes simplex lesions, cutaneous fungal
infections, and oral leukoplakia portend
progression to AIDS-defining infections.
 The risk of reactivating tuberculosis is
increased to >30%.
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 Clinical manifestations of HIV infection

 Symptomatic infection of HIV /

malignant tumor:
 The Centers for Disease Control and
Prevention has identified certain cancers as
AIDS-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).
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 Clinical manifestations of HIV infection

 Symptomatic infection of HIV /

malignant tumor:
 Many other kinds of cancer may be
more likely to develop in people with HIV
infection. Of course, people without HIV or
AIDS can also have these types of cancer.
 About four people out of 10 who have
AIDS will develop a cancer at some time
during their illness.
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 Laboratory tests
 Blood routine test:
WBC, PLT, RBC and Hb decrease at
different levels
 Detection of the pathogen:
Anti-HIV; p24; PCR for DNA; RT-PCR
for HIV RNA; HIV isolation from blood etc.
 Immunologic detection:
CD4+ T cells decreased (<0.5~1.5×109/L)
CD4/CD8≤1.0 (1.5~1.7:1)
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 Diagnosis

 Epidemiologic data: groups at risks

 Clinical manifestations:
Acute 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 AIDS is readily established.
 Laboratory tests: positive anti-HIV
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 Therapy

 Antiretroviral Agents Currently Available

(generic name/Trade name)
 Nucleoside Analogs:
 zidovudine/Retrovir (AZT, ZDV)
 didanosine/Videx, Videx EC (ddI)
 zalcitabine/HIVID (ddC)
 stavudine/Zerit (d4T)
 lamivudine/Epivir (3TC)
 abacavir/Ziagen (ABC) 51
 Therapy

 Non-Nucleoside Reverse Transcriptase

Inhibitors:
 nevirapine/Viramune (NVP)
 delavirdine/Rescriptor (DLV)
 efavirenz/Sustiva (EFV)

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 Therapy

 Protease Inhibitors:
 indinavir/Crixivan
 ritonavir/Norvir
 saquinavir/Invirase, Fortovase
 nelfinavir/Viracept
 amprenavir/Agenerase
 lopinavir/ritonavir, Kaletra

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 HAART:
Highly Active Anti-Retroviral Therapy

 HAART is the therapy, composed of

multiple anti-HIV drugs, that is prescribed to
many HIV-positive people, even before they
develop symptoms of AIDS. The therapy
usually includes one nucleoside analog (DNA
chain terminator), one protease inhibitor and
either a second nucleoside analog (“nuke”) or a
non-nucleoside reverse transcription inhibitor
(NNRTI).
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 Pneumocystis carinii Pneumonia (PCP)

 P. carinii was originally considered a

protozoan, but is now considered to be
more closely related to fungi.
 It is thought that infection is
transmitted from human to human or from
environmental reservoirs to humans.
 About 80% who have AIDS will
develop PCP at some time during their
illness.
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 Pneumocystis carinii Pneumonia (PCP)

 Typically, patient presents with cough

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

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 Pneumocystis carinii Pneumonia (PCP)

 Chest examination is mostly

normal. However, diffuse rales may
be encountered.

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 Pneumocystis carinii Pneumonia (PCP)

 The chest X-ray may provide a clue

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

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 Pneumocystis carinii Pneumonia (PCP)

 Except 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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 Pneumocystis carinii Pneumonia (PCP)

 Diagnosis of PCP relies on

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

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 Pneumocystis carinii Pneumonia (PCP)

 For initial treatment of PCP,

Trimethoprim-Sulphamethoxazole
(TMP-SMX) is the drug of choice. 2
tablets t.i.d for 3 weeks.

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 Pneumocystis carinii Pneumonia (PCP)

 After recovery from an initial

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

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 Kaposi’s Sarcoma (KS)

 A 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 1872.

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 Kaposi’s Sarcoma (KS)

 In most cases, KS causes

widespread lesions that erupt at many
places on the body soon after AIDS
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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 Kaposi’s Sarcoma (KS)

 Eventually, in almost all cases, KS

spreads throughout the body. Extensive
lung involvement by KS can be fatal.
More often, however, patients die of other
AIDS-related complications such as
infections.
 In contrast, classic KS usually
involves only one or a few areas of skin,
most often the lower legs.
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 Kaposi’s Sarcoma (KS)

 Treatment:
 Systemic chemotherapy with
vincristine, vinblastine, etoposide,
bleomycin, paclitaxel, liposomal
daunorubicin, or doxorubicin may be
helpful.
 Radiotherapy may provide palliation if
patients refuse or are intolerant of
chemotherapy.
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Kaposi’s Sarcoma (KS)

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Kaposi’s Sarcoma (KS)

Purplish 68
Kaposi’s Sarcoma (KS)

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Patient of AIDS

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BEST WISHES
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