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

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.


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

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) 14

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 IDU Through blood transfusion nosocomial homosexual Sexual contact Male to female Female to male Mother to baby Infection rate 0.67% 90%-100% 0.3%-0.5% 5%-10% 0.1%-0.2% 0.03%-0.1% 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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( 1 2 3 4 5 6 7 8 9 10 HIV/AIDS COPD 12.67 9.91 7.08 4.78 4.75 4.21 3.95 2.98 2.20 2.13 7.089 5.544 3.963 2.673 2.660 2.356 2.213 1.669 1.230 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 reversetranscribed 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 individuals 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 (<0.5~1.5109/L) CD4/CD81.0 (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)

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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 HIVpositive 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 nonnucleoside 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 subacute 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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Kaposis 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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Kaposis 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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Kaposis 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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Kaposis 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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Kaposis Sarcoma (KS)

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Kaposis Sarcoma (KS)

Purplish

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Kaposis Sarcoma (KS)

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Patient of AIDS

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