Human Immunodeficiency Virus (HIV) By: Dr.Mona Badr As sistant Professor & Consultant Virologist College of Medicine & KKUH

Human Immunodeficiency Virus  Retroviridae family is divided into three subfamilies:  Oncovirinae includes human T-lymphotropic virus types 1 & 2 (HTLV-1 Adult T-cell leukemia  (HTLV-2 No human infection)  Lentivirinae includes HIV 1 Worldwide AIDS (Pandemic) HIV2 West Africa AIDS  Spumavirinae No human infection

 HIV consists of an outer envelope covered with glycoprotein spikes.  An internal core genome consists of two identical ss-RNA genome of which enzyme reverse transcriptase is bound.  The viral genome has 3-structural genes termed 1.gag core protein, (p24) 2.Env (envelop glycoproteins),gp120,gp41. 3.Pol (Reverse Transcriptase,protease,integrase) Human Immunodeficiency Virus (Continued)

Structure of genetic Map of HIV

HIV replication cycle

 HIV is known to infect mainly T-helper cells(CD4), macrophages and monocytes that have(CD4)proteins on their surfaces.  Destroying T-helper cells(CD4)lead to severe immunologic impairment, leading to multiple opportunistic infections, unusual cancers and death. Human Immunodeficiency Virus (Continued)

Transmission: 1.Sexually:  By sexual contact with infected individual especially homosexual  The virus is present in semens and vaginal secretions 2.Parenterally:  Direct exposure to infected blood and blood products.  Use contaminated needles and syringes as in (drug abuser) and Tattooing.  Through contaminated surgical and dental instruments.  Sharing contaminated razors and tooth brushes,nail cutters. Human Immunodeficiency Virus

Transmission: 3.From mother to child  Infected mother transmit HIV to their babies transplacentally(25%),but Treatment of the mother with antiviral therapy(Zidovudine) during pregnancy can reduce transmission in most cases.  Virus spread to child perinatally mainly (50%)during delivery given (Nevirapine) as single dose during delivery can reduce the transmission. breast feeding also an important way of peri natal transmission (25%). Human Immunodeficiency Virus (Continued)

Virus Inactivation  HIV is easily inactivated by treatment for 10 min at 37 o C with any of the following  10% house hold bleach, Sodium Hypochlorite  50%ethanol  35%isopropanol  0.5%Paraformaldehyde  0.3%hydrogen peroxide

The Course of HIV-infection  The course of HIV-infection can be divided into three stages:  The acute phase  The chronic phase 1- A(PGL) 2-B(ARC)  AIDS

The Course of HIV-infection 1.The acute phase  Incubation period (1-4) weeks  Mostly asymptomatic, in 25-50% of cases patients may have symptoms resembling infectious mononucleosis or influenza like illness for short period& maculopapular rash.  Characterized by normal no of CD4 and the appearance of viral RNA in the blood (p24 ) core Ag followed by:  Appearance of two antibodies, one directed to the envelope(Anti-gp120) and the other to the core proteins(Anti-p24) start the chronic phase.

The Course of HIV-infection (Continued) 2.The chronic phase  This phase totally asymptomatic, which lasts for about 1-10 years in adults, 1-5 years in children.  Characterized by the disappearance of HIV-Ag (p24) from circulation and the presence of anti-envelope and anti- core.  CD4 counts are generally within normal limits (usually above 350 x10 6 cells/L)  At the end of this stage, two syndromes appear:  Persistent generalized lymph-adenopathy (PGL)  AIDS-related complex (ARC)

The Course of HIV-infection (Continued) A.Persistent Generalized Lymphadenopathy:  Is present in 25-30% of patient who are otherwise asymptomatic.  Enlarged lymph nodes ( at least 1 cm in diameter ), in two or more extra-inguinal sites, persisting for at least 3-months in the absence of any current illness or medication known to cause enlarge lymph node. Blood markers:  HIV Ag p24 (indicate active viral replication)  Anti-envelop (+ve ) Anti-gp120.  Anti-core( –ve )Anti-p24 disappear from circulation. CD4 count decrease but still more than 200 x10 6 cells/L

The Course of HIV-infection (Continued) B.AIDS-related complex (ARC):  Are indicative of a defect in cell-mediated immunity. Characterized by candidacies (oral thrush) symptoms and signs of AIDS, but lack the opportunistic infections as Pneumocytosis OR tumors as Kaposi sarcoma.  ARC Characterized by:  Fever, diarrhea persisting more than a month with weight loss greater than 10% (Slim disease), night sweat, fatigue and malaise  Neurological disease as myelopathy and peripheral neuropathy.

The Course of HIV-infection (Continued) Blood markers:  HIV Ag +ve p24 (indicate active viral replication)  Anti-envelop +ve(Anti-gp120)  Anti-core -ve (Anti-p24)  CD4 count decreased but still more than 200 x10 6 cells/L

The Course of HIV-infection (Continued) 3.AIDS  The end stage of the disease characterized by:  Marked decrease in CD4 T-helper cells < 200 x 10 6 cells/L  Severe immunologic impairment, cell mediated immunity  Opportunistic infections e.g. pneumocystis carinii pneumonia, toxoplasmosis of brain, disseminated or extra pulmonary myco-baceriosis etc.  Unusual cancers ( Kaposi’s sarcoma) Blood markers:  HIV Ag p24  Anti envelop +ve(Anti-gp120), Anti-core –ve (Anti-p24) Marked CD4 count less than 200 x10 6 cells/L

Slim disease

Kaposi’s sarcoma

Kaposi’s sarcoma & Slim disease

Kaposi’s sarcoma

Pneumocystis pneumonia

Laboratory Diagnosis Screening Elisa HIV-antibody Confirming W.B. Riba HIV Ag p24 PCR

Laboratory Diagnosis  By detection of both HIV-Ab and HIV-Ag, using EISA (screening test).  If results are negative, report negative.  If results are positive, repeat the screening test in duplicate  Repeatedly reactive specimens, must be confirmed by Western blot and HIV-Ag test by Eliza.  If the confirmatory results are negative, report negative  If the confirmatory test results are positive, report positive

Laboratory Diagnosis (Continued) Western Blot:  To confirm the presence of Anti –HIV to the structural proteins of the virus gag core protein byelectrophoresis env envelop protein pol reverse transcreptase HIV Ag p24: ( ELIZA)  To confirm the presence of the major protein of the core. PCR:  For detection of HIV RNA in the blood plasma (viral load) this test is important for HIV diagnosis in infant of infected mother and also to monitor the antiviral treatment

LABORATORY DIAGNOSIS Indeterminate results:  Western blot indeterminate result, means that the test specimen not positive nor negative.  The individual must be retested after 8-12 weeks.  If the result is negative, report negative  If the result is positive, report positive  If the individual still indeterminate then he or she must be referred to medical evaluation  The aim of medical evaluation is to look for signs and symptoms suggesting HIV-infection.  Or PCR to look for HIV-RNA genome.

Treatment  Treatment does not eradicate the virus, but suppress the HIV replication.  Treatment, should continue for all life  The aim of treatment is to maintain the immune system of the patient near normal as possible  At the present time the combined therapy is used two reverse transcriptase inhibitors pulse one protease inhibitor

Treatment (Continued) A.Reverse Transcriptase Inhibitors:  AZTZidovudine  ddCZalcitabine  ddIDidanosine  d4TStavudine  3TCLamivudine  All the above anti-viral drugs are nucleoside analogues. B.Protease inhibitors  Saquinavir  Indiniavir  Ritonavir  Nelfinavir

Treatment (Continued) Prevention & Control:  There is no vaccine available yet for HIV  Practice safer sex by having one sexual partner  Do not share razors, tooth brushes, etc  Do not share needles and syringes  Avoid direct exposure to body fluids  Educate the public about HIV-infection.

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