Human Immunodeficiency Virus By Dr Mona Badr Assistant

Human Immunodeficiency Virus By: Dr. Mona Badr Assistant Professor & Consultant Virologist College of Medicine & KKUH

Human Immunodeficiency Virus Ø 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 HIV 2 § Spumavirinae Worldwide AIDS (Pandemic) West Africa AIDS No human infection

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

Structure of genetic Map of HIV

HIV replication cycle

Human Immunodeficiency Virus (Continued) Ø HIV is known to infect mainly T-helper cells and macrophages. Ø Destroying T-helper cells results and severe immunologic impairment, leading to multiple opportunistic infections, unusual cancers and death.

Human Immunodeficiency Virus Transmission: 1. Sexually: § By sexual contact especially homosexual § The virus is present in semen 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 (Continued) Transmission: 3. From mother to child § Infected mother transmit HIV to their babies in approximately 15 -30% of cases. Treatment of the mother with antiviral therapy can prevent this in most cases. § HIV is transmitted from mother to child , in utero, during delivery or perinatally via breast feeding.

Virus Inactivation Ø 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 Ø The course of HIV-infection can be divided into three stages: § The acute phase § The chronic phase § AIDS

The Course of HIV-infection 1. The acute phase Ø Incubation period 1 -4 weeks Ø Mostly asymptomatic, in 25 -50% of cases patients may have symptoms resembling infectious mononucleosis or influenza like illness for short period. § Characterized by the appearance of HIV-Ag in the blood (p 24 Ag core Ag) followed by: § Appearance of two antibodies, one directed to the envelope and the other to the core proteins

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 (p 24) from circulation and the presence of anti-envelope and anti-core. § CD 4 counts are generally within normal limits (usually above 350 x 106 cells/L) § At the end of this stage, two syndromes appear: § Persistent generalized lymphadenopathy (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 non-contagious extra-inguinal sites, persisting for at least 3 -months in the absence of any other illness or medication known to cause enlarge lymph node Blood markers: § HIV Ag p 24 (indicate active viral replication) § Anti-envelop +ve § Anti-core –ve § CD 4 count but still >200 x 106 cells/L

The Course of HIV-infection (Continued) B. AIDS-related complex (ARC): Ø Are indicative of a defect in cell-mediated immunity and often manifested as candidiasis(oral thrush) seborrhoeic dermatitis, and disseminated zoster (shingles). Ø. constitutional symptoms; § Fever, diarrhea persisting more than a month with weight loss greater than 10% (Slim disease), night sweat, fatigue and malaise § Neurological disease as myelopathies and peripheral neuropathy.

The Course of HIV-infection (Continued) Blood markers: § HIV Ag +ve( p 24 indicate active viral replication) § Anti-envelop +ve § Anti-core -ve § Decrease count of 200 x 106 cells/L CD 4 but still more than

The Course of HIV-infection (Continued) 3. AIDS Ø The end stage of the disease characterized by: § Marked decrease in CD 4 T-helper cells < 200 x 106 cells/L § Severe immunologic impairment, cell mediated immunity § Opportunistic infections e. g. pneumocystis § Unusual cancers (Kaposi’s carinii pneumonia, toxoplasmosis of brain, disseminated or extra pulmonary mycobaceriosis etc. sarcoma)

Blood markers § § § HIV Ag +ve( replication). p 24 . § Anti-envelop +ve. indicate active viral

Slim disease

Kaposi’s sarcoma

Pneumocystis pneumonia

Laboratory Diagnosis Screening Elisa HIV-antibody Confirming W. B. Riba HIV Ag p 24 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(twice) § 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 envelop Protein pol reverse transctpise HIV Ag p 24: § To confirm the presence of the major protein of the core. PCR: § For detection of HIV RNA in the blood by using reverse transcriptase.

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

Treatment (Continued) A. Reverse Transcriptase Inhibitors: § AZT Zidovudine § dd. C Zalcitabine § dd. I Didanosine § d 4 T Stavudine § 3 TC Lamivudine § 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 § Significant reduction in mother-to –child HIV transmition if ZIDOVUDINE is given during pregnancy OR NEVIRAPINE given as a single dose during delivary.