HIV and AIDS Fahad Almajid MD KKUH 1437
- Slides: 63
HIV and AIDS Fahad Almajid. MD KKUH. 1437
HIV and AIDS Definition: HIV Infection with Human immundefeciency Virus which leads to : Chronic and without treatment usually fatal infection characterized by : A} Progressive immundeficiency B} Long latency period C} Opportunistic infection
HIV: It is an RNA Lentivirus belong to retrovirus family. It is called “ Retrovirus “ : Retrovirus: Information in the form of RNA is transcribed into DNA in the host cell. It tis most likely originated from simian immunodeficiency virus.
There are two viruses HIV 1 and HIV 2. HIV 1 : Predominate world wide HIV 2 : Closely resmeble HIV-1 BUT is a much slower progression to AIDS. It Predominate in western africa. It causes diseases by disrupting the immune system function as measured by CD 4 cell depletion called : AIDS Acquired Immune Deficiency Syndrome.
The hallmark of HIV Disease: Infection and viral replication within T-lymphocyte expressing the CD 4 antigen resulting in : Qualitative defect in CD 4 responsiveness Progressive depletion in CD 4 cell counts : AND This effect on CD 4 (helper-inducer lymphocyte) will increase the risk of: 1) Opportunistic infections such as Pneumocystis Jiroveci 2) Neoplasm such as Lymphoma and Kaposi sarcoma
History 1 st recogonised in USA 1981 CDC reported the occurance of : 1) Unexplained occurance of pneumocyctis pneumonia in 5 healthy homosexual in LA 2) Kaposi saarcoma in 25 healthy homosexual men in NY and LA. . . later on ; 3) The disease became recogonised in both male and female with (IUDs) as well as 4) Recipients of blood transfusion and haemophilics
HISTORY 1983 : HIV was isolated from patient with lymphadenopathy 1984 : HIV was demonstradted to be the causative agent of AIDS 1985 : ELISA test was developed
epidemiology HIV infection/AIDS is a global pandemic Cases reported everywhere. Ranging 30— 36 million. More than 95% reside in low and middle –income countries 50% are females 2. 5 million are children (less than 13 ) Epidemic was first recognised in USA and shortly thereafter in western Europe. More than 2/3 rd of all people with HIV live in subsaharan africa
Global situation and trends Since the beginning of the epidemic: Almost 78 million people have been infected with the HIV virus. and about 39 million people have died of HIV. Globally, 35. 0 million [33. 2– 37. 2 million] people were living with HIV at the end of 2013. .
An estimated 0. 8% of adults aged 15– 49 years worldwide are living with HIV. The burden of the epidemic continues to vary considerably between countries and regions. Sub-Saharan Africa remains most severely affected, with nearly 1 in every 20 adults living with HIV and accounting for nearly 70% of the people living with HIV worldwide.
Asia 4. 9 million people living with HIV National HIV prevalence is highest in Southeast Asia 4. 0 million HIV prevalence is decreasing in Myanamar, Combodia and Thailand , but Increasing in Indonesia and Vietnam. Epidemic is expanding in Eastern Europe and central asia : 1. 6 million
South East Asia
Adults and children estimated to be living with HIV, by WHO Region, 2010 Europe 2. 3 million Americas 3. 0 million [2. 6 million – 3. 5 million] South-East Asia [2. 1 million – 2. 5 3. 5 million] [3. 0 million – 3. 9 million] Eastern Mediterranean 560 000 [410 000 – 790 000] Africa Western Pacific [21. 7 million – 24. 2 million] [1. 1 million – 1. 5 million] 22. 9 million Total: 34. 0 million 1. 3 million
Estimated adult and child deaths from AIDS, by WHO Region, 2010 Europe 99 000 Americas 96 000 [71 000 – 120 000] South-East Asia 230 000 [84 000 – 120 000] [190 000 – 260 000] Eastern Mediterranean 38 000 [27 000 – 53 000] Africa Western Pacific [1. 1 million – 1. 4 million] [64 000 – 99 000] 1. 2 million 80 000 Total: 1. 8 million [1. 6 million – 1. 9 million]
Regional HIV and AIDS statistics and features 2010 22. 9 million Adults and children newly infected with HIV 1. 9 million [21. 6 million – 24. 1 million] [1. 7 million – 2. 1 million] Adults and children living with HIV Sub-Saharan Africa Middle East and North Africa South and South-East Asia Latin America Caribbean Eastern Europe and Central Asia Western and Central Europe North America Oceania TOTAL 5. 0% Adult & child deaths due to AIDS 1. 2 million [4. 7% – 5. 2%] [1. 1 million – 1. 4 million] Adult prevalence (15‒ 49) [%] 470 000 59 000 0. 2% 35 000 [350 000 – 570 000] [40 000 – 73 000] [0. 2% – 0. 3%] [25 000 – 42 000] 4. 0 million 270 000 0. 3% 250 000 [3. 6 million – 4. 5 million] [230 000 – 340 000] [0. 3% – 0. 3%] [210 000 – 280 000] 790 000 88 000 0. 1% 56 000 [580 000 – 1. 1 million] [48 000 – 160 000] [0. 1% – 0. 1%] [40 000 – 76 000] 1. 5 million 100 0. 4% 67 000 [1. 2 million – 1. 7 million] [73 000 – 140 000] [0. 3% – 0. 5%] [45 000 – 92 000] 200 000 12 000 0. 9% 9000 [170 000 – 220 000] [9400 – 17 000] [0. 8% – 1. 0%] [6900 – 12 000] 1. 5 million 160 000 0. 9% 90 000 [1. 3 million – 1. 7 million] [110 000 – 200 000] [0. 8% – 1. 1%] [74 000 – 110 000] 840 000 30 000 0. 2% 9900 [770 000 – 930 000] [22 000 – 39 000] [0. 2% – 0. 2%] [8900 – 11 000] 1. 3 million 58 000 0. 6% 20 000 [1. 0 million – 1. 9 million] [24 000 – 130 000] [0. 5% – 0. 9%] [16 000 – 27 000] 54 000 3300 0. 3% 1600 [48 000 – 62 000] [2400 – 4200] [0. 2% – 0. 3%] [1200 – 2000] 34. 0 million 2. 7 million 0. 8% 1. 8 million [31. 6 million – 35. 2 million] [2. 4 million – 2. 9 million] [0. 8% - 0. 8%] [1. 6 million – 1. 9 million] The ranges around the estimates in this table define the boundaries within which the actual numbers lie, based on the best available information.
• HIV is a fragile virus. It cannot live for very long outside the body • HIV is primerly found in high contity in the blood, semen, or vaginal fluid of an infected person , so it is transmitted through : 12/06 e AIDS Epidemic Update December 2006
HIV and AIDS Transmission Sexual (heterosexual , msm , others) Heterosexual is the most common mode of transmission worldwide. Vertical transmission from pregnant woman to the newborn (MTCT) is the main mode of infection in children. Blood and body fluid. Blood transfusion , occupational exposure IVDU. No evidence of spread by : casual contact or by insects such as by mosquito
Structure of the virus It is an RNA virus It is an icosahedral ﻣﺘﻌﺪﺩ ﺍﻟﺴﻄﻮﺡ structure of : 1) Lipid Envelope (env) derived from infected cell, containing numerous external spikes formed by two major envelope protiens : a) The external gp 120 b) The transmembrane gp 41 2) Nucleocapsid (gag) with P 24 major core protien. The core contains two single strands of RNA. 3) Polymearse (pol)
HIV life cycle & replication 1) Attachment of Viral gp 120 protein to CD 4 receptor containing cells T cell, maccrrophages, and microglial cells : CD 4 ---pg 120 then gp 120 and gp 41 bind to the chemokines : CCXR 5 and CXCR 4 2) Fusion between cell membrane and the virion.
2) Penetration 3) Upcoating 4) Reverse transcription Formation of c. DNA 4) Integration 5) Transcription of proviral DNA A) formation of genomic RNA b) formation of structual m. RNA
HIV life cycle & replication 6) Translation of structural m RNA a) Formation of viral structural protien b) Packaging of genomic RNA of strucrural protien 7) Final assembly a) insertion of viral specific glycoprotien into plasma membran b) Budding c) Release of mature virions 8) Final maturation BY cleavage of gag and pol by polymerase enzyme
HIV life cycle & replication
HIV life cycle
Pathogenesis HIV infection
pathophysiology Early stage: Massive replication of the virus in the lymphatic tissues . subsequently Chronic immune system activation determine the course of the illness. Permanent viral reservoirs containing proviral DNA are established in the latent T cell or macrophages.
DIAGNOSIS 1984. . Rapid develpment of screening test 1985. . blood donors were routinaly screened for antibody 1996 : blood banks added th 2 p 24 antigen capture assay to detect early cases.
HIV and AIDS Diagnosis: ELISA: is the screening test , used to screen products and patients. blood Combo test : will detect HIV 1 and HIV 2 and P 24 antigen. Sensitivity of more than 99. 5% The fourth generation test: : Combined synthetic HIV peptide detect both HIV and Monoclonal antibody to detect HIV p 24 antigen. Extremely sensitive but specificity is not optimal. . low risk. . only 10% who are positive by this test turned to be real positive,
Diagnosis Confirmation : The INNO-LIA™ HIV I/II Score is a Line Immuno Assay (LIA®), to confirm : The presence of antibodies against the human immunodeficiency virus type (HIV-1) and (HIV-2) in human serum or plasma. Also differentiates between HIV-1 and HIV-2 infections. Sensitivity 100% … specificity : 96%
Diagnosis Western blot test: It might miss the cases in EARLY stage especially since this is the most contagious period in all of HIV infection. Thers is a problem with the indeterminate cases. ( Window period).
Diagnosis PCR: (polymerase chain reaction) for quantitative RNA assay and used as : 1) Confirmatory test for undetermined cases. 2) To asses the viral load. 3) Babies born to HIV-positive mothers, because their blood contains their mother's HIV antibodies for several months. 4) Blood supplies Not for routine testing: a) Decreased sensitivity and specificity at lower viral load b) Significant cost.
Algorithm testing for HIV
HIV Progression
WHO staging Primary HIV infection Asymptomatic Acute retroviral syndrome Clinical stage 1 Asymptomatic Persistent generalized lymphadenopathy
HIV and AIDS Immunological staging: CD 4 positive T lymphocytes level is the main method of assessing the immune status of the HIV positive patient. 1. >500 cells/mm³ normal immunity. 2. 350 -500 cells/mm³ mild deficiency. 3. 200 -350 cells/mm³ moderate immune deficiency. 4. <200 cells/mm³ sever immune deficiency
Clinical presentation Acute HIV infection: From exposure to symptoms: 2 -4 wks. It resmble infectious mononucleosis with : Fever Pharyngitis Adenopathy Rash myalgia, fatigue, oral ulcer GIT symptoms: diarrhoea, anorexia.
Result: 1) Massive response with evolution of HIV-specific immunity (CD 8 -cytotoxic T lymphocyte. ) 2 )HIV RNA level falls and the symptoms resolve. CD 4 cell count rebounds but remains below the basline.
Chronic HIV infection Asymptomatic chronic phase: Active viral replication is ongoing and progressive. Patient with high HIV RNA may progress to symptomatic disease than those with low HIV RNA level. Chronic immune activation lead to increase in various inflammatory markers. This increase the risk of Non-AIDS related comorbidities: Cardiovascular and Renal dysfunction
Clinical manifestation Physical examination: Skin: condition associated with HIV seborrheic dermatitis, Oropharynx: 1) oral trush 2) hairy leukoplakia 3) mucosal kaposi sarcoma Lymph node: Generalized lympadenopathy (TB , Lymphoma). Eyes: Fundoscopy : CMV retinitis. ( CD 4 less than 50 ). Genital exam: ulcers, condylomatous lesions , women : discharge and cervical lesions.
Seborrheic dermatitis
Oral Trush Hairy Oral
KAPOSI SARCOMA
HIV and AIDS Natural history : The average time from acquisition of HIV to an AIDS- defining illness : Is about 10 yrs…then survival averages 1 -2 yrs……. . BUT There is tremendous individual variability in these time intervals: Patients progress from acute HIV infection to death within 1 -2 yrs……and others Not manifesting HIV- related immunosuppression for 20 yrs
HIV and AIDS q Stages of HIV infections: A] Viral Transmission : The mode of transmission does not affect history of HIV disease. the natural B] Acute HIV infection : Acute HIV occurs 1 -4 wks after transmission and accompanied by Burst HIV replication with a decline in CD 4 cell count. Most patient manifest a symptomatic mononucleosis likesyndrom which is usually overlooked.
HIV and AIDS C] Seroconversion : Development of a positive HIV antibody test usually occurs within 4 wks and invariably by 6 months. D] Asymptomatic HIV infection It lasts variable amount of time ( average 8 -10 yrs) and is accompanied by a gradual decline in CD 4 counts with relatively stable HIV RNA level. ( the viral ‘set point’ )
Goals of Antiretroviral Therapy (ART) Eradication of HIV? Not possible with currently available antiretroviral medications.
Goals of Therapy & Tools to Achieve Goals Improvement of quality of life Reduction of HIV-related morbidity and mortality Restoration and/or preservation of immunologic function Maximal and durable suppression of viral load
Treatment Dual – nucleoside reverse transcriptase inhibitor ( NRTI) PLUS : § None-nucleoside reverse transcriptase inhibitor (NNRTI) or § Protease inhibitor ( PIs) § Strand- Transfer Integrase Inhibitor ( INSTI).
HIV life cycle RTIs Fusion inhibitors Integrase inhibitors PIs
Antiretroviral Drugs Nucleoside Analogue RTI; Abacavir(ABC) Didanosine(ddi) Emtricitabine(FTC) Lamivudine(3 TC) Stavudine(d 4 T) Tenofovire DF Zalcitabine (dd. C) Zidovudine (AZT, ZDV) Non-nucleoside RTIs; Delavirdine Efavirenz Nevirapine
Antiretroviral Drugs Protease Inhibitors (PIs); Amprenavir Atazanavir Darunavir Fosamprenavir Indinavir Lopinavir/Ritonavir (Kaletra) Nelfinavir Ritonavir
Treatment Indication of initiation of antiretroviral drugs chronic infection a) Symptomatic disease. b) A symptomatic disease with 1) CD 4 count less than 350 2) pregnancy post exposure prophylaxis.
prevention The only absolute way to prevent sexual transmission of HIV infection is : : ﺍ ﺍﻟ ﻯ ﻳﻘﻮﻝ ﺍﻟﻠﻪ ﺗﻌﺎﻟﻰ ﺍﺓ ﻭﺍ { ﻳﺍ ﺍ ﺍ } Abstinence from extra marital sexual relation completely Safer sexual contact : Use of condom. . . 10% failure rate. Circumcision : results in 50% reduction of HIV acquisition Stop using IDUs Screen all blood and blood products
Prevention The corner stone of an HIV prevention strategy is : Education Counseling Behaviour modification If more than 25% of infected patient does not know. What to do ? . . Routine testing between 13 and 64 ys. . (CDC recomondation without written consent)
Prevention Why we can not control spread : 1. Untested and untreated person is responsible for ongoing viral spread. 2. One third of HIV infected people are unaware of their diagnosis. 3. Most infected people are living in poor countries where ARTs are not available. 4. Use of injection drug and illegal sexual activity is increasing which will add to the incidence and
Prgnancy and HIV infection Pregnant women infected with HIV infection caries risk to infect her baby by: 1) In utero. . . 25 -40% 2) Intrapartum. . . 60 -75% 3) Breast feeding : 1) Established infection 14% 2) Primary infection 29% Current evidence suggests most transmission occur during the intrapartum period. Overall risk for mother to child transmission (MTCT) is 16 - 25 % ( without antiretroviral Rx)
Perinatal hiv transmission Today the risk of perinatal transmission is : Less than 2% with : ü Effective antiretroviral therapy (ART) ü Elective caesarean section when appropiate ü Formula feeding
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