Definitions n HIV stands for H uman I mmunodeficiency V irus. It is a - PDF document

Definitions n HIV stands for H uman I mmunodeficiency V irus. It is a Retrovirus. n HIV Infection is the state where the virus is in the body. In most instances this is the asymptomatic state, which is a prelude to AIDS n AIDS stands for A cquired I mmune D eficiency S yndrome. n “Acquired” means it is transmissible, and n “Immune-Deficiency” means it damages the body defense system n “Syndrome” refers to a group of illnesses Historical Background of HIV n 1981 – Doctors in the United States recognized Pneumocystis Carinii Pneumonia (PCP) in homosexual males,

a condition previously unreported in healthy adults. Later they recognized that all these patients were immunosuppressed. n 1983/4 – Scientists described the cause of this acquired immunodeficiency syndrome (AIDS) as a retrovirus: n Lymphadenopathy Associated Virus (LAV). n AIDs Associated Retrovirus (ARV). n Human T- lymphotrophic Virus Ш (HTLV - Ш). Historical Background of HIV n 1984 – The first case in Kenya was described n 1986 – Human Immunodeficiency Virus (HIV) was accepted as the international designation for

theretrovirus in a WHO consultative meeting n 1996 – ARVs became available in the world. n 1997 – ARVs became available in the private sector in Kenya. n 2003 – ARVs became available in public sector in Kenya. n 2006 – Approximately 90,000 Kenyans are taking ARV treatment. Epidemic update Global update n Estimated 40 million living with HIV by end of 2005 n About one-third of PLHA are between 15-24 years n Most people are still unaware they are infectedYoung

women are more vulnerable Adults And Children Estimated To Be Living With HIV As Of End 2005 Children (<15 years) estimated to be living with HIV as of end 2005 Epidemic Update: Sub- Saharan Africa n HIV is now the leading cause of death n 25.0 – 28.2 million living with HIV infection by end of 2003 n 10-15% of need ARV n Estimated 3-3.4 million new HIV infections in 2003 n 70% found in sub Saharan Africa n 10% (600 million) of world’s population live in sub Saharan African n By 2010, an estimated 106 million children under age 15 will have lost oneor both parents, with 25 million of this

group orphaned due to HIV/AIDS District estimates are summed to the province and national level(NACC) National HIV estimates for 2006 Epidemic update: Kenya .. Epidemiology/Impact of HIV/AIDS in Kenya n 60% medical beds- HIV/AIDS n 40% Paediatric beds- HIV/AIDS n >50% TB patients – HIV

+>25% STI patients – HIV+ n Health workers face both the medical and social challenges of HIV/AIDS on a daily basis MODES OF TRANSMISSION SUMMARY n Over the past 2 decades HIV has spread worldwide with devastating epidemiological consequences particularly in Sub Saharan Africa n MTCT is the main mode of transmission of HIV infection to children n HIV/AIDS is a major cause

ofmorbidity and mortality Unit 2: Human Immunology & Biology Of HIV Objectives n Define the cells involved in the immune system and their function. n Know the host immune response during and after infection. n Basic HIV structure. n The significance of genetic diversity and classification of HIV. n The replication cycle of HIV. The target sites for antiretroviral drugs Components of the

Immune System n Found in blood and tissues n White blood cells (WBC)- key players in immune response (humoral and cellular) ¨ Macrophages act as clearing cells ¨ Neutrophils attack bacteria ¨ Eosinophils attack helminths (and mediate allergies) ¨ B-lymphocytes make antibodies ¨ T-lymphocytes n Responsible for attacking viruses, fungi and some bacteria n T helper cells central in orchestrating function of other immune cells n T killer cells are able to destroy infected cells n How HIV affects the Immune System HIV attaches to cells of the immune system with special

surface markers called CD4 receptors n Immune cells with CD4 receptors include: ¨ T-helper Lymphocytes ¨ Macrophages ¨ Monocytes ¨ Dendritic cells ¨ Microglial cells HIV effect on Immune System n The hallmark of HIV/AIDS is profound immunodeficiency as a result depletion of CD4+ T lymphocytes. The CD4+ T cell dysfunction is two fold ¨ Reduction in numbers

¨ Impairment in function The Biology Of The Human Immunodeficiency Virus Basic Virology: There are two types of HIV. HIV – 1 n Is found worldwide ¨ Is the main cause of the worldwide ¨ pandemic HIV – 2 n Is mainly found in West Africa, ¨ Mozambique and Angola. ¨ Causes a similar illness to HIV – 1 Less efficiently transmissible rarely ¨ causing vertical transmission Less aggressive with slower disease progression Structure Of Human Immunodeficiency Virus

HIV Life Cycle SUMMARY n HIV attacks the Immune system of human being and leads to profound immunodeficiency. n Rapid replication of HIV causes genetic diversity of the virus. n Knowledge of the HIV structure is important in understanding the mechanismof ARV drugs UNIT 3:

Natural progression of HIV Objectives n Describe stages of HIV progression - serocoversion, asymptomatic, symptomatic and AIDS phases n Be able to stage HIV infection by WHO classification n Host immune response during HIV infection Primary HIV Infection ¨ On exposure, there is a 2-4

week period of intense viral replication and widespread dissemination of virus characterized by n High plasma viral load (RNA) n Rapid decline in CD4 count n In some cases an acute illness occurs ¨ Lasts from 1-2 weeks, but it is rarely diagnosed ¨ Symptoms if present resemble those of other viral illnesses; requires high index of suspicion n Symptom resolution with reduction in plasma viremia due to development of an immune response and antibodies to the virus Asymptomatic Disease(Latency) n Patients then enter a stage of

asymptomatic disease phase lasting on average 2-10 years (clinical latency) n Characterized by gradual decline in CD4 count ¨ Rate depends on viral load n Long term non-progressors ¨ Rare ¨ >>10-15 year survival without ART ¨ CD4>500; low viral load ¨ Host genetic/immunological or viral factors may be involved Symptomatic Disease and AIDS n Viral load continues to rise causing ¨ Increased demands on immune system as production of CD4 cells cannot match destructionIncreased susceptibility to common infections (URTI, pneumonia, skin etc) ¨ Late-stage disease is characterized

by a CD4 count <200cells/mm 3 and the development of opportunistic infections, selected tumors, wasting, and neurological complications). Revised WHO Classification Clinical Stages I & II Revised WHO Classification Clinical Stage III Revised WHO Classification Clinical Stage IV Selected Symptoms Conditions where a presumptive diagnosis can be made using clinical signs or simpleinvestigations: n HIV wasting syndrome n Pneumocystis carinii pneumonia (PCP) n Recurrent severe bacterial pneumonia

n Cryptococcal meningitis n Toxoplasmosis of the brain n Chronic orolabial, genital or anorectal herpes simplex infection for > 1month n Kaposi’s sarcoma (KS) n HIV encephalopathy n Extrapulmonary tuberculosis n Cryptosporidiosis, with diarrhea >1 month n Isosporiasis Conditions where confirmatory diagnostic testing is necessary n Candidiasis of the esophagus or airways n Cytomegalovirus (CMV) retinitis or disease of organs (other than liver, spleen, or lymph nodes) n Non-typhoid salmonella septicemia (NTS) n Lymphoma cerebral or B cell NHL n Invasive cervical carcinoma n Visceral Leishmaniasis n Cryptococcosis (extrapulmonary) n Disseminated non tuberculous mycobacterial infection n Progressive multifocal leukoencephalopathy n Any disseminated endemic mycosis (e.g. histoplasmosis) WHO Clinical Staging Pediatric Stage 1

n Asymptomatic n Persistent generalised lymphadenopathy (PGL) WHO Clinical Staging Pediatric WHO Stage 2 n Unexplained persistent hepatosplenomegaly n Papular pruritic eruptions n Extensive wart virus infections n Fungal nail infections n Lineal gingival erythema WHO Clinical StagingPediatric WHO Stage 2 , cont’d n Extensive molluscum contagiosum

infection n Recurrent oral ulcerations n Unexplained persistent parotid enlargement n Herpes zoster n Recurrent or chronic upper respiratory infection (URI): otitis media, otorrhea, sinsusitis, tonsillitis WHO Clinical Staging Pediatric Stage 3 n moderate Unexplained malnutrition not adequately responding to standard therapyUnexplained persistent diarrhoea (14 days or more) n Unexplained persistent fever (>37.5 O C, intermittent or constant >1 mo) n Persistent oral candidiasis (outside 1 st 6-

8 weeks of life) n Oral hairy leukoplakia n Lymph node TB WHO Clinical Staging Pediatric Stage 3 n Pulmonary tuberculosis n Severe recurrent presumed bacterial pneumonia n Acute necrotizing ulcerative gingivitis/periodontis n Symptomatic Lymphoid interstitial pneumonitis (LIP) n Unexplained anemia (<8 gm/dL), neutropenia (<1,000/mm 3 ), or chronic thrombocytopenia (<50,000/mm 3 ) for >1 month. HIV-associated cardiomyopathy or HIV-related nephropathy n Chronic HIV-associated lung disease including bronchiectasis