HIV 2024-1.pdf

Human Immunodeficiency Virus Disease  EPIDEMIOLOGY AND BIOLOGY OF HIV The acquired immunodeficiency syndrome (AIDS) was first recognized in 1981. It is caused by the human immunodeficiency virus (HIV-1). HIV-2 causes a similar illness to HIV-1 but is less aggressive and restricted...

Human Immunodeficiency Virus Disease  EPIDEMIOLOGY AND BIOLOGY OF HIV The acquired immunodeficiency syndrome (AIDS) was first recognized in 1981. It is caused by the human immunodeficiency virus (HIV-1). HIV-2 causes a similar illness to HIV-1 but is less aggressive and restricted mainly to western Africa. The viruses almost certainly originated from closely related African primate viruses, simian immunodeficiency viruses (SIVs). Sequence analysis has led to the estimate that HIV-1 was introduced into humans in the early 1930s.  SIV is weak virus suppress by human immunity within weeks of infection several transmit ion of virus from human to human in quick succession necessary to allow enough time to mutate in to HIV Since 1981 AIDS has grown to be the second leading cause of disease burden world-wide and the leading cause of death in Africa, where it accounts for over 20% of deaths. Highly active retroviral therapy (HAART) with three or more drugs has improved life expectancy to near normal in the majority of patients receiving it, with an 80% reduction of mortality since its introduction. Immune deficiency is a consequence of continuous high- level HIV replication leading to virus and immune- mediated destruction of the key immune effector cell, the CD4 lymphocyte. In 2012, the World Health Organization (WHO) estimated that there were 35.3 million people living with HIV/AIDS, 2.5 million new infections and 2.1 million deaths. The cumulative death toll since the epidemic began is over 36 million(2012) in 2013 1.4 million death, the vast majority of cases occurring in sub-Saharan Africa where over 11.4 million children are now orphaned. No cure no vaccin Figure 14.1 World-wide distribution of HIV infection. Downloaded from: StudentConsult (on 9 April 2011 02:20 PM) © 2005 Elsevier  MODES OF TRANSMISSION HIV is present in blood, semen and other body fluids such as breast milk and saliva..The modes of spread are 1. Sexual (man to man, heterosexual and oral). 2. Parenteral (blood or blood product recipients, injection drug- users and those experiencing occupational injury) and 3. Vertical (pregnancy dilivery breast feeding). World-wide, the major route of transmission (> 75%) is heterosexual. About 5-10% of new HIV infections are in children and more than 90% of these are infected during pregnancy, birth or breastfeeding.  RISK OF TRANSMISSION The transmission risk after exposure is over 90% for blood or blood products, 15-40% for the vertical route, 0.5-1.0% for injection drug use, 0.2-0.5% for genital mucous membrane spread and under 0.1% for non-genital mucous membrane spread. After >25 years of scrutiny, there is no evidence that HIV is transmitted by casual contact or that the virus can be spread by insects, such as by a mosquito bite. There have been approximately 100 definite and 200 possible cases of HIV acquired occupationally in health-care workers. Such infections are substantially more frequent in developing nations, where it is estimated that 40% of syringes/needles used in injections are reused without sterilisation.  VIROLOGY AND IMMUNOLOGY HIV is a single-stranded RNA retrovirus from the Lentivirus family. After mucosal exposure, HIV is transported to the lymph nodes via dendritic, CD4 or Langerhans cells, where infection becomes established.. Free or cell-associated virus is then disseminated widely through the blood with ‫ﻣﻼذ‬seeding of 'sanctuary' sites 1-(e.g. central nervous system) and 2- latent CD4 cell reservoirs. With time, there is gradual attrition of ‫اﻧﮭﺎك‬the CD4 cell population, resulting in increasing impairment of cell-mediated immunity and susceptibility to opportunistic infections. Figure 14.3 Virological and immunological progression of HIV infection. (ARC = AIDS-related complex) Downloaded from: StudentConsult (on 9 April 2011 02:20 PM) © 2005 Elsevier  NATURAL HISTORY AND CLASSIFICATION OF HIV 1-Primary infection is symptomatic in 70-80% of cases and usually occurs 2-6 weeks after exposure: CLINICAL FEATURES OF PRIMARY INFECTION Fever with rash Pharyngitis with cervical lymphadenopathy Myalgia/arthralgia Headache Mucosal ulceration Rarely, presentation may be neurological (aseptic meningitis, encephalitis, myelitis, polyneuritis). 2-Asymptomatic infection follows primary infection and lasts for a variable period, during which the infected individual remains well with no evidence of disease except for the possible presence of persistent generalised lymphadenopathy (PGL, defined as enlarged glands at ≥ 2 extra-inguinal sites). 3-Mildly symptomatic disease( ARC) Mildly symptomatic disease then develops in the majority, indicating some impairment of the cellular immune system. These diseases correspond to AIDS- related complex (ARC) conditions but by definition are not AIDS-defining. The median interval from infection to the development of symptoms is around 7-10 years. HIV SYMPTOMATIC DISEASES Oral hairy leucoplakia Recurrent oropharyngeal candidiasis Recurrent vaginal candidiasis Severe pelvic inflammatory disease Bacillary angiomatosis Cervical dysplasia Idiopathic thrombocytopenic purpura Weight loss Chronic diarrhoea Herpes zoster Peripheral neuropathy Low-grade fever/night sweats  4-Acquired immunodeficiency syndrome (AIDS) AIDS is defined by the development of specified opportunistic infections, tumours etc. AIDS-DEFINING DISEASES Oesophageal candidiasis Cryptococcal meningitis Chronic cryptosporidial diarrhoea CMV retinitis or colitis Chronic mucocutaneous herpes simplex Disseminated Mycobacterium avium intracellulare Pulmonary or extrapulmonary tuberculosis Pneumocystis carinii pneumonia Progressive multifocal leucoencephalopathy Recurrent non-typhi Salmonella septicemia Cerebral toxoplasmosis Extrapulmonary coccidioidomycosis Invasive cervical cancer Extrapulmonary histoplasmosis Kaposi's sarcoma Non-Hodgkin lymphoma Primary cerebral lymphoma HIV-associated wasting HIV-associated dementia  Diagnosis of HIV Infection BY A-demonstration of antibodies to HIV and/or B-the direct detection of HIV or one of its components. A- Detect Antibodies to HIV generally appear in the circulation 2–12 weeks following infection. The standard blood screening test for HIV infection is the -1-1- ELISA, also referred to as (EIA) an enzyme immunoassay is an extremely good screening test with a sensitivity of >99.5%... EIA tests are generally scored as positive (highly reactive), negative (nonreactive), or indeterminate) partially reactive. ( if the blood contains antibodies to HIV, it will bind with the antigen and cause the cassette’s contents to change color  2-Western blot test a Western blot demonstrating antibodies to products of all three of the major antigenes of of HIV (env, pol &gag)…Here, an enzyme is added to cause color changes that signal the presence of HIV antibodies. The most commonly used confirmatory test is the Western blot.. In a patient with a positive or indeterminate EIA and a negative Western blot, one can conclude with certainty that the EIA reactivity was a false positive. On the other hand, a Western blot demonstrating antibodies to products of all three of the major genes of of HIV (env, pol &gag) is conclusive evidence of infection with HIV. B-direct detection of HIV or its components. 1 For diagnosis -when the Western blot results are indeterminate. , The simplest of the direct detection tests is the p24 antigen capture assay. The p24 antigen capture assay has its greatest use as a screening test for HIV infection in patients suspected of having the acute HIV syndrome, as high levels of p24 antigen are present prior to the development of antibodies.  During acute HIV infection, the HIV RNA is always detectable, and the HIV p24 antigen is often positive. People with acute HIV may have an abrupt onset of clinical symptoms. Recent Infection: The term recent infection usually describes the period after acute HIV when anti-HIV antibodies are developing out to 6 months after HIV acquisition.  2- detecting levels of HIV RNA They are reverse transcriptase PCR, branched DNA, and nucleic acid sequence–based amplification. These tests are of value in1- making a diagnosis of HIV infection, 2-in establishing initial prognosis, 3- in determining the need for therapy, 4-and for monitoring the effects of therapy  CD4+ T Cell Counts The reduction in the number of CD4 cells circulating in peripheral blood is tightly correlated with the amount of plasma viral load. Both are monitored closely in patients and are used as measures of disease progression. Patients with CD4+ T cell counts