Human Immunodeficiency Virus Acquired Immunodeficiency Syndrome OBJECTIVES At the end of this learning module, the student will be able to: Describe the etiology, incidence, symptoms, diagnosis, and treatment for HIV and AIDS Group Project Students will work in groups of 2-3 and develop a trifold handout that will explain and educate the targeted population of young adults on the following: list the signs and symptoms of the three stages of HIV discuss ways that transmission does and does not take place define the difference between HIV and AIDS raise the awareness of those with HIV and AIDS so as to prevent them from being shunned or feared in society Test Your Knowledge 1. What is the difference between HIV and AIDS? a. HIV is a virus and AIDS is a bacterial disease b. There is no difference between HIV and AIDS c. HIV is the virus that causes AIDS Answer: C. HIV is the virus that causes AIDS. A person can live a relatively normal life for many years if they are diagnosed with HIV, but they are said to have AIDS when they develop an HIV related illness. 2. Is there a cure for AIDS? a. Yes b. NO Answer: b. There is no cure for AIDS 3. Approximately how many people are living with AIDS worldwide? a. 33 million b. 23 million c. 13 million Answer: 33 million at the end of 2007. The majority were in sub-Saharan Africa Avert,(2009) 5. Can you get AIDS from sharing the cup of someone with HIV? a. Yes b. No c. Only if you don’t wash the cup Answer: It is not possible to become infected with HIV from everyday casual contact such as sharing food, shaking hands, or touching the same objects. 6. Can Insects transmit HIV? a. Yes b. No c. Only mosquitoes Answer: b. Insects cannot transmit HIV 7. HIV can make a person ill because…. a. It makes a person lose weight very suddenly b. It reduces the body’s core temperature c. It attacks the immune system Answer: HIV affects a person’s immune system which makes them more vulnerable to infections Avert (2009). What is HIV? HIV stands for human immunodeficiency virus, which attacks the body’s immune system. HIV is a blood-borne pathogen HIV depletes a portion of the immune system (Th cells), making individuals extremely susceptible to life-threatening infections and malignancies Our immune system has no protection against HIV Mallory, W.W. (2009). Know the facts about HIV/AIDS. National Network for Family Resistency. McCance & Huether (2006) page 278 What is AIDS? AIDS, which stands for acquired immunodeficiency syndrome, is caused by HIV. AIDS develops when the immune system can no longer protect itself from lifethreatening diseases. If you have less than 200 CD4+ cells or if your CD4 percentage is less than 14%, you have AIDS. There is no cure for AIDS Mallory, W.W. (2009). Know the facts about HIV/AIDS. National Network for Family Resistency. HIV PREVALENCE ESTIMATE Prevalence is the number of people living with HIV infection at the end of a given year. At the end of 2006, an estimated 1,106,400 persons in the United States were living with HIV infection, with 21% undiagnosed. CDC. (2006). HIV Prevalence Estimates- United States. HIV INCIDENCE RATE Incidence is the number of new HIV infections that occur during a given year. In 2008, CDC estimated that approximately 56,300 people were newly infected with HIV in 2006 (the most recent year that data are available). Over half (53%) of these new infections occurred in gay and bisexual men. Black/African American men and women were also strongly affected and were estimated to have an incidence rate than was 7 times as high as the incidence rate among whites. CDC. (2006). HIV Prevalence Estimates- United States. AIDS CASES In 2007, the estimated number of persons diagnosed with AIDS in the United States and dependent areas was 37,041. Of these, 35,962 were diagnosed in the 50 states and the District of Columbia and 812 were diagnosed in the dependent areas. In the 50 states and the District of Columbia, adult and adolescent AIDS cases totaled 35,934 with 26,355 cases in males and 9,579 cases in females, and 28 cases estimated in children under age 13 years. CDC. (2006). HIV Prevalence Estimates- United States. Two million people died from AIDS in 2007 (5,500 people per day), and 72 percent of these deaths were in subSaharan Africa. Untl There’s a Cure Foundation 2009 Illustration: GfK GeoMarketing Epidemiology Routes of transmission: blood or blood products IV drug abuse Heterosexual & Homosexual activity Maternal-child transmission before or during childbirth Predominant means of transmission is heterosexual contact Click to watch immunity video http://www.virtualmedicalcentre.com/humanatlas1/vmc _white.asp?anid=0002 Virtualmedicalcenter.com Meet the wily HIV virus Viruses are simple microorganisms consisting of nucleic acid protected from the environment by a layer of proteins. Viruses have surface molecules that act as receptors for molecules found on the surface of target cells. The specificity of the receptors helps viruses infect selected target cells which determines the symptoms of that particular infection. A virus will attach to the target cell, insert its genome into the cell, utilize the cell’s protein synthesizing capacity to translate viral proteins, replicate these proteins, and release them from the cell to infect other cells. Pathogenesis HIV is a type of virus called retrovirus, which carries genetic information in the form of RNA rather than DNA. Retroviruses use a viral enzyme, reverse transcriptase, to convert RNA into double-stranded DNA. Using a second viral enzyme, an integrase, the new DNA is inserted into the infected cell’s genetic material where it may remain dormant, and can remain latent for years. However, if the cell is activated, translation of the viral information may be initiated, resulting in the formation of new virions, lysis and death of the infected cell, and shedding of infectious HIV particles. McCance & Huether (2006). Pages 280-1. Picture: The Body (2009). The Complete HIV?AIDS Resourse HIV Infection The main type of cell that HIV infects is the T helper lymphocyte. These cells play a crucial role in the immune system, by coordinating the actions of other immune system cells. A large reduction in the number of T helper cells seriously weakens the immune system. Avert (2009) The Different Stages of HIV Infection. HIV infects the T helper cell because it has the protein CD4 on its surface, which HIV uses to attach itself to the cell before gaining entry. This is why the T helper cell is sometimes referred to as a CD4+ lymphocyte. Once it has found its way into a cell, HIV produces new copies of itself, which can then go on to infect other cells Avert (2009) The Different Stages of HIV Infection. HIV AND LYMPHOCYTES Over time, HIV infection leads to a severe reduction in the number of T helper cells available to help fight disease. The process usually takes several years. Avert (2009) The Different Stages of HIV Infection. Mature HIV viruses (above) and the lymphocyte from which they emerged (below). Two immature viruses can be seen budding on the surface of the lymphocyte (right of center). Image: Science Clarified (2009) What is CD4? CD4 cells are a type of lymphocyte (white blood cell). They are an important part of the immune system. CD4 cells are sometimes called T-cells. There are two main types of CD4 cells. T-4 cells, also called CD4+, are "helper" cells. They lead the attack against infections. When someone is infected with HIV for a long time, the number of CD4 cells they have (their CD4 cell count) goes down. This is a sign that the immune system is being weakened. The lower the CD4 cell count, the more likely the person will get sick. The Body. (2009). Fact Sheet 129 T-8 cells (CD8+) are "suppressor" cells that end the immune response. CD8 cells can also be "killer" cells that kill cancer cells and cells infected with a virus. Researchers can tell these cells apart by specific proteins on the cell surface. A T-4 cell is a T-cell with CD4 molecules on its surface. This type of T-cell is also called "CD4 positive," or CD4. The Body (2009). Fact Sheet 129 The CD4 cell count is a key measure of the health of the immune system. The lower the count, the greater damage HIV has done. Anyone who has less than 200 CD4 cells, or a CD4 percentage less than 14%, is considered to have AIDS CD4 counts are used together with the viral load to estimate how long someone will stay healthy. CD4 counts are also used to indicate when to start certain types of drug therapy The Body (2009). Fact Sheet 129 HIV The primary surface receptor on HIV is the envelope protein gp120, which binds to the molecule CD4, found primarily on the surface of helper T cells. Other coreceptors on the target cells are the chemokine receptors CXCR4 and CCR5. Different strains of HIV1 are selective for the CXCR4 or CXCR5 coreceptors. McCance & Huether (2006). Page 282 Image : Kortright, (2008) Primary cellular targets for HIV •CD4-positive Th cells •Dendritic cells •Macrophages •CD8-positive Tcells •Double-positive thymic cells •NK cells •Neural cells McCance & Huether (2006). Page 282 PRIMARY SITES OF INFECTION Primary sites of infection are usually the lymphoid areas of the mucosal surfaces. Dendritic cells and mucosal T cells spread the infection to other lymphoid organs in the lymph nodes. McCance & Huether (2006). Page 282 EARLY PHASE At the time of diagnosis, the patient may manifest one of several different conditions: Serologically negative (no detectable antibody) Serologically positive (positive for antibody against HIV –but asymptomatic) Early stages of HIV or AIDS PHASES OF THE DISEASE During the initial phase antibodies against HIV-1 are not yet detectable (window period), but viral products, including p24 antigen,viral RNA, and infectious virus, may be detectable in the blood a few weeks after infection, and not detected by routine essays. During the latent phase antibody levels against p24 and other viral proteins, as well as HIV-specific CTLs, generally increase, then remain constant until the development of AIDS. As the immune system becomes severely depressed, excess viral antigen is released into the blood, and measuraable antibody levels decrease. McCance & Huether (2006). Pages 284 CLINICAL MANIFESTATIONS Within weeks after infection the virus aggressively infects and spreads, depleting CD4+ cells causing HIV related diseases, such as: Protozoal and helminthic infections Fungal Infections Bacterial Infections Viral Infections Neoplasms Patients with the early stages of HIV usually present with relatively mild symptoms resembling influenza, such as night sweats, swollen lymph nodes, diarrhea, or fatigue. This early stage may last as long as 10 years. During this time, the disease is actively proliferating in lymph nodes. McCance & Huether (2006). Pages 284-5 Answers.com (2009) Answers.com (2009) Kaposi Sarcoma Kaposi sarcoma (KS) is a cancer that develops from the cells that line lymph or blood vessels. The abnormal cells of KS form purple, red, or brown blotches or tumors on the skin. These affected areas are called lesions. The skin lesions of KS may look bad, but in many cases, the lesions cause no symptoms. In other cases, the disease causes painful swelling, especially in the legs, groin area, or skin around the eyes. KS can cause serious problems (or even become life threatening) when the lesions are in the lungs, liver, or digestive tract. KS in the digestive tract, for example, can cause bleeding, while tumors in the lungs may cause difficulty breathing. American Cancer Society 2009 (AIDS-related) Kaposi sarcoma The most common type of Kaposi sarcoma in the United States is epidemic or AIDS-related KS. This type of KS develops in people who are infected with HIV, the virus that causes AIDS. When HIV damages the immune system, people who also are infected with Kaposi sarcoma herpes virus are more likely to develop KS. KS is considered to be an "AIDS defining" illness. This means that when KS occurs in someone infected with HIV, that person officially has AIDS (and is not just HIV positive). American Cancer Society 2009 ScienceClarified 2009 Antibodies appear rapidly after infection through blood products, usually within 4-7 weeks. After sexual transmission, the individual can be infected yet seronegative for 6-14 months, even years In the late stages of the disease, some individuals become seronegative because of a deficient immune system McCance & Huether (2006). Pages 285 HIV infection can generally be broken down into four distinct stages: primary infection clinically asymptomatic stage symptomatic HIV infection progression from HIV to AIDS LABORATORY TESTS 1. Serology - the diagnosis of HIV infection is usually based on serological tests. a. Antibody tests b. Antigen tests 2. Virus isolation 3. Demonstration of viral NA 4. Prognostic Tests a. HIV viral load b. CD4 count 5. Antiviral susceptibility assays Wong, D. (2009) Laboratory Diagnosis Laboratory Diagnosis 1. Serology - the diagnosis of HIV infection is usually based on serological tests. (a)Antibody tests - ELISAs are the most frequently used method for screening of blood samples for HIV antibody. The sensitivity and specificity of the presently available commercial systems approaches 100% but false positive and false negative reactions occur. Wong, D. (2009) Other test systems available include passive particle agglutination, immunofluorescence, Western blots and RIPA bioassays. Western blots are regarded as the gold standard and seropositivity is diagnosed when antibodies against both the env and the gag proteins are detected. The sensitivity of the test systems are currently being improved by the use of recombinant antigens. Wong, D. (2009) (b) Antigen tests - HIV antigen can be detected early in the course of HIV infection before the appearance of antibody. It is undetectable during the latent period (antigen-antibody complexes are present) but become detectable during the final stages of the infection Wong, D. (2009) 2. Virus isolation - virus isolation is accomplished by the cocultivation of the patient's lymphocytes with fresh peripheral blood cells of healthy donors or with suitable culture lines such as T-lymphomas. The presence of the virus can be confirmed by reverse transcriptase assays, serological tests, or by changes in growth pattern of the indicator cells. However virus isolation is tedious and time consuming (weeks) and is successful in only 70 to 90% of cases. Therefore virus isolation is mainly used for the characterization of the virus. Wong, D. (2009) 3. Demonstration of viral NA - this can be accomplished by probes or by PCR techniques. The latter may be useful because of its extremely high sensitivity. Wong, D. (2009) 4. Prognostic Tests - the following may be useful as prognostic tests; (1)HIV antigen (2) (2) Serial CD4 counts (3) Neopterin (4) B2-microglobulin. (5) Viral load. Of these tests, only serial CD4 counts and HIV viral load are still routinely used. Wong, D. (2009) a. HIV viral load - It appears that HIV viral load has the greatest prognostic value. HIV viral load in serum may be measured by assays which detect HIV-RNA e.g. RT-PCR, NASBA, or bDNA. HIV viral load has now been established as having good prognostic value, and in monitoring response to antiviral chemotherapy. Patients with a low viral load during the incubation period had a better prognosis than those with a high viral load. Patients whose viral load decreased significantly following the commencement of antiviral therapy had a better prognosis than those who did not respond. Wong, D. (2009) b. CD4 counts - despite the increasing use of HIV-RNA assays, measurement of CD4 still has important value in monitoring disease progression and response to antiviral chemotherapy. whereas CD4 count gives an indication of the stage of disease. “The measurement of HIV viral load tells us where the disease is going, whereas CD4 count tells us where the disease is at this moment” Wong, D. (2009) TREATMENT Therapy of HIV is complicated by the fact that the HIV genome is incorporated into the host cell genome and can remain there in a dormant state for prolonged periods until it is reactivated. Effective therapy must be directed against both free virus and virus-infected cells. The main group of substances described are Wong, D. (2009) The main group of substances described are: 1. Nucleoside analogues reverse transcriptase inhibitors. AZT, DDC, DDI and lamuvidine. 2. Non-nucleoside analogue reverse transcriptase inhibitors e.g. Nevirapine 3. HIV Protease inhibitors e.g. Ritonavir, and Indivavir. They are the most potent inhibitors of HIV replication to date. Wong,D. (2009) DRUG THERAPY Zidovudine (AZT) was the first anti-viral agent shown to have beneficial effect against HIV infection. However, after prolonged use, AZTresistant strains rapidly appears which limits the effect of AZT Wong, D. (2009) Recent clinical trials reported significant benefit in the use of combination therapy over the use of monotherapy. The rationale for this approach is that by combining drugs that are synergistic, non-cross-resistant and no overlapping toxicity, it may be possible to reduce toxicity, improve efficacy and prevent resistance from arising. Wong, D. (2009) HAART In fact, significant success has now been reported for trials involving multiple agents including protease inhibitors. The aim of anti-HIV therapy has now shifted from simply delaying the progression of disease to finding a permanent cure. We have now entered the era of highly active antiretroviral therapy (HAART). Wong, D. (2009) The current consensus is that one should give a potent combination of agents HAART right from the start when treatment is indicated. The most popular combination is AZT and lamivudine plus a protease inhibitor. Wong, D. (2009) GeorgeHouseTrust (2000) Lamivudine has greater anti-retroviral activity that AZT alone and is active against many AZT-resistant strains without significant increase in toxicity. Wong, D. (2009) REFERENCES American Cancer Society (2009). What Is Kaposi Sarcoma? Retrieved November 15, 2009 from: http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_kaposis_sarcoma_21.asp Answers.com (2009). Main symptoms of acute HIV infection. Retrieved November 10, 2009 from: http://wpcontent.answers.com/wikipedia/commons/thumb/4/4a/Symptoms_of_acute_HIV_infection.png/300 px-Symptoms_of_acute_HIV_infection.png Avert, (2009). The Different Stages of HIV Infection. Retrieved November 19, 2009 from: http://www.avert.org/ CDC. (2006). HIV Prevalence Estimates- United States. Retrieved November 7, 2009 from: http://www.cdc.gov/ George House Trust (2009). Still Life with HIV. Retrieved November 14, 2009 from: http://www.ght.org.uk/news/category/BBC GfK GeoMarketing (2007). 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