WEEK+10+AIDS

4. Discuss the epidemiology of human immunodeficiency virus (HIV), and acquired immunodeficiency syndrome (AIDS).

5. Differentiate between human immunodeficiency virus (HIV), and acquired immunodeficiency syndrome (AIDS).

6. Examine the transmission of the human immunodeficiency virus (HIV) and the related factors that affect the transmission. **(Lewis 250, Huether 198 & 199-Health alert box)** -HIV transmission occurs through homosexual and heterosexual intercourse, exposure to HIV-infected blood or blood products, and perinatal transmission. **Factors that increase transmission**; Look @ Huether; health alert p.199 -duration and frequency of contact -volume of fluid -virulence and concentration of org. -host immune status -viral load (# of viruses in blood, semen, vag secretions, or breast milk) -Time; Large amts of HIV is found during first 6 mths of infection and again in late stages of the disease **(good** **TEST ?!) see 250 Lewis fig 15-1** -through deep puncture wounds, a hollow bore needle w/ visible blood, a device for venous or arterial access -splash exposure of blood on skin w/ an open lesion can present some risk
 * Sexual contact** w/ infected person is most common mode of transmission through semen, vaginal secretions, and/or blood. Riskiest; unprotected anal sex, the person receiving the semen in any sex, sex w/ blood present (menstruation or tissue trauma), genital lesions from other STIs. (look @ Huether 199-health alert)
 * Blood and Blood Products;** drug-using equipment (contaminated needles, ect); Blood screenings for infected persons trying to donate have reduced exposure of infected blood transfusions, which account for 1% in US. It still could be possible in some cases b/c the 1st few mths of infection may not test positive for HIV antibodies; Puncture wounds are most common work related means to infection. Needle-stick exposure to HIV infected blood is 3-4 out of 1000 (Yikes!)
 * Perinatal Exposure;** most common route for children; can occurs during pregnancy, in delivery, or after birth through breastfeeding. Only 25% of kids born to untreated infected women get HIV.


 * HIV NOT spread through;** tears, saliva, urine, emesis, sputum, feces, or sweat. No sign of transmission through resp. droplets either. No hugging, kissing, handshake, sharing food utensils, toilet seats, or being around person w/ HIV. Not spread casually (Test ? possibly… what is the most likely way to get HIV…)

7. Analyze the pathophysiology of human immunodeficiency virus (HIV), and acquired immunodeficiency syndrome (AIDS). **(Lewis 250-252, 251 fig 15-3, Huether 199)** -all daughter cells will be infected -viral DNA will direct cell to make new HIV Initially there is viremia (large amts of virus in blood), W/in a few weeks, HIV blood levels will be low, even w/out treatment. Low levels can last 10-12 yrs, w/ few symptoms. Even w/out symptoms, HIV replication occurs rapidly and at a constant rate in blood and lymph tissues. Because replication is occurring rapidly, mutations can occur, causing problems in treatment and vaccine development. HIV infects cells w/ CD4 receptors- lymphocytes, monocytes/macrophages, astrocyes, and oligodendrocyes. Immune dysfunction occurs mostly in T helper cells or CD4 T lymphocytes. (targeted b/c they have more CD4 receptor sites) **Review the role of T helpers in immune fx.** -Normal #s of T helpers in adults; 800-1200 per microliter of blood. -The norm life span of T helper cell is 100 days, but w/ HIV infected T helpers die in average of 2 days
 * HIV (human immunodeficiency virus)** is a ribonucleic acid (RNA) virus or rovirus-called that b/c they replicate in a “backward” manner-going from RNA to DNA. The virus cannot replicate unless it’s **inside** a living cell. HIV has gp 120 glycoproteins that attach to CD4 and chemokine CXCR4 & CCR5 receptors on the surface of CD4 T cells. Viral RNA enters the cell, transcribes into a single strand of DNA w/ reverse transcriptase (an enzyme) and produces viral DNA. The viral DNA enters the nucleus and with the enzyme integrase, splices itself into the genome and becomes a permanent part of the cell’s genetic structure. As a result;

Viral activity destroys 1 billion T helpers per day, but bone marrow and thymus can effectively replace cells for years. Eventually cannot keep up w/ efficient replacement, resulting in decline of CD4 T cells. -Immune system can remain healthy w/ >500 CD4 T cells/ microliter. -Once CD4 T cell count is low, the main concern is development of opportunistic diseases **AIDS (Lewis 253 table 15-10)** is diagnosed when individual develops one of following; (immune system becomes severely compromised) a)-C  a  **)    CD4 T cell count <200 cell/microliter of blood ** ** b) b  **) Development of 1 of following opportunistic infections -Fungal infection resp tract -Viral infection -Protozoa infection -Bacterial infection d) Wasting syndrome occurs; loss of 10% or more of ideal body mass e) AIDS dementia complex (ADC) develops
 * c)** Development of opportunistic cancers

AIDS.__** (Mod 6 #11 L)
 * __8. Describe clinical symptoms that indicate potential HIV infection and its progression to


 * Early Disease**

Primary infection with HIV is characterized by a flu-like illness with fever, myalgia, and adenopathy that often goes unrecognized as HIV infection. In subsequent weeks, months, and years, the immune system is able to combat the HIV infection so that the individual is most often asymptomatic. During this time, the individual may be unaware that the virus is being shed in body secretions and therefore may unwittingly infect others.


 * Progressive and Late Disease**

Once immune dysfunction develops (average of 10 to 11 years in otherwise healthy adults, but occurs much sooner in infants, the elderly, and those with comorbid conditions such as hepatitis), individuals experience nonspecific conditions such as fungal infections (e.g., thrush), eczema, or sexually transmitted diseases such as venereal warts and vaginitis. Progressive deterioration in immune function results in more serious opportunistic infections with organisms such as //Pneumocystis jerovici// (previously called //Pneumocystis carinii//), //Mycobacterium tuberculosis, Toxoplasmosis gondii,// and cytomegalovirus.

In addition, malignancies such as Kaposi sarcoma (caused by coinfection with a herpesvirus) and lymphomas may develop. Other complications of HIV infection include wasting syndrome and AIDS-related dementia.

(M/S p252)

The median interval between untreated HIV infection and a diagnosis of AIDS is about 11 years. During this time, CD4+ T-lymphocyte counts remain above 500 cells/ml (normal or slightly decreased) and the viral load in the blood will be low. This phase has been referred to as //asymptomatic disease,// although fatigue, headache, low-grade fever, night sweats, //persistent generalized lymphadenopathy// (PGL), and other symptoms often occur. As the CD4+ T cell count drops to 200 to 500 cells/ml and the viral load increases, HIV advances to a more active stage. Symptoms seen in earlier phases tend to become worse at this point, causing persistent fever, frequent drenching night sweats, chronic diarrhea, recurrent headaches, and fatigue severe enough to interrupt normal routines. Other problems that may occur at this time include localized infections, lymphadenopathy, and nervous system manifestations. The most common infection associated with this phase of HIV disease is oropharyngeal candidiasis or thrush. //Candida// rarely causes problems in healthy adults, but will eventually occur in most HIV-infected people. Other infections that can occur at this time include shingles (caused by the varicella-zoster virus), persistent vaginal candidal infections, outbreaks of oral or genital herpes, bacterial infections, and Kaposi sarcoma (KS), caused by human herpesvirus 8. **Oral hairy leukoplakia,** an Epstein-Barr virus infection that causes painless, white, raised lesions on the lateral aspect of the tongue, can also occur. Oral hairy leukoplakia is also an indicator of disease progression. A diagnosis of **acquired immunodeficiency syndrome (AIDS)** cannot be made until the HIV-infected patient meets the criteria established by the CDC. These criteria ([|Table 15-10]) are more likely to occur when the immune system becomes severely compromised. As the viral load increases, decreases in the absolute number of lymphocytes, as well as the percentage of lymphocytes, may also occur, and the risk of developing one or more of the opportunistic diseases that contribute to disability and death increases
 * __Acute Infection__** Development of HIV-specific antibodies **(seroconversion)** is frequently accompanied by a flulike syndrome of fever, swollen lymph glands, sore throat, headache, malaise, nausea, muscle and joint pain, diarrhea, and/or a diffuse rash. Some people develop neurologic complications, such as aseptic meningitis, peripheral neuropathy, facial palsy, or Guillain-Barré syndrome. These symptoms, called **acute HIV infection,** generally occur 1 to 3 weeks after the initial infection and last for 1 to 2 weeks, although some symptoms may persist for several months. During this time, a high viral load is noted and CD4+ T cell counts fall temporarily but quickly return to baseline Many people, including health care providers, mistake acute symptoms for a bad case of the flu and do not associate them with HIV.
 * __Chronic HIV Infection__**
 * Early Chronic Infection**
 * Intermediate Chronic Infection**
 * Late Chronic Infection or AIDS**

~CD4+ T cell counts provide marker for immune assessment. Normal is 800-1200 cells/mcl ~Viral load provides assessment of disease progression ~ decreased WBC, Neutropenia ~thrombocytopenia ~anemia ~altered liver func. tests ~coinfection with Hep B or C ~genotype assay detects drug-resistant viral mutations that are present in reverse transcriptase and protease genes. ~The //phenotype assay// measures the growth of the virus in various concentrations of antiretroviral drugs (much like bacteria-antibiotic sensitivity tests). These assays are especially useful in making decisions about new drug combinations in patients who do not respond to therapy.
 * __9. Describe the diagnostic data associated with the diagnosis of HIV infection and progression of HIV infection and AIDS.__**
 * __(M/S p. 253 table15-10, 256 table 15-12)__**
 * 2 important lab assessments:**
 * Other abnormal blood tests:**
 * Resistence to antiviral drugs**

• //Fungal//: candidiasis of bronchi, trachea, lungs, or esophagus; //Pneumocystis jiroveci// pneumonia (PCP); disseminated or extrapulmonary coccidioidomycosis; disseminated or extrapulmonary histoplasmosis • //Viral//: cytomegalovirus (CMV) disease other than liver, spleen, or nodes; CMV retinitis (with loss of vision); herpes simplex with chronic ulcer(s) or bronchitis, pneumonitis, or esophagitis; progressive multifocal leukoencephalopathy (PML); extrapulmonary cryptococcosis • //Protozoal//: toxoplasmosis of the brain, chronic intestinal isosporiasis; chronic intestinal cryptosporidiosis • //Bacterial//: //Mycobacterium tuberculosis// (any site); any disseminated or extrapulmonary //Mycobacterium,// including //M. avium// complex (MAC) or //M. kansasii;// recurrent pneumonia; recurrent //Salmonella// septicemia • Invasive cervical cancer, Kaposi's sarcoma (KS), Burkitt's lymphoma, immunoblastic lymphoma, or primary lymphoma of the brain
 * AIDS is diagnosed when an individual with HIV develops at least one of these conditions:**
 * 1. CD4+ T cell count drops below 200 cells/ml.**
 * 2. Development of one of the following opportunistic infections (OIs):**
 * 3. Development of one of the following opportunistic cancers:**
 * 4. Wasting syndrome occurs. //Wasting// is defined as a loss of 10% or more of ideal body mass.**
 * 5**. **AIDS dementia complex (ADC) develops.**

All HIV testing should be accompanied by pretest and posttest counseling. The following additional steps are used in the process of testing blood for antibodies to HIV: • WB testing uses purified HIV antigens electrophoresed on gels. These are incubated with serum samples. If antibody in the serum is present, it can be detected. • IFA is used to identify HIV in infected cells. Blood is treated with a fluorescent antibody against p17 or p24 antigen and then examined using a fluorescent microscope. **4.** Blood that is reactive in all of the first three steps is reported as HIV-antibody positive. 5. If the results are indeterminate, the following steps are taken: • If in-depth risk assessment reveals that the individual does not have a history of high-risk activities, reassure the patient that she or he is extremely unlikely to be infected with HIV and suggest retesting in 3 months. • If in-depth risk assessment reveals that the individual does have a history of high-risk activities, repeat antibody test at 1, 2, and 6 months; discuss risk reduction measures to protect partners from infection; consider tests for HIV-antigen detection
 * **1**. A highly sensitive enzyme immunoassay (EIA) is done to detect serum antibodies that bind to HIV antigens on test plates. Blood samples that are negative on this test are reported as negative.
 * • Posttest counseling should include an assessment of risk behaviors, especially looking for recent risks.
 * • If recent risks are found, encourage retesting at 3 weeks, 6 weeks, and 3 months.
 * **2**. If the blood is EIA-antibody positive, the test is repeated.
 * **3.** If the blood is repeatedly EIA-antibody positive, a more specific confirming test, such as the Western blot (WB) or immunofluorescence assay (IFA), is done.

**5.** If the results are indeterminate, the following steps are taken: • If in-depth risk assessment reveals that the individual does not have a history of high-risk activities, reassure the patient that she or he is extremely unlikely to be infected with HIV and suggest retesting in 3 months. • If in-depth risk assessment reveals that the individual does have a history of high-risk activities, repeat antibody test at 1, 2, and 6 months; discuss risk reduction measures to protect partners from infection; consider tests for HIV-antigen detection.

with their clinical manifestations.(Heuther 391) (Lewis 254, table 15-11) VERY BIG TABLE LOOK AT THIS__//**
 * //__10. Examine the opportunistic infections and neoplasms associated with HIV infection, along
 * Bacterial infections** are caused by unusual microorganisms


 * Cryptococcal** (FUNGAL) most common & 3rd leading cause of nuero disease
 * Meningitis, cognitive impairement motor dysfuntion, vague symtome fever HA, malaise, meningismus
 * Candida albicans**
 * thrush, esophagitis, vagintis, white yeallow patches
 * Herpes simplex**
 * orolabial vesicular lesions, keratitis-visual disturbances, cns manifestations,
 * Varicella zoster**
 * Shingles
 * Papovavirus**
 * demyelinating disorders, Leucoencephalopathy, metal & motor decline
 * Cytomegalovirus**
 * Retinitis, blurred, loss of vision
 * Toxoplasmosis**
 * focal encephaliti, cognitive impairement
 * Pneumocysistis Jiroveci**
 * Pneumonia, SOB, night sweats, fever, non-productive cough
 * Oral hairy leukoplakia**
 * painless, white, raises lesions on the lateral tongue (sign of disease progression)

11. Analyze the neurologic complications of AIDS.
 * Neoplasms**
 * CNS lymphoma**
 * Large cell tumor presents rapidly developing intercranial lesion
 * systemic non-Hodgkin lymphoma**
 * Invades the meniges, cranial nerves and spinal cord
 * Metastatic Kaposi sarcome**
 * Vascular lesions on skin, Mucous membranes, and viscera wide range of presentation

12. Analyze the cardiovascular complications of AIDS. (pg. 647, Lewis) People w/HIV or AIDS are at risk for dilated cardiomyopathy (caused by extensive coronary artery disease, -ventricles enlarge but are not able to pump enough blood to the body, resulting in heart failure), myocarditis, pericardial effusion, endocarditis, pulmonary HTN, and non-antiretroviral drug-related cardiotoxicity. Tx w/HAART can cause hyperlipidemia and atherosclerotic disease. Left-sided HF is most common complication of HIV infection & is related to left ventricular dilation & dysfunction. Malignancies such as lymphoma & Kaposi sarcoma (often seen in AIDS pts) can affect the heart. Cardiac problems may also be induced by the accompanying inflammatory response to HIV, or by bacterial, viral, protozoan, mycobacterial, & fungal pathogens that may be present due to immunodeficiency.