HIV Disease and AIDS

Diagnostic Testing: OraQuick

OraQuick Rapid HIV-1 New, rapid fingerstick-based HIV assay Test results can be obtained in 20 minutes Positive results must be confirmed by Western blot False-negative results can occur

Monitoring HIV Progression

Other laboratory/diagnostic tests used to detect infections/changes CBC Detects anemia, neutropenia, thrombocytopenia (advanced disease) Chemistry panel/screen Chest radiographs Hepatitis A, B, C STDs Hep B and C risks liver failure if it is reacted

Diagnostic Testing: P24

P24 antigen test (p24 ag) do this test if patient comes in after sex with HIV person right away - tests for main core of HIV virus, can test right after exposure/infection Cant do ELISA since they wont have antibodies yet since it takes 3 weeks to 6 months Looks for viral antigen

Diagnostic Testing: neonates

Best method to test neonates: culture virus from blood and peripheral tissue

Pathogenesis: Progression of HIV to AIDS

-AIDS is a syndrome (many diseases) and the virus may express itself in multiple ways -HIV virion enters the body and quickly replicates: present in blood and CSF, not detected by usual lab tests at first, usually asymptomatic, infectious but dont know -over time people will start feel sick -wont get HIV antibodies until 3-4 weeks because it takes time for body to make antibodies which is when they are detectable in lab tests

Monitoring HIV Progression: CD4 lymphocytes

-Absolute CD4+ cell count -Specific indicator of disease progression of HIV to AIDS -CD4+ cell count declines; risk of progression to AIDS, development of malignancies and opportunistic infections increases -Drops below 200 cells/μl: increases number/severity low-virulence diseases and opportunistic infections & Begin use of prophylactic medications Under 200 people get prophylactic antivirals (valtrex),PCP pneumonia (vatrin), and antifungal CD4+ lymphocyte percentage <20%: risk of AIDS development higher Monitor viral load and CD4 Want viral load low and CD4 high The more cd4 falls the higher risk of infection

Successful factors for antiretroviral therapy

-Appropriate polydrug therapy -Compliance and convenience of dosing -Early detection of HIV -Low baseline viremia -High CD4+ counts -Most importance for success is compliance** -Frequent follow up - make sure CD4 is high and low viral load -HIV resistance is a major problem for successful therapy -Most important for success: patient compliance

AIDS diagnosis

-CD4 t cell count less than 200 -one or more opportunistic infection (even if cd4 is greater than 200) -one or more tumor or cancers -once you drop under 200 for cd4 count you have aids even if you go over 200 again -CDC and WHO have diagnosis for AIDS

Cardiovascular Manifestations

-Cardiovascular events, hypertriglyceridemia, lipidemia -Cardiovascular and renal disease higher in HIV patients not effectively treated -Immunosuppression/HIV viremia/HAART involved in pathophysiology of cardiovascular disease -HIV therapy may help protect from HIV-induced cardiovascular disease -A lot due to medication the patient takes which causes high lipid levels leading to cardiovascular disease in PT not effectively treated -Even though side effects raise lipid levels, HIV therapy protects against heart attacks and strokes

Gastrointestinal Manifestations (cont)

-Chronic diarrhea leads to cachexia -Oral candidiasis - white tongue plaques -Oral leukoplakia - white plaques on tongue with black stuff on it -Anorexia -Nausea/vomiting -Mucous membrane ulcers -Primary manifestation or secondary to inflammation -Retrosternal pain on swallowing -Abdominal pain -Low serum vitamin B12 - poor absorption -AIDS people will get oral prophylaxis to prevent candidiasis

Antiretroviral Therapy Recommendations

-Current recommendations: start therapy for: -Anyone with AIDS-defining illness or severe symptoms at any CD4+ count or viral load -All asymptomatic HIV-infected persons with a CD4+ cell count <350 cells/mm3 -Anyone with HIV-associated nephropathy renal failure or hepatitis B virus (HBV) coinfection -You can have aids with a decent cd4 count (like if you have PCP) -Get started on HAART if you have aids defining criteria regardless of CD4 count

Drug therapy evolution

-Drug management has evolved from monotherapy to polydrug therapy: ART and HAART -Provides better viral suppression -Complete viral elimination is currently not possible -Continuous therapy produces best results -Polydrug due to genetic mutation and resistant in drugs caused by lack of compliance -Poly drug called HAAART but just dropped the H so now just AART (highly) Active antiretroviral therapy -Suppress viral replication and increase t cell count -Requires daily dosing and compliance

Neurologic Manifestations

-HIV encephalopathy -Symptoms: Inattentiveness, confusion, forgetfulness, concentration loss,Slower verbal response,Headache, Apathy, Inability to complete, perform complex tasks -Way advance aids -Affects brain function

Pathogenesis: viral production and cell death

-HIV replicates prolifically from infection onset. high level of virion turnover (replication) overwhelms body's defenses / high level of CD4 turnover (cell death) - HIV infected cells undergo viral budding to generate and produce new virions -GI major site of replication -from onset/contact replication occurs. pt may not feel anything initially, but as the viral load increases, ppl feel flu like symptoms -high levels of virions (little pieces of virus) made every second and overwhelms bodies defenses -high level of CD4 turnover induces apoptosis/ also induces apoptosis of B cells which makes antibodies -HIV infected cells undergo viral budding to generate and produce new virions that go on to replicate more -HIV replicates very rapidly and in order to reproduce rapidly it needs to replicate in an area with high cell turnover like GI tract -a lot of clinical manifestations are GI in nature b/c of this

Systemic manifestations

-Malnutrition/wasting syndrome -Unintended, involuntary loss of greater than 10% of body weight due to HIV infection -Major muscle wasting -Malnutrition from elevated metabolic rate, chronic inflammation, malabsorption, anorexia, decreased food intake, effect of multiple opportunistic insults -A lot are GI in nature -These are people who arent being treated or are inadequately treated

Gastrointestinal Manifestations

-Nearly universal in HIV-infected people; GI tract may be major target organ -Major GI complication—chronic diarrhea -Watery or bloody -Causes malabsorption/severe weight loss that leads to muscle loss, increased morbidity, death -Treatment: antiemetics and antidiarrheals -Oral candidiasis white plaques on tongue

Mucocutaneous Manifestations: neoplasms

-Neoplasms: Kaposi sarcoma, squamous cell carcinoma, basal cell carcinoma, cutaneous lymphomas -Kaposi sarcoma: AIDS-related malignancy, Affects skin, mucous membranes, lymphatics, other internal organs -One of few neoplasms that indicate immune systems dysfunction -Kaposi sarcoma - exclusively in people with immunodeficiency , purple lesions all over body, can also affect internal organs -Can get a number of carcinoma: adenocarcinoma, carcinoma of mucous membrane because of rapid replication of these areas / get carcinoma of tissue that rapidly turns over -Usually carcinoma of mucous membranes -Basal cell carcinoma - aids defining even if cd4 count is okay

Mucocutaneous Manifestations

-Occur early and late in HIV -HIV viral exanthem—usually first symptom -Erythematous, fine maculopapular rash on face, trunk, and arms -Self-limiting: in 40% to 60% of HIV infected people -Viral exanthema - rash that appears when first exposed , red, fine, maculopapular (little bump with red base)

Pulmonary Manifestations: PCP pneumocystis jirovecii pneumonia

-PCP most common opportunistic infection of AIDS defining criteria -Incidence has decreased with use of prophylaxis (vatrim) -With immunodeficiency and CD4+ cell counts <200/μl, pneumocystis activates causing PCP -Nonspecific symptoms: flu-like fever, fatigue, weight loss -Major pulmonary feature: severe hypoxemia, PaO2 <60 mm Hg normal is 82-100 -Very lethal because fluid build up causes hypoxia and can die -PT with HIV diagnosis and presents with symptoms of pneumonia, concern is of PCP and treat them empirically for PCP with IV antibiotics -Pt with PCP don't oxygenate because they get a lot of fluid in the lungs and cause inflammation and gas cant pass through water/ poor ventilation leading to poor perfusion

Monitoring HIV Progression: plasma viral load

-Plasma viral load -Indicates amount of viral replication and the effectiveness of therapy -Helps predict disease progression -Level of HIV RNA in plasma strongest predictor of outcome over time -Goal: reduce viral load -Plasma viral load indicates amount of viral replication going on; helps check disease progression -If viral load is detectable, work to get that load down

Other system manifestations

-Renal impairment: HIV affects kidneys, causes AIDS-associated nephropathy, drug-induced ischemia, renal failure -Hematologic impairment: Anemia, thrombocytopenia, granulocytopenia -Liver dysfunction: Increased risk of concomitant hepatitis C, B; Effects of multiple drugs taken for HIV -Hep C alone without HIV is high risk of hepatocellular carcinoma, with HIV / AIDS super high risk for liver cancer

Pulmonary Manifestations: PCP

-Severe pulmonary symptoms similar to ARDS: decreased surfactant production, early dry cough, dyspnea, tachypnea, chest discomfort, marked pallor, cyanosis -Diagnosis: chest radiography, Wright-Giemsa stain (sputum); other tests include bronchoalveolar lavage, biopsy, gallium scanning -Definitive diagnoses is sputum -Culture biopsy- definitive diagnosis anytime -Bronchoalveolar lavage - sending actual tissue to lab so pretty diagnostic - breathing tube in, wash lungs out, get some cells in normal saline, suck normal saline out and send it to lab

HIV/AIDS overview

-acquired immunodeficiency disorder that results in a defective immune functioning -HALLMARK: defective cell-mediated immunity -there is a decrease in CD4+ (t-helper/inducer) lymphocytes, which normally mediate between antigen-presenting cells and B cells and other T cells -HIV virus get via exchange of bodily fluid (sex, sharing needles) -HIV leads to development of AIDS but having HIV does not mean you automatically have AIDS -effects helper t-cells (CD$ lymphocytes) so decreases cell-mediated immunity -also affects antibody production because needs t cells to help plasma cells make antibodies so affects humoral immunity 2 types of immunity in adaptive immune system: humoral and cell mediated: humoral also depends on helper t cells - cant make antibodies w/o helper t cells/ cd8 attacks viruses and cancer and infectious agents

symptoms of chronic HIV infection

-complete anergy; no response to skin testing -complete chronic anergy is when immune system is so weak that it cant mount an immune response/ skin test for TB comes back negative because PT doesnt have t cells for the reaction/ no response as body cant produce type 4 hypersensitivity reaction since it doesnt have enough t cells to react to antigens -severe viral/fungal skin/mucous membrane infections -oral and genital herpes simplex infections may develop, also oral hairy leukoplakia -75-85% of people have herpes but don't get blisters because immune system can keep it under control but HIV people cant so get blisters a lot -HIV hair - fine, straight, thin

When PT seroconverts they get a number of signs of inflammation:

-elevated SED rate (erythrocyte sedimentation rate ESR) , which is the rate at which RBC will sediment in one hour; says body has inflammation just doesn't say where -ESR is the rate at which rbc fall in a tube per mL (the higher the rate the greater the inflammation) -blood cells sticky b/c of fibrinogen and when there is inflammation there is increase in fibrinogen so cells get sticky and dense and stick faster -when pt has infection (viral or bacterial) sed rates will be high -crp test (c reactive protein test) is a measurement of inflammation (nonspecific) that says there is inflammation but doesn't say where -high levels of virus in genital fluid when initially infected (highly infectious from primary infection to seroconversion even if asymptomatic)

Diagnostic testing: ELISA

-enzyme-linked immunosorbent assay: get back in a couple mins, days, hours -positive for HIV antibodies if blood or oral mucosal transudate of an infected person reacts with the surface antigen of a killed HIV virus -highly sensitive and specific & must be performed for HIV1 &HIV2 -tests for antibodies; if you dont have HIV antibodies you negative, but doesnt mean you dont have aids-can be highly infectious) -quick, cheap test -western blot is confirmatory test that is more expensive and uses electrophoresis to identify diagnosis of HIV antibody -Elisa is screening -When doing ELISA test for HIV 1 and 2; HIV1 strain is more common in North America and Europe HIV2 is less virulent seen in sub-Saharan Africa Medication is based on the genetic makeup of the HIV strain you have- type of HIV determines what treatment you get

Symptoms of primary HIV infection

-flu or mononucleosis like symptoms -cd4+ t cell count greater than 400 cells /microliter -decreased number of WBC including lymphocytes except for increased number in cd8+ t cells since they fight cancers and viral infections -decreased platelets -elevated ESP -HIV count in genital fluids very high & very infectious even when symptoms go away in 1-4 weeks

AIDS diagnosis symptoms

-general symptoms are coughing, SOB, difficult/painful swallowing, mental symptoms, severe/persistent diarrhea, fever, vision loss, nausea/vomiting, abnormal cramps, weight loss, extreme fatigue, severe headaches -affects all organs -cachexia, cough, SOB, pain, memory blocks, skin lesions, thin, fatigue b/c anemic -diarrhea because a lot of turnover in GI tract and virus replicates there

Pathogenesis: effect on immune cells at cellular level

-hallmark of HIV infection: decreased CD4 t-helper/inducer lymphocytes -macrophages become functionally impaired as infection progresses and also contribute to T-cell decline by increasing CD4 cell death -macrophages are wbc involved in phagocytosis and become frequently impaired as PT HIV progresses -contributes to a decline in helper T-cells -B cell changes: overproduction of nonessential antibodies, antibodies ineffective against disease, increased apoptosis -b cells are plasma cells that make antibodies...infection results in them making ineffective antibodies

Pathogenesis: viral production and cell death 2

-long term survival need is low viral load and strong CD8 CD4 killer t cell activity -acute infection: HIV widespread throughout body with viremia and viral seeding of lymph tissues -survival: some ppl are genetically unable to get HIV because they lack receptors on cells (European descent) (120 receptor crs5 receptor) -some people are rapid progress and get AIDS in 2 years -most people dont progress to aids until 10-12 years -some people may not progress if getting good treatment -long term survival need is low viral load and high t cell count (CD4?). Low viral load means there is undetectable amount in blood, less than 40,000 copies). still have HIV and can infect people

symptoms of chronic HIV infection 2

-persistent skin rashes, flakey skin, ST memory loss, PID nonresponsive to treatment -children have growth delays and frequently get sick -may develop opportunistic infections -women get PID that isnt responsive to treatment

etiology

-rna retrovirus that causes defect in cell mediated immunity that may progress to AIDS -viral RNA must be converted to DNA before viral genes can be expressed to make copies of RNA virus -once cells get infected, virus has RNA that must be converted to DNA to make copies of the viral gene in order to proliferate more -virus incorporates itself into cell DNA and messages to make more viral RNA ro make more HIV virus and more RNA that gets copied into the DNA -rapid proliferation

Pathogenesis: seroconversion

-seroconversion is when there are enough antibodies in the blood to detect the virus -PT usually seroconverts between 3 weeks and 6 months after exposure -signs and symptoms of acute retroviral syndrome or primary HIV infection (flu like symptoms that can mimic other viral illnesses) -refers to period in time that the pT has antibodies to HIV (enough that can be detected in blood) -if PT hasn't seroconverted yet and they are exposed then they are very contagious because rapid replications is occurring but its not evident by checking antibodies -if PT is seroconverted they can detect antibodies on blood work

Monitoring HIV Progression: anergy

Anergy/delayed hypersensitivity (type IV) test Tests for M. tuberculosis, mumps, or measles viruses Early HIV: skin test results normal Advanced cases: patient has no response to testing

Treatment Goals

Antiretroviral Therapy Recommendations: Delay disease progression Avoid drug resistance Minimize clinical manifestations Prolong survival Compliance used to be an issue with medications because there were 30 pills daily, now there is 3 in 1

CDC HIV classification (CD4 t cell count and symptomatic way)

CD4+ T-cell categories Category 1: CD4+ T-cell count ≥500/μl Category 2: CD4+ T-cell count ranges from 200/μl to 499/μl Category 3: CD4+ T-cell count <200/μl AIDS symptomatology way to diagnose aids is mutually exclusive of t cell count; cervical cancer, TB, pneumonia you have AIDS no matter CD4 #

empirical vs. prophylactic treatment

Empirical treatment - symptoms look like you have it but we don't know for sure Prophylactic - treat to prevent . Don't have anything

Diagnostic Testing: Western Blot

Used when ELISA test is positive Used to confirm the presence of HIV Uses electrophoresis (very expensive) Identifies specific antibodies against the HIV protein antigen Specificity (in combination with ELISA) >99.9% Patient must wait 1-2 wk for confirmation Now may have to wait less than a week