Chapter 12 Flashcards
Hallmark of AIDS and HIV
- decrease in CD4+ (t-helper/introducer) lymphocytes
Epidemiology of AIDS
- primary immunodeficiency caused by the retroviruses HIV type 1 and type 2
- virus has continued to mutate and spread globally
- increasingly becoming a disease of poor, uneducated, or undereducated people of color
HIV type 1
- thought to have originated in central africa
- cause of most AIDS cases found in central africa, US, Europe, Australia
- has at least 10 subtypes
HIV type 2
- thought to have originated in west africa
- found primarily in west africa
- characterized by a longer latency/asymptomatic periosd, a milder form of the disease and lower mortality rates, can progress to AIDS
Transmission of AIDS
3 types
- sexual (most common)
- parenteral
- perinatal
Parenteral
transmission via blood, blood products, or blood contaminated needles or syringes
HIV (Human immunodeficiency Virus)
RNA retrovirus that causes defect in cell-mediated immunity that may progress to AIDS
Chemokine Coreceptors
must be present for the virus to gain entry into cells in order for the virion to fuse with the host cell
- CCR5 must be present for HIV particles to bind to CD4+
- CXCR4 must be present in later infection
Antiretroviral Therapy
This polydrug therapy approach
involves the administration of multiple antiretroviral agents. It provides
better viral suppression, thereby decreasing viral load, increasing
CD4+ counts, and decreasing resistance for a longer period.
AIDS B cell changes
overproduction of nonessential anitbodies
antibodies are ineffective against diseases
increased apoptosis
HIV disguises itself
with large amount of carbohydrate on surface of gp120
Acute Infection oh HIV
HIV is widespread throughout body, with viremia and viral seeding of lymph tissures
Progression to asymptomatic phase
seeded HIV replicates in lymph nodes; graduly destroy’s lymph tissues
Verimia
virus enters the blood stream; recurs after lymph tissues are destroyed
AIDS
is syndrome, the virus can express itself in multiple ways
HIV virion
- enters body and quickly repllicates
- present in the blood and cerebrospinal fluid
- not detected by usual laboratory tests
- usually asymptomatic
Seroconversion
the time in which enough HIV antibodies develop and become detectable in the blood
- occurs between 3 weeks to 6 months after exposure
Symptoms of primary HIV infection
- flu or mono like symptoms
- CD4+ t cell count greater thatn 400cells/ul
- ## elevated ESR
ESR
erythrocyte sedimentation rate - a measurement of sedimentation
CRP
C reactive protein - preferred test for inflammation
Clinical latency period after seroconversion
ranges from 3 to 12 years
- CD4+ cell count greater that 400/ul
- virus is extremely active, producing up to 2 mil per day
Rapid virus production after latency period
persistent and continuing drop in CD4+ T-cell count to less than 400/ul
Symptomatic stage/chronic HIV infection
- complete anergy, no response to skin testing
- development of skin/membrane infections/problems
- in children there are growth delays and they are frequently sick
AIDS Diagnosis
- CD4+ t cell count is less than 200/ul
- one or more opportunistic infections
- one or more tumors or cancers
- most common symptoms are night sweats, fever, and nausea
Steps of HIV
infection of mucous tissue -> death of mucosal cd4+ cells -> Infection establishes in lymph tissues -> infection spreads throughout body -> immune response -> clinical latency -> AIDS
CD4+ T cell categories
Category A = count >or= 500ul
Categoty B= count ranges from 200 to 499
Category C= count < 200
Clinical Category A
variety of clinical conditions, asymptomatic persistent generalized lymphadenopathy, history of or current acute HIV infection
Clinical Category B
conditions secondary to impaired cell mediated immunity
Clinical Category C
Conditions listed in AIDS surveillance case condition
ELISA (enzyme - linked immunosorbent assay)
- positive for HIV antibodies if blood or oral mucosal transudate of an infected person reacts with the surface antigen of killed HIV virus
- highly sensitive and specific
- must be performed with both HIV 1 and 2 viral antigens
Western Blot
- used when ELISA test is positive
- used to confirm the presence of HIV
- uses electrophoresis
- identifies specific antibodies against the HIV protein antigen
- specificity (combo’d with ELISA) > 99.9%
- patient must wait 1-2 wks for confirmation
Absolute CD4+ cell count
- specific indicator of disease progression of HIV to AIDS
CD4+ lymphocyte percentage
<20% risk of AIDS development is higher
Plasma Viral Load
- indicates the amount of viral replication and the effectiveness of therapy
- helps to predict disease progression
- goal: to reduce viral load
Genotypic Resistance Testing
- identifies gene mutations
- very expensive
HAART Therapy
Highly Active Antiretroviral Therapy
Anergy/delayed hypersensitivity (type IV) test
- tests for M. tuberculosis, mumps, or measles viruses
- Early HIV: Skin test results normal
Megestrol acetate
a progestational agent; patients are at risk for blood clots in the legs
Dronabinol
antiemetic: decrease nausea and increase appetite
Systemic Manifestations of HIV/AIDS
-Malnutrition/wasting syndrome
Gastrointestinal Manifestations
- nearly universal in HIV infected people
- chronic diarrhea is a Major GI complication (common cause is protozoa cryptosporidum)
- candida albiacans infections
GI Symptoms
- chronic diarrhea
- oral candidiasis
- anorexia
- nausea/vomiting
- mucous membrane ulcers
- retrosternal pain on swallowing
- abdominal pain
- low serum vitamin B12
Pulmonary Manifestations
- major source of morbidity/mortality in AIDS patients
- opportunistic pneumonias
- parenchymal lung diseases
Mucocutaneous Manifestations
- occur early and late in HIV
- HIV viral exanthem is usually the first symptom
- can have allergic, infectious, or neoplastic origin
Types of Mucocutaneuous manifestations
herpes zoster oral hairy leukoplakia Herpes simplex 1 & 2 S aureus Fungal skin infections Kaposi Sarcoma
Gynecologic manifestations
persistent monilial vaginitis, cervual dysplasia, cervical neoplasia, PID
Neurologic Manifestations
- neurologic system is invaded early
- primarily HIV encephalopathy
Ocular Manifestations
CMV retinitis
HIV associated retinopathy
Cardiovascular Manifestations
hypertriglyceridemia
lipidemia
Manifestations in other systems
renal impairment
hematologic impairment
liver dysfunction
endocrine dysfunction
Major classes of Antiretroviral Therapt
nucleotide reverse transcriptase inhibitors (NRTIs)
Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Protease Inhibitors (PIs)
fusion inhibitors
Integrase strand transfer inhibitors (INSTIs)
CCR5 antagonists
NRTIs
prevent HIV replication by preventing DNA synthesis
NNRTIs
inhibit reverse transcriptase
do not need to be converted intracellularly
potent antiretrovirals
only given in combination with other antiretrovirals
Protease Inhibitors
inhibits protease that clips the viral protein precursors to the appropriate size
extremely expnsive
names typically end in “vir”
Fusion inhibitors
blocks fusion between viral and target cell membranes
CCR5 antagonists
blocks infection by blocking CCR5 and preventing HIV binding to cell membrane
Integrase transfer inhibitors
target and inhibit integrase encoded by the viral pol gene
