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63 Cards in this Set

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  • Back
What was the first FDA approved anti-HIV drug?
AZT in 1987 (zidovudine)
Describe the 3 phases of the FDA drug approval process:
Phase 1: 20-80 healthy volunteers test the drug's safety.

Phase 2: 100-300 patients with the disease assess the drug's effectiveness and identify side effects.

Phase 3: 1000-3000 patients verify effectiveness and identify adverse reactions.
About _____ drugs that begin a clinical trial is approved for consumer use.
1 in 5
List the 4 classes of drugs currently in use:
1. Reverse Transcriptase Inhibitors
a. non-nucleoside analogs
b. nucleoside analogs
2. Protease Inhibitors
3. Integrase Inhibitors
4. Entry and Fusion Inhibitors
What are the current standards of HIV therapy?
-All anti HIV drugs must be used in combination.
-Antiretroviral Therapy (AVT) includes 3 or more drugs: 2 RT & PI
-It is more difficult for viruses to develop that are resistant to several drugs.
-The drugs slow replication of virus and slow mutation rate.
Salvage Therapies
New treatment regimens for patients with resistant HIV.
Cross Resistance
When HIV becomes resistant to one drug, it may easily become resistant to other drugs which function in the same manner.
What are the 2 markers used to evaluate effectiveness of anti-HIV drugs?
1. T4 and CD4+ cells
Important because they need to be up to prevent opportunistic infection.
2. Viral load
Current guidelines for starting anti-viral therapy:
-If T cell count is 350 or higher, don't start medication unless viral load is 55,000 or higher.
-If T cell count is between 200-349, treatment should be considered.
-If T cell count is below 200, treatment is indicated.
Phenotypic
Drug resistance testing where drug is added to a sample of the patients virus to see if the drug can stop the growth of HIV.
Genotypic tests
Drug resistance testing which sequences the virus and looks for known resistant mutations in the reverse transcriptase and protease genes. This is cheaper and faster.
Can HIV be cured?
No, because there is no way to remove the provirus from the cell's DNA.
List important side effects:
-liver damage/failure
-diabetes
-lipodystrophy (abnormal accumulation of fat in back and abdomen)
-high cholesteral
-high triglycerides
-heart disease
-bone loss
-kidney stones
Current problems using HIV therapy:
1. Duration: for life
2. Adherence or compliance: taking all drugs at the scheduled times.
3. Cost - $19000-150000 per year
4. Side effects can be severe
How could HIV drugs make things worse?
-Antibiotics help spread and strengthen bacteria which cause STDs.
-When penicillin became available, STD edu ended.
-The sexual rev was spurred on by a belief STDs were curable.
-HIV mutates quicker than any other virus and strains have evolved to evade every drug.
-New combination therapies are expensive and difficult to take (non-compliance increases number of resistant strains)
-Apathy & a false sense of security - AIDS prevention efforts have faltered. Infection rates have remained high and unsafe sex practices low.
What is a surrogate marker?
A physiological measurement that serves as a substitute for a major clinical event.
After starting antiretroviral therapy, what is an acceptable target for virus load that indicates therapy is effective?
5000 copies/mL
When your virus becomes resistant to a drug in your drug combination, your viral load may go up. Resistance is an all or nothing deal - the drugs work perfectly or not at all.
False
Functions of the immune system:
1. Distinguish between self and non-self.
2. Filter out foregin substances.
3. Destroy and remove pathogens.
4. Control normal flora & prevent from overgrowth.
5. Remove damaged and dead cells.
6. Destroy mutant and cancer cells.
Without an immune system:
1. Any microbe can grow to high numbers in the body and cause disease.
2. Microbes normally found in a healthy body are in a large number and cause disease.
3. Antimicrobial drugs help stop microbes from growing, but ultimately the microbes become resistant and cause disease.
4. Higher risk of cancer.
Antigen
(foregin invader) anything that is recognized as foregin or nonself by the immune system.
Antibody
(defensive weapon) a Y-shaped protein which is produced and secreted by B cells in response to a specific antigen. Antibodies bind to and contribute to the destruction of antigens.
Characteristics of T cells
-Derived from bone marrow and mature in the thymus.
-Make 70-80% of circulating lymphocytes.
-Each T cell has a T cell antigen receptor which recognizes a peptide bound to a self MHC molecule
-Do not recognize soluble antigen
-Antigen must be displayed on surface of an antigen presenting cell like a B cell or macrophage.
Two types of T cells and their functions:
1. Helper T4: conductor of the immune system. Activates other cells of the immune system. Target of HIV.
2. Cytotoxic T8: Destroy target cells on contact.
How does the immune system distinguish between self and non-self?
-All body cells have class 1 MHC proteins on their surfaces that mark the cells as self.
-Immune system tries to destroy anything that does not have class 1 proteins because they are nonself or antigens.
What cells does HIV infect?
-T4 cells
-Macrophages, dendrite cells, scavenger white blood cells that digest antigens.
What percent of HIV is in lymph nodes?
98%
What percent of HIV is in blood?
2%
What happens as a HIV infection progresses?
-HIV replicates rapidly in lymph nodes and generates lots of mutant strains.
-B cells produce antibodies against each new variant of HIV until they are overwhelmed.
-Viral load relates to production rates: clearance is constant.
How does HIV infection lower the number of T4 cells?
1. Directly-HIV replication sometimes kills cells
2. HIV can fill CD4 receptors with free gp 120, cell cannot function and will be destroyed.
3. HIV can cause syncytia formation - T4 cells fuse together.
4. HIV can produce superantigens - cause loss of response.
5. HIV can trigger apoptosis (cell suicide)
6. Autoimmune mechanisms - HIV may trick the immune system into attacking itself.
7. Cofactors help deplete T cells
- poor nutrition, stress drugs, other infections.
8. HIV may cause less T cells to be produced
Opportunistic Infections
-Disease caused by microorganism that normally live in or on the body without causing disease in people with normal immune systems.
-Suppression of the immune system allows for harmless to become harmful.
-Caused by viruses, bacteria, fungi and protozoa that are kept in check by an intact immune system.
-Caused by over 100 microbes
-Can become disseminated (systemic)
Cause of death related to HIV:
-90% opportunistic infection
-7% cancer
-3% others
Why did opportunistic infections decrease in 1997?
Due to use of protease inhibitors
Six most common opportunistic infections:
1. Bacterial pneumonia - numerous causes
2. Mycobacterium avium - complex disease
3. Mycobacterium tuberculosis
4. Pneumocystis carnii - pneumonia
5. Candida albicans - esophagitis
6. Herpes simplex virus
Worldwide, ________ is the leading cause of death in HIV infected people.
tuberculosis
List 4 fungi and the diseases they cause:
1. Pneumocystis carinii - pneumonia
2. Candidias - oral thruch, esophagitis, vaginitis
3. Histopiasmosis - Histoplasma capsulatum
-inhaled spores, pneumonia, dissemination to other organs
-flu like symptoms, shortness of breathe
4. Crytococcus neoformans - meningitis, pneumonia
Herpesviruses are a big problem for AIDS patients.
True
List 4 Herpesviruses and the diseases that they cause:
1. Herpes Simplex (HSV 1 & 2)
-mouth, genital, rectal
2. Cytomegalovirus (CMV)
-fever, hepatitis
3. Varicella zoster virus (VZV)
-shingles, encephalitis
4. Epstein-Barr (EBV)
-oral hairy leukopiakia, B cell lymphoma
List 2 non-herpes viruses:
1. Human papilloma virus (HPV)-warts
2. Hepatitis C (HCV) - hepititis
Nairobi prostitude study:
-Repeated exposure to HIV - 25% or more of clients are HIV+
-Free of disease for more than 12 years and completely resistant to infection
-Association between their resistance to infection and their class 1 and class 2 MHC.
-This particular class of 1 MHC
--may allow very high efficent cytotoxic T cell responses.
--may present highly conserved parts of different HIV strains
-The key epidemiologic correlate of late seroconversion was a reduction in sex work over the preceeding year.
-In persistently uninfected controls, a break from sex work was associated with a loss of HIV- specific CD8+ responses.
-May relate to the waning of HIV- specific CD8+ responses due to reduced antigenic exposure
Kaposis's sarcoma is caused by HIV
False - HIV has not been found in KS lesions. There is a Kaposis's sarcoma virus aka HH8 that grows and causes cancer when the immune system is suppressed.
Neuropathis
Functional changes in the PNS. Nerve damage characterized by sensation of pins and needles, burning, stiffness or numbness.
Window period
Time before seroconversion, anti HIV antibodies are not detectable.
-Give a false negative HIV test
-High viral replication
-May infect others
Clinical latency
Period from infection until expression of opportunistic infection; may last 1-20 years, average is 10 years.
Four Stages of HIV Disease:
1. Acute or Primary Infection Stage
2. Asyptomatic HIV disease stage
3. Chronic Symptomatic HIV disease stage
4. Advanced HIV disease stage: AIDS
Acute of Primary Infection Stage - Acute retroviral syndrome
2-8 weeks after infection
70% of people have brief flu like illness
High levels of HIV in organs
- Very infectious
Asyptomatic HIV disease stage
6 months to 11 years
Set point: steady state of HIV replication
T4 cells constantly destroyed and replaced.
-Infectious to others
Chronic Symptomatic HIV disease stage
Last months - years
T4 cells drop to 200 or less per mL of blood
Fever, weight loss, loss of appitite, night sweats, etc.
Destruction of lymph nodes
Onset of opportunistic infection and cancer
Advanced HIV disease stage: AIDS
Final stage of HIV infection
T4 cell count below 200 per mL of blood
Long term non-progressors (with out drugs)
0.8% of people infected by HIV don't develop AIDS
- About 1 in 3000 people can maintain no more than 50 copies of HIV/mL of blood over a period of at lease 1 to 2 years despite never having taken antiviral meds
Six causes of long term non-progressors:
1. High level of responsive cytotoxic T8 cells
2. Defective viruses
3. HIV specific neutralizing antibodies
4. Increased numbers of CD4 T cells specific for p24, HIV viral capsid protein.
5. Low levels of spontaneous lymphocyte apoptosis (programmed cell death) compared to progressor
6. Mutant CoKR5 coreceptor gene - more common in caucasians of European decent.
HIV infection of the CNS:
-O.I. malignancies and HIV infection of CNS causes neurological dysfunction.
-HIV invades brain within a few weeks after HIV enters the body.
-HIV infected macrophages migrate to brain
-HIV does not infect neurons
-HIV in the CNS may evolve independently from HIV in the blood
-Progressive dementia due to HIV in the CNS develops in 55-65% of AIDS patients.
-Mental impairment begins after HIV infection becomes symptomatic.
Four types of cancer common in AIDS:
1. Kaposis's sarcoma - linked to HHV8 outgrowth of blood vessels
-disseminated lesions involving skin, lymph nodes and organs
-more common in homosexual men
2. Lymphoma - generalized lymphadenopathy, site of growth at brain, heart and anorectal area.
3. Progressive multifocal leukoenphalopathy (PML) - caused by Papovavirus JCV - 4% of AIDS patiets, fatal, no treatment
4. Squamous cell carcinoma - anal, oral
How is HIV transmitted?
1. Sex - anal, oral, vaginal
2. Parenteral - IV drug users, blood transfusions.
3. Perinatel - mother to fetus, in utero, during delivery
HIV is NOT transmitted by:
Insects
Toliet Seats
Casually by household contact
Kissing, hugging, etc
Urine
Saliva
_________ percent of untreated HIV+ pregnant women pass the infection to their babies.
25-33%
____ percent of treated HIV+ pregnant women pass the infection to their babies.
3%
What is the most common route of HIV transmission?
unprotected sex
The proportion of AIDS cases among black Americans doubled between 1985 and 2006, a sharp increase compared to the other most populous ethnic groups.
True
HIV is found in almost all body fluids EXCEPT:
Sweat and bronchial fluids
Where is HIV found in greatest number?
Within T4 cells, macrophages of blood, vaginal fluid and semen.
- Low levels of cell free HIV is found in these fluids.
Among hetrosexuals, HIV transmission from male to female and from female to male are equally efficent.
False - HIV is more efficently transmitted to females
Unprotected receptive anal intercouse the the sexual activity with the greatest risk of HIV transmission.
True