Ortoski Objectives Flashcards
What are the 3 conditions for transmission of HIV?
HIV must be present in…
- Body fluid
- In sufficient quantity
- Portal of entry into bloodstream
What 3 things is transmission of HIV leading to disease progression dependent on?
- Size of viral inoculin
- Virulence of infecting virus (how fit is the virus and what is it’s replication capacity)
- Patients cytotoxic lymphocyte response (CD8)
What are the 3 basic modes of HIV transmission?
- Sexual
- Blood
- Vertical
What is sexual transmission associated with?
Traumatic sex (anal), multiple partners, and lack of protection
What are some influencing factors with sexual transmission?
Oral/vaginal/anal receptive, no condom, genital ulcer (syphilis, active herpes)
What is associated with blood HIV transmission?
Transfusion/transplant before 1985, drug use, occupational exposure
What can reduce the risk of vertical transmission during pregnancy?
AZT
There are 14 AIDS defining conditions listed… name as many as you can.
- Candidiasis of respiratory system, esophagus
- Cervical cancer – invasive
- Coccidioidomycosis
- Cryptosporidiosis
- CMV (retinitis)
- Herpes simplex chronic ulcers (> 1 mo duration)
- HIV related encephalopathy
- Isorporiasis (chronic intestinal)
- Kaposi’s sarcoma (HHV8)
- Lymphoma
- MAC complex, mycobacterium TB, PCP, toxoplasmosis
- Recurrent pneumonia (>2 infections in 12 mo)
- Progressive multifocal leukoencephalopathy (PML)
- Salmonellosis
What are main general categories of HIV testing?
Antibody testing and viral assays
When can antibody testing be done for HIV?
6 month waiting period exists after infection (the time needed for the immune system to make Antibodies
What are 6 tests for HIV that are antibody tests?
- ELISA
- Western blot
- OraSure OraQuick Advance
- Unti-Gold Recombigen and Reveal G2
- Multispot
- P24 Antigen Capture Assay
What antibody test is a screening test that is non-specific?
ELISA
What antibody test is a confirmatory test with decreasing false results?
Western Blot
What antibody test detects Ab to HIV1 and HIV2 in whole blood, oral fluids, and plasma with results in 20 minutes?
OraSure, OraQuick Advance
What antibody test detects antibodies to HIV1 in serum and plasma?
Uni-Gold Recombigen and Reveal G2
What antibody test detects antibodies to HIV1 and HIV2 in serum and plasma?
Multispot
What antibody test measures the chief component of nucleocapsid?
P24 antigen capture assay
What is a vrial RNA Assay?
Measures the viral load of HIV…HIV RNA by PCR and HIV branched DNA
When is a DNA PCR assay used?
In newborns and needle exposure patiens
When can you say HIV+?
Multiple antibody results or a single viral load assay
Ex. 2 ELISAs and 1 Western Blot
What will be positive with an acute retroviral infection symptoms in a primary HIV infection?
1 Viral Load Assay
ACTG
AIDS clinical trials group
ADAP
AIDS drug assistance program
AMfar
American foundations of AIDS research
CD4 cells
T-Helper Cells
CD8 cells
Cytotoxic Cells
Discordant couples
Those sexually active partners where one is HIV+ and the other is HIV-
Expanded Acess
Initial monitored access to medications prior to public access
HAART/ART
High active antiretroviral therapy (the cocktail)
HIV1
Virus that causes AIDS/ HIV2 most prevalent in Africa
IDU
Intravenous drug user
Immune Reconstitution
Ability of immune system cells to replenish themselves with memory
Index (source) patient
The individual known to have been the source of the infection
MAC/DM Avium
Mycobacterium Avium Complex/ Disseminated Mycobacterium Avium
MSM
Men who have sex with men
Entry Inhibitor
Inhibits HIV entry into the host cells
Integrase
Inhibits integrase within the host nucleus
Inhibitor
Inhibits maturation of virion at exit from host cell
Maturation
Nucleoside reverse transcriptase inhibitors
Inhibitor
Necleotide reverse transcriptase inhibitor
NRTI
Non-nucleoside reverse transcriptase inhibitors
NtRTI
Protease Inhibitors
NNRTI
D4t, ddl, ddC, AZT
Mutations
Amino acid changes that occur within the genome of the virus
Nadir CD4
Lowest number reached
Naive
No prior exposure to a certain drug
OIs
Opportunistic infections, AIDS defining illness
PHI/Acute Retroviral Syndrome
Primary HIV infection: Flu-mono-like symptoms associated with acute infection
Reverse Transcriptase/Protease/Integrase
Viral enzymes, proteins, needed for viral replication
Sequestered virus/mutations
Those viruses or viral mutations that are in the minority and not detectable
Sexual Exposure
Passive versus active/Receptive versus insertive
VL
Viral load- Estimated amount of virus in the blood stream
VL set point
Highest viral load without HAART
Viral Fitness
Ability of virus to replicate in a defined environment
Replication capacity
Reasonable proxy for viral fitness
Viral Reservoir
Areas where virus is maintained and not read into serum viral load assay
Wild Type Virus
Original virus without mutations
Quasi Species
Multiple mutations in the virus of one host
What should be done on examination for HIV infected individual?
- Weight
- LN Enlargement
- CMV retinitis
- Oral Lesion
- Hepatosplenomegaly
- Abdominal masses
- Genital sores/warts/STD lesions
- DRE or anal cancer (caution/not done in severely immunocompromised patients)
- Neuro
- Joint and muscle pain
What serial tests should be done every 3 months and when needed for HIV patients?
- CBC and Plts – leucopenia, anemia, thrombocytopenia (can be due to HIV or meds)
- Chemical profile - Liver enzymes, elevated globulin fraction of total protein, serum albumin, amylase and lipase, renal function (creatinine clearance can dec due to meds, urinalysis shows positive proteins in renal damage)
What are 2 HIV related lab tests done on patients with HIV?
- CD4 absolute count and percent
2. Viral load assays: PCR (bDNA, NASBA)
What are 2 examinations that are done on a different schedule in HIV patients?
- Cervical/Rectal Pap (more frequently done)
2. PSA/Prostate (earlier)
What testing should be done yearly as indicated?
- PPD Mantoux
- STD Testing (GC/CT, RPR)
- Urine Protein (especially for those on tenofovir)
What testing should be done initially and at intermittent screening? (5 things)
- HLAB 5701: For hypersensitivity reaction with abacavir
- Hepatitis A/B/C
- Toxoplasmosis and CMV: Requires baseline IgG
- Free testosterone levels: For wasting/depression in men
- Lactic acid levels: W/ use of D drugs and for unexplained pain
What are 6 vaccines given to HIV patients?
- Hepatitis A/B
- Influenza (yearly)
- MMR
- Tdap
- Pneumococcal
6, HPV (females 9-26)
What vaccines are contraindicated in HIV patients?
LIVE ONES
- Varicella Zoster
- MMR (Only if patients CD4 count is under 200)
What can assess relative risk of disease progression and time of death along with providing an assessment of efficacy of antiretroviral therapies for HIV patients?
Viral Load Assays
What are 3 things that a viral load assay can do?
- Measure HIV
- Study pathogenesis
- Determine HIV Kinetics (replication)
With respect to a viral load assay, equilibrium is established between what?
Viral replication and immune response
True or False: Viral load assays can show viremia when culture reveals none
TRUE
How fast should HIV RNA decrease upon starting treatment?
With in days
If you have an adherent patient, how long until Nadir (or lowest possible viral load count) is reached in a HIV patient after starting treatment?
16-24 weeks
What can increases of RNA viral load reveal?
Outgrowth of drug-resistant HIV-variants or non-adherence to drugs
What RNA level change is associated with a biologically and clinically relevant change?
Over 0.5log10
What are viral blips?
Insignificant low level rises
True or False: Undetectable means eradication
FALSE: Undetectable doesn’t mean eradication…this is not possible with today’s drugs
What are some viral reservoirs?
Lymphoreticular system, GALT (GI Lymph Tissue), CNS, Gential tract
What are 3 uses of CD4 counts?
- Assess extent of immune system damage
- Assess relative risk of disease progression and time of death
- Provide assessment of risk of developing opportunistic infections
What is done with regards to CD4 number?
Prophylactic medication is given
True or False: With immune reconstitution, discontinuation of meds is possible
TRUE
With a CD4 count under 200, what do you give for prophylaxis?
TMP-SMX for pnuemocystis jiroveci (PCP)
With a CD4 count under 100, what do give for prophylaxis?
TMP-SMX for toxoplasma gondii
With a CD4 count under 50, what do you give for prophylaxis?
Biaxin and azithromycin for Mycobacterium avium complex
What is the significance of CD4 Nadir?
When ART is stopped…they body will easily return to the CD4 nadir level
Who should CD4 levels be performed on?
All new diagnosed patients
-Levels can vary up to 30%- Monitoring levels over time is important
True or False: Levels must be monitored (even in untreated patients) to check disease progression and degree of immunodeficiency
True
What % of newly infected patients and resistant to at least 1 drug?
15%- Transmitted drug resistance (some persists in absence of treatment)
What is clinical resistance?
Lack of clinical benefit from antiretroviral agents
Where is the mutation/resistance located at in viral resistnace?
The codon of the enzyme genome
What reveals changes in viral genome that appear as consequence of drug exposure and natural replication?
Genotype testing for genotype resistance
What is the interpretation for genotype testing for gentypic resistance?
For each list of mutations, which drugs will still work in the patient
What reveals the ability of virus to grow in culture despite persistance of antiretroviral agent?
Phenotype testing for phenotypic resistnace
What is the interpretation of phentotype testing for phenotypic resistance?
For each drug, how large a fold change makes the drug no longer work
What does a virtual phenotype reveal?
The % of drugs responses as seen in database of known mutations
What is a trofile?
Tropism test- a specific phenotypic assay
What are the 2 HIV trophisms?
- M-tropic
2. T-Tropic
What virus is M-tropic associated with and what is it attracted to and what is the timeline?
R5 Virus
CCR5 co-receptors (macrophages)
EARLY
What virus is T-Tropic associated with and what is it attracted to and what is the timeline?
X4 Virus
CXCR4 co-receptors (T-cell)
LATE
What does T-tropic X4 virus correlate to?
Rapid progression to AIDS
What does resistance analysis require?
A sample of greater than 1000 viral load copies
What does resistance analysis measure?
Majority variants (20% or more of the viral population)
What can false positives with resistance analysis result from?
Amplification
What is the availability of resistance analysis for genotypes and phenotypes?
Genotypes: Many labs (2-4 weeks for results)
Phenotypes: 2 labs in the world (SF and Ireland) (4-6 weeks for esults)
Nomenclature on reported mutations….what do the 3 components stand for?
M184V
M: AA found in wild type
184: AA position
V: AA substitution
What 3 circumstances do you order resistance testing?
- Acute HIV infection
- All chronically infected patients prior to therapy initiation
- Virologic failure
What is virologic failure?
Failure to achieve or sustain a viral load under 50c/ml after 16-24 weeks of HAART and within 4 weeks after therapy discontinuation
What does it mean for a drug to have a low genetic barrier to resistance?
It is easy for these drugs to obtain resistance after certain mutations
What are 2 drugs that have a low barrier to resistance and don’t kill the virus after a 184V mutation?
Lamivudine and emtricitabine
What is a drug that has a low carrier to resistance and is ineffective with 103 mutation?
Efavirenz and other NNRTIs (Whole class really?)
How many approved agents are there and with how many fixed dose combination medications?
27 approved agents with 7 fixed dose combination medications
What are 5 examples of classes of drugs for HIV?
- Reverse transcriptase inhibitors: Nucleoside, nucleotide, non-nucleoside
- Protease inhibitors: Attachment, CCR5, CXCR4, Fusion, T-20
- Integrase inhibitors
- Entry inhibitors
- Maturation inhibitors
What is important for AIDS patients with regards to opportunistic disease?
Prophylaxis
What is the treatment for wasting syndrome?
-Anabolic steroids, testosterone replacement, appetite stimulants, growth hormone injections, Egrifta, GH-releasing factor analog
What 3 things constitute HIV related illness?
Anemia, dementia, opportunistic diseases
What is one big SE of antiretrovirals?
Lipodystrophy syndrome (fat redistribution and metabolic complications)
What is HAART used for?
Long term management of chronic infection
What are some general guidelines for beginning antiretroviral therapy? (9)
- Acute HIV infection?
- Symptomatic HIV disease
- AIDS defining illness
- Severe symptoms of HIV infection
- CD4 100,000 (treatment may be considered)
- Pregnant women
- Pts w/ HIV-associated neuropathy
- Hepatitis B virus co-infection
What is the goal of therapy?
To get HIV RNA to undetectable levels
-THIS DOES NOT MEAN ERADICATION…virus reservoirs like CNS, lymph, ect.
True or False: Mutated virus can be given to an infected patient by the index/source patient
TRUE
Why shouldn’t monotherapy be used for patient treatment?
Drug resistance and cross-resistance
What is the 1 exception where monotherapy can be used for HIV?
ACTG 076 where AZT alone is given to mother and newborn–> TREATMENT IS AIMED TOWARDS FETUS
When initiation combination treatment, are all drugs started at once?
YES
After initiation, what does the patient have to take their meds at?
THE RECOMMENDED DRUG DOSE
Antiretroviral rug resistance is less likely under what circumstance?
If all therapy is temporarily stopped versus dose-reduction or one component being withheld
Patient education on what is mandatory?
COMPLIANCE
What are the HIV drug interactions due to?
Liver metabolism
NNRTIs decrease the level of what?
PIs
What drugs require dosage adjustment in renal dysfunction?
NRTIs
What drugs can cause liver damage or dysfunction?
AZT, NNRTIs, PIs
What do ED agents like VIagra do to HIV meds?
Increase concentration when given with a bunch of drugs, but NO EFFECT on PIs
Can you use a PPI with a PIs?
NEVER USE PPI with ATAZANAVIR
What are some other drugs that have interactions with antiretrovirals?
-Anticonvulsants, antifungals, anti-mycobacterials (TB drugs), benzodiazapines, cardiac drugs (CCBs), statins, macrolides, methadone (IV drug use), oral contraceptives, grapefruit juice, theophylline, disipramine, st. john’s wort, vitamin E
What does nevirapine cause?
Hepatic necrosis
WHat does abacavir cause?
HS reaction
What causes lactic acidosis (mitochondrial toxicities)?
NRTI or “d drugs”
What does Stevens-Johnson Syndrome?
NNRTI
What does tipranavir cause?
Bleeding and intracranial hemorrhage
What does zidovudine cause?
BM suppression
What drug causes hepatotoxicity?
ALL OF THEM
What 2 drugs cause nephrolithiasis?
Indinivir and atazanavir
What 2 drugs cause nephrotoxicity?
Indinivir and tenofovir
What 2 drugs cause pancreatitis?
Didanosine and stavudine
What are 4 long-term complications of PIs?
CV effects, hyperlipidemia, insulin resistnace, osteonecrosis
What drug can cause CNS effects?
Efavirenz
What class of drugs causes fat maldistribution and GI intolerance?
PIs
What drug causes injection site reactions?
Enfuvirtide
What does dianosine, stavidine, and “d drugs” cause?
Peripheral neuropathy
What is the result of HIV associated lipodystrophy syndrome?
Fat redistribution
This is when there is subQ adipose wasting in face, chest, buttocks, legs and is treated by changing the drug regimen
Lipoatrophy
This is when there is visceral adipose tissue accumulation and resultant increased abdominal girth (crix belly, protease paunch), bloating, and dyspepsia?
Lipohypertrophy
What are 2 other sites of fat accumulation in HIV associated lipodystrophy syndrome?
Breasts and dosrocervical region (buffalo hump)
What are 3 metabolic complications from HIV drugs?
- Dyslipidemia
- Insulin resistance
- Mitochondrial dysfunction toxicities
What is seem in terms of dyslipiemia?
Increase TGs (especially with RTV combinations), increased total cholesterol and LDL, normal HLD
Can you treat a person on HIV drugs with Simvastatin or Lovastatin?
NOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO
What drug induces insulin resistance and decreases insulin secretion?
Indinivir
-This results in glucose intolerance and diabetes
What are some mitochondrial dysfunction toxicities seen?
Lactic acidosis (stop NRTI’s if this condition exsists), peripheral neuropathy, pancreatitis, lipodystrophy, myopathy, cardiomyopathy
True or False: CAD is more prevalent in HIV patients
TRUE
What regimen is linked to more MIs than NNRTI regimens?
PI regimens
Why do you need to order DEXA scans in HIV patients?
They have decreased bone mineral density resulting in osteopenia, osteoporosis, and osteomalacia
How do you treat decreased bone density in HIV patients?
Calcium and Vitamin D
What are 4 things that can cause osteonecrosis (avascular necrosis) in an HIV patient?
- Corticosteroid use
- Alcohol abuse
- Smoking
- Hypercholesterolemia
How do you diagnose avascular necrosis?
CT or MRI
What is given to treat avascular necrosis?
ERT, bisphosphates (fosamax or actonel), evista (estrogen replacement), calcitonin
What are 5 malignancies associated with HIV?
- Kaposi Sarcoma
- Non-Hodgkin’s Lymphoma
- Cervical CA
- Primary CNS lymphoma
- Anal CA
What are the risk factors with Non-Hogkin lymphoma?
- Duration of HIV
- Low CD4
- Older age
- Chronic B cell stimulation
What % of HIV patients with Non-Hodkin’s lymphoma have uncontrolled HIV?
75%
What 3 things are seen in HIV patients with Non-Hodgkin’s Lymphoma?
- Frequent CNS disease
- Poor prognosis
- Survival 6-20 months
What is recommended in both genders for HIV patients to look for dysplasia caused by HPV?
Annual DRE and Rectal Paps
Who is anal cancer more common in in patients with HIV?
Patients over 50, women, blacks, and men who have sex with men
What is seen in the nervous system with HIV patients?
Hepatitis C co-infection and penetration of the BBB
What are the secondary HIV complications relating to the nervous system due to?
Immunosuppression
What are primary HIV complications of the nervous system?
Dementia, encephalopathy, myelopathy, peripheral neuropathy
True or False: Patients with psychiatric disorders are more likely to get HIV, get less treatment, and die.
TRUE
What are 2 renal concerns for patients with HIV?
- Nephrolithiasis
2. Fanconi syndrome (proximal tubular dysfunction leading to acidosis)
Name 8 metabolic issues seen in HIV patients
- Insulin resistance
- DM
- Dyslipidemia
- Lypodystrophy
- Bone Density Loss
- Mitochondrial Toxicity
- Chronic Inflammation
- HTN
Name 8 Organ-Related issues seen in HIV patients
- Liver disease
- Kidney disease
- Peripheral vascular disease
- Cardiovascular disease/MI
- Cerebrovascular disease
- Osteopenia/osteoporosis
- Non-AIDS CA
- CA caused by chronic infection (anal, liver, Hodgkins)
Name 7 neuropsychiatric conditions seen in HIV patients
- HIV-associated dementia
- HIV encephalopathy
- Depression
- Mild neurocognitive impairment
- Delirium
- Depression
- Anxiety
What CD4 count is TMP-SMZ given to prevent pneumocystis jiroveci?
Under 200
What is the mm reaction for mycobacterium tuberculosis to give isoniazid prophylaxis?
Over 5mm
What is required to start TMP-SMZ prophylaxis for toxoplasma gondii?
CD4 under 100 and IgG+
When is biaxin and zithromax given prophylactically for mycobacterium avium complex?
CD4 under 50
When is Varicella zoster immune globulin given prophylactically?
With significant exposure
What CD4 count do you give the pneumococcal vaccine for Strep Pneumo?
Under 200
Do all HIV patients get 3 doses of Hep B Vaccine?
Yes… all that are susceptible
Do all HIV patients get influenza vaccine?
Yes- Inactivated vaccine
Oseltamivir, Rimantadine, Amantadine
Who gets 2 doses of Hep A Vaccine?
All susceptible with chronic Hep C
When is G-CSF given for an HIV patient?
When there is neutropenia
What CD4 count if fluconazole given at for cryptococcus neoformans?
Uner 50
When is itraconazole given for histoplasma capsulatum?
CD4 under 100
When is oral gancyclovir given for CMV?
CD4 under 50 or CMV Ab+
What is given to reduce vertical transmission of HIV from mom to baby?
AZT
What drug is used alone during labor to reduce vertical transmission?
Nevirapine
What is Mom on throughout pregnancy to prevent HIV transmission?
HAART
When is AZT given to the baby?
At birth…given first 6 weeks of life and discontinued at 6 weeks in the DNA PCR is negative
How many DNA PCR positive results are sufficient for newborn HIV diagnosis?
2
WHat is required for exclusion of HIV in newborn?
2 DNA PCR negative results when done at >1 month and >4 months
When are 2 positive antibody tests with confirmatories sufficient for diagnosis of HIV in child?
After 18 months
When may 2 negative antibody tests exclude HIV1 infection?
When both are done at >6 months
Children who havne’t seroconverted should continue to be monitored until they have what?
Negative HIV antibody tests
What if given for PCP prophylaxis in newborn to HIV mom?
Start bactrim at 6 weeks… if HIV + or is positivity is still unknown or negative
What must be given to all HIV-exposed infants?
Vaccinations
True or False: Breastfeeding is contraindicated in an HIV positive Mom
TRUE
There is a better outcome if an HIV-infected individual was treated by a clinician that had at least how many patients they were following?
5
True or False: Clinicians that manage a small number of HIV-infected patients shouldn’t treat without assistance from more expert colleagues
TRUE
