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HIV clinical aspects II
cmbm exam V
75
Chemistry
Graduate
02/13/2010

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Term
define HAART
Definition
highly active anti-retroviral therapy - applies to most current anti retroviral therapy, includes protease inhibitors etc
Term
what is the first 1-6 wks of HIV infection characterized by?
Definition
viral load increase followed by dramatic CD4+ decrease
Term
what is the next 6-8 wks of HIV infection characterized by? what happens in this time?
Definition
gradual leveling of CD4 cells = clinical latency, this is the time where 25% of HIV infected individuals are unaware and spreading disease
Term
what is the first 5 years of HIV infection characterized by?
Definition
some symptoms manifest themselves: diarrhea/vomiting
Term
what happens around year 7-8 in HIV infected individuals?
Definition
opportunistic infections and malignancies begin to arise
Term
what happens around year 8-9 in untreated HIV infected individuals?
Definition
death
Term
what % of pts do not follow the expected curve of HIV infection?
Definition
2-3%
Term
what are rapid progressors?
Definition
pts who go through the "natural curve" of HIV within a year
Term
who are non-progressors?
Definition
HIV+ pts with low viremia, relatively normal CD4+ counts
Term
has HAART use been effective?
Definition
yes since 1995, the number of AIDs cases/deaths has dropped and the CDC estimates that from 1994-2003, ~ 3 million lives have been saved by HAART
Term
what is the avg life expectancy for HIV+ pts? is there a disparity across race?
Definition
HIV+ life expectancy is from 10.5 - 22.5 years, which is higher for whites relative to blacks and hispanics
Term
what is maraviroc (MVC)? what are some concerns associated with its use?
Definition
maraviroc is a CCR5 inhibitor, but there are some concerns about blocking receptors on CD4+ cells - harmful effects downstream such as west nile infiltration are possible
Term
what does raltegravir (RAL) do?
Definition
raltegravir is an integrases inhibitor, which blocks integration of the HIV genome
Term
what are atazanavir (ATV) and darunavir (DRV)?
Definition
protease inhibitors that block cleavage of viral proteins - these really changed the course of HIV/AIDs
Term
should anyone with an AIDs defining illness be treated with ARV? does their CD4+ factor into this decision?
Definition
pts with an AIDs defining illness should be treated with ARV regardless of CD4+ count
Term
what is the appropriate level of CD4+ for ARV to be started in asymptomatic HIV+ pts?
Definition
350-500 cells/ul
Term
what is the recommendation for asymptomatic HIV+ pts w/a CD4+ count >500?
Definition
ARV tx is optional
Term
what is the recommendation for pregnant asymptomatic HIV+ pts at any CD4+ level?
Definition
pregnant asymptomatic HIV+ pts should be treated with ARV at any CD4+ level to prevent transmission to the child
Term
what is the ARV tx recommendation for asymptomatic HIV+ pts w/any CD4+ count as well as HIV-associated nephropathy (HIVAN) or Hep B coninfection
Definition
ARV tx is recommended regardless of CD4+ value
Term
what is the controversy with ARV therapy for asymptomatic HIV+ pts at a CD4+ counter >500?
Definition
50% of panel favors starting ART & 50% of panel views ART as optional due to toxicity/resistant issues
Term
what are potential complications that can be avoided by starting early ARV therapy for asymptomatic pts with CD4+ counts >500?
Definition
HIV-associated neuropathy, cardiovascular disease, malignancies (both AIDs/non-AIDs defining), neurocognitive disease, liver disease progression, blunted immunological response due to earlier ARV initiation, persistent T cell activation/inflammation
Term
what are benefits of starting ARV therapy earlier?
Definition
prevention of HIV sexual transmission, prevention of blood-borne transmission, prevention of mother to child HIV transmission
Term
what are potential limitations of early ARV therapy?
Definition
ARV-related toxicities, non-adherence to ARV (leading to drug resistance), cost of medications (1000-1500/month)
Term
what are some recommendations for ARV therapy initiation?
Definition
ensure the pt is willing to commit to lifelong tx and that you as the dr are not forcing it on them
Term
what are the goals of ARV therapy?
Definition
*restoration and/or preservation of immunologic function - increase CD4+ count*, maximal & durable suppression of viral load, improved quality of life, reduction in HIV-related morbiditiy, improved quality of life, and reduction in HIV-related morbidity/mortality, prevention of vertical MTC transmission, prevention of transmission to sexual partners
Term
what are the 3 main categories of ARV regimens?
Definition
1 NNRTI + 2 NRTIs, 1 protease inhibitor + 2 NRTIs, (both the first two options are preferred), and 1 integrase inhibitor + 2 NRTIs
Term
what are important considerations for ARV administration? what are two specific considerations for nevirapine and abacavir?
Definition
comorbidities, (liver, psych, CV, TB, pregnancy), dosing convenience (pill burden/dosing frequency), potenial side effects/interactions, pregnancy potential, drug resistance testing results, gender/CD4 count (if considering nevirapine), and HLA B 5701 test results (genetic marker for specific allele - likely to have a hypersensitivity response to abacavir)
Term
what characterizes preferred ART regimens?
Definition
randomized controlled trials show optimal efficacy and durability as well was favorable tolerability/toxicity profiles. drugs in this category include: the NNRTI based choice efavirenz/tenofovir/emtricitabine in one tablet - atripla, the protease inhibitor choices: atazanavir or darunavir with ritonavir/emtricitabine/tenovir, the integrase inhibitor choice: raltegravir w/emtricitabine/tenovir, and the choice for pregnant pts: lopinavir w/zidovudine/lamivudine
Term
what characterizes alternative ART regimens?
Definition
these are effective but have potential disadvantages, but still can be preferred tx in individual pts.
Term
what characterizes acceptable ART regimens?
Definition
these have less virologic efficacy (or lack of data) or greater toxicities.
Term
what side effect is seen with ZDV?
Definition
anemia
Term
what side effect is seen with abacavir?
Definition
hypersensistivity w/HLA B 5701
Term
what side effect is seen with protease inhibitors?
Definition
GI intolerance
Term
what side effect is seen with NRTIs?
Definition
rashes
Term
what side effect is seen with mult ARVs?
Definition
hepatotoxicity esp if HCV+
Term
what side effect is seen with ddC, ddl, d4T?
Definition
neuropathy and pancreatitis
Term
what side effect is seen with all NRTIs?
Definition
lactic acidosis/steatorrhea
Term
what are multiple long term side effects with protease inhibitors and NRTIs?
Definition
lipidystrophy (increase/decrease in body fat), hyperlipemia (increased cholesterol, glucose intolerance/diabetes, *coronary disease/MI
Term
how long do most pts maintain virologic suppression with ARVs? what should be done to maintain this as long as possible?
Definition
3-7 years. simplification of regimen and assessment of adherence should be done frequently
Term
why do HIV+ pts fail virologically? what defines this?
Definition
skipped doses, mutations. virologic failure is defined as: HIV RNA >400 copies/mL after 24 weeks, >50 copies/mL after 48 weeks or >400 copies/mL after viral suppression
Term
why do HIV+ pts fail immunologically?
Definition
poor CD4+ count rebound, generally unknown etiology
Term
do HIV+ pts fail clinically?
Definition
this is rare, but can happen
Term
what was PACTG 076? who was involved? what was the result?
Definition
a phase III randomized placebo-controlled trial of zidovudine (ZDV) for the prevention of maternal-fetal HIV transmission done in 1994. it involved tx for the mother as well as the baby for 6 wks afer birth. efficacy was observed across all subgroups and ZDV became the standard of care and at this point infected neonates should no longer be a problem.
Term
is ARV therapy recommended in all HIV + pregnant women? when is it started? what is the goal
Definition
yes. ARV is typically started in the 2nd trimester unless they are already being treated. the goal of tx is to reduce the maternal HIV load to undetectable (or at least <1000 copies)
Term
what ARV is contraindicated in pregnancy?
Definition
efavirenz (sustiva - category D)
Term
what is the ARV standard of care for pregnant women?
Definition
3-drug regimen containing AZT (zidovudine), and lopinavir/ritonavir
Term
what do all infants born to HIV+ recieve in terms of therapy?
Definition
AZT for 6 wks post-delivery
Term
after delivery, can HIV+ mothers stop ARV if their CD4+ count is >500?
Definition
yes
Term
when is vaginal vs V-section birth recommended for HIV+ mothers?
Definition
vaginal is ok if viral load is <1000 copies, if not elective C-sections can be performed at 38 wks (this is high risk for other reasons). vaginal birth has a slightly reduced risk of transmission.
Term
should women with HIV in the US breastfeed? globally?
Definition
no. globally, the risk is less w/breastfeeding due to contaminated water
Term
is pregnancy contraindicated with HIV+ women?
Definition
no, but avoidance of transmission to the partner needs to be addressed
Term
has HAART helped to decrease the rate of AIDs-related opportunisitic infections?
Definition
yes
Term
where are opportunistic infections still seen?
Definition
in previously undiagnosed late stage AIDs pts, diagnosed by untreated pts, pts who stop their ARV rx, pts whose ARV medications may be failing, and shortly after the initiation of ARV meds (1-6 months)
Term
what opportunistic infections are seen with AIDs pts in the brain?
Definition
toxoplasmosis (present with seizures/headaches/fever), cryptococcal meningitis, lymphoma, JC virus infections causing progressive multifocal leukoencephalopathy (PML) which consists of de-mylenation leading to excessive loss of white matter (even w/antiviral therapy, pts do not thrive)
Term
what opportunistic infections are seen with AIDs pts in the eyes? how is this diagnosed?
Definition
CMV retinitis, toxoplasmosis. CMV retinitis appears as hemorrhage and retinal exudates in a fundoscopic exam and leads to blindness
Term
what opportunistic infections are seen with AIDs pts in the mouth? how is this treated?
Definition
oral candidiasis (however it can also be due to corticosteroid inhalers) as well as esophageal candidiasis
Term
what is the most common AIDs opportunistic infection?
Definition
pneumocystis pneumonia (p jiroveci)
Term
what else besides retinitis can CMV (an opportunistic pathogen) cause in AIDs pts?
Definition
colitis
Term
what is an AIDs defining illness affecting the skin and is associated with HHV-8? can it be treated? how is it transmitted?
Definition
kaposi's sarcoma, which appears as non-tender, purplish, indurated skin lesions. they are common in the mouth and may disseminated to the viscera. it can usually be treated pretty successfully. it can be sexually transmitted.
Term
can herpes zoster activate with AIDs pts as an opportunistic pathogen?
Definition
yes
Term
what is a common clinical manifestation of HPV in AIDs pts? is it considered an opportunistic pathogen?
Definition
anal, genital and oral warts, usually asymptomatic - but hard to get rid of. it is considered an opportunistic pathogen
Term
what are examples of disseminated opportunistic infections?
Definition
mycobacterium avium complex, histoplasmosis, coccidiomycosis
Term
when do opportunistic pathogens usually start becoming a problem with HIV+ pts? can antiviral/antibacterial/antifungal tx usually help?
Definition
around when CD4+ drops below 200. antiviral/antibacterial/antifungal usually will help
Term
what are non-infectious body fluids for HIV?
Definition
urine, feces, vomitus, saliva, sweat, tears
Term
what are infectious body fluids for HIV?
Definition
blood, CSF, pleural, synovial, pericardial, amniotic, vaginal secerations, semen, breast milk
Term
how common is HIV infection along healthcare workers? who is most at risk?
Definition
very rare, but nurses and physicians are at the highest risk
Term
what is the risk of HIV transmission via needle stick, non-intact skin, and mucus membrane?
Definition
needle stick: 0.3% or 1/300
non-intact skin: <0.1% or 1/1000
mucous membrane: 0.09% or 1/1000
Term
what is needed to assess HIV infection risk in healthcare personell?
Definition
the type of exposure, (percutaneous, mucous membrane, non-intact skin, bites), the body substance, (blood, bloody fluid, potentially infectious fluid or tissue), and the source pt, (HIV antibody, HCV antibody, HBV surface antigen should be tested for)
Term
how is post HIV exposure prophylaxis carried out?
Definition
PEP must be given within 72 hrs, at least 2 drugs should be given, tx should be for at least 28 days if source is HIV infected, and the possibility of a drug resistant virus should be considered
Term
what are the basic PEP recommendations?
Definition
zidovudine + lamivudine (combivir) or tenofovir + emtricitabine (truvada - normal go to)
Term
what are the alternate PEP recommendations?
Definition
lamivudine or emtricitabine + stavudine or lamivudine or emtricitabine + didanosine
Term
what is recommended in the case of very high risk possible HIV exposure?
Definition
basica NRTI regimen plus lopinavir/ritonavir, atazanavir/ritonavir, fosamprenavir/ritonavir, nelfinavir, or efavirenz
Term
if the source pt is HIV+, how is testing performed?
Definition
the exposed person is tested at baseline, then @ 1,3,6 months via ELISA. f/u is extended to 12 mo if the exposed becomes infected with HCV (it might take longer to serocovert to HIV in this case)
Term
what is considered a substantial risk for HIV exposure?
Definition
if the vagina, rectum, eye, mouth (or other mucous membrane), non intact skin or percutanous contact is met with blood, semen, vaginal secretion, rectal secretion, breast milk, or any blood contaminated body fluid from an HIV+ individual
Term
can/should PEP be given after 72 hrs?
Definition
PEP has not been shown to help with exposure after 72 hours
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