HIV
integrates
HIV DNA enters the nucleus of CD4 cell & is integrated into host (CD4) DNA > proviral DNA
AID-defining condition
HIV plus opportunistic infection, T-cell counts began to drop under 200, patients always have label, but their health will vacillate back and forth
HIV
Human Immunodeficiency Virus, chronic dx & pt has responsibility to maintain healthy lifestyle
Why are HIV clinics so strict?
Missing one appointment may get kicked out of clinic bc missing 1 refill may mean total new replication
Viruses
decrease cellular protein synthesis, alter host cell antigenic properties, and transform host cells into cancerous cells
CCR5 or CXCR4 inhibitors
inhibits receptor, new drug, so when virus comes in contact with receptor on CD4 it doesn't look like receptor and so virus is unable to "put the key into the lock"
integrates inhibitors
interfere in nucleus of CD4 cell, new drug (only one approved by FDA thus far), keep viral DNA from infecting host by interfering w/ genetic material
Oral HIV-1 Antibody Testing
keep in mind when you hear "rapid HIV test" they are not western blot...more like ELIZA. Be aware of how to conduct test, and make sure you send pt to f/u for western blot. Also educate its they are absolutely correct that HIV is not in saliva, but that you are checking for HIV antibodies w/ this test
reverse transcriptase inhibitors
keep viral RNA from changing into viral DNA, NNRTIs (non nucleatide reverse transcriptase inhibitors), nucleatide RTI, and NRTIs (includes AZT)
oral hairy leukoplakia
little white hairy filaments on top & underneath tongue, pt has no symptoms with this, viral in etiology, antifungals (like u would use to tx thrush) do not help at all, self-limiting & resolves on its own, sometimes will give antiviral if they are not already on one
protease enzyme
long viral protein chains produced & cut into necessary pieces to produce more HIV
oral candidiasis (thrush)
lots of folks can get this (steroids), a lot of its think leukoplakia is thrush, remind pts not to use toothbrush to scrape off thrush bc it destroys the protective mechanism set in place & they can get down into tissue that was not destroyed for organisms
herpes zoster
lots of folks have this...brought on by stress to the body: chemo, radiation, HIV, severe social stressors, lots of dermatologists catch, if it gets close to eye call 911: can make you go blind
HIV rash
macular papular, relatively small lesions all over body (but mostly chest or face) not a lot on extremities, esp. lower extremities
seroconversion
means you are producing antibodies in the blood
Molloscum Contagiosum
nail fungal infection, see when T-cells are falling
post-herpetic neuralgia
nerve pain that can take days, weeks, years to treat & is very difficult to deal with
Immune reconstitution syndrome
occurs when individuals are so compromised that even the bad guys can't come to the surface to make them sick, when you give them HIV medicine you stimulate immune system & help out the good guys, but bad guys know have energy to come to the surface & you can give the an opportunistic infections, most commonly PCP & kaposi's sarcoma...must educate its about this!!!!
How does the virus mutate?
only one person's virus looks like the the original virus, mutates person to person & within person (RT is error prone), people can also pass on drug resistant virus to each other (ex. AZT resistant HIV)
proviral DNA
part virus part CD4 cell, makes it productive virus able replicate & to cause damage (programmed to be HIV factory)
false positive
persons w/o the dx who were deemed by the test to have or be at risk for the dx, results in worry, time, resources to prove health
false negative
persons with the disease who were deemed by the test to be at low risk or w/o the disease; false reassurance, missed opportunity to intervene
Rash on palms & soles
possibly secondary syphilis
risks to limit perinatally acquired AIDS
prenatal care including monitoring viral load (if < 1000 can have vaginal delivery), keep ruptured membranes down < 4 hrs., make sure mother receives HIV meds in IV during labor, case mgmt impt in non-infected infant
incidence
proportion of individuals who develop a condition over a defined period of time
prevalence
proportion of sampled individuals possessing the condition at a given time
AIDs
pt considered to have aids if they have T cell count < 200 or a T cell percentage of total lymphocytes of less than 14% (normally 30-60%)
diagnostic window/window period
time period that elapses between the time of acquisition of HIV infection until detectable antibodies are present (if you test too early you will get a false negative bc your body has not been able to dev. antibodies yet) 80% can be dx after 6wks. and after 12th wk (3mo) 99% of cases
Should HIV/AIDS patients get vaccinated?
treat like immunocompromised pt, it T-cell count is less than 200 they cannot get LIVE vaccine, but all of these patients should get vaccinated
HIV reverse transciptase
very error prone, lots of genetic variants, "dumb," every time it goes through replication process it can change how it alters RNA > DNA...makes mutant virus or strain of virus unlike strain of virus patient was infected with
What happens after individual is infected?
virus sits in lymph nodes until it needs to be used (like in case of infection), travel companion is CD4 and our lymph nodes are loaded w/ CD4s, when you have an opportunistic infection it calls the CD4s to help but they are infected w/ HIV virus so they don't help
CD4
where most HIV replicates in our body, CD4 is like the "birthing center of HIV" but it uses CD4 to make more virus it has to eventually kill CD4, not good for immune system & then increasing viral load > opportunistic infections & death
Who receives more effects with HIV?
women
Additional red flags with HIV
TB (no correlation, just same population group), STDs, substance abuse (esp. meth), thrombocytopenia (these pt had very low platelet cts as low as 10,000), leukopenia (CD4 included), abnormal pap smear, refractory vaginal candidiasis
timeframe for hiv/aids
6-8 weeks...up to 6 mo to seroconvert, symptoms 5-8 yrs, AIDS 10-25 yrs
Western blot
confirmatory test for HIV, reflex test to ELISA, looks at bands or proteins in someones blood, no bands means negative, positive means reactive to a certain pattern, indeterminate means a pattern of reactivity that does not meet criteria for positive, extremely SPECIFIC, alone has 2% false positives, cannot tell anyone they have HIV unless they test positive for confirmatory Western blot
primary disorders
congenital, caused by genetic anomaly, usually 6 mo-2yrs.
reverse transcriptase enzyme
converts RNA > DNA
fusion inhibitors
"cadillac" med (20-25 grand/yr), works at site of CD4 & virus connecting (why it is called a fusion inhibitor), difficult to mix, only lasts 24 hrs, long-term injection site trauma
disseminated lymphadenopathy
increased lymph nodes size, occurs bc lymph nodes become filled with CD4s trying to help
A positive HIV antibody test signifies the
individual is infected with HIV and likely so for life
secondary disorders
infection, malnutrition, aging, immunosuppression
Steps of replication & survival of HIV
1) HIV gains entry into CD4 by binding onto receptors on the outside of the CD4 & fuse w/ the lipid outer layer of cell (think of virus as key & CD4 as lock) 2) Once inside CD4 cell, had to take off "coat" exposing its RNA (retrovirus) and convert RNA > DNA by releasing reverse transcriptase enzyme 3) HIV DNA enters the nucleus of CD4 cell & is integrated into host (CD4) DNA which requires integrase enzyme (now proviral DNA) 4) long viral protein chains produced & cut into necessary pieces to produce more HIV activated by protease enzyme (EACH OF THESE STEPS IS TARGET FOR ANTIRETROVIRAL THERAPY)
3 possible results from western blot
1) negative - meaning there are no bands 2) positive - meaning it reacted to a certain proteins 3) indeterminate - meaning there a couple proteins, but not enough to say yes it is positive
How fast does HIV replicate?
1-10 billion cells/day, sloppy virus
life expectancy of CD4
1.6d
tripla
3 drugs rolled into one, once a day med
protease inhibitors
inhibit protease enzyme from allowing proteins to line up on amino acid chain
What cell does HIV target?
CD4
What does HIV target?
CD4 cells & lymphocytes, macrophages (to lesser degree), ACTIVE PROCESS, activated & proliferating cells (billions of visions made each day), establishes chronic infection
Who might show up with HIV after the typical diagnostic window of 3 mo?
R/t host not virus: older individuals take longer to mount immune response, individuals w/ competing infections (bc body can only produce so much antibodies at one time), immunocompromised
retrovirus
RNA virus that replicates in a host cell, uses its own RT enzyme to convert to DNA, must target certain cells, has specific coating unrecognized by host cell, has additional envelope that wraps around the virus
SnNout
Sensitivity a negative result rules out the disorder ex. ELISA, if test is sensitive, will not miss infection, picks up on all kinds of antibodies
SpPin
Specificity a positive result rules in the disorder ex. western blot, less likely to get false positives (2% with western blot)
What is the AIDS/HIV continuum?
Viral load peaks in acute stage of HIV while body is making antibodies. As antibodies peak, viral load drops bc antibodies are working. Some need no medical intervention other than this in beginning stages, and fools go back & forth on continuum. Viral line high, and antibodies low in acute phase. Viral line low, antibodies & CD4 high in asymptomatic/seropositive phase, in major s/s phase viral line starting to rise again, antibodies & CD4 began to drop, AIDS viral line high, antibodies & CD4 low
t cells < 50
aspergillus, MAC, CMV
An immunodeficiency occurs due to the impaired function of
b and t cells, phagocytic cells, complement
If someone has been exposed to HIV
beneficial to take antiretroviral therapy for 1 mo. if you know you are exposed, like in case of a needlestick
HIV medications
birth control for the virus
cervical cancer
can be AIDs defining illness, HIV patients must get pap smears q6 mo until they have 2 normals and then they get them annually, for women port of entry for HIV is frequently inflammed cervix, can lead to PID, difficult for patients to discern
mucutaneous ulcerations
can be found in mouth esophagus or on genitals with HIV, may look like mono or primary herpetic infection
Does HIV virus ever die out?
eventually virus dies out when CD4 cells are all gone, but at this point pt has opportunistic infections that can kill them
dental issues with HIV
hard to find dentists that will see HIV pts, these its can die from dental abcesses, ASSESS dental needs
t cells < 200
herpes simplex, candida esophagitis, PCP
t cells < 100
histoplasmosis, toxoplasmosis, cryptococcosis, cryptosporcollosis, microsporcollosis, aspergillus, MAC, CMV
methamphetamine
hypersexual medicine, can be coupled with viagra & ecstasy, do not think about protection, considered normal to have multiple partners whose name you do not know
What is your main red flag for HIV?
rash + viral symptoms (rash is often misdiagnosed)
viral load/PCR
relatively new test done to give an idea of where the HIV infected individual is in the process of HIV replication (used to just have CD4 test), expensive, never first line
Antiretroviral therapy examples
reverse transciptase inhibitors, protease inhibitors, fusion inhibitors (allows lock & key not to be efficient), integrate inhibitor (brand-new)
Enzymes involved in HIV replication
reverse transcriptase enzyme, integrase, protease
ELISA
screening test for HIV antibodies, overly SENSITIVE, not as specific, cheap, if test positive does not mean you have HIV, only reported as reactive or nonreactive, requires repeat reactive results & confirmatory testing (western blot), ned 2nd screening test (western blot) 6 mo later if reactive
signs of HIV
see all of the following when T-cell count <200, folliculitis, herpes zoster, oral hairy leukoplakia, thrush, dental abcesses, cervical cancer, molloscum contagiosum
opportunistic infection
should be able to fight but cannot bc of lack of antibodies, pneumocystitis carinii pneumonia (PCP) should be treated prophylactically if T-cells < than 200(bactrim, dapsone, or meprone), if T-cells < 50, once weekly Zithromax should be given for prophylaxis for Mycobacterium Avium Complex (MAC)
symptoms of HIV
skin changes (largest organ to reflect immune system), weight loss (immune system using up calories, not able to absorb nutrients), neuro changes (ex. adult-onset seizure), low grade fever, lymphadenopathy (systemic, usually in non-hiv individuals it is only at area of infection...but with HIV that pt could have pharyngitis & axillary lymphadenopathy)
Why is it so important to start drug therapy early?
some of the drugs only work in the early phase of the dx, drug resistance is common & problematic...so if pts miss the early meds & are resistant to the late ones, may not be anything for them...don't just think of it as a chronic dx
What has contributed to decreasing perinatally acquired AIDS?
started offering AZT to pregnant mothers infected w/HIV, risk <2% w/ effective antiretroviral therapy (ART) and strict bottle feeding.
true positive
the number of sick people correctly classified by the test
true negative
the number of well people correctly classified by the test
Acute retroviral syndrome
thrush, esophagitis, PCP
t cells 200-500
thrush, oral hairy leukoplakia, tb, shingles