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