HIV/AIDS Flashcards
when does HIV become “AIDs”?
CD4 count below 200/ mm3 : when Opportunistic infections come about is “AIDS-defining illness”
what is the sequence that we use to Dx HIV?
HIV infection by ELISA (enzyme assay for antibodies) and then confirmatory Western blot
Viral load calculated by PCR, in copies/ mm3 (mm3 = microliter, or ul)
3 stages of HIV/AIDs
1) . Acute retroviral syndrome
2) . Asymptomatic stage
3) . Symptomatic stage (AIDS): Opportunistic infections (primary and reactivation)
what is the median duration of the asymptomatic stage?
10 years
what is going on with the virus during the asymptomatic stage? What about symptomatic? (weeds)
asymp: undergoing replication
symptoms: enough insult to the immune system to see an effect
when are the peak levels for viral load?
peak: around 2-4 wks after HIV exposure (acute syndrome)
drops down: for 8-10 years (latency)
peak: 12 -13 years post-exposure (overt AIDS)
when are the drops/rise for CD4 counts during the course of HIV/AIDS?
drop: around 2-4wks after HIV exposure (acute syndrome)
rise: 8-10 years (latency)
drop: 12-13 years post-exposure (overt AIDS)
transmission of HIV
via infected body fluids
excludes tears, aerosoles, saliva, GI contents
vertical HIV transmission:
~__% with no treatment (untreated HIV mom to baby), but
___ % with ____ monotherapy
30% no treatment
<10% with AZT (zidovudine) monotherapy
current therapy for vertical treatment of HIV? no breastfeeding reduces risk to < __%.
Current therapy: “triple therapy” (multidrug therapy)
no breastfeeding reduces risk to <1%
HIV is a ___ virus. with a ___ envelope and _____ on the surface
RNA, lipid envelope, glycoproteins (gps)
____ binds to T-helper cell CD4 receptor for attack
_______ are required for successful infection
gp 120 (glycoprotien) coreceptors.
what are the HIV coreceptors? What about those individuals who lack these?
CCR5 and CXCR4 (CCR5 for initial infection);
rare individuals who lack CCR5 can be exposed but are not infected
4 parts of HIV replication cycle
- Receptor binding
- Reverse transcriptase (RNA to DNA) by incorporating nucleosides
- Integrase incorporates into host DNA
- Protease is necessary to cleave viral proteins into structural peptides to produce new viral particles
if infected with HIV, one of three things can happen to CD4+ T cell. what are they?
- Replicate and fuse with cellular DNA or
- Cell death (apoptosis) or
- Virus sits in cell in latent state
what else can HIV virus directly infect (other than T cells) and what can it cause?
Brain –> encephalitis
Always check for all the ___ you can think of for an HIV person who has a single STI
STIs
much more aggressive course of TB infection if the patient has ___ as well.
HIV
Pearl: if a patient has current complaints of more than one distinct kind of ______ _____ or _______, be suspicious of HIV
Also be suspicious with _______ or ________
skin complaint or infection
widespread MRSA furuncles or boils
CDC recommends routine HIV screening for all persons ___ to ____ years of age in the United States. what is the “philosophy” for this testing.
13- 64
“Opt out”, rather than “opt in” philosophy for testing
- Minimally, if you test for any STD, include HIV in the test
Lab testing for HIV:
- order HIV test, will include _____ and if this is positive, will do confirmatory _____.
- Also if positive, Then need to do _____ and _____.
- _____ ______ (also helpful)
- if all positive…. what do you do?
- Order HIV test, will include a preliminary ELISA, and if positive, lab will do confirmatory Western blot
- May be indeterminate on WB - genotyping and phenotyping as a guide to retroviral therapy (some mutations confer resistance to specific drugs)
- viral load
- REFER!
acute HIV illness presentation ?
presents like any other acute viral illness
Clinical presentation for more advanced HIV: what three things should you note?
dementia, wasting, NOTICE opportunistic infections!
AIDS = HIV infection plus..
CD4+ count <200
or
Presence of an opportunistic infection
two major opportunistic infection types to note
candidiasis and lung infections (like pnuemocystic pneumonia (PCP) and toxoplasmosis)
what is the most common presentation of lung infection in AIDS? symptoms?
Pneumocystis jiroveci (PCP): (dyspnea, cyanosis, rales etc)
how do you Dx PCP?
induced sputum or bronchial lavage
txt for pcp
Treatment (21 days): Trimethoprim-Sulfamethoxazole (Bactrim)
how does one get toxoplasmosis?
Exposed through consumption of undercooked meat, ingestion of oocysts from cat feces
toxoplasmosis: how does one present if normal immune system and infection vs immunocompromised w/ infection?
normal: asymptomatic
Immunosupressed (AIDS) get symptomatic, progressive lethal infection
someone is at risk of symptomatic, lethal toxoplasmosis if T-cell count is < ____ . What does this lead to?
At risk if T-cell count < 100
-encephalopathy
Dx of toxoplasmosis in immunocompromised pt? two types
Dx. Serology will tell if previously exposed
Dx. CT or MRI of brain for characteristic lesions
txt for toxoplasmosis in immunocompromised pts? (weeds)
Start empiric therapy based on clinical picture and imaging
Should dramatically improve
If not improving – brain biopsy
Cryptococcal meningitis: where does this come from?
encapsulated fungus in soil and bird droppings
chronic meningitis in AIDs is likely what?
cryptococcal meningitis
Dx of crytococcal meningitis
lumbar puncture
Txt for cryptococcal meningitis
antifungals
maybe weeds: (Treatment: Amphotericin then Fluconazole maintenance until CD4 > 200 for 6 months and no symptoms)
mycobacterium avium (MAC) usually presents when in the course of AIDS?
Usually late in the course of AIDS (CD4 < 50)
MAC presentation (weeds)
Persistent fevers, night sweats, fatigue, weight loss, and anorexia
Hepatosplenomegaly, lymphadenopathy, and occasionally jaundice
txt for MAC
weeds maybe
Use 2 or 3 drugs
Clarithromycin
Ethambutol
Rifabutin
(similar to TB txt)
CMV- cytomegalovirus
Ubiquitous herpes virus: Congenital infection can be serious in immunocompetent
HIV pts with CMV get ____ and _____ (weeds)
HIV patients – retinitis (optho- white exudates with hemorrhage), colitis/esophagitis (diarrhea, bleeding)
overall for immunocompromised txts… what is the goal?
increase CD4 counts, get immune system working again!
CMV txt (weeds)
ganiclovir
Progressive Multifocal Leukoencephalopathy: is what? key features? MRI shows what?
opportunistic infection
(associated with JC virus- dont need to know what this virus is)
- cognitive impairment
-MRI: dense white matter lesions without edema
Persons with AIDS have a high incidence of certain malignancies, especially _____, _____ and _______
Kaposi sarcoma (KS), non-Hodgkin lymphoma, and noninvasive cervical carcinoma
Kaposi purple skin lesion but ALSO likes the ____
lungs
“looks like toxoplasmosis, no fever, doesnt respond to toxo therapy” … what is this?
CNS lymphoma
cervical cancer: what is the schedule for pap smears for those with HIV? Women with HIV have ___ fold increase in the chance of getting cervical cancer
Pap smear at baseline, at 6 months, then annually
(after initial Dx)
1.7 fold increase if HIV positive.
what are the “sites of anti-retroviral drug action”?
many places where we can interfere in the replication cycle of the virus: different classes of HIV drugs
what is the “triple therapy” for HIV txt?
HAART “triple therapy” or more, now often called simply “ART”
3+ classes of antivirals
-usually NRTI plus NNRTI plus PI
NRTI (nucleoside reverse transcriptase inhibitor)
NNRTI (non-nucleoside RTI)
PI (protease inhibitor)
why can’t you start HIV drugs in primary care practice?
NEED to know CD4 counts, genotype and viral load. Send to an expert!
what is the most important thing about HIV txt? why?
Adherence, adherence, adherence!!!
High mutation rate of virus speeds resistance
how do you change drug therapies for HIV pts?
VERY carefully
do you delay therapy for HIV?
NO!
what are the 4 major opportunistic infections for HIV?
TB
pneumocystitis jiroveci (PCP)
toxoplasmosis
Mycobacterium avium complex(MAC)
prophylaxis for some conditions will be _____. It is better to remember what _____ need prophylaxis than to remember all the infections and prophylactic agents.
what are the triggers?!
The important point is to remember that prophylaxis for some conditions will be necessary!!
It is better to remember what triggers the need for prophylaxis than to remember all the infections and all the prophylactic agents
trigger: Low CD4 counts!!!
what is the goal of ART (acute retroviral therapy)?
Undetectable viral load by PCR
monitoring for ART: continual monitoring for ____. monitor ____ and _____ . surveillance for _____ _______
Continual monitoring for adherence
Monitor CD4, viral load
Surveillance for opportunistic infections
what are the monitoring complications for ART?
Metabolic complications (i.e. metabolic syndrome, insulin resistance, lipodystrophy, etc) * lipid and glucose metabolism are effected
3 key signs of metabolic complications with ART?
lipoatrophy (thinning in fat areas like cheeks) protease paunch (looks like "beer gut"), buffalo hump (hunchback)
two major aspects of prevention
“Routine” HIV testing (CDC recommendation)
PrEP (pre-exposure prophylaxis)
PrEP has up to __% risk reduction
90
who have the highest rates of transmission ?
teens and elderly (nursing homes)
what does “treatment as prevention” mean?
achieve undetectable viral loads through ART = risk of transmitting infection is low
what is “U=U”?
“undetectable=untransmittable”
Late 2017 international consensus
U=U: Data from multiple large studies have shown negligible risk of transmission in people with HIV, with _____ ______ _____
undetectable viral loads (< 200 copies/ml)
post-exposure prophylaxis: chance of contracting the virus from a needle stick (without treatment) is __:____ . while needle sharing is a __:____
needle stick 1:300
needle sharing 1:150
which needle is more dangerous than others?
hollow bore: holds more blood in it
is there practicality behind the “cure” for HIV?
unsure… given the need for both HLA matching, and CCR5 mutation, and the need for a stem cell transplant
what is the “cure” for HIV that was discovered? (maybe weeds)
2 case reports of people with HIV who received stem cell transplants for lymphoma Tx, one in Germany, one in England
Bone marrow donors had CCR5 mutation, which was conferred to recipients
HIV undetectable on no ART
what are the only 2 non-HIV retroviruses with clear pathologies?
HTLV-1 and HTLV-2 (Human T-cell Lymphotrophic Viruses)
what is a non-HIV retrovirus?
RNA viruses that use reverse transcriptase and infect T-cells. but unlike HIV, not devastating effect on immune system like HIV/AIDS does
