Lecture 1 - HIV Flashcards
How often are people getting tested for HIV?
@ risk pts get tested annually
The general public should get tested at least once in their life
PrEP
Pre-exposure prophylaxis for @ risk pts
nPEP
Non-occupational post-exposure prophylaxis
How is HIV dx?
4th generation immunofluorescence assay
Confirmed with multispot HIV1/HIV2 differential assay
3rd generation ELISA
Confirmed with Western Blot
PCR of viral RNA
Dx of acute retroviral infection
What is the HIV life cycle?
1) Binding –binds to CD4
2) Fusion - binds to the membrane gaining access to cell
3) Reverse transcriptase – RNA to DNA
4) Integration
Into the host DNA (in the nucelus)
5) Transcription
6) Assembly
7) Budding
8) Maturation
GALT
Gut-associated lymphoid tissue
60% of immune cells are in the gut
Major site for T cell loss and early HIV replication
Intestinal CD4 count is never restored to original levels
When does the primary infection of HIV occur?
2-4 weeks after infection
What does the primary infection of HIV look like?
Fever Malaise N/V/D Maculopapular rash (blanchable) Neurologic sxs
What baseline evaluations should be ordered for a newly dx HIV + pt?
CD4 cell count HIV RNA viral load HLA B5701 Renal LFTs CBC Glucose
What common comorbidities are see with pts with HIV?
Syphilis TB Hep A,B,C Chlamydia, gonorrhea HPV Toxoplasma CMV Mental health: depression, substance abuse
How often are you following up and running labs for your HIV pts and what are you testing for?
Monitor HIV and ART every 3-6 months Monitor medication adverse effects every 3-6 months CBC, CMP, HgA1C, fasting lipid Evaluate > annually for STIs TB > annually Cancer screening (pap and anal)
Which vaccinations are recommended for HIV pts and when?
Any CD4: Hep A, B Influenza tetanus/diptheria Pneumococcus
When is resistance seen with HIV treatment?
For pts you only take medications every now and then. If the viral load is detectable while on antiretrovirals then there is a risk for resistance. While on antiretrovirals there should be no detectable viral load.
What must you be sure to check for before beginning treatment for a newly dx HIV pt?
HBV, CD4, VL, genotype (for resistance), HLA-B5701
Which HIV drugs should be avoided in pregnant pts?
Efavirenz - during the first 8 weeks (look up in her slides where she talks about efavirenz elsewhere)
What drugs should be started on a pt who is newly dx with HIV?
Options:
Once daily dosing (single tablet)
Trumeq (dolutegravir/abacavir/lamivudine)
HLAb5701 and HBV Ag MUST be negative
Genovya/Stirbild (Elvitegravir/Cobicistat/Tenofovir (TAF/TAD)/emtricitabine)
Elvitegravir is a “boosted” drug and MUST be taken with food
Once daily dosing (2-3 tablets)
Dolutegravir + tenofovir (TAF/TDF)/emtricitabine
Tivicay = dolutegravir
TAF/emtricitabine = descovy
TDF/emtricitabine = truvada
Twice daily dosing
Raltegravir (isentress) twice daily
+
Trvada or Descoy once daily
What is the main difference between TAF and TDF?
I believe TAF is more new and is less harsh on the kidneys and bones compared to TDF
A newly dx HIV pt also has HBV, which medication MUST they go on?
Tenofovir
And the must be warned not to d/c the drug
Newly dx HIV pts being prescribed a combo drug with abacavir in it must have what testing done?
They must be HLAb5701 negative and must be HBV Ag negative
Which HIV drugs work against HBV in addition to HIV?
Tenofovir/emtricitabine (the one the MUST be used with HBV +)
D/c of tenofovir can cause HBV rebound
Lamivudine
However if tenofovir can not be safely used for some reason then entecavir should be used (look up in her slides where entecavir has been mentioned before)
HIV drugs have a lot of drug-drug interactions, name a few.
Metformin, OCP, anticonvulsants, antidepressants, statins, antacids, benzos
Renal damage and osteoporosis is a SE seen with which HIV drug?
Tenofovir DF
What are some overall side effects of HIV drugs?
DM, CVD
Hypercholesterolemia (this is why we check lipids)
Fat redistribution
Lactic acidosis, liver toxicity, hypersensitivity
PEP
Post-exposure drugs
Recommendations:
Raletgravir (isentress) 400mg twice daily + tenofovir DF/emtracitabine (truvada) once daily
PrEP
Pre-exposure prophylaxis
Recommendations:
Tenofovir DF 300mg/emtricitabine 200mg (truvada) once daily (PO) —90 day supply
F/u every 3 months
Renal functions at 3 months and then every 6 months
Who gets offered PrEP? (CDC guidelines)
“Substantial risk of HIV infection” Men who have sex with men or heterosexual individuals if: HIV+ partner Recent bacterial STI High number of sex partners (subjective much?) History of no condom use Commercial sex work Injection drug users if: HIV+ injecting partner Sharing injection equipment
What complications are correlated with CD4 cell count <500?
Acute retroviral syndrome Candidal infections Persistent generalized lymphadenopathy Guillain-Barre syndrome Myopathy Aseptic meningitis
Which oropharyngeal infections are often seen as complications with HIV?
HSV: small painful ulcers on erythematous base
CMV: large, shallow ulcers
Aphthous stomatitis
Kaposi’s Sarcoma
Associated with herpes virus (8)
Seen as a complication of HIV with declining CD4 count
VZV
Recurrent dermatomal outbreaks and disseminated disease can occur
A complications seen with declining CD4 count (although reactivation can even occur at high CD4 counts)
HSV
Genital lesions may coalesce, form large ulcers. Ulcers may become secondarily infected with bacteria.
Infection can be complicated by radiculomyeltitis, proctitis
Frequent recurrences can occur irrespective of a high CD4 count
What complications are correlated with CD4 count <200?
PJP Histoplasmosis Coccidiomycosis TB Wasting Dementia Cardiomyopathy Non-hodgkin’s lymphoma
Which pulmonary infections are commonly seen with CD4 count <200?
Strep pneumoniae, H. Flu, S. Aureus, Gram negative pneumonia
PJP
Fungal PNAs
TB
PCP
Aka PJP (pneumocystis jiroveci pneumonia)
Clinical presentation:
Insidious onset of fever, sweats, fatigue, non-productive cough
Dyspnea is initially exertional, but progresses with impairment of gas exchange
Workup
CXR
Diffuse interstitial infiltrates (80%)
Lactate dehydrogenase (LDH), sputum, blood gases
Bronchoscopy is diagnostic
What is the most common non-tuberculosis pulmonary mycobacterial infection?
M. kansasii
IRIS
Immune reconstitution inflammatory syndrome
Seen in HIV pts with CD4 count <100
CMV Retinitis
Medical Emergency
Sxs include progressive visual loss, blurring, and “floaters”
Fundoscopic exam reveals coalescing white exudates with surrounding hemorrhage and edema
Without treatment will progress to retinal detachment and visual loss
Owl’s eye inclusions on histopathology dx
Seen in HIV pts with CD4 <50
PML
Progressive multifocal leukoencephalopathy (PML) - JC virus (polyomavirus)
CNS infection
Rapidly progressive focal neurological deficits, most commonly hemiparesis, visual field defects, cognitive impairment
Dx: CSF JC Virus PCR, MRI
Toxoplasmosis
Toxoplasma gondii protozoal parastie
HA, confusion, behavioral/mood changes
Ring enhancing lesion or lesions on CT or MRI
Dx: CSF PCR
CMV
Polyradiucloapthy: acsending weakness and loss of reflexes, as well as, meningoencephalitis
Can progress to flaccid paralysis
Dx: CSF CMV PCR, CT
Cryptococal Meningitis
Cryptococus neoformans or gotti - encapsulated fungus
HA, AMS, seizure
Dx: CSF analysis, India Ink Stain
CMV
Can affect the entire GI system: esophagitis, gastritis, colitits
Odnophagia, diarrhea, proctitis, fever, abdominal pain
Dx: endoscopy or colonoscopy with biopsy and ME
Which intestinal parasitic infections are commonly seen in HIV pts as a complication of low CD4 count?
Microsporidium
Isospora
Giardia
Entamoeba histolytic
MAC
Mycobacterirum avium complex
Pts present with fever, sweats, weight loss, hepatosplenomegaly, adenopathy, and anemia
Focal disease with isolated adenitis can also occur
Dx: blood cultures, bone marrow biopsy, lymph node biopsy
How can PCP be avoided in HIV pts?
Being prophylaxis at CD4 count <200
Bactrim DS (trimethoprim-sulfamethoxazole)
Also protects against toxoplasma
How can MAC be avoided in HIV pts?
Begin prophylaxis at CD4 count <50
Prophylaxis with azithromycin 1200mg weekly
How can TB be avoided in HIV pts?
Prophylaxis with isoniazid for all pts with a positive PPD or close contacts of a pt with TB
IRIS
Severe decline in clinical status after ART initiation despite improved immune function due to inflammatory response against infectious agent
Generally CD4 <50 and rapid decline in viral load; onset usually with 6 weeks of ART initiation, but sometimes several months later.
Related to MAC, MTB, CMV, cyptococcus, PCP, HSV, VZV, HBV, HCV, JC virus (PML) and others
How does HIV progression and treatment differ between young pts vs older pts?
Older pts progress much faster and antiretroviral therapy is less effective
What did MACs show?
Mens AIDS Cohort Study
A 55yo HIV infected person has similar frailty as a 65 yo HIV negative person
Proposed mechanism:
Mitochondrial dysfunction and increased number of free radicals and cytokines activate inflammatory pathways, ultimately leading to frailty
What are the risk factors for kidney disease in HIV pts?
Age, race, family hx (non-modifiable)
HIV, ART, HepC, DM, HTN (modifiable)
What is the risk of DM in an HIV pt?
DM in HIV positive men with ART >4x more likely than that of an HIV negative man
Insulin resistance is becoming a common complication seen in HIV pts d/t a metabolic syndrome that may also lead to the development of what disorders?
Type 2 DM
Atherosclerosis
HTN
Lipodystrophy is a complication seen with some HIV medications, what lifestyle modifications can be made to change this?
Reduce saturated fat/cholesterol intake
Increase physical activity
Stop smoking
Tenofovir DF is associated with what SE?
Decrease in bone mineralization
Renal disease
Tenofovir AF or abacavir have less bone SE if given with what?
Bisphosphonate
Which cancers are more commonly associated with HIV?
Kaposi’s Lymphoma HPV related (Cervical Penile and rectal)
What are the guidelines for cervical cancer screening in HIV infected women?
Screen twice a year when first dx
If normal, screen yearly if no change in sexual partner, use of safe sexual practices, no hx of sexual abuse, and no sxs
Why do HIV drug regimens change as the pt ages?
Advanced age results in decrease P450 function and decrease in renal tubular secretion and glomerular filtration
Decrease in body weight/total body water can lead to higher serum levels of the drug and thus toxicities
NRTIs have which SE?
Lipodystrophy
Lipoatrophy
NNRTIs have which SE?
Lipid changes
Protease inhibitors have which SE?
Lipid changes
Heart disease
Lipodystrophy
If an HIV pt is on PIs or boosters (ritonavir or cobistat), which other drugs can they NOT take?
Statins (simvastatin, lovastatin, pitavastatin)
If an HIV pt is on PIs or NNRTIs, which drugs should they NOT take?
St Johns wort PDE5 inhibitors (viagra) levels increase with PIs and decrease with NNRTIs
How do PIs alter other drugs pts might be on?
CCBs (dihydropyridine) levels rise
Fluticasone levels rise
PDE5 inhibitor levels rise
Benzos should be avoided
At what CD4 count to we start prophylaxing HIV pts, and for what?
CD4 <200 PCP Bactrim DS Dapsone Atovaquone
CD4 <50
MAC
Azithromycin
Clarithromycin
