HIV-1 schoenwald Flashcards
HIV is a disease of cell mediated immunity– ____ cells
CD4 cells* (T cells)
HIV cases are presented with opportunistic infections i.e. ____
PCP
HIV transmission: list 3 routes and ex’s of each
- Blood (ie transfusion/injections (drugs)
- Sexual intercourse (heterosexual** male to male MC)
- Perinatal (ie intrapartum and breast feeding)
___:___ is the risk from sharing needles in IVD
1:150
___:___ is the risk to hcw w/ needlestick
1:300. (hcw=healthcare worker)
Blood transfusion with infected blood risk?
Perinatal risk w/ antiretriviral?
- 95%
- 13-40%
HIV=
presence of virus without AIDS defining illness
AIDs (list 2 definitions)
- HIV + with AIDS defining illnesses (as listed in Current Medical Diagnosis and Treatment)
- **HIV + with CD4 count <200
List Ex’s of AIDS defining illnesses
-THRUSH is NOT an AIDs defining illness BUT–> Candidiasis of bronchi, trachea, or lungs or esophageal is
-Kaposi’s sarcoma
-Pneumocystis carinii (jirovicci) PNA
Burkitt’s lymphoma
-
HIV Sx:
HIV MC presentation?
- can be asymptomatic for years
- +/- Fever, night sweats, unexpected weight loss, LAD
-MC: asymptomatic and found via screening tests, **commonly presents w/ opportunistic infxn THEN found to have HIV
Recommended to screen anyone with new dx of ______ for HIV
Syphilis
_____ HIV most likely to have sx
acute
Pneumocystis jiroveci (humans):
- classified as: ?
- gold standard dx test?
- Newer tests ?
- a fungus
- Gold standard**= silver stain on sputum sample
- newer= PCR based methodology
Pneumocystis Jiroveci:
-Chest X ray reveals** ______
**Bilateral hilar infiltrate
-CT scan shows brown glass opacity
Pneumocystis pneumonia Sx: (list)
Fever
Dry cough
Shortness of breath-desaturation of oxygen
fatigue
Pneumocystis tx ?
High dose trimethoprim/sulfamethoxazole
15-20 mg/kg IV q day divided into q 6-8 hour dosing
-Prednisone 40 mg PO BID added if paO2<70mm/HG
**PEARL: often present w/ severe hypoxemia
PCP prophylaxis at CD4 count of _____
<200
first line: Trimethoprim/sulfamethoxazole po
-Dapsone or inhaled pentamidine are alternates if sulfa allergic
Kaposi’s Sarcoma= Human herpes virus __
8**
Kaposi’s SarcomaSx?
-tx?
- **Purplish, brownish lesions
- Can be body wide, including inside of mouth
tx: reconstitute the immune system
HIV:
-can be a retrovirus that depends on ______
reverse transcriptase–RNA dependent DNA polymerase to replicate
- *HIV 1 most prevalent in US
- HIV 2 is rare in the US, but less virulent– most confined to west africa
when HIV enters the body, it enters ____ cells via _____ receptors
CD4 cells via chemokine receptors(CCR5 and CXCR4)
- **people w/ CCR5 deletions are less likely to become infected
- once in cell–> HIV replicates and causes cell fusion/or death
HIV latent state (describe)
-what happens to CD4 count
integration of HIV genome into cell genome
**CD4 count falls with increasing length of infection
HIV: list ex’s of S/Sx
Asymptomatic Fever, night sweats and weight loss Presence of opportunistic infection Kaposi’s sarcoma Lymphoma -Oral lesions such as hairy leukoplakia
Acute HIV aka _____
-describe sx?
Acute Retroviral Syndrome (time frame of first 12 weeks post exposure to HIV infxn)
- Non specific “flu-like Sx”
- Fever, fatigue, pharyngitis, LAD, Body wide maculopapular Rash*
Who should be tested for HIV?
- 13 and 64yo
- Injection drug users and their sex partners
- Persons who exchange sex for money or drugs
- Sex partners of HIV infected persons
- MSM or heterosexual persons who themselves or whose sex partners have had sex with more than one sex partner since their most recent sex partner
testing for HIV?
-combination aka 4th generation testing (EIA) is reccomended over ELISA for screening
Describe mechanism for Combination HIV testing
- Measurses HIV AB and p24 Ag
- Confirmation is HIV RNA by PCR
Other HIV testing methods?
- CD4
- Ultrasensitive quantitative rna by PCR (viral load)
- Rapid testing
ELISA (aka the old test of choice for HIV)–> looks for _____
vs
combination or 4th generation–> looks for both ____ and _____
antibody only*
-and it takes 4-12 weeks for antibody to develop
-HIV antibody and p 24 antigen
2-6 weeks from exposure to positivity —>Now test of choice for testing, confirm with NAT-(HIV rna by pcr)
How to measure a Pt’s response to HIV tx?
- CD4 count
- Viral load (VL) –> Drug resistance= VL >1000
HIV Pts:
-what other screening tests should be performed?
- Hep A,B, and C
- TB and Toxoplasmosis
- STDs (syphilis, chlamydia, gonorrhea, etc)
HIV tx:
-list Ex’s
- *HAART= highly active antiretroviral therapy– now referred to as antiretroviral therapy**
- -> Protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTI), non nucleoside reverse transcriptase inhibitors (NNRTI) and integrase inhibitors standard
Goals of HIV therapy (list top 5)
- Suppression of viral load to <50 copies per ml
- Restoration of immune function (CD4 count)
- Prevention of HIV transmission
- Prevention of drug resistance
- Improvement in quality of life
HIV regimen:
-backbone=
2 nucleoside reverse transcriptase inhibitors (NRTIs)
HIV regimen:
-base=
traditionally included either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or Protease Inhibitor (PI), or integrase inhibitor reltegravir
Nucleoside Reverse Transcriptase Inhibitors (NRTIs):
Newer choices?
- Emtricitabine (FTC)
- Tenofovir (TAF)
Less Use 2° ADRs
- Didanosine (ddI)
- Stavudine (d4T)
- Abacavir (ABC)
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
-1st line choices?
Nevirapine (NVP)
Delavirdine (DLV)
Efavirenz (EFV)
HIV meds:
-Tenofovir has 2 formulations–> list? (why is the newer formulation better?)
Tenofovir disoproxil(old) higher risk of causing renal failure and osteoporosis
**Tenofovir alafenamide-(new) lessened renal and bone risks
Protease Inhibitors (PIs) (-"navir drugs"**) -list the ones that are STILL recommended
- Ritonavir (RTV)
- Lopinavir (LPV)
- Atazanavir (ATV)
- Darunavir (DRV) preferred= 1st line (KNOW)
Integrase Strand Transfer Inhibitors (INSTIs) (-egravir drugs) list ex’s
Use 2 nucleoside inhibitors and add in 1 integrase strand transfer inhibitors like: Raltegravir or Elvitegravir
HIV combination meds (once daily dosing) (list Ex’s of common combination pills)
- Atripla: (Tenofovir disoproxil/emtricitabine/efavirenz
- Stribild: (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil
- Genvoya: elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide
- Complera: emtricitabine/rilpivirine/tenofovir disoproxil fumarate
- Odefsey: emtricitabine/rilpivirine/tenofovir alafenamide
When should treatment be started:
-historically based on ______ count
VS
MOST recent guideline?
*CD4 count –>500- monitor
<500 consider initiation of treatment
<350 treatment initiated
- January 2020: states that all HIV + should be considered for initiation of treatment
- -Continuation of 1st recommendation in 2016 (ANYTIME someone is dx w/ HIV they should be offered tx)
Initial Treatment: Choosing Regimens
-3 main categories?
-1 II + 2 NRTIs
-1 PK-boosted PI + 2 NRTIs
-1 NNRTI + 2 NRTIs
–Combination of II, boosted PI, or NNRTI + 2 NRTIs is preferred for most patients
NRTI pair should include 3TC or FTC
MC regimen**
2 NRTIs (FTC + TAF) + 1 NNRTI (ex.EFV) (historic option)
OR
+ 1 INSTIs (ex. RAL) (preferred)
OR
+ “boosted”PI (DRV)
OR
*boosted with ritonavir or cobicistat
Untreated HIV is assoc. w/ development of _____ and ______
*AIDS and non-AIDS-defining conditions
Earlier Aids related therapy (ART) may prevent:
HIV-related end-organ damage; deferred ART may not reliably repair damage acquired earlier
-ALSO: more evidence that HIV in of itself causes enough inflammation to cause end organ damage
which NRTIs are MC used?
**Emtricitabine (FTC) &
Tenofovir (TAF)
+ ! **INSTI– Raltegravir (RAL)- 1st line (preferred to do INSTI + 2 NRTIs)
OR
+
1 NNRTI (ie Efavirenz (EFV)) (historic choice)
Benefits of Early therapy:
Potential decrease in risk of many complications, including–> list Ex’s
HIV-associated nephropathy
Liver disease progression from hepatitis B or C
Cardiovascular disease
Malignancies (AIDS defining and non-AIDS defining)
Neurocognitive decline
Blunted immunological response owing to ART initiation at older age
Persistent T-cell activation and inflammation
Describe CD4 monitoring with HIV therapy:
- check @ baseline (x2) and every 3-6 months
- immediately before initiating ART
- Every 3-6 months during first 2 yrs of ART or if CD4 <300
- After 2 yrs on ART w/ HIV RNA consistently surpressed:
- -CD4 300-500: Q 12 months
- -CD4 >500: optional
- -more frequent testing if on meds that lower CD4 count
What screening assessment is needed prior to Pt starting ABC (abacavir)?
**HLA-B*5701 (MUST screen for all newly diagnosed HIV PTs) either they are + or -.
**Positive Pts should NOT recieve ABC (abacavir)
-Positive status should be recorded as ABC allergy–> this drug can cause a severe hypersensitivity rxn (HSR) that can result in death
High potential for adverse effects w/ ART meds: (list ex’s)
Rash Diarrhea Pancreatitis Hyperlipidemia and lipodystrophy Increased cardiac risk CNS effect-psychological disturbances
Adverse Effects: PIs (protease inhibitors) list Ex’s
Hyperlipidemia Lipodystrophy Hepatotoxicity GI intolerance Possibility of increased bleeding riskfor hemophiliacs Drug-drug interactions
Adverse Effects of NRTIs (lsit ex’s)
Lactic acidosis and hepatic steatosis (highest incidence with d4T, then ddI and ZDV, lower with TDF, ABC, 3TC, and FTC)
-Lipodystrophy(higher incidence with d4T)
Adverse Effects of NNRTIs
Rash, including Stevens-Johnson syndrome
Hepatotoxicity (especially NVP)
Drug-drug interactions
IRIS=
immune reconstitution syndrome= occurs after initiation of HAART
- Inflammatory reaction in response to rapid reconstitution of CD4 counts
- –Can “unmask” underlying opportunistic infection
*Diagnosis of exclusion
HIV management: (list all tests)
- Cd4 and viral load Q 6-12 months
- PPD/Quantiferon gold testing
- RPR
- Toxoplasmosis antibody
- Anal PAP smears,Cervical PAP smears (6-12 months)
- If CD4 ct < 200-PCP prophylaxis,<50 MAI prophylaxis
Pathogen: PCP
-Indication: CD4
<200
-Bactrim
Pathogen: Toxo
–Indication: CD4
- CD4 <100 and IgG +
- Trimethoprim-sulfa or Dapsone + Pyrimethamine
Pathogen: MAC
-Indication: CD4
CD4 <50
-Clarithro/Azith
Pathogen: TB
- Indication: ____
- Regimen= ?
+PPD(5mm)
-INH (9 months)
Vaccinations for all HIV PTs
Pneumococcal Hepatitis A and B Tetanus, diphtheria, pertusis Meningitis Influenza COVID-19 Shingles in >50 years of age
-HPV?-definitely in those aged 26 years and younger
Postexposure prophylaxis
Antiretroviral therapy decreases risk of converting to infection
Begin within 72 hours of exposure
–If source is HIV +, prophylax with agents known to be effective against that patient’s virus
- -Generally given for 1 month
- Truvada/Raltagravir**
(think health care workers that were exposed via needle stick, or someone that had sex with an HIV Pt, or rape victims**)
Pre exposure prophylaxis: List meds**
- Can reduce risk of HIV infection by 92%(8-2-2017)(JAMA 2019)
- Truvada:tenofovir/emtricitabine–Daily dosing
Recommended PREP by MSM:
-describe this demographic
- Adult man without acute or established HIV infection
- Any male sex partners in past 6 months
- Not in a monogamous partnership with a recently tested, HIV-negative man
AND at least one of the following:
- -Any anal sex without condoms (receptive or insertive) in past 6 months
- -Any STI diagnosed or reported in past 6 months
–Is in an ongoing sexual relationship with an HIV-positive male partner
Recommended PREP by MSM:
-regimen?
- Tenofovir/emtricitabine (Truvada) once daily
- Tenofovir alafenamide/emtricitabine (Descovy) approved for PrEP Oct 2019
- -Check HIV status every 3-6 months
PrEP Pearls
- Assess HIV status prior to initiation and every 3 months after initiation
- PrEP does NOT reduce the risk of other STIs**
- Check renal function**
- Check Hep B immunity!!!!** KNOW for boards
F/U: what tests are required at every 3-month visit?
HIV testing
Medication monitoring/stress adherence
Counseling/behavioral risk reduction
Assess renal function, if normal, then q 6 months
Oral/rectal std screening if appropriate
Pregnancy testing if appropriate
Perinatal transmission:
-what med should be administered to the pregnant mother w/ HIV?
**AZT,Zidovudine administered during pregnancy, labor and delivery , vertical transmission decreased by 2/3.
-Can start as early as 14 weeks into the pregnancy.
List 4 Ex’s of Miscellaneous Opportunistic infxns
- Coccidioidomycosis
- Histoplasmosis
- Blastomycosis (HIV defining illness)
- Toxoplasmosis
Coccidioidomycosis:
- Sx?
- Dx?
- Tx?
-Coccidioides immitis
aka “San Joaquin Valley fever”
sx: 40% present with influenza-like illness
high fever, night sweats common
dx: serology (IgM/IgG)
tx: no tx indicated unless specific risk factors (immunosuppression)–> tx=diflucan**
Histoplasmosis:
- Sx?
- Dx?
- Tx?
-Histoplasma capsulatum–>Linked to bird droppings or **bat guano exposure along Ohio River Valley
- Many infections “asymptomatic”; usually **pulmonary symptoms if presenting
- Disseminated disease common in AIDs/ immunocompromised states
-dx: antigen test (serum/urine or CSF) or tissue bx
-Tx: itraconazole (mild/mod dz)
and Amphotericin B (severe dz)
Blastomycosis:
- Sx?
- Dx?
- Tx?
**Linked to soil exposure along Ohio River Valley, especially dust exposure (ex. construction)
- Many infections “asymptomatic”; usually start as pulmonary infections with cutaneous dissemination
- -Disseminated disease possible in all Pts
-Dx: bx & culture
-Tx: itraconazole (mild/mod dz)
and Amphotericin B (severe dz)
toxoplasmosis:
- Sx?
- Dx?
- Tx?
aka toxoplasma gondii
- Assoc w/ cat boxes**
- Usually reactivation in setting of HIV, not primary infection
- Sx: focal neurologic findings, fever, Characteristic lesion on MRI-punched out lesion
tx: If you have HIV/AIDS, the TOC for toxoplasmosis is also pyrimethamine and sulfadiazine, with folinic acid (leucovorin).
Histo vs blasto: what is the differentiator?
- Histo= immunosuppression (AIDS defining illness)
- Blasto= no immunosuppression
