Term
| What viral classification is HIV? |
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Definition
| HIV is considered a class VI virus because it's positive ssRNA is converted into a dsDNA. |
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Term
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Definition
| Class I viruses have dsDNA genomes. |
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Term
| Describe the genome of retroviruses. |
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Definition
| Retroviruses have positive, non-segmented ssRNA genomes. |
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Term
| What genes do all retroviruses have? Describe each one. |
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Definition
Gag - major structural polyprotein
Pro - viral protease
Pol - reverse transcriptase, RNAse H, and integrase
Env - viral surface glycoproteins and transmembrane proteins |
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Term
| What are the two known human retroviruses? |
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Definition
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Term
| What are the common symptoms of an HIV infection? |
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Definition
| Fever, night sweats, swollen lymph glands, chills, weakness, and weight loss |
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Term
| At what CD4 T-cell count is AIDS diagnosed? |
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Definition
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Term
| <350 cells/mm3, what kind of secondary infections usually occur? |
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Definition
| Herpes simplex virus, TB, oral/vaginal thrush, and non-Hodgkin's lymphoma |
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Term
| When CD4 T cell <200, what kind of secondary infections do you see? |
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Definition
| Candida esophagitis and pneumonia |
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Term
| If CD4 T cell falls <100 cells/mm3, what kind of secondary infections do you expect? |
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Definition
| Cryptococcal meningitis and toxoplasma encephalitis |
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Term
| What are the two important glycoproteins involved in HIV attachment and fusion? |
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Definition
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Term
| How is HIV so rapidly resistant? |
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Definition
| HIV replicates quickly and has an error prone reverse transcriptase, leading to a high mutation rate |
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Term
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Definition
| They competitively inhibit reverse transcriptase as base analogues. |
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Term
| What are the black box warnings for NRTIs? |
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Definition
| Lactic acidosis and hepatic steatosis |
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Term
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Definition
| NRTIs need to be phosphorylated three times via cellular enzymes. |
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Term
| What allele do you need to screen for before using abacavir and why? |
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Definition
| HLA-B*5701 due to increased risk for hypersensitivity reactions |
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Term
| What is unusual about the hypersensitivity reaction to abacavir? |
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Definition
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Term
| What do we need to watch out for when discontinuing lamivudine? |
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Definition
| Hepatitis B flares because the drug suppresses hepatitis B |
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Term
| What is unique about the activation of tenofavir? |
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Definition
| It only requires TWO phosphorylation steps unlike three for other NRTI's |
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Term
| Which drug is emtricitabine an analog of? Based on your answer, what do we have to worry about when stopping this drug? |
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Definition
| Lamivudine; hepatitis B flares |
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Term
| Do NNRTI's and NRTI's interact? |
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Definition
| No, the binding sites are different |
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Term
| Which of the NNRTI's do not have cross resistance within the NNRTI class? |
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Definition
| Etravirine does not have cross resistance depending on the type of mutation. |
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Term
| Which of the NNRTI is given at labor onset and to the newborn? |
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Definition
| Nevirapine can be given to the mother at onset and to the newborn three days later. |
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Term
| How do protease inhibitors work? |
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Definition
| PIs inhibit the protease needed to splice the polypeptide that contains both Gag and Pol peptide chains into active proteins. |
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Term
| What is the one side effect of ritonavir that is physically visible, especially on the patient's face? |
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Definition
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Term
| What is fosamprenavir a prodrug for? How is it activated? |
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Definition
| It is a prodrug for amprenavir and needs hydrolyzation in the GI tract. |
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Term
| Recall the structure of fosamprenavir. What kind of allergy should you be concerned with? |
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Definition
| The drug has a sulfonamide group, which causes concern for sulfa allergies. |
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Term
| What drug would you not take with atazanavir and why? |
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Definition
| A PPI such as prilosec because atazanavir requires an acidic environment |
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Term
| What kind of allergy should you worry about for darunavir? |
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Definition
| Sulfa allergy because of the sulfonamide group |
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Term
| How does enfuvirtide work? |
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Definition
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Term
| In what HIV patients would you not use maraviroc in? |
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Definition
| Patients with CXCR4 strains or mixed strains |
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Term
| Which ends of HIV DNA does integrase process? What else does integrase do? |
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Definition
3' ends
It is also involved in strand transfer |
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Term
| Which classes are active for HIV-2? |
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Definition
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Term
| In terms of interactions, why is raltegravir convenient? What interactions should be of concern? |
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Definition
| It has NO P450 interactions, but interacts with polyvalent cations and antacids |
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Term
| What drug is given with elvitegravir and why? |
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Definition
| Cobicistat to boost elvitegravir |
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Term
*
35 yo John Doe came in today feeling very sick with night sweats, weight loss, and a fever. He admits that two weeks ago, he had a sexual encounter with someone he had met at the bar last night. Worried that he might have HIV, he demands testing. What should you tell him? Is post-prophylaxis appropriate? |
|
Definition
Although testing can be completed today, results are not reliable because seroconversion will take 2-3 months after transmission. He should return in 10 weeks (making it 3 months since that encounter) for an EIA.
Post-prophylaxis is not appropriate because it was way past the 72 hour window. |
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Term
*
What is the CDC recommendation for HIV testing? |
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Definition
| All patients between 13-65 years should be tested. |
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Term
|
Definition
HIV infection with
CD4 count <200
OR
AIDS defining illness |
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Term
*
Name some AIDS defining illnesses. |
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Definition
| Herpes simplex, recurrent pneumonia, candidiasis, HIV-associated dementia, HIV-associated wasting, and TB are some |
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Term
*
Sally is a confirmed HIV patient. Her CD4 cell count is around 350. She has had a cold sore in the past week, which is due to Herpes simplex. Does she qualify for AIDS? |
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Definition
| No, she will qualify if the lesion has not resolved after four weeks. Herpes simplex patients do not automatically qualify. |
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Term
*
When should HIV therapy be initiated? |
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Definition
| In all patients regardless of CD4 count as long as patient is willing and understands the risks |
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Term
*
What is the key CD4 count for having the greatest increase in outcomes when starting treatment? |
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Definition
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Term
*
How many times does tenofavir need to be phosphorylated? |
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Definition
| Only TWO times instead of usual three |
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Term
*
What drugs are in Combivir? |
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Definition
| Zidovudine and lamivudine |
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Term
*
What are the components of Truvada? |
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Definition
| Zidovudine, lamuvidine, and abacavir |
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Term
|
Definition
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Term
*
If a patient can't use Sustiva, what can you use instead? |
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Definition
| You can replace efavirenz with rilpivirine |
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Term
*
What drugs are in Kaletra? |
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Definition
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Term
*
Why is Crixivan inconvenient? |
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Definition
| Indinavir needs to be taken with 1.5L of water or else kidney stones may occur. |
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Term
*
Which PI is available by itself? What is the brand name of the other PI that must come in a combination? |
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Definition
Raltegravir can be given alone.
Elvitegravir is only available in Stribild |
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Term
*
What are the components of Stribild? |
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Definition
| Elvitegravir, cobicistat, emtricitabine, and tenofavir |
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Term
*
How do NRTI's cause mitochondrial toxicity? |
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Definition
| They inhibit gamma DNA polymerase, leading to lactate build up, causing lactic acidosis or metabolic steatosis |
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Term
*
Which two drugs have the highest risk for mitochondrial toxicity? |
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Definition
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Term
*
What are the two black box warnings for NNRTIs? |
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Definition
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Term
*
Which NNRTI is the most hepatotoxic? |
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Definition
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Term
*
Jack comes into the pharmacy. He has been on HIV medications for about a week. However, lately, he complains of very vivid dreams. What is the most likely drug causing this side effect? |
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Definition
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Term
*
What is the key counseling point for etravirine? |
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Definition
| A mild rash will occur and last for about two weeks |
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Term
*
Sally is in the pharmacy today requesting a refill for Complera. You pull up her profile on the computer to refill when she mentions she also needs a refill on her Zantac. You go on the fill out the two prescriptions when you recall something important. What is it? |
|
Definition
Complera contains rilpivirine, tenofavir, and tenofavir.
Rilpivirine requires an acidic medium for absorption so you need to take ranitidine at least 12 hours before or four hours after rilpivirine |
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Term
*
Of the PIs, which drug does not have metabolic complications such as lipodystrophy and lipoatrophy? |
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Definition
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Term
*
What doses of ritonavir are given for PK boosting? |
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Definition
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Term
*
What are all PIs substrates for? |
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Definition
|
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Term
*
What are the two mechanisms by which ritonavir boosts other PI's? |
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Definition
| CYP3A4 inhibition and PGP efflux pump inhibition |
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Term
*
What is the only injectable HIV drug? What is the dosing and frequency? |
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Definition
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Term
*
What is a common medication error for Insentress? |
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Definition
| It is often given as QD, but MUST BE BID!! Data shows better outcomes for BID. |
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Term
*
What are the components of Atripla? |
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Definition
| Tenofair, emtricitabine, and efavirenz |
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Term
*
Which PK booster has anti-HIV effects? |
|
Definition
Ritonavir at higher doses
Cobicistat DOES NOT HAVE ANY ANTI-HIV EFFECTS AT ANY DOSE! |
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Term
*
What are the rules of HIV resistance? |
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Definition
| Inevitable, permanent, potentially cross resistant, and limits therapy options |
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Term
*
What is archived resistance? |
|
Definition
It refers to how resistance is permanent. If a population of HIV virions were to become resistant to a drug, then therapy would be changed to a second drug. The second drug will kill MOST of that population. However, some will remain undetected. If a patient were to switch back to the first drug, the survivors will be able to grow again because they are still resistant.
These small survival populations are archived resistant populations. |
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Term
*
What are the components of resistance? |
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Definition
| Fast HIV turnover (10^8 to 10^10 virions made daily) and erroneous reverse transcriptase (one mutation per genome transcribed, leading to a possible 20 billion mutations per day) |
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Term
*
What is the foundation for ANY HAART regimen? |
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Definition
|
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Term
*
What are the preferred regimens for naive patients? |
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Definition
1. Efavirenz + emtricitabine + tenofavir
2. Emtricitabine + tenofavir with atazanavir/ritonavir OR darunavir/ritonavir
3. Raltegravir (BID) + emtricitabine + tenofavir
4. Lopinavir/ritonavir (BID) + lamivudine + zidovudine (BID) |
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Term
*
What is the brand name for the combination of drugs that make up the NNRTI-based preferred regimen? |
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Definition
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Term
| If using a preferred PI-based regimen, what combination drug can you use to lower pill burden? |
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Definition
| Truvada because it contains emtricitabine and tenofavir; you still need to add on atazanavir/ritonavir or darunavir/ritonavir |
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Term
*
If a patient is taking 30mg of omeprazole, which preferred regimen would you not use? |
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Definition
| Truvada + atazanavir/ritonavir because atazanavir requires acid for absorption |
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Term
| Which regimen would you not use in pregnant women or women trying to become pregnant? |
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Definition
Efavirenz + emtricitabine + tenofavir
because efavirenz is class D and not good for the first trimester. |
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Term
*
What is the preferred HIV treatment for pregnant women? Name all the two combination drugs that you can use to lower pill burden. What needs to be changed in the third trimester? |
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Definition
Kaletra (lopinavir + ritonavir) and Combivir (lamivudine + zidovudine)
In the third trimester, lopinavir/ritonavir needs to be increased from two tablets BID to THREE tablets BID.
NOTES
Combivir - 150mg lamivudine 300mg zidovudine
Normal dosing for lamuvidine is 150mg BID
Normal dosing for zidovudin is 300mg BID
Thus, the combination product is okay to use in pregnant preferred regimen as BID. |
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Term
*
What combination drug can you use for INSTI-based preferred treatment to lower pill burden? |
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Definition
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Term
*
Why would you not use didanosine and stavudine together even though both are NRTI's? |
|
Definition
DDI = adenosine analog
D4T = thymidine analog
You will get the two pairing together, decreasing efficacy |
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Term
*
Why is adherence so important? |
|
Definition
| For success AND preventing the opportunity for resistant strains to develop |
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Term
*
What does genotyping tell you in regards to resistance? |
|
Definition
| The MUTATIONS that the strain has, but not degress of resistance |
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Term
*
What does phenotyping tell you in regards to resistance? |
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Definition
| DEGREE of resistance to specific drugs, but not specific mutation |
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