HAART

Question 1

When is Highly Active Antiretroviral Therapy (HAART) usage most indicated?

Answer 1

-CD4+ below 500cells/mm3-high viral load

Question 2

HAART is a 3-drug regimen consisting of:

Answer 2

-2 NRTIs and 1 of the following:NNRTI or protease inhibitor or integrase inhibitor

Question 3

What should be done following HIV diagnosis (via multiple positive ELISA and Western blot test)?

Answer 3

Perform viral load and resistance and begin a preferred ARV regimen

Question 4

What is the appropriate action if a viral load is detectable after 12-24 weeks of treatment OR if a viral rebound is seen after suppression?

Answer 4

-make sure the patient is adhering to treatment-If they are, perform resistance testing and change to a different, non-resistant regimen of 3 drugs

Question 5

What are the NRTIs?

Answer 5

-Abacavir-Lamivudine-tenofovir-zidovudine-Emtricitabine-didanosine-stavudine

Question 6

What are the NNRTIs?

Answer 6

EfavirenzNevirapineDelavirdine

Question 7

What are the HIV-1 protease inhibitors?

Answer 7

atazanavir, ritonavir, indinavir, lopinavir, saquinavir (others)

Question 8

What are the HIV inhibitors?

Answer 8

-enfuviritude-maravaroc

Question 9

What are the integrase inhibitors?

Answer 9

Raltegravir

Question 10

How are NRTIs given?

Answer 10

PO 1x-2x daily (NNRTIs same)

Question 11

CYP interactions of NRTIs?

Answer 11

Nope

Question 12

Other interactions of NRTIs?

Answer 12

substrates for glucuronide

Question 13

Elimination of NRTIs?

Answer 13

urine as drug + metabolites

Question 14

CYP interactions of Delvirdine (NNRTI)?

Answer 14

-inhibits 3A4, 2D6, 2C9, and 2C10

Question 15

CYP interactions of nevirapine and efavirenz (NNRTI)?

Answer 15

induce 3A4 and 2B6

Question 16

Elimination of NNRTs?

Answer 16

urine as metabolites

Question 17

How are HIV protease inhibitors given?

Answer 17

PO 1x-2x daily

Question 18

Interactions of Atazanavir?

Answer 18

inhibits 3A4 and UGT-3A4 substrate

Question 19

Interactions of Ritonavir?

Answer 19

inhibits 3A4, UGT, P-gp, and 2D6

Question 20

Interactions of Saquinavir?

Answer 20

inhibits 3A4 and UGT

Question 21

Interactions of Lopinavir?

Answer 21

3A4 substrate (Darunavir is same)

Question 22

Interactions of Indinavir?

Answer 22

3A4 and P-gp substrate and 3A4 inhibitor

Question 23

How are HIV protease inhibitors eliminated?

Answer 23

stool as metabolites

Question 24

How is Enfuvirtide given?

Answer 24

S.C.

Question 25

Metabolism of Enfuvirtide?

Answer 25

catbolized to AAs

Question 26

How is Maraviroc given?

Answer 26

PO 1-2x daily

Question 27

Interactions of Maraviroc?

Answer 27

3A4, P-gp substrate

Question 28

Elimination of Maraviroc?

Answer 28

stool/urine as drug + metals

Question 29

How is Raltegravir given?

Answer 29

PO 1-2x daily

Question 30

Interactions of Raltegravir?

Answer 30

glucuronide metabolite

Question 31

Elimination of Raltegravir?

Answer 31

stool/urine as drug + metals

Question 32

What is Cobicistat?

Answer 32

An orally active CYP3A4 inhibitor used as a pharmacokinetic enhancer to increase the serum concentration of CYP3A substrates, such as theprotease inhibitors atazanavir and darunavirHas no antiviral activity

Question 33

What is ATRIPLA?

Answer 33

a once daily pill consisting of tenofovir, entricitabine and efavirenz- a complete regimen

Question 34

Side effects of Abacavir?

Answer 34

hypersensitivityhepatic disease

Question 35

Which NRTIs have a BBW for hepatic disease?

Answer 35

-all but Abacavirespecially in obese patients and with prolonged exposure, especially in women

Question 36

Which NRTIs have a BBW for lactic acidosis?

Answer 36

allespecially in obese patients and with prolonged exposure, especially in women

Question 37

What are the BBWs for Zidovudine?

Answer 37

-anemia (only one)-hepatic disease-lactic acidosis-myopathy-neutropenia

Question 38

Which NRTIs have a BBW for pancreatitis?

Answer 38

Didanosine and stavudine

Question 39

Which NRTI have the most intense neuropathy impact?

Answer 39

Stavudine (but all but Abacavir do to some extent)

Question 40

What are some contraindications of Nevirapine?

Answer 40

-female-hepatic disease-hepatitis-nevirapine hypersensitivity-serious rash

Question 41

Which side effects of Nevirapine are common to all NNRTIs?

Answer 41

hepatic disease and serious rash

Question 42

Side effects of Efavirenz?

Answer 42

vivid dreamsCNS symptoms

Question 43

Which NNRTIs are contraindicated in pregnancy?

Answer 43

Delavirdine and Efavirenz

Question 44

Side effects of PIs?

Answer 44

-GI pain, N/V-Lipodystrophy-Hyperglycemia/Diabetes mellitus-Dyslipidemia-Nephrolithiasis -Severe rash including SJS

Question 45

How do PIs cause hyperglycemia/diabetes?

Answer 45

PIs acutely inhibit GLUT4

Question 46

The Nephrolithiasis seen in PIs is most common in which one?

Answer 46

Indinavir

Question 47

T or F. Peripheral neuropathy is a common consequence of HIV

Answer 47

T. Mainly attributed to myelinated fiber involvementIt is also exacerbated by HAART (mainly NNRTI, NRTIs, and some PIs)

Question 48

Whats the recommended ART in pregnancy (assuming a NRTI, NNRTI, and PI combo regimen)?

Answer 48

-NRTIs- lamivudine, zidovudine-NNRTIs- nevirapine-PI- lopinavir/ritonavir

Question 49

Infection is an obvious consequence of HIV progression. What is the recommended treatment for a Pneumocystis jiroveci infection?

Answer 49

trimethoprim-sulfamethoxazole (QT prolongation common)

Question 50

Infection is an obvious consequence of HIV progression. What is the recommended treatment for a M. tuberculosis infection?

Answer 50

isoniazid + Pyridoxine

Question 51

Infection is an obvious consequence of HIV progression. What is the recommended treatment for a Toxoplasmosis infection?

Answer 51

trimethoprim-sulfamethoxazole

Question 52

Infection is an obvious consequence of HIV progression. What is the recommended treatment for a CMV infection?

Answer 52

ganciclovir (foscarnet and cidofovir can be useful with retinitis treatment)

Question 53

Infection is an obvious consequence of HIV progression. What is the recommended treatment for a Cryptococcosis, candidiasis, endemic fungal infections?

Answer 53

Fluconazole (QT prolongation common and 3A4/2D6 inhibitor)

Question 54

T or F. CMV infections occur primarily in the setting of advanced immunosuppression and are typically due to reactivationof latent infection

Answer 54

T.

Question 55

What is the end-game of unrelated CMV?

Answer 55

-retinitis-colitis-esophagitis-CNS disease-pneumonitis

Question 56

Several drugs are available for CMV treatment. What is the ROA for them?

Answer 56

valganciclovir- PO (can be used for CMV retinitis treatment and prophylaxis for transplant patients)ganciclovir, foscarnet, cidofovir- IV (all approved for CMV retains treatment only)

Question 57

Side effects of valganciclovir?

Answer 57

-leukopenia-neutropenia-thrombocytopenia-renal toxicity (metabolized via GF and active RTS)

Question 58

What is Foscarnet?

Answer 58

A viral DNA polymerase inhibitor that binds pyrophosphate binding site and does NOT need viralactivation

Question 59

How can resistance arise against Foscarnet?

Answer 59

mutated viral DNA polymerase

Question 60

How is foscarnet given?

Answer 60

It is a very insoluble drug so you saline hydrate the patient and give by infusion pump

Question 61

What are the toxicities of foscarnet?

Answer 61

– genital ulcerations due to high levels of ionized drug in urine-Nephrotoxicity – electrolyte imbalances– hyper- and hypo- calcemia, phosphatemia, hypokalemia andhypomagnesemia can lead to seizures

Question 62

What is Vidarabine?

Answer 62

A nucleoside analog used for EBV treatment that requires phosphorylation for activity– ara-ATP is a substrate & inhibitor of viral DNA polymerase– Viral DNA polymerase mutation gives resistance

Question 63

How is vidarabine given?

Answer 63

Very poor oral bioavailability – applied to eye as ointment

Question 64

Side effects of vidarabine?

Answer 64

Risk of systemic side effects is low because of the drugs insolubility and low ocular penetration

Question 65

What drugs are used to treat Kaposi's sarcoma-associated herpesvirus?

Answer 65

Antiviral drugs, such as ganciclovir, valganciclovir and cidofovir• Cidofovir, IV is the main

Question 66

Does Cidofovir need to be activated? How does it work?

Answer 66

Yes, Intracellular conversion to active diphosphate form-- Competes with deoxycytosine triphospate (dCTP) for incorporation into viral DNA– Selective for viral DNA polymerase versus host

Question 67

How is Cidofovir cleared?

Answer 67

renal with active RTS

Question 68

Side effects of Cidofovir?

Answer 68

-Dose-dependent nephrotoxicity (proximal tubular cells)– monitor serum creatinine & urinary protein• Adverse effects include, but are not limited to,neutropenia, ocular hypotonia, GI toxicity & rash/alopecia