HIV Part 1 (Dr.Lam)

1. What are the 3 enzymes involved in the HIV life cycle?

Reverse transcriptase

Integrase

Protease

1. Based on the current HHS HIV treatment guidelines, which class is the preferred effective backbone for an antiretroviral therapy (ART)? Which class is preferred as the anchoring class for an effective ART regimen?

Backbone: NRTI x2

Anchoring: INSTI x 1

1. Which antiretrovirals (ARVs) inhibit the integrase enzyme? (Select all that apply)

   1. Darunavir

   2. Dolutegravir

   3. Elvitegravir

   4. Rilpivirine

2,3

1. Which ARVs inhibit the reverse transcriptase enzyme? (Select all that apply)

   1. Tenofovir disoproxil fumarate (TDF)

   2. Darunavir

   3. Abacavir

   4. Doravirine

   5. Cabotegravir

1,3,4

1. Which ARVs inhibit the protease enzyme? (Select all that apply)

   1. Darunavir

   2. Dolutegravir

   3. Atazanavir

   4. Tenofovir alafenamide (TAF)

   5. Lopinavir/ritonavir

1,3,5

1. Describe the class specific adverse effects of NRTIs.

Lactic acidosis, hepatic steatosis, myopathy, lipodystrophy (rare) 

1. Describe the class specific adverse effects of NNRTIs.

Rash, SJS (rare): NVP > EFV > RPV= ETr

Hepatotoxicity risk

1. Describe the class specific adverse effects of PIs.

Insulin resistance → T2DM 

Hyperlipidemia (except ATV & DRV) 

Lipodystrophy 

1. Before initiating a person with HIV (PWH) on maraviroc (Selzentry®), what test needs to be performed for this patient?

Tropism Assay

1. Before initiating a PWH on an abacavir-based regimen, what genetic test needs to be performed? What does it mean if the test result is positive?

HLA-B *5701

Positive allele test → do not initiate due to risk of rash and hypersensitivity reaction

1. (True/False): A patient can be rechallenged on abacavir after developing hypersensitivity reaction.

False

1. List 2 laboratory biomarkers that should be monitored when a person is on TAF and TDF.

eGFR (serum creatinine)

Lipid Panel (TAF)

1. Provide 2 reasons why TAF is better than TDF.

Same risks as TDF but less (more forgiving on bones & kidneys) 

Improvement in eGFR, hip and spine bone mineral density

1. Provide 2 reasons why TDF is better than TAF.

TAF is associated with increased risk of  >10% weight gain 

Better lipid profile than TAF 

1. A 55-year-old patient is newly diagnosed with HIV-1 infection. She presents to the clinic for discussion about antiretroviral treatment (ART) options. Based on her labs, you notice that she has mild-to-moderate renal impairment (CrCl 45 mL/min). She has NKDA. Which NRTI could be considered as part of her ART regimen with NO dose adjustment needed? 

   1. Tenofovir alafenamide (Vemlidy®, TAF)

   2. Abacavir (Ziagen®, ABC)

   3. Tenofovir disoproxil fumarate (Viread®, TDF)

   4. Lamivudine (Epivir®, 3TC)

2

1. Which 2 NNRTI agents could cause bothersome CNS side effects? (Hint: one is C/I with PPIs) 

Efavirenz, Rilpivirine 

1. What is the main difference between Stribild® and Genvoya®? What is the main difference between Complera® and Odefsey®?

1. Stribild & Genvoya

   1. Stribild: EVG/cobi/TDF/FTC

   2. Genvoya: EVG/cobi/TAF/FTC

2. Complera & Odefsey

   1. Complera: RPV/TDF/FTC

   2. Odefsey: RPV/TAF/FTC

1. Which NNRTI and INSTI should be taken with food to increase their absorption and AUC? 

NNRTI: Rilpivirine  

INSTI: Elvetegravir (needs to be boosted) 

1. (True/False): Cobicistat and low dose ritonavir have antiviral activity against HIV.

false

1. Explain the rationale for adding either cobicistat or ritonavir to an ART regimen.

• Adding either to ART regimen boosts PI and INSTIs 

• PI have less viral resistance , but INSTIs have some viral resistance

• Lower pill burden 

  • Reduce frequency

1. Which protease inhibitors are considered “lipid friendly” (do not adversely affect the lipids)? (Select all that apply)

   1. Atazanavir

   2. Darunavir

   3. Fosamprenavir

   4. Ritonavir

1,2

1. Which ARV agents are pH dependent (acid labile)? (Select all that apply)

   1. Atazanavir

   2. Darunavir

   3. Rilpivirine

   4. Doravirine

1,3

1. Which ART combinations contain abacavir and require the HLA-B*5701 allele testing prior to initiation? (Select all that apply)

   1. Dovato®

   2. Epzicom®

   3. Triumeq®

   4. Biktarvy®

2,3

1. HC is newly diagnosed with HIV. His HIV VL is 130,000 copies/mL and CD4+ is 450 cells/mm3. The physician heard about Juluca® as an available single tablet regimen (STR) for HIV. She wants to give HC an ART regimen with two active agents to minimize long-term drug-related toxicity. She asks you if Juluca® will be an appropriate treatment regimen to initiate for HC. Do you agree or disagree? (Please explain).

Juluca: DTG/RPV

• Can be considered for patients who are already stable on ART regimen for >6 months → Julica is not appropriate (it is only for switching with a regimen) 

• Not stable since RPV is approved for VL<100,000 and CD4 >200

1. Provide 3 counseling points for a patient taking a rilpivirine-based regimen. List the fixed-dose combinations that contain rilpivirine?

CI with PPI, space out with H2RAs, HA, CNS, take with food, take it at bedtime 

• Cabenuva (IM): cabotegravir + rilpivirine 

• Juluca: DTG/RPV

• Odefsey: RPV/TAF/FTC

• Complera: RPV/TDF/FTC

1. (True/False): Maraviroc is effective in HIV-positive patients with CCR5 tropic virus only.

true

1. Which of the following ARVs are available in a long-acting injectable formulation? (Select all that apply)

   1. Cabotegravir

   2. Dolutegravir

   3. Doravirine

   4. Lenacapavir

1,4

1. Which NRTI agent should be avoided in PWH who have underlying CVD risk factors?

   1. Abacavir

   2. Atazanavir

   3. Tenofovir alafenamide

   4. Tenofovir disoproxil fumarate

1

1. Which fixed-dose combinations contain a “booster” or PK enhancer? (Select all that apply)

   1. Evotaz® (ATV/cobicistat)

   2. Prezcobix® (DRV/cobicistat)

   3. Biktarvy® (BIC/TAF/FTC)

   4. Dovato® (DTG/3TC) 

   5. Triumeq® (DTG/ABC/3TC) 

   
   

2,1

1. Which antiretroviral agent contains a sulfonamide moiety and should be used with caution in patients with serious sulfa or sulfonamide allergies (e.g., SJS or anaphylaxis)?

   1. Abacavir

   2. Atazanavir

   3. Darunavir

   4. Doravirine

3

1. What is ibalizumab’s MOA, its brand name, dose, frequency, and how is it administered?

• Ibalizumab MOA: humanized monoclonal antibody that targets CD4 receptor and gp120 → prevents viral entry 

• Brand name: Trogarzo

• Dose/Frequency: loading dose= 2000mg IV x 1 time , maintenance dose: 800mg IV Q2 weeks 

• Administration: IV, administer with other ARV agent 

1. What is enfuvirtide’s MOA, its brand name, dose, frequency, and how is it administered?  

• Enfuviritide MOA: binds to gp41 → prevent fusion of virus to host CD4+ cell surface

• Brand name: Fuzeon, T-20

• Dose/Frequency: 90mg SQ BID (combo with another ARV)

• Administration: SQ

1. What is fostemsavir’s MOA, its brand name, dose, frequency, and how is it administered?

• Fostemsavir MOA: binds to gp120 → prevents the cirus from attaching to host CD4+ cell 

• Brand name: Rukobia 

• Dose/Frequency: 600mg PO BID without regard to food (combo with other ARV)

• Administration : PO

1. Which new ARV combination has an optional oral lead-in phase for 30 days, followed by a monthly or bi-monthly injection? What is its ROA?

• Cabotegravir + Rilpivirine (Cabenuva) 

• ROA: ventrogluteal injection

1. What is the only FDA-approved HIV-1 capsid inhibitor called (generic and brand names)? How is it administered and how often?

• Lencapavir (Sunlenca) 

• SQ after oral , administer every 6 months from last injection

1. Describe the two main differences between Cabenuva® and SunlencaTM.

• Cabenuva: first long acting injectable; Q2 months 

• Sunlenca: heavily treatment experienced; Q6 months

1. (True/False): Rilpivirine-based regimens can be initiated in patients with an HIV viral load <100,000 copies/mL and CD4+ count >200 cells/mm3.

true

1. When should entry and capsid inhibitors be considered for PWH?

Heavily treatment experienced patients who are currently failing their ART therapy 

1. Identify the antiretroviral agents that are available in parenteral formulation (Hint: there are 4 agents). —> LICE

• Cabenuva, Lenacapavir, Ibalizumab, Enfuvirtide 

1. Describe the NRTTI’s mechanism of action and the name of the ARV agent for this class What other ARV is it combined with?

• MOA: exerts a dual action inhibitory effect on reverse transcriptase 

• Drug name: Islatravir 

• Combined with Doravirine/Islatravir (Idvynso)