Brief Overview of ART

Overview of Antiretroviral Therapy – Joseph Quintana

 

Fixed Dose

Combination regimens

Renal Dose

Adj.

Specific Considerations

Biktarvy®

Bictegravir/ Emtricitabine/ Tenofovir (Alafenamide)

d/c if CrCl < 30; ok w/HD

  Metformin levels

Contraindicated w/:

rifampin, dofetilide, rifabutin

Avoid close admin.  w/: laxatives, sucralfate, iron, calcium

Triumeq®

Abacavir/ Dolutegravir/ Lamivudine

Dose adj individual components <50 mg/min

Dolutegravir can metformin & dofetilide levels; dose adj needed w/rifampin use

Same absorption issues with polyvalent cation administration (as below with bictegravir) also apply to dolutegravir

Genvoya®

Elvitegravir/ Cobicistat/ Emtricitabine/ Tenofovir (Alafenamide)

d/c if CrCl < 30; ok in HD

Many DDI with Genvoya (and other regimens with pharmacologic booster [cobicistat] due to CYP 3A4 inhibition

 

 

Nuceloside RTI

Dose adj

Specific SE

Major DDI

Special Points

Abacavir (ABC)

Hepatic dysfunction

LDL/TG

risk MI

Tenofovir (df)

Requires testing for HLA B5701; Avoid if previous hyper-sensitivity

Emtricitabine

(FTC)

Renal (adj by CrCl)

Rash, Insomnia,

Rhabdomyolysis,

Hyperpigmentation in palms/soles

Lamivudine

Active against HBV

Lamivudine

(3TC)

Renal (adj by CrCl)

Nausea, HA, peripheral neuropathy, neutropenia, rash

Emtritabine

Active against HBV

Tenofovir Alafenamide (TAF)

D/c for CrCl < 15

 

lipids in TAF vs TDF

AED’s may $ levels

Tx of choice for HBV; lipids

Tenofovir Disoproxil (TDF)

 

Renal (adj by CrCl)

N/V, # LFT, asymptomatic # CK

--

Active against HBV

NRTI Additional Information

          •  
  • Tenofovir alone is indicated for HBV, in which case you should be mindful of renal clearance when dosing. In HIV, it is only indicated in combination with emtricitabine and fixed-dose combination formulations, in which it is contraindicated if CrCl<30
  • Class-wide Side Effect: Lactic acidosis, steatosis and lipoatrophy
  • Resistance: M184V confers high resistance to emtricitabine and lamivudine, mid-level resistance to abacavir

 

 

 

Integrase

Inhibitor

Dose

Adj.

Specific

SE

Major DDI

Special Points

Raltegravir

(RAL)

--

--

Rifampin, AED’s

--

Dolutegravir

(DTG)

*see special points*

Hyperglycemia

Weight gain

Rifampin, Efavirenz

metformin lvls

Avoid close admin w/

laxatives, sucralfate,

 iron, calcium

May Cr, w/o effect on

renal fxn

 

 

NNRTIs

Hepatic

Adj

Specific SE

Major DDI

Special Points

Efavirenz

D/c if Child Pugh B/C

Psychosis, vivid dreams, SI, mania, seizures;

Lipids & glucose

Plavix, Azole, antifungals,

some statins *

clarithromycin, Buprenorphine

Give before meals; d/c if rash develops

Etravirine (ETR)

 

Hypersensitivity

  Lipids & glucose

Plavix, clarithromycin

 

Nevirapine (NVP)

D/c if Child Pugh B/C

Steven Johnson

Syndrome

Azoles,

OCP’s, statins,

clarithro-mycin

Don’t start if CD4 >250 in women,

CD4 >400 in men;

Don’t admin w/antacids

Rilpivirine (RPV)

 

Depression

 

AED’s, PPI’s, dexamethasone

Must be taken w/ full meal; Don’t use if HIV RNA >100k + CD4 < 200;

Don’t admin w/antacids

Doravirine

 

Nightmares

 

 

NNRTI Additional Information

          •  
  • Class-wide Side Effect: hepatitis, rashes
  • Resistance: K103N resistance to efavirenz and nevirapine

 

 

 

Protease inhibitors

Hepatic

Dose adj

Specific SE

Major DDI

Special Points

Atazanavir (ATV)

Based on Childs Pugh

Jaundice, Kidney stones

AV block, Pancreatitis

Rhabdomyolysis

CYP3A4 Inhibitors

PPI and H2 blockers

Admin w/ meals

Darunavir (DRV)

 

 

Rashes

Pancreatitis

 

CYP3A4 Inhibitors

Azoles can be used cautiously with drug level monitoring

Must d/c if rash

 

Lopinavir (LPV)

 

 

AV block, QT changes

Pancreatitis

Hepatitis

CYP3A4 Inhibitors

 

Admin w/ meals

Protease Inhibitor Additional Information

          •  
  • All protease inhibitors must be boosted:
    • Ritonavir: can cause MSK pain, rhabdomyolysis, not expected at usual doses
    • Cobicistat: may increase Cr without effect on renal function
  • Class-wide Side Effects: hepatitis, hypersensitivity reactions, # cholesterol/TG, hyperglycemia, GI upset, lipodystrophy