Overview of Antiretroviral Therapy¶
Kathryn Snyder and Quinton Taylor
Combination ART¶
| Fixed Dose Combination regimens | Renal Dosing | Specific Considerations | |
|---|---|---|---|
| Biktarvy® | Bictegravir/ Emtricitabine/ Tenofovir (Alafenamide) | Discontinue if CrCl < 30; ok w/HD | ↑ Metformin levels Contraindicated with: rifampin, dofetilide, rifabutin Avoid close admin. with: laxatives, sucralfate, polyvalent cations (iron, calcium, etc.) |
| Dovato® | Doltegravir/ Lamivudine | CrCl 30-50: monitor for hematologic toxicities with lamivudine CrCl<30: do not use combo pill; dose-adjust individual components |
↑ Metformin levels Dose adjustment needed w/ rifampin use Contraindicated w/dofetilide and multiple antiepileptic drugs Avoid close admin. with polyvalent cations (iron, calcium, etc.) Test all pts for HBV prior to initiation |
| Symtuza® | Tenofovir alafenamide/ Emtricitabine/ Darunavir/ Cobistat | Discontinue if CrCl<30; ok w/HD but dose after HD on dialysis days | Contraindicated w/rifampin, rifabutin, simvastatin, multiple antiepileptic drugs Note that cobicistat can increase serum creatinine without affecting glomerular filtration so cautiously interpret serum creatinine levels |
| Triumeq® | Abacavir/ Dolutegravir/ Lamivudine | CrCL 30-50: monitor for hematologic toxicities with lamivudine CrCl< 30; do not use combo pill; dose-adjust individual components |
↑ Metformin levels Dose adjustment needed with rifampin use Contraindicated w/dofetilide and multiple antiepileptic drugs Avoid close admin. with polyvalent cations (iron, calcium, etc.) Test all pts for HBV prior to initiation |
| Genvoya® | Elvitegravir/ Cobicistat/ Emtricitabin/ Tenofovir (Alafenamide) | Discontinue if CrCl < 30; ok w/HD | Many drug-drug interactions due to CYP 3A4 inhibition with cobicistat |
NRTIs¶
| Nucleoside RTI | Dose adj | Specific Side Effects | Major DDI | Special Points |
|---|---|---|---|---|
| Abacavir (ABC) | Hepatic dysfunction | ↑ LDL/TG ↑ risk MI |
Tenofovir | Requires testing for HLA B5701 |
| Emtricitabine (FTC) | Renal | Rash, insomnia, rhabdomyolysis, hyperpigmentation in palms/soles | Lamivudine | Active against HBV |
| Lamivudine (3TC) | Renal | Nausea, HA, peripheral neuropathy, neutropenia, rash | Emtricitabine | Active against HBV |
| Tenofovir Alafenamide (TAF) | Discontinue if CrCl < 15 | ↑ lipids | AED’s may ↑ levels | Tx of choice for HBV |
| Tenofovir Disoproxil (TDF) | Renal | N/V, ↑ LFTs, asymptomatic ↑CK, renal dysfunction, bone mineral density loss | -- | 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 used in combination with emtricitabine and third agent. Contraindicated if CrCl<30
- Class-wide side effect: Lactic acidosis, steatosis and lipoatrophy (though very rare with contemporary NRTIs)
- Resistance: M184V confers high resistance to emtricitabine and lamivudine, mid-level resistance to abacavir, hypersusceptibility to tenofovir
NNRTIs¶
| NNRTIs | Hepatic Adj | Specific Side Effects | Major DDI | Special Points |
|---|---|---|---|---|
| Efavirenz | Stop if Child Pugh B/C | Psychosis, vivid dreams, SI, mania, seizures; ↑ Lipids & glucose |
Azoles, antifungals, clopidogrel, some statins, clarithromycin, Buprenorphine | Give before meals; discontinue if rash develops |
| Etravirine (ETR) | Hypersensitivity ↑ Lipids & glucose |
Clopidogrel, clarithromycin | ||
| Nevirapine (NVP) | Stop if Child Pugh B/C | Steven Johnson Syndrome | Azoles, OCP’s, statins, clarithromycin | Don’t start if CD4 >250 in women, CD4 >400 in men; Don’t admin with antacids |
| Rilpivirine (RPV) | None | AED’s, PPI’s, dexamethasone | Must be taken with full meal; Don’t use if HIV RNA >100k + CD4 < 200; Don’t admin with antacids |
NNRTI Additional Information¶
- Class-wide side effect: hepatitis, rashes
- Resistance: K103N resistance to efavirenz and nevirapine
Integrase Inhibitors¶
| Integrase Inhibitor | Dose Adj. | Specific Side Effects | Major DDI | Special Points |
|---|---|---|---|---|
| Raltegravir (RAL) | -- | -- | Rifampin, AED’s | -- |
| Dolutegravir (DTG) | -- | Hyperglycemia Weight gain |
Rifampin, Efavirenz ↑Metformin |
Avoid close admin with laxatives, sucralfate, iron, calcium May ↑Cr, without effect on renal function |
Protease Inhibitors¶
| Protease inhibitors | Hepatic Dose adj | Specific Side Effects | Major DDI | Special Points |
|---|---|---|---|---|
| Atazanavir (ATV) | Based on Childs Pugh | Jaundice, Kidney stones, AV block, Pancreatitis, Rhabdomyolysis | CYP3A4 Inhibitors PPI and H2 blockers |
Admin with meals |
| Darunavir (DRV) | Rashes Pancreatitis |
CYP3A4 Inhibitors Azoles can be used cautiously with drug level monitoring |
Must stop if rash | |
| Lopinavir (LPV) | AV block, QT changes Pancreatitis Hepatitis |
CYP3A4 Inhibitors | Admin with meals |
Protease Inhibitor Additional Information¶
- All protease inhibitors must be boosted:
- Ritonavir: can cause MSK pain, rhabdomyolysis, although not expected at usual doses
- Cobicistat: may increase Cr without effect on renal function
- Class-wide side effects: hepatitis, hypersensitivity reactions, increased cholesterol/TG, hyperglycemia, GI upset, lipodystrophy