Drug Interactions With HIV-Related Medications

HIV related medications, or antiretrovirals (ARV's), are drugs which are used to manage and maintain the viral load of HIV infected patients. Controlling the viral load in the body allows the body's immune system to strengthen, since HIV suppresses the body's immunity by negatively affecting CD4 cells.

ARV's are also prescribed for patients who have been accidentally exposed to the virus. These scenarios can include condoms tearing during intercourse, needle-prick injuries, exposure to blood or blood products, blood splashes in the face or eyes and in cases of sexual abuse or assault.

ARV's are a very important medical breakthrough in terms of managing patients infected with HIV. Although they can't cure the disease, they can improve a patient's immune system and therefore offer them prolonged quality of life.

Interactions which affect drug absorption

• The absorption of ARV's, such as rilpivarine (RPV) and atazanavir (ATV) which require gastric acidity for optimal absorption, are decreased by acid reducing medications such as antacids, proton pump inhibitors and H2 receptor antagonists. 
• Products which contain calcium, aluminum, magnesium-based antacids, iron products or vitamin and mineral  supplements bind to the integrase inhibitors (INSTI) and this results in reduced absorption of these ARV drugs.
• Drugs that inhibit or reduce the enzyme CYP3A4 can also promote or decrease the absorption of other drugs.

Interactions which affect liver metabolism

• The cytochrome P450 enzyme system is responsible for the metabolism of many drugs. There are different groups of ARV's which are all affected by this enzyme system and these include the protease inhibitors (PI), the non-nucleoside reverse transcriptase inhibitors (NNRTI), the CCR5 antagonist maraviroc (MVC) and the INSTI elvitegravir (EVG) . The specific enzyme, cytochrome P450 3A4 (CYP3A4), is responsible for drug metabolism although there are multiple enzymes that are involved in the metabolism of certain drugs.
• The uridine diphosphate-glucuronosyltransferase (UGT) 1A1 enzyme is the one responsible for the metabolism of the INSTI's dolutegravir (DTG) and raltegravir (RAL). Drugs which inhibit or induce this UGT enzyme can therefore affect the pharmacokinetics of these INSTI's.

Pharmacokinetic enhancers or boosters

• Pharmacokinetic enhancing is a procedure used to increase exposure of an ARV by administering, at the same time, a drug that inhibits the enzymes that metabolize the ARV agent. Two agents which are currently being used as pharmacokinetic enhancers are ritonavir (RTV) and cobicistat (COBI). These medications are potent blockers of the CYP3A4 enzyme, which results in the co-administered ARV's levels being increased in the body.

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• It's unknown though what the results of interactions with these pharmacokinetic boosters will be with certain other drugs and therefore caution needs to be exercised here.. These medications would include phenytoin, warfarin, voriconazole, oral contraceptives and certain statins.

Other Mechanisms of Pharmacokinetic Interactions

• Dolutegravir (DTG) reduces renal clearance of the diabetic drug metformin by inhibiting the anion transporters located in the tubular cells of the kidneys.
• Other similar transporters can help with renal, hepatic and biliary clearance of drugs and can be prone to drug interactions.

Specific Drug Interactions And Contraindications Regarding ARV Use

ATV +/− RTV or COBI

• Cardiac medications - ranolazine and dronedarone.
• Statins - lovastatin and simvastatin.
• Tuberculosis medications - rifampin and rifapentine.
• Neurological agents - midazolam, lurasidone, pimozide, triazolam.
• Herbs - St. John's wort.
• Hepatitis C (HCV) drugs - boceprevir and simeprevir.
• Others - alfuzosin, cisapride, irinotecan, salmeterol, ergot derivatives and sildenafil.

DRV/r or DRV/c

• Cardiac medications - dronedarone and ranolazine.
• Statins - lovastatin and simvastatin.
• Tuberculosis medications - rifampin and rifapentine.
• Neurological agents - lurasidone, midazolam, pimozide, triazolam.
• Herbs - St. John's wort.
• HCV drugs - dasabuvir, boceprevir, paritaprevir, ombitasvir and simeprevir
• Others - alfuzosin, cisapride,salmeterol, sildenafil and ergot derivatives.

FPV +/− RTV

• Cardiac medications - flecainide, dronedarone, ranolazine and propafenone.
• Statins - lovastatin and simvastatin.
• Tuberculosis medications - rifampin and rifapentine.
• Neurological agents - midazolam, lurasidone, pimozide, triazolam.
• Herbs - St. John's wort.
• HCV drugs - dasabuvir, boceprevir, paritaprevir, ombitasvir and simeprevir.
• Others - alfuzosin, cisapride, salmeterol, sildenafil and ergot derivatives.

LPV/r

• Cardiac medications - dronedarone and ranolazine.
• Statins - lovastatin and simvastatin.
• Tuberculosis medications - rifampin and rifapentine.
• Neurological agents - pimozide, lurasidone, midazolam, triazolam.
• Herbs - St. John's wort.
• HCV drugs - dasabuvir, boceprevir, ombitasvir, paritaprevir and simeprevir.
• Others - alfuzosin, cisapride,salmeterol, ergot derivatives and sildenafil.

SQV/r

• Cardiac medications - amiodarone, flecainide, dofetilide, dronedarone, lidocaine, propafenone, quinidine, ranolazine.
• Statins - lovastatin and simvastatin.
• Tuberculosis medications - rifampin and rifapentine.
• Neurological agents - midazolam, lurasidone, pimozide, trazodone, triazolam.
• Herbs - St. John's wort and garlic supplements.
• HCV drugs - boceprevir, dasabuvir, ombitasvir, paritaprevir and simeprevir.
• Others - alfuzosin, cisapride,salmeterol, ergot derivatives and sildenafil.

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TPV/r

• Cardiac medications - dronedarone, amiodarone, flecainide, quinidine,  propafenone and ranolazine.
• Statins - lovastatin and simvastatin.
• Tuberculosis medications - rifampin and rifapentine.
• Neurological agents - midazolam, lurasidone, pimozide and triazolam.
• Herbs - St. John's wort and garlic supplements.
• HCV drugs -  ledipasvir, boceprevir, dasabuvir,, ombitasvir, paritaprevir, simeprevir and sofosbuvir.
• Others - alfuzosin, cisapride,salmeterol, ergot derivatives and sildenafil.

EFV

• Tuberculosis medication - rifapentine.
• Herbs - St. John's wort.
• HCV drugs - boceprevir, dasabuvir, ombitasvir, paritaprevir and simeprevir.

ETR

• Tuberculosis medication - rifampin, rifapentine.
• Antiepileptic medication - carbamazepine, Phenobarbital and phenytoin.
• Herbs - St. John's wort.
• HCV drugs - ombitasvir, dasabuvir, paritaprevir and simeprevir.
• Antiplatelet medication - clopidogrel.

NVP

• Tuberculosis medication - rifapentine.
• Herbs - St. John's wort.
• HCV drugs - dasabuvir, ombitasvir, paritaprevir and simeprevir.
• Antifungal agent - ketoconazole.

RPV

• Tuberculosis medication - rifampin, rifapentine.
• Antiepileptic medication - oxcarbazepine, carbamazepine, phenobarbital and phenytoin.
• Herbs - St. John's wort.
• HCV drugs - dasabuvir, ombitasvir and paritaprevir.
• Anti-gastric acid medication - proton pump inhibitors.

MVC

• Tuberculosis medication - rifapentine.
• Herbs - St. John's wort.
• HCV drugs - dasabuvir, ombitasvir and paritaprevir.

DTG

• Cardiac agents - dofetilide.
• Tuberculosis medication - rifapentine.
• Herbs - St. John's wort.

EVG/c/TDF/ FTC or EVG + PI/r combinations

• Cardiac medications - ranolazine.
• Statins - lovastatin and simvastatin.
• Tuberculosis medications - rifampin and rifapentine.
• Neurological agents - lurasidone, midazolam, pimozide, triazolam.
• Herbs - St. John's wort.
• HCV drugs - boceprevir, dasabuvir, ombitasvir, paritaprevir and simeprevir for EVG + PI/r. The aforementioned including ledipasvir are contraindicated for EVG/c/TDF/ FTC.
• Others - alfuzosin, cisapride, ergot derivatives,salmeterol and sildenafil.