Isentress

Integrase Strand Transfer Inhibitor (INSTI)s

NOTE: The 400 mg and 600 mg film-coated tablets are not bioequivalent to the chewable tablets or powder for oral suspension. Do NOT substitute the chewable tablets or powder for oral suspension for the film-coated tablets, or vice versa.
Administer with or without food.

Film-coated tablets: Do not cut, crush, or chew; swallow whole.
Chewable tablets: May be chewed or swallowed whole. The 100-mg chewable tablet can be divided into equal halves. For pediatric patients who have difficulty swallowing, the 25-mg chewable tablet may be crushed and administered in liquid.
Preparation of crushed 25-mg chewable tablet
Place the tablet(s) in a small, clean cup. For each tablet, add approximately 5 mL of liquid (e.g., water, juice, or breast milk).
Within 2 minutes, the tablet(s) will absorb the liquid and fall apart.
Using a spoon, crush any remaining pieces of the tablet(s). Immediately administer the entire dose orally.
If any portion of the dose is left in the cup, add approximately 5 mL of liquid, swirl, and administer immediately.[33530]

Powder for oral suspension
Each single-use packet contains 100 mg of raltegravir.
Using the provided mixing cup, combine 10 mL of water and the entire contents of 1 packet and mix (final concentration 10 mg/mL). Gently swirl the mixing cup for 45 seconds in a circular motion to mix the suspension; do NOT shake.
Calculate the required volume of the 10 mg/mL suspension for the prescribed dose.
Measure and administer the dose using an oral syringe. The dose should be administered orally within 30 minutes of mixing.
Discard any remaining suspension.

renal failure (unspecified) / Delayed / 0-2.0
suicidal ideation / Delayed / 0-2.0
rhabdomyolysis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 3.0-44.0
hyperbilirubinemia / Delayed / 2.0-17.0
hyperglycemia / Delayed / 2.0-10.0
neutropenia / Delayed / 1.0-4.0
hyperamylasemia / Delayed / 0-4.0
gastritis / Delayed / 0-2.0
nephrolithiasis / Delayed / 0-2.0
hepatitis / Delayed / 0-2.0
depression / Delayed / 0-2.0
anemia / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
myopathy / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
oral ulceration / Delayed / Incidence not known

headache / Early / 2.0-4.0
insomnia / Early / 4.0-4.0
nausea / Early / 3.0-3.0
vomiting / Early / 0-2.0
abdominal pain / Early / 0-2.0
dyspepsia / Early / 0-2.0
dizziness / Early / 2.0-2.0
fatigue / Early / 2.0-2.0
asthenia / Delayed / 0-2.0
infection / Delayed / 0-2.0
diarrhea / Early / Incidence not known
weight gain / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
paranoia / Early / Incidence not known
myalgia / Early / Incidence not known
arthralgia / Delayed / Incidence not known
malaise / Early / Incidence not known
fever / Early / Incidence not known
rash / Early / Incidence not known

Isentress, Isentress HD

Rx

First FDA-approved HIV integrase strand transfer inhibitor (HIV-1 INSTI)
Used for treatment of HIV-1 infection in combination with other antiretrovirals
Elevated CPK, muscle weakness, and rhabdomyolysis reported

NOTE: Due to differences in exposure observed between the formulations in clinical trials, the 400 mg film-coated tablet is the preferred formulation in pediatric patients weighing 25 kg or more; however, the chewable tablet may be used in patients who are unable to swallow the film-coated tablet. There are no data in pediatrics to guide dosage during coadministration with rifampin.

400 mg PO twice daily. During coadministration with rifampin, the recommended dosage is 800 mg PO twice daily.

400 mg PO twice daily.

1,200 mg PO once daily. The high dose regimen is indicated for treatment-naive patients or patients who are virologically suppressed on an initial regimen of 400 mg twice daily. Coadministration with rifampin is not recommended.

1,200 mg PO once daily. The high dose (HD) regimen is indicated for treatment-naive patients or patients who are virologically suppressed on an initial regimen of 400 mg twice daily. Coadministration with rifampin is not recommended.[33530] While modeling and simulations for pediatric patients indicate that pharmacokinetic targets are met using the once-daily raltegravir HD regimen, there are no clinical data on the use of this dose in children weighing less than 50 kg.

NOTE: Due to differences in exposure observed between the formulations in clinical trials, the 400 mg film-coated tablet is the preferred formulation in pediatric patients weighing 25 kg or more; however, the chewable tablet may be used in patients who are unable to swallow the film-coated tablet. There are no data in pediatrics to guide dosage during coadministration with rifampin.

300 mg PO twice daily.

200 mg PO twice daily.

150 mg PO twice daily.

100 mg PO twice daily.

75 mg PO twice daily.

NOTE: There are no data in pediatrics to guide dosage during coadministration with rifampin.

100 mg PO twice daily.

80 mg PO twice daily.

60 mg PO twice daily.

40 mg PO twice daily.

30 mg PO twice daily.

25 mg PO twice daily.

15 mg PO twice daily (approximately 3 mg/kg/dose).

10 mg PO twice daily (approximately 3 mg/kg/dose).

8 mg PO twice daily (approximately 3 mg/kg/dose).

7 mg PO once daily (approximately 1.5 mg/kg/dose). If the mother has taken raltegravir 2 to 24 hours before delivery, administer the neonate's first dose 24 to 48 hours after birth.

5 mg PO once daily (approximately 1.5 mg/kg/dose). If the mother has taken raltegravir 2 to 24 hours before delivery, administer the neonate's first dose 24 to 48 hours after birth.

4 mg PO once daily (approximately 1.5 mg/kg/dose). If the mother has taken raltegravir 2 to 24 hours before delivery, administer the neonate's first dose 24 to 48 hours after birth.

400 mg PO twice daily in combination with tenofovir and either emtricitabine or lamivudine for 28 days are preferred HIV post-exposure prophylaxis (PEP) regimens. A 3-drug regimen is recommended; however, the use of a 2-drug regimen would be preferred to discontinuing prophylaxis completely if tolerability is a concern. Begin prophylaxis as soon as possible, ideally within 2 hours of exposure. If initiation of prophylaxis is delayed (beyond 36 hours or 72 hours after exposure), efficacy of the antiretroviral regimen may be diminished and treatment should be determined on a case-by-case basis. Exposures for which PEP is indicated include: skin puncture by a sharp object that has been contaminated with blood, body fluid, or other infectious material; bite from a patient with visible bleeding in the mouth which causes bleeding by the exposed worker; splash of blood, body fluid, or other infectious material onto the workers mouth, nose, or eyes; exposure of blood, body fluid, or other infectious material on a workers non-intact skin (i.e., open wound, chapped skin, abrasion, dermatitis).

400 mg PO twice daily in combination with tenofovir and emtricitabine for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adults. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

400 mg PO twice daily in combination with tenofovir and emtricitabine for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children and adolescents weighing 25 kg or more. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

300 mg PO twice daily in combination with tenofovir and emtricitabine for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

200 mg PO twice daily in combination with tenofovir and emtricitabine for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

150 mg PO twice daily in combination with tenofovir and emtricitabine for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

100 mg PO twice daily in combination with tenofovir and emtricitabine for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

75 mg PO twice daily in combination with tenofovir and emtricitabine for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in children 2 years and older. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

40 mg (4 mL) PO twice daily (approximately 6 mg/kg/dose) in combination with zidovudine and lamivudine. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For raltegravir and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

30 mg (3 mL) PO twice daily (approximately 6 mg/kg/dose) in combination with zidovudine and lamivudine. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For raltegravir and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

25 mg (2.5 mL) PO twice daily (approximately 6 mg/kg/dose) in combination with zidovudine and lamivudine. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For raltegravir and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

15 mg (1.5 mL) PO twice daily (approximately 3 mg/kg/dose) in combination with zidovudine and lamivudine. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For raltegravir and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

10 mg (1 mL) PO twice daily (approximately 3 mg/kg/dose) in combination with zidovudine and lamivudine. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For raltegravir and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

8 mg (0.8 mL) PO twice daily (approximately 3 mg/kg/dose) in combination with zidovudine and lamivudine. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For raltegravir and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

7 mg (0.7 mL) PO once daily (approximately 1.5 mg/kg/dose) in combination with zidovudine and lamivudine. Initiate treatment as close to the time of birth as possible, preferably within 6 hours of delivery. However, if the mother has taken raltegravir 2 to 24 hours prior to delivery, delay the neonate's first dose of raltegravir until 24 to 48 hours after birth; zidovudine and lamivudine should still be started as soon as possible. To minimize dosing changes during outpatient use, some experts increase to 3 mg/kg/dose twice daily dose upon discharge on day 4 or 5 of life. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For raltegravir and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

5 mg (0.5 mL) PO once daily (approximately 1.5 mg/kg/dose) in combination with zidovudine and lamivudine. Initiate treatment as close to the time of birth as possible, preferably within 6 hours of delivery. However, if the mother has taken raltegravir 2 to 24 hours prior to delivery, delay the neonate's first dose of raltegravir until 24 to 48 hours after birth; zidovudine and lamivudine should still be started as soon as possible. To minimize dosing changes during outpatient use, some experts increase to 3 mg/kg/dose twice daily dose upon discharge on day 4 or 5 of life. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For raltegravir and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

4 mg (0.4 mL) PO once daily (approximately 1.5 mg/kg/dose) in combination with zidovudine and lamivudine. Initiate treatment as close to the time of birth as possible, preferably within 6 hours of delivery. However, if the mother has taken raltegravir 2 to 24 hours prior to delivery, delay the neonate's first dose of raltegravir until 24 to 48 hours after birth; zidovudine and lamivudine should still be started as soon as possible. To minimize dosing changes during outpatient use, some experts increase to 3 mg/kg/dose twice daily dose upon discharge on day 4 or 5 of life. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For raltegravir and lamivudine, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512]

†Indicates off-label use

The 600 mg tablet is not recommended for use in patients with any degree of hepatic impairment as studies have not been conducted. For the other formulations, no dosage adjustment is necessary for patients with mild to moderate hepatic impairment; caution is advised for patients with severe hepatic impairment as studies have not been conducted.

No dosage adjustment is necessary in patients with renal impairment; however, because the extent to which raltegravir may be dialyzable is unknown, dosing before a dialysis session should be avoided.

Aluminum Hydroxide: (Major) Coadministration or staggered administration of aluminum and/or magnesium-containing antacids is not recommended during treatment with raltegravir. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. In a drug interaction study, the AUC for raltegravir was decreased by 49% (90% CI, 35% to 60%), 51% (90% CI, 33% to 65%), and 30% (90% CI, 4% to 50%), when administered with, 2 hours before, and 2 hours after aluminum/magnesium hydroxide antacids, respectively.
Aluminum Hydroxide; Magnesium Carbonate: (Major) Coadministration or staggered administration of aluminum and/or magnesium-containing antacids is not recommended during treatment with raltegravir. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. In a drug interaction study, the AUC for raltegravir was decreased by 49% (90% CI, 35% to 60%), 51% (90% CI, 33% to 65%), and 30% (90% CI, 4% to 50%), when administered with, 2 hours before, and 2 hours after aluminum/magnesium hydroxide antacids, respectively.
Aluminum Hydroxide; Magnesium Hydroxide: (Major) Coadministration or staggered administration of aluminum and/or magnesium-containing antacids is not recommended during treatment with raltegravir. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. In a drug interaction study, the AUC for raltegravir was decreased by 49% (90% CI, 35% to 60%), 51% (90% CI, 33% to 65%), and 30% (90% CI, 4% to 50%), when administered with, 2 hours before, and 2 hours after aluminum/magnesium hydroxide antacids, respectively.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Coadministration or staggered administration of aluminum and/or magnesium-containing antacids is not recommended during treatment with raltegravir. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. In a drug interaction study, the AUC for raltegravir was decreased by 49% (90% CI, 35% to 60%), 51% (90% CI, 33% to 65%), and 30% (90% CI, 4% to 50%), when administered with, 2 hours before, and 2 hours after aluminum/magnesium hydroxide antacids, respectively.
Aluminum Hydroxide; Magnesium Trisilicate: (Major) Coadministration or staggered administration of aluminum and/or magnesium-containing antacids is not recommended during treatment with raltegravir. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. In a drug interaction study, the AUC for raltegravir was decreased by 49% (90% CI, 35% to 60%), 51% (90% CI, 33% to 65%), and 30% (90% CI, 4% to 50%), when administered with, 2 hours before, and 2 hours after aluminum/magnesium hydroxide antacids, respectively.
Amlodipine; Atorvastatin: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Antacids: (Major) Coadministration or staggered administration of aluminum and/or magnesium-containing antacids is not recommended during treatment with raltegravir. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. In a drug interaction study, the AUC for raltegravir was decreased by 49% (90% CI, 35% to 60%), 51% (90% CI, 33% to 65%), and 30% (90% CI, 4% to 50%), when administered with, 2 hours before, and 2 hours after aluminum/magnesium hydroxide antacids, respectively.
Atorvastatin: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Atorvastatin; Ezetimibe: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Calcium Carbonate: (Major) Coadministration of calcium carbonate with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. Calcium carbonate may be given with other dosage regimens of raltegravir with no dose adjustments necessary. In a drug interaction study (n = 19), the AUC of raltegravir, given as a single 1200 mg dose, was decreased by 72% (90% CI, 68% to 76%) when administered with a calcium carbonate antacid.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Coadministration of calcium carbonate with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. Calcium carbonate may be given with other dosage regimens of raltegravir with no dose adjustments necessary. In a drug interaction study (n = 19), the AUC of raltegravir, given as a single 1200 mg dose, was decreased by 72% (90% CI, 68% to 76%) when administered with a calcium carbonate antacid.
Calcium Carbonate; Magnesium Hydroxide: (Major) Coadministration of calcium carbonate with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. Calcium carbonate may be given with other dosage regimens of raltegravir with no dose adjustments necessary. In a drug interaction study (n = 19), the AUC of raltegravir, given as a single 1200 mg dose, was decreased by 72% (90% CI, 68% to 76%) when administered with a calcium carbonate antacid.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Coadministration of calcium carbonate with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. Calcium carbonate may be given with other dosage regimens of raltegravir with no dose adjustments necessary. In a drug interaction study (n = 19), the AUC of raltegravir, given as a single 1200 mg dose, was decreased by 72% (90% CI, 68% to 76%) when administered with a calcium carbonate antacid.
Calcium Carbonate; Simethicone: (Major) Coadministration of calcium carbonate with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. Calcium carbonate may be given with other dosage regimens of raltegravir with no dose adjustments necessary. In a drug interaction study (n = 19), the AUC of raltegravir, given as a single 1200 mg dose, was decreased by 72% (90% CI, 68% to 76%) when administered with a calcium carbonate antacid.
Calcium; Vitamin D: (Major) Coadministration of calcium carbonate with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. Calcium carbonate may be given with other dosage regimens of raltegravir with no dose adjustments necessary. In a drug interaction study (n = 19), the AUC of raltegravir, given as a single 1200 mg dose, was decreased by 72% (90% CI, 68% to 76%) when administered with a calcium carbonate antacid.
Carbamazepine: (Major) Coadministration of carbamazepine with raltegravir is not recommended. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; carbamazepine is a strong UGT1A1 inducer. Although not specifically studied with carbamazepine, other strong UGT1A1 inducers have been shown to decrease plasma concentrations of raltegravir, which may lead to HIV treatment failure or to the development of viral resistance.
Etravirine: (Major) Coadministration of etravirine with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A; etravirine is a UGT1A1 inducer. Coadministration may result in decreased raltegravir concentrations, although the effects of etravirine on the pharmacokinetics of raltegravir administered once daily have not been studied. Etravirine may be given with other dosage regimens of raltegravir with no dose adjustments necessary. In drug interaction studies, etravirine had no clinically meaningful effect on the pharmacokinetics of raltegravir 400 mg twice daily.
Ezetimibe; Simvastatin: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Fenofibrate: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as fibric acid derivatives.
Fenofibric Acid: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as fibric acid derivatives.
Fibric acid derivatives: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as fibric acid derivatives.
Fluvastatin: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Fosamprenavir: (Moderate) Coadministration of fosamprenavir with raltegravir may alter the serum concentrations of both medications. According to the manufacturer, the appropriate dose adjustments for coadministration have not been established. During clinical studies, ampenavir pharmacokinetic parameters were altered when various fosamprenavir doses (i.e., 700 mg BID, 1400 mg BID, 1400 mg daily) were administered concurrently with raltegravir 400 mg PO twice daily. The recorded amprenavir pharmacokinetic parameters ranged from a Cmax reduction of 27% to an increase of 27%, an AUC reduction of 36% to an increase of 13%, and a Cmin reduction of 17% to 50%.
Fosphenytoin: (Major) Coadministration of fosphenytoin with raltegravir is not recommended. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; fosphenytoin is a strong UGT1A1 inducer. Although not specifically studied with fosphenytoin, other strong UGT1A1 inducers have been shown to decrease plasma concentrations of raltegravir, which may lead to HIV treatment failure or to the development of viral resistance.
Gemfibrozil: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as fibric acid derivatives.
HMG-CoA reductase inhibitors: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Coadministration of rifampin with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Increase the raltegravir dose to 800 mg PO twice daily when administered as the twice daily regimen in adults. Concurrent use of raltegravir with rifampin has not been studied in pediatric patients. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; rifampin is a strong UGT1A1 inducer. Coadministration may result in decreased plasma raltegravir concentrations, which could lead to HIV treatment failure or to the development of viral resistance. In a drug interaction study, the AUC for raltegravir 400 mg was reduced by 40% when coadministered with rifampin. The effects of rifampin on the pharmacokinetics of raltegravir administered once daily are not known.
Isoniazid, INH; Rifampin: (Major) Coadministration of rifampin with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Increase the raltegravir dose to 800 mg PO twice daily when administered as the twice daily regimen in adults. Concurrent use of raltegravir with rifampin has not been studied in pediatric patients. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; rifampin is a strong UGT1A1 inducer. Coadministration may result in decreased plasma raltegravir concentrations, which could lead to HIV treatment failure or to the development of viral resistance. In a drug interaction study, the AUC for raltegravir 400 mg was reduced by 40% when coadministered with rifampin. The effects of rifampin on the pharmacokinetics of raltegravir administered once daily are not known.
Lovastatin: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Magnesium Hydroxide: (Major) Coadministration or staggered administration of aluminum and/or magnesium-containing antacids is not recommended during treatment with raltegravir. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. In a drug interaction study, the AUC for raltegravir was decreased by 49% (90% CI, 35% to 60%), 51% (90% CI, 33% to 65%), and 30% (90% CI, 4% to 50%), when administered with, 2 hours before, and 2 hours after aluminum/magnesium hydroxide antacids, respectively.
Niacin; Simvastatin: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Phenobarbital: (Major) Coadministration of phenobarbital with raltegravir is not recommended. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; phenobarbital is a strong UGT1A1 inducer. Although not specifically studied with phenobarbital, other strong UGT1A1 inducers have been shown to decrease plasma concentrations of raltegravir, which may lead to HIV treatment failure or to the development of viral resistance.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Coadministration of phenobarbital with raltegravir is not recommended. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; phenobarbital is a strong UGT1A1 inducer. Although not specifically studied with phenobarbital, other strong UGT1A1 inducers have been shown to decrease plasma concentrations of raltegravir, which may lead to HIV treatment failure or to the development of viral resistance.
Phenytoin: (Major) Coadministration of phenytoin with raltegravir is not recommended. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; phenytoin is a strong UGT1A1 inducer. Although not specifically studied with phenytoin, other strong UGT1A1 inducers have been shown to decrease plasma concentrations of raltegravir, which may lead to HIV treatment failure or to the development of viral resistance.
Pitavastatin: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Pravastatin: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Primidone: (Major) Coadministration of primidone with raltegravir is not recommended. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; phenobarbital, the active metabolite of primidone, is a strong UGT1A1 inducer. Although not specifically studied with phenobarbital, other strong UGT1A1 inducers have been shown to decrease plasma concentrations of raltegravir, which may lead to HIV treatment failure or to the development of viral resistance.
Rifampin: (Major) Coadministration of rifampin with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Increase the raltegravir dose to 800 mg PO twice daily when administered as the twice daily regimen in adults. Concurrent use of raltegravir with rifampin has not been studied in pediatric patients. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; rifampin is a strong UGT1A1 inducer. Coadministration may result in decreased plasma raltegravir concentrations, which could lead to HIV treatment failure or to the development of viral resistance. In a drug interaction study, the AUC for raltegravir 400 mg was reduced by 40% when coadministered with rifampin. The effects of rifampin on the pharmacokinetics of raltegravir administered once daily are not known.
Rosuvastatin: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Rosuvastatin; Ezetimibe: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Simvastatin: (Moderate) Raltegravir use has been associated with elevated creatinine kinase concentrations; myopathy and rhabdomyolysis have been reported. Use raltegravir cautiously with drugs that increase the risk of myopathy or rhabdomyolysis such as HMG-CoA reductase inhibitors (Statins).
Tipranavir: (Major) Coadministration of tipranavir plus ritonavir with raltegravir administered as a once daily dose (high dose regimen) is not recommended, as concurrent use results in decreased raltegravir concentrations. Tipranavir/ritonavir may be given with other dosage regimens of raltegravir with no dose adjustments necessary. Raltegravir is a substrate of uridine diphosphate glucuronosyltransferase (UGT) 1A1; tipranavir given with ritonavir is a UGT1A1 inducer. In drug interaction studies, tipranavir; ritonavir had no clinically meaningful effect on the pharmacokinetics of raltegravir 400 mg twice daily.

Isentress Oral Gran F/Recon: 100mg
Isentress Oral Tab Chew: 25mg, 100mg
Isentress/Isentress HD Oral Tab: 400mg, 600mg

800 mg/day PO for the 400 mg film-coated tablet; 1,600 mg/day PO with concomitant rifampin; 1,200 mg/day for the 600 mg film-coated tablet; safety and efficacy of other formulations have not been established.

800 mg/day PO for the 400 mg film-coated tablet; 1,600 mg/day PO with concomitant rifampin; 1,200 mg/day for the 600 mg film-coated tablet; safety and efficacy of other formulations have not been established.

weight 40 kg or more: 600 mg/day PO for the chewable tablet; 800 mg/day PO for the 400 mg film-coated tablet; 1,200 mg/day for the 600 mg film-coated tablet; safety and efficacy have not been established for the oral suspension.
weight 28 to 39 kg: 400 mg/day PO for the chewable tablet; 800 mg/day PO for the 400 mg film-coated tablet; safety and efficacy of other formulations have not been established.

weight 40 kg or more: 600 mg/day PO for the chewable tablet; 800 mg/day PO for the 400 mg film-coated tablet; 1,200 mg/day for the 600 mg film-coated tablet; safety and efficacy have not been established for the oral suspension.
weight 28 to 39 kg: 400 mg/day PO for the chewable tablet; 800 mg/day PO for the 400 mg film-coated tablet; safety and efficacy of other formulations have not been established.
weight 25 to 27 kg: 300 mg/day PO for the chewable tablet; 800 mg/day PO for the 400 mg film-coated tablet; safety and efficacy of other formulations have not been established.
weight 20 to 24 kg: 300 mg/day PO for the chewable tablet; safety and efficacy of other formulations have not been established.
weight 14 to 19 kg: 200 mg/day PO for the oral suspension or chewable tablet; safety and efficacy have not been established for the film-coated tablets.
weight 11 to 13 kg: 160 mg/day PO for the oral suspension; 150 mg/day PO for the chewable tablet; safety and efficacy have not been established for the film-coated tablets.
weight 8 to 10 kg: 120 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.

weight 11 to 13 kg: 160 mg/day PO for the oral suspension; 150 mg/day PO for the chewable tablet; safety and efficacy have not been established for the film-coated tablets.
weight 8 to 10 kg: 120 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.
weight 6 to 7 kg: 80 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.
weight 4 to 5 kg: 60 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.
weight 3 kg: 50 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.

Term Neonates 8 days and older weighing 4 kg: 30 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.
Term Neonates 8 days and older weighing 3 kg: 20 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.
Term Neonates 8 days and older weighing 2 kg: 16 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.
Term Neonates 0 to 7 days weighing 4 kg: 7 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.
Term Neonates 0 to 7 days weighing 3 kg: 5 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.
Term Neonates 0 to 7 days weighing 2 kg: 4 mg/day PO for the oral suspension; safety and efficacy of other formulations have not been established.
Premature and Term Neonates weighing less than 2 kg: Safety and efficacy have not been established.

Raltegravir inhibits the catalytic activity of HIV integrase, which is an HIV encoded enzyme required for viral replication. Integrase is 1 of the 3 HIV-1 enzymes required for viral replication. Integration of HIV into cellular DNA is a multi-step process. First, the assembly of integrase in a stable complex with the viral DNA occurs. Second, the terminal dinucleotide from each 39 end of the viral DNA is removed by endonucleolytic processing. Lastly, the viral DNA 3' ends are covalently linked to the cellular (target) DNA by strand transfer. The last 2 processes, which are catalytic, require integrase to be appropriately assembled on a specific viral DNA substrate. Inhibition of integrase by raltegravir prevents the covalent insertion, or integration, of unintegrated linear HIV DNA into the host cell genome preventing the formation of the HIV provirus. The provirus is required to direct the production of progeny virus, so inhibiting integration prevents propagation of the viral infection. Raltegravir did not significantly inhibit human phosphoryl transferases including DNA polymerases alpha, beta, and gamma.
 
No dose-response effect occurred over the dose range of 200 to 600 mg orally twice daily. After 24 weeks of raltegravir plus optimized background therapy, the mean viral load reduction from baseline was 1.8 log10 copies/mL for raltegravir 200 mg twice daily, 1.87 log10 copies/mL for 400 mg twice daily, and 1.84 log10 copies/ml for 600 mg twice daily. A similar percentage of patients had a HIV-1 RNA of less than 400 copies/mL: 69.8% of the 200 mg group, 71.1% of the 400 mg group, and 71.1% of the 600 mg group. Of note, 72% of the study population's viral isolate was not sensitive to any antiretroviral in their optimized background regimen.
 
Twice daily administration led to a mean concentration of 70.6 nM 12 hours after a 100 mg dose. The geometric mean concentration was 107.1 nM after dosing with 200 mg and 200.6 nM after dosing with 400 mg. Raltegravir at concentrations of 31 +/- 20 nM resulted in 95% inhibition (EC95) of viral spread relative to an untreated virus-infected culture in human T-lymphoid cell cultures infected with the cell-line adapted HIV-1 variant H9IIIB. In addition, concentrations of 6 to 50 nM resulted in 95% inhibition of viral spread in cultures of mitogen-activated human peripheral blood mononuclear cells infected with diverse, primary clinical isolates of HIV-1, including isolates resistant to reverse transcriptase inhibitors and protease inhibitors. Raltegravir also inhibited replication of an HIV-2 isolate when tested in CEMx174 cells (EC95 of 6 nM). Additive to synergistic antiretroviral activity was observed when human T-lymphoid cells infected with the H9IIIB variant of HIV-1 were incubated with raltegravir and delavirdine, efavirenz, nevirapine, abacavir, didanosine, lamivudine, stavudine, tenofovir, zalcitabine, zidovudine, amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, or enfuvirtide.
 
Among 160 treatment-naive patients who got raltegravir, lamivudine, and tenofovir for 48 weeks, 5 had virologic failure. The N155H amino acid substitution in the integrase region was noted in 2 patients; the substitution was not present before treatment. Two other patients had resistance-conferring mutations detected in the reverse transcriptase region only. The last patient had virus with no known resistance mutations. Mutations observed in the HIV-1 integrase coding sequence that contributed to raltegravir resistance generally included an amino acid substitution at either Y143, Q148, or N155 plus one or more additional substitutions.
 
Cross-resistance with other HIV-1 integrase strand transfer inhibitors (ISTIs) has been identified; generally, mutations conferring resistance to raltegravir also confer resistance to elvitegravir. Specific amino acid substitutions resulting in reduced susceptibility to the ISTI class include Y143, E92Q, and Q148 plus.

Raltegravir is administered orally. It is approximately 83% bound to human plasma protein over the concentration range of 2 to 10 micromole. It distributes into the cerebrospinal fluid (CSF) at a proportion 3-fold lower than the free fraction in plasma, with median CSF concentration being 5.8% (range: 1% to 53.5%) of the corresponding plasma concentration. Elimination is mainly by metabolism via a UDP-glucuronosyltransferases 1A1 (UGT1A1)-mediated glucuronidation pathway. Data are not sufficient to determine the impact of UGT1A1 polymorphism on pharmacokinetic parameter values. The apparent terminal half-life is approximately 9 hours. Approximately 51% of an oral, radiolabeled dose was excreted in the feces, and 32% was excreted in urine. In feces, only raltegravir was present. Most of the drug in the feces is likely derived from hydrolysis of raltegravir-glucuronide secreted in bile. In urine, both raltegravir (9%) and raltegravir-glucuronide (23%) were detected. The major circulating entity was raltegravir and represented approximately 70% of the total radioactivity; the remaining radioactivity in plasma was accounted for by raltegravir-glucuronide.
 
Affected cytochrome P450 isoenzymes: none
In vitro, raltegravir does not induce cytochrome P450 (CYP) 3A4, CYP1A2, or CYP2B6, nor does it inhibit UGT1A1, UGT2B7, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A. It does not inhibit P-glycoprotein (P-gp)-mediated transport. Raltegravir is not a substrate of CYP enzymes.

The absolute bioavailability of raltegravir is unknown. Based on a formulation comparison study in healthy adults, the oral suspension has a higher bioavailability than the chewable tablets, and both have a higher bioavailability than the 400 mg film-coated tablet. Relative to the 400 mg film-coated tablet, the 600 mg film-coated tablet has a higher bioavailability. The AUC and Cmax increase proportionally over the dosage range of 100 to 1,600 mg. The concentration 12 hours after administration increases slightly less than proportionally over the dosage range of 100 to 1,600 mg. Steady state is achieved within approximately the first 2 days of dosing. Little to no accumulation in AUC and Cmax occurs for the 400 mg twice daily and 1,200 mg once daily formulations.
 
Effects of Food
Raltegravir may be taken with or without food; it was administered without regard to food in the pivotal safety and efficacy studies. The time to maximum absorption in the fasted state is approximately 3 hours for the 400 mg film-coated tablet and 1.5 to 2 hours for the 600 mg film-coated tablet. When the 400 mg film-coated tablet was administered with a high-fat meal, the systemic exposure (AUC) and Cmax were increased by about 2-fold. Administration with a moderate-fat meal did not affect the AUC to a clinically meaningful degree. Administration with a low-fat meal decreased the AUC by 46% and the Cmax by 52%. When the 600 mg film-coated tablet was administered with a high-fat meal, the AUC was not affected to a clinically meaningful degree. The Cmax was decreased by 28%. Administration with a low-fat meal decreased the AUC by 42% and the Cmax by 52%. When the chewable tablet was administered with a high fat-meal, the AUC was not affected to a clinically meaningful degree. The Cmax was decreased by 62%. The effects of food on the pharmacokinetic parameters of the oral suspension have not been studied.

Antiretroviral therapy should be provided to all patients during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. HIV guidelines recommend raltegravir, administered via twice-daily dosing, plus a 2-NRTI backbone as an alternative treatment option for use in pregnant patients and those trying to conceive. Available data from the Antiretroviral Pregnancy Registry (APR), which includes over 535 first trimester exposures to raltegravir, have shown no difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. The prevalence of birth defects was 3.4% (95% CI: 2% to 5.3%) when exposure occurred in the first trimester. Supplemental data from the APR regarding central nervous system birth defects are available. Among the reported exposures to raltegravir (441 periconception, 150 late first trimester, 457 second/third trimester), 1 central nervous system birth defect was identified during the last first trimester; however, this was not a neural tube or encephalocele defect. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years, patients with CD4 count less than 300 cells/mm3, or patients with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in patients receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a patient decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to raltegravir; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.

HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission; thus, replacement feeding is recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). There are no data on the presence of raltegravir in human milk, the effects on the breastfed infant, or the effects on the milk production. Antiretroviral medications whose passage into human breast milk have been evaluated include nevirapine, zidovudine, lamivudine, and nelfinavir.