Select antiretroviral therapy agents with level AI evidence for treating HIV, potential CYP3A4 interactions, and other considerations for concurrent use with chemotherapy
| Class/drugs . | Dose . | CYP3A4 interactions . | Side effects . | Other considerations . |
|---|---|---|---|---|
| First-choice agents* | ||||
| NRTIs | ||||
| Emtricitabine/tenofovir (Truvada) | 1 tablet (200 mg/300 mg) daily | — | Nephrotoxicity (<3%) | Dose adjust for creatinine clearance <50 mL/min |
| Dual anti-HBV activity, preferred in HBV coinfected patients | ||||
| AI† NRTI in several NNRTI-, PI-, and INSTI-based regimens | ||||
| Abacavir/lamivudine (Epzicom) | 1 tablet (600 mg/300 mg) daily | — | Life-threatening hypersensitivity reactions in patients with HLA-B57*01 allele | Pharmacogenomic testing for HLA-B57*01 required before use of abacavir |
| Avoid Epzicom if creatinine clearance <50 mL/min; instead, use renally dosed individual agents | ||||
| AI† NRTI in combination with dolutegravir | ||||
| INSTIs | ||||
| Dolutegravir (Tivicay) | 1 tablet (50 mg) daily | — | Elevated AST/ALT | Metabolized by UGT1A1; dose increase required with efavirenz, rifampin, or select ritonavir-based combinations, and possibly other UGT1A1 inducers |
| Increase dose to 50 mg twice daily for patients with certain INSTI-related mutations | ||||
| AI in combination with dual NRTIs above | ||||
| Raltegravir (Isentress) | 1 tablet (400 mg) twice daily | — | Elevated AST/ALT | Metabolized by UGT1A1; dose increase required with rifampin |
| Elevated creatine phosphokinase | AI† in combination with emtricitabine/tenofovir | |||
| Additional second-choice options‡ | ||||
| NNRTIs | ||||
| Rilpivirine (Edurant) | 1 tablet (25 mg) daily | Weak induction | Depressed mood, insomnia (<10%) | Contraindicated in combination with strong CYP3A4 inducers or proton pump inhibitors |
| AI† in combination with emtricitabine/tenofovir (once-a-day combination; Complera) in patients with HIV viral load <100 000 copies per mL and CD4+ count >200 cells per mm3 | ||||
| Efavirenz (Sustiva; also included in once-a-day combination with emtricitabine/tenofovir (Atripla) | 1 tablet (600 mg) daily; in Atripla, 1 tablet (600/300/ 200 mg) daily | Strong induction | Depressed mood (5%) and increased rate of suicidality | CYP3A4 metabolized; dose adjust if used in combination with voriconazole or rifampin |
| Nervous system symptoms (headache, insomnia, dizziness) <30%, general resolve within 2-4 wk | AI† as Atripla, or in combination with abacavir/lamivudine in patients with HIV viral load <100 000 copies per mL | |||
| Rash (10%-15%) | ||||
| Contraindicated§ | ||||
| PIs | ||||
| Darunavir (Prezista) boosted by ritonavir (Norvir) | 1 tablet (800 mg) daily combined with ritonavir 1 tablet (100 mg) daily | Strong inhibition | Gastrointestinal symptoms (10%-20%) | AI† in combination with emtricitibine/tenofovir |
| Dyslipidemia (20%-25%) | Increased dose recommended for cART-experienced patients or those with specific HIV mutations | |||
| AST/ALT abnormalities (12%) | Contraindicated with strong CYP3A4 inducers | |||
| Rash (6%) | ||||
| Atazanavir (Reyataz) boosted by ritonavir (Norvir) | 1 tablet (300 mg) daily combined with ritonavir 1 tablet (100 mg) daily | Strong inhibition | Hyperbilirubinemia (44%) | A1† in combination with NRTIs above |
| Gastrointestinal symptoms (<5%) | Take with food | |||
| Dyslipidemia (24%) | Concurrent strong CYP3A4 inducers contraindicated | |||
| Rash (5%-7%) | Atazanavir is strong UGT1A1 inhibitor, contraindicated with irinotecan | |||
| Cobicistat-boosted once-a-day regimens | ||||
| Elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild) | 1 tablet (150 mg/150 mg/200 mg/300 mg) daily | Strong inhibition | Gastrointestinal symptoms (10%-20%) | Take with food |
| Headache (7%) | Do not initiate if creatinine clearance <70 mL/min | |||
| Nephrotoxicity (10%) | Concurrent strong CYP3A4 inducers contraindicated | |||
| Class/drugs . | Dose . | CYP3A4 interactions . | Side effects . | Other considerations . |
|---|---|---|---|---|
| First-choice agents* | ||||
| NRTIs | ||||
| Emtricitabine/tenofovir (Truvada) | 1 tablet (200 mg/300 mg) daily | — | Nephrotoxicity (<3%) | Dose adjust for creatinine clearance <50 mL/min |
| Dual anti-HBV activity, preferred in HBV coinfected patients | ||||
| AI† NRTI in several NNRTI-, PI-, and INSTI-based regimens | ||||
| Abacavir/lamivudine (Epzicom) | 1 tablet (600 mg/300 mg) daily | — | Life-threatening hypersensitivity reactions in patients with HLA-B57*01 allele | Pharmacogenomic testing for HLA-B57*01 required before use of abacavir |
| Avoid Epzicom if creatinine clearance <50 mL/min; instead, use renally dosed individual agents | ||||
| AI† NRTI in combination with dolutegravir | ||||
| INSTIs | ||||
| Dolutegravir (Tivicay) | 1 tablet (50 mg) daily | — | Elevated AST/ALT | Metabolized by UGT1A1; dose increase required with efavirenz, rifampin, or select ritonavir-based combinations, and possibly other UGT1A1 inducers |
| Increase dose to 50 mg twice daily for patients with certain INSTI-related mutations | ||||
| AI in combination with dual NRTIs above | ||||
| Raltegravir (Isentress) | 1 tablet (400 mg) twice daily | — | Elevated AST/ALT | Metabolized by UGT1A1; dose increase required with rifampin |
| Elevated creatine phosphokinase | AI† in combination with emtricitabine/tenofovir | |||
| Additional second-choice options‡ | ||||
| NNRTIs | ||||
| Rilpivirine (Edurant) | 1 tablet (25 mg) daily | Weak induction | Depressed mood, insomnia (<10%) | Contraindicated in combination with strong CYP3A4 inducers or proton pump inhibitors |
| AI† in combination with emtricitabine/tenofovir (once-a-day combination; Complera) in patients with HIV viral load <100 000 copies per mL and CD4+ count >200 cells per mm3 | ||||
| Efavirenz (Sustiva; also included in once-a-day combination with emtricitabine/tenofovir (Atripla) | 1 tablet (600 mg) daily; in Atripla, 1 tablet (600/300/ 200 mg) daily | Strong induction | Depressed mood (5%) and increased rate of suicidality | CYP3A4 metabolized; dose adjust if used in combination with voriconazole or rifampin |
| Nervous system symptoms (headache, insomnia, dizziness) <30%, general resolve within 2-4 wk | AI† as Atripla, or in combination with abacavir/lamivudine in patients with HIV viral load <100 000 copies per mL | |||
| Rash (10%-15%) | ||||
| Contraindicated§ | ||||
| PIs | ||||
| Darunavir (Prezista) boosted by ritonavir (Norvir) | 1 tablet (800 mg) daily combined with ritonavir 1 tablet (100 mg) daily | Strong inhibition | Gastrointestinal symptoms (10%-20%) | AI† in combination with emtricitibine/tenofovir |
| Dyslipidemia (20%-25%) | Increased dose recommended for cART-experienced patients or those with specific HIV mutations | |||
| AST/ALT abnormalities (12%) | Contraindicated with strong CYP3A4 inducers | |||
| Rash (6%) | ||||
| Atazanavir (Reyataz) boosted by ritonavir (Norvir) | 1 tablet (300 mg) daily combined with ritonavir 1 tablet (100 mg) daily | Strong inhibition | Hyperbilirubinemia (44%) | A1† in combination with NRTIs above |
| Gastrointestinal symptoms (<5%) | Take with food | |||
| Dyslipidemia (24%) | Concurrent strong CYP3A4 inducers contraindicated | |||
| Rash (5%-7%) | Atazanavir is strong UGT1A1 inhibitor, contraindicated with irinotecan | |||
| Cobicistat-boosted once-a-day regimens | ||||
| Elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild) | 1 tablet (150 mg/150 mg/200 mg/300 mg) daily | Strong inhibition | Gastrointestinal symptoms (10%-20%) | Take with food |
| Headache (7%) | Do not initiate if creatinine clearance <70 mL/min | |||
| Nephrotoxicity (10%) | Concurrent strong CYP3A4 inducers contraindicated | |||
Appropriate HIV therapy generally consists of an INSTI, NNRTI, or PI combined with 2 NTRIs, often in the form of a combination tablet.
Potential drug-drug interaction considerations are underlined.
First choice antiretroviral agents in combination with chemotherapy regimens containing CYP3A4 substrates are those that are not metabolized via CYP3A4 system.
—; no significant effect on CYP3A4 metabolism of other drugs.
Strong level of evidence (AI) in antiretroviral-naïve patients on the basis of randomized controlled trials; recommendations are in concordance with the Department of Health and Human Services Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.56
Use of these second-choice options is somewhat more likely to be limited by potential drug-drug interactions during chemotherapy.
Contraindicated in combination with vinblastine and other chemotherapy drugs heavily dependent on CYP3A4 metabolism; they may be useful after completion of chemotherapy.
Anti-HBV, antibody to HBV; AST/ALT, aspartate aminotransferase/alanine aminotransferase; HLA, human leukocyte antigen; INSTI, integrase strand transfer inhibitor; NNRTI, nonnucleoside reverse-transcriptase inhibitor; NRTI, nucleoside reverse-transcriptase inhibitor; UGT1A1, uridine diphosphate glucuronosyltransferase 1 polypeptide A1.