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©2013 UpToDate ® Print Email Advantages and disadvantages of antiretroviral components recommended as initial antiretroviral therapy ARV class ARV agent(s) Advantages Disadvantages NNRTIs (in alphabetical order) NNRTI class advantages: Long half-lives NNRTI class disadvantages: Greater risk of resistance at the time of treatment failure with NNRTIs than with PIs Potential for cross resistance Skin rash Potential for CYP450 drug interactions Transmitted resistance more common with NNRTIs than with PIs EFV Virologic responses equivalent or superior to all comparators to date Once-daily dosing Coformulated with TDF/FTC Neuropsychiatric side effects Teratogenic in nonhuman primates. Several cases of neural tube defect in infants born to women who were exposed to EFV in the first trimester of pregnancy reported. EFV use should be avoided in women with potential for pregnancy and is contraindicated in the first trimester. Dyslipidemia NVP No food effect Fewer lipid effects than EFV Once-daily dosing with extended- release tablet formulation Higher incidence of rash, including rare but serious HSRs (SJS or TEN), than with other NNRTIs Higher incidence of hepatotoxicity, including serious and even fatal cases of hepatic necrosis, than with other NNRTIs Contraindicated in patients with moderate or severe (Child-Pugh B or C) hepatic impairment Some data suggest that ART-naive patients with high pre-NVP CD4 counts (>250 cells/mm 3 for females, >400 cells/mm 3 for males) are at higher risk of symptomatic hepatic events. NVP is not recommended in these patients unless benefit clearly outweighs risk. Early virologic failure of NVP + TDF + (FTC or 3TC) in small clinical trials RPV Once-daily dosing Coformulated with TDF/FTC Compared with EFV: Fewer discontinuations for CNS adverse effects Fewer lipid effects Fewer rashes More virologic failures in patients with pretreatment HIV RNA >100,000 copies/mL than with EFV-based regimen More NNRTI- and 3TC-associated mutations at virological failure than with regimen containing EFV + two NRTIs Food requirement Absorption depends on lower gastric pH Contraindicated with PPIs RPV-associated depression reported Use RPV with caution when coadministered with a drug having a known risk of torsades de pointes PIs (in alphabetical order) PI class advantages: Higher genetic barrier to resistance than NNRTIs and RAL PI resistance uncommon with failure while on first PI regimen PI class disadvantages:

Contraindicated with PPIs RPV-associated depression reported Use RPV with caution when coadministered with a drug having a known risk of torsades de pointes PIs (in alphabetical order) PI class advantages: Higher genetic barrier to resistance than NNRTIs and RAL PI resistance uncommon with failure while on first PI regimen PI class disadvantages: Metabolic complications such as dyslipidemia, insulin resistance, hepatotoxicity GI adverse effects CYP3A4 inhibitors and substrates: potential for drug interactions (more pronounced with RTV-based regimens) ATV Fewer adverse effects on lipids than other PIs Once-daily dosing Low pill burden Good GI tolerability Signature mutation (I50L) not associated with broad PI cross resistance Indirect hyperbilirubinemia sometimes leading to jaundice or scleral icterus PR interval prolongation: generally inconsequential unless ATV combined with another drug with similar effect Cannot be coadministered with TDF, EFV, or NVP (see ATV/r) Nephrolithiasis Skin rash Food requirement Absorption depends on food and low gastric pH ATV/r RTV boosting: higher trough ATV concentration and greater antiviral effect Once-daily dosing Low pill burden More adverse effects on lipids than unboosted ATV More hyperbilirubinemia and jaundice than unboosted ATV Food requirement Absorption depends on food and low gastric pH RTV boosting required with TDF and EFV. With EFV, use ATV 400 mg and RTV 100 mg once daily (PI-naive patients only). Should not be coadministered with NVP DRV/r Once-daily dosing Potent virologic efficacy Skin rash Food requirement FPV/r Twice-daily dosing resulted in efficacy comparable to LPV/r RTV boosting results in higher trough APV concentration and greater antiviral effect Once-daily dosing possible with RTV 100 mg or 200 mg daily No food effect Skin rash Hyperlipidemia Once-daily dosing results in lower APV concentrations than twice-daily dosing For FPV 1400 mg + RTV 200 mg: requires 200 mg of RTV and no coformulation Fewer data on FPV 1400 mg + RTV 100 mg dose than on DRV/r and ATV/r LPV/r Coformulated No food requirement Recommended PI in pregnant women (twice daily only) Greater CD4 count increase than with EFV-based regimens Requires 200 mg per day of RTV Lower drug exposure in pregnant women. May need dose increase in third trimester. Once-daily dosing not recommended in pregnant women Once-daily dosing results in lower trough concentration than twice-daily dosing

Recommended PI in pregnant women (twice daily only) Greater CD4 count increase than with EFV-based regimens Requires 200 mg per day of RTV Lower drug exposure in pregnant women. May need dose increase in third trimester. Once-daily dosing not recommended in pregnant women Once-daily dosing results in lower trough concentration than twice-daily dosing Possible higher risk of MI associated with cumulative use of LPV/r PR and QT interval prolongation have been reported. Use with caution in patients at risk of cardiac conduction abnormalities or receiving other drugs with similar effect. SQV/r Similar efficacy but less hyperlipidemia than with LPV/r Highest pill burden (6 pills per day) among available PI regimens Requires 200 mg of RTV Food requirement PR and/or QT interval prolongations in a healthy volunteer study Pretreatment ECG recommended SQV/r is not recommended for patients with any of the following conditions: Congenital or acquired QT prolongation Pretreatment ECG >450 msec On concomitant therapy with other drugs that prolong QT interval Complete AV block without implanted pacemakers Risk of complete AV block INSTI RAL Virologic response noninferior to EFV Fewer drug-related adverse events and lipid changes than EFV No food effect Fewer drug-drug interactions than PI- or NNRTI-based regimens Twice-daily dosing Lower genetic barrier to resistance than with boosted PI- based regimens No data with NRTIs other than TDF/FTC in ART-naive patients Increase in creatine kinase, myopathy, and rhabdomyolysis have been reported Rare cases of severe skin reactions (including SJS and TEN) have been reported and systemic HSRs with rash and constitutional symptoms, with or without hepatitis, have been reported CCR5 antagonist MVC Virologic response noninferior to EFV in post hoc analysis of MERIT study Fewer adverse effects than EFV Requires viral tropism testing prior to initiation of therapy, which results in additional cost and possible delay in initiation of therapy More MVC-treated than EFV-treated patients discontinued therapy due to lack of efficacy in MERIT study Less long-term experience in ART-naive patients than with boosted PI- or NNRTI-based regimens Limited experience with dual-NRTIs other than ZDV/3TC Twice-daily dosing CYP 3A4 substrate; dosing depends on presence or absence of concomitant CYP3A4 inducer(s) or inhibitor(s) Dual-NRTI pairs (in alphabetical order) ABC/3TC Virologic response noninferior to ZDV/3TC

Less long-term experience in ART-naive patients than with boosted PI- or NNRTI-based regimens Limited experience with dual-NRTIs other than ZDV/3TC Twice-daily dosing CYP 3A4 substrate; dosing depends on presence or absence of concomitant CYP3A4 inducer(s) or inhibitor(s) Dual-NRTI pairs (in alphabetical order) ABC/3TC Virologic response noninferior to ZDV/3TC Better CD4 count responses than with ZDV/3TC Once-daily dosing Coformulation No food effect No cumulative TAM-mediated resistance Potential for ABC HSR in patients with HLA-B*5701 Increased potential for cardiovascular events, especially in patients with cardiovascular risk factors Inferior virologic responses in patients with baseline HIV RNA >100,000 copies/mL when compared with TDF/FTC in ACTG 5202 study; however, this was not seen in the HEAT study TDF/FTC Better virologic responses than with ZDV/3TC Better virologic responses than with ABC/3TC in patients with baseline HIV RNA >100,000 copies/mL in ACTG 5202 study; however, this was not seen in the HEAT study Active against HBV; recommended dual- NRTI for HIV/HBV coinfection Once-daily dosing No food effect Coformulated (TDF/FTC, EFV/TDF/FTC, and RPV/TDF/FTC) No cumulative TAM-mediated resistance Potential for renal impairment, including Fanconi syndrome and acute renal insufficiency Early virologic failure of NVP + TDF + (FTC or 3TC) in small clinical trials Potential for decrease in BMD ZDV/3TC Coformulated (ZDV/3TC and ZDV/3TC/ABC) No food effect (although better tolerated with food) Preferred dual NRTI in pregnant women Bone marrow suppression, especially anemia and neutropenia GI intolerance, headache Mitochondrial toxicity, including lipoatrophy, lactic acidosis, hepatic steatosis Compared with TDF/FTC, inferior in combination with EFV Less CD4 increase compared with ABC/3TC Twice-daily dosing

No food effect (although better tolerated with food) Preferred dual NRTI in pregnant women Bone marrow suppression, especially anemia and neutropenia GI intolerance, headache Mitochondrial toxicity, including lipoatrophy, lactic acidosis, hepatic steatosis Compared with TDF/FTC, inferior in combination with EFV Less CD4 increase compared with ABC/3TC Twice-daily dosing 3TC: lamivudine; ABC: abacavir; APV: amprenavir; ART: antiretroviral therapy; ARV: antiretroviral; ATV: atazanavir; ATV/r: atazanavir/ritonavir; AV: atrioventricular; BMD: bone mineral density; CNS: central nervous system; CYP: cytochrome P; d4T: stavudine; ddI: didanosine; DRV/r: darunavir/ritonavir; ECG: electrocardiogram; EFV: efavirenz; FPV: fosamprenavir; FPV/r: fosamprenavir/ritonavir; FTC: emtricitabine; GI: gastrointestinal; HBV: hepatitis B virus; HSR: hypersensitivity reaction; INSTI: integrase strand transfer inhibitor; LPV/r: lopinavir/ritonavir; MI: myocardial infarction; msec: milliseconds; MVC: maraviroc; NNRTI: non-nucleoside reverse transcriptase inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; NVP: nevirapine; PI: protease inhibitor; PPI: proton pump inhibitor; RAL: raltegravir; RPV: rilpivirine; RTV: ritonavir; SJS: Stevens-Johnson syndrome; SQV/r: saquinavir/ritonavir; TAM: thymidine analogue mutation; TDF: tenofovir; TEN: toxic epidermal necrosis; ZDV: zidovudine. Reproduced from: Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. file://aidsinfo.nih.gov/guidelines .