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 Table 6.  Advantages and Disadvantages of Antiretroviral Components Recommended as Initial Antiretroviral Therapy (Updated January 10, 2011) Page 1 of 3 

ARV Class ARV Agent(s) Advantages Disadvantages 

NNRTI (in alphabetical order) 

 NNRTI Class Advantages: • Long half-lives  

NNRTI Class Disadvantages: • Low genetic barrier to resistance (single mutation confers resistance for 

EFV, NVP, and DLV); greater risk of resistance at the time of failure or treatment interruption 

• Potential for cross resistance • Skin rash • Potential for CYP450 drug interactions (See Tables 14, 15b, and 16b.) • Transmitted resistance to NNRTIs more common than resistance to PIs 

EFV • Virologic responses equivalent or superior to all comparators to date 

• Lowest pill burden; once-daily dosing • Fixed-dose combination with TDF/FTC  

• Neuropsychiatric side effects • Teratogenic in nonhuman primates, and several cases of neural tube defect 

reported in infants of women with first-trimester exposure. EFV is contraindicated in first trimester of pregnancy; avoid use in women with pregnancy potential. 

• Dyslipidemia   

NVP • No food effect • Fewer lipid effects than EFV   

• Higher incidence of rash than with other NNRTIs, including rare but serious hypersensitivity reactions (Stevens-Johnson syndrome or toxic epidermal necrolysis) 

• Higher incidence of hepatotoxicity than with other NNRTIs, including serious and even fatal cases of hepatic necrosis 

• Contraindicated in patients with moderate or severe (Child-Pugh B or C) hepatic impairment 

• Some data suggest that ART-naïve patients with high pre-NVP CD4 counts (>250 cells/mm3 for females, >400 cells/mm3 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 

• Fewer clinical trial data than for EFV 

 PI (in alphabetical order)  

 PI Class Advantages: • Higher genetic barrier to resistance • PI resistance uncommon with failure 

(boosted PIs) 

PI Class Disadvantages: • Metabolic complications (e.g., dyslipidemia, insulin resistance, 

hepatotoxicity) • Gastrointestinal adverse effects • CYP3A4 inhibitors and substrates: potential for drug interactions (more 

pronounced with RTV-based regimens) (See Tables 14 and 15a.)  

ATV • Fewer adverse effects on lipids than other PI 

• Once-daily dosing • Low pill burden (two pills per day) • 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 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 (See Table 15a for 

detailed information regarding interactions with H2 antagonists, antacids, and PPIs.) 

ATV/r • RTV boosting: higher trough ATV concentration and greater antiviral effect 

• Once-daily dosing • Low pill burden (two pills per day)  

• 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 (See Table 15a for 

interactions with H2 antagonists, antacids, and PPIs.) • RTV boosting required with TDF and EFV. With EFV, use ATV 400 mg 

and RTV 100 mg once daily (PI-naïve patients only). • Should not be coadministered with NVP 

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 ARV Class ARV 

Agent(s) Advantages Disadvantages 

 DRV/r • Once-daily dosing • Skin rash • Food requirement 

FPV • No food effect • Skin rash • Potential for PI resistance with failure, including emergence of mutations 

that can cause DRV cross resistance 

FPV/r • Twice-daily dosing resulted in efficacy comparable to LPV/r 

• RTV boosting: 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 1,400 mg + RTV 200 mg: requires 200 mg of RTV and no 

coformulation • Fewer data on FPV 1,400 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: 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 • Efficacy similar to LPV/r with less hyperlipidemia 

• Highest pill burden among available PI regimens (6 pills per day) • 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: (1) congenital or acquired QT prolongation; (2) pretreatment ECG >450 msec; (3) on concomitant therapy with other drugs that prolong QT interval; (4) complete AV block without implanted pacemakers; (5) 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 

• Less long-term experience in ART-naïve patients than with boosted 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-naïve patients 

CCR5 Antagonist 

MVC • Virologic response noninferior to EFV in post-hoc analysis of MERIT study (See text.) 

• Fewer adverse effects than EFV 

•  Requires viral tropism testing prior to initiation of therapy with 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-naïve patients than with boosted PI- or NNRTI-based regimens • Limited experience with 2-NRTI 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 NRTIs  Dual-NRTI Class Advantage: Established backbone of combination ART 

Dual-NRTI Class Disadvantage: Rare but serious cases of lactic acidosis with hepatic steatosis reported with d4T, ddI, and ZDV 

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 Dual-NRTI pairs (in alphabetical order)  

ABC/3TC • Virologic response noninferior to ZDV/3TC 

• Better CD4 count response 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 • Potential for increased cardiovascular events, especially in patients with 

cardiovascular risk factors • Inferior virologic responses when compared with TDF/FTC in patients 

with baseline HIV RNA >100,000 copies/mL in ACTG 5202 study; however, this was not seen in the HEAT study. 

ddI + (3TC or FTC) 

• Once-daily dosing • No cumulative TAM-mediated resistance 

• Peripheral neuropathy, pancreatitis • Reports of noncirrhotic portal hypertension • Food effect; must be taken on an empty stomach • Requires dosing separation from some PIs • Increase in toxicities when used with ribavirin, TDF, d4T, or hydroxyurea • Preliminary data showed inferior virologic responses of ATV/ddI/FTC 

when compared with EFV/ZDV/3TC or EFV/TDF/FTC. Combination of ATV/ddI/FTC should be avoided. 

 TDF/FTC or TDF + 3TC 

• 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 HBV/HIV coinfection 

• Once-daily dosing • No food effect • Coformulated (TDF/FTC) and 

(EFV/TDF/FTC) • No cumulative TAM-mediated resistance 

• Potential for renal impairment, including rare reports of Fanconi syndrome and acute renal insufficiency 

• Early virologic failure of NVP + TDF + (FTC or 3TC) in small clinical trials 

• Potential for decrease in bone mineral density 

  ZDV/3TC • Coformulated (ZDV/3TC and ZDV/3TC/ABC) 

• No food effect (although better tolerated with food) 

• Preferred 2 NRTI in pregnant women  

• Bone marrow suppression, especially anemia and neutropenia • GI intolerance, headache • Mitochondrial toxicity, including lipoatrophy, lactic acidosis, hepatic 

steatosis • Inferior to TDF/FTC in combination with EFV • Diminished CD4 T-cell responses compared with ABC/3TC 

 Acronyms: 3TC = lamivudine, ABC = abacavir, ART = antiretroviral therapy, ARV = antiretroviral, ATV = atazanavir, ATV/r = atazanavir/ritonavir,  AV = atrioventricular, CYP = cytochrome P, ddI = didanosine, DLV = delavirdine, 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, SQV/r = saquinavir/ritonavir, TAM = thymidine analogue mutation, TDF = tenofovir, ZDV = zidovudine 

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