Triple-NRTI regimens studied in several clinical trials have shown suboptimal virologic activity.22-23, 109-112
Abacavir/Lamivudine/Zidovudine (coformulated). ABC/3TC/ZDV is the only triple-NRTI combination for which randomized, controlled trials are available. ABC/3TC/ZDV demonstrated comparable ARV activity to IDV-based104-105 and NFV-based regimens112 but was inferior virologically to an EFV-based regimen.22 This combination is generally not recommended (BI) and should be used only when a preferred, an alternative, or an acceptable NNRTI-, PI-, or INSTI- based regimen is less desirable because of concerns about toxicities, drug interactions, or regimen complexity.
Zidovudine/Lamivudine + Tenofovir. The DART study demonstrated that the combination of ZDV/3TC + TDF has antiviral activity.113 However, because comparative data with standard regimens are not available, this combination cannot be recommended in routine clinical practice (BIII).
Zidovudine/Lamivudine + Abacavir + Tenofovir. A quadruple-NRTI regimen of ZDV/3TC + ABC + TDF first showed comparable virologic responses to an EFV-based regimen in a small pilot study.114 A larger study randomized 322 subjects to receive TDF/FTC combined with EFV, ATV/RTV, or a quadruple-NRTI regimen with ZDV and ABC. Although the threshold of noninferiority for the protocol-defined virologic response was satisfied by the quadruple-NRTI regimen, the proportion of patients reaching HIV RNA <50 copies/mL was lower with the quadruple-NRTI regimen and the rate of serious toxicity was twice as high as that observed with the EFV-based regimen.115 Thus, this regimen cannot be recommended (BI).
Table 6. Advantages and Disadvantages of Antiretroviral Components Recommended as Initial Antiretroviral Therapy
|ARV Class||ARV Agent(s)||Advantages||Disadvantages|
|Key to Abbreviations: 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|
|NNRTIs (in alphabetical order)||NNRTI Class Advantages:
||NNRTI Class Disadvantages:|
|PIs (in alphabetical order)||PI Class Advantages:
||PI Class Disadvantages:|
|PIs (in alphabetical order)||LPV/r||
|Dual-NRTI pairs (in alphabetical order)||ABC/3TC||
|ARV drugs or components (in alphabetical order)||Reasons for NOT recommending as initial therapy|
|Key to Abbreviations: 3TC = lamivudine, ABC = abacavir, ART = antiretroviral therapy, ARV = antiretroviral, d4T = stavudine, ddI = didanosine, DLV = delavirdine, DRV = darunavir, ETR = etravirine, FPV = fosamprenavir, FTC = emtricitabine, GI = gastrointestinal, IDV = indinavir, NFV = nelfinavir, NRTI = nucleoside reverse transcriptase inhibitor, PI = protease inhibitor, RTV = ritonavir, SQV = saquinavir, T20 = enfuvirtide, TDF = tenofovir, TPV = tipranavir, ZDV = zidovudine|
|ABC/3TC/ZDV (coformulated) as triple-NRTI combination regimen (BI)||
|ABC + 3TC + ZDV + TDF as quadruple-NRTI combination regimen (BI)||
|ddI + 3TC (or FTC) (BIII)||
|ddI + TDF (BII)||
|FPV (unboosted) (BIII)||
|IDV (unboosted) (BIII)||
|IDV (RTV-boosted) (BIII)||
|RTV as sole PI (BIII)||
|SQV (unboosted) (BI)||
|d4T + 3TC (BI)||
|TPV (RTV-boosted) (BI)||
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