Updated
Reviewed Jun. 03, 2021

Table 10. Antiretroviral Components or Regimens Not Recommended as Initial Therapy

ARV Components or Regimens Reasons for Not Recommending as Initial Therapy
Combination INSTI + NNRTI
CAB plus RPV (PO or IM)
  • This regimen only is approved for people who have achieved viral suppression on another ARV regimen. It has not been studied as initial ARV regimen.
DTG plus RPV
  • This regimen only is approved for people who have achieved viral suppression on another ARV regimen. It has not been studied as initial ARV regimen.
NRTIs
ABC/3TC/ZDV (Coformulated)
As triple-NRTI combination regimen
  • Inferior virologic efficacy
ABC/3TC/ZDV plus TDF
As quadruple-NRTI combination regimen
  • Inferior virologic efficacy
d4T plus 3TC
  • Significant toxicities (including lipoatrophy and peripheral neuropathy) and hyperlactatemia (including symptomatic and life-threatening lactic acidosis, hepatic steatosis, and pancreatitis)
ddI plus 3TC (or FTC)
  • Inferior virologic efficacy
  • Limited clinical trial experience in ART-naive patients
  • ddI toxicities, such as pancreatitis and peripheral neuropathy
ddI plus TDF
  • High rate of early virologic failure
  • Rapid selection of resistance mutations
  • Potential for immunologic nonresponse/CD4 cell decline
  • Increased ddI drug exposure and toxicities
ZDV/3TC
  • Greater toxicities (including bone marrow suppression, GI toxicities, skeletal muscle myopathy, cardiomyopathy, and mitochondrial toxicities, such as lipoatrophy, lactic acidosis, and hepatic steatosis) than recommended NRTIs
NNRTIs
DLV
  • Inferior virologic efficacy
  • Inconvenient (three times daily) dosing
ETR
  • Insufficient data in ART-naive patients
NVP
  • Associated with serious and potentially fatal toxicity (hepatic events and severe rash, including SJS and TEN)
  • When compared to EFV, NVP did not meet noninferiority criteria
PIs
ATV (Unboosted)
  • Less potent than boosted ATV
DRV (Unboosted)
  • Use without RTV or COBI has not been studied
FPV (Unboosted) or FPV/r
  • Virologic failure with unboosted FPV-based regimen may result in selection of mutations that confer resistance to FPV and DRV
  • Less clinical trial data for FPV/r than for other RTV-boosted PIs
IDV (Unboosted)
  • Inconvenient dosing (3 times daily with meal restrictions)
  • Fluid requirement
  • IDV toxicities, such as nephrolithiasis and crystalluria
IDV/r
  • Fluid requirement
  • IDV toxicities, such as nephrolithiasis and crystalluria
LPV/r
  • Higher pill burden than other PI-based regimens
  • Higher RTV dose than other PI-based regimens
  • GI intolerance
NFV
  • Inferior virologic efficacy
  • Diarrhea
RTV as sole PI
  • High pill burden
  • GI intolerance
  • Metabolic toxicity
SQV (Unboosted)
  • Inadequate bioavailability
  • Inferior virologic efficacy
SQV/r
  • High pill burden
  • Can cause QT and PR prolongation; requires pretreatment and follow-up ECG
TPV/r
  • Inferior virologic efficacy
  • Higher rate of adverse events than other RTV-boosted PIs
  • Higher dose of RTV required for boosting than other RTV-boosted PIs
Entry Inhibitors
FTR
gp120 Attachment Inhibitor
  • Only studied in a very small number of patients with virologic failure
IBA
CD4 Post-Attachment Inhibitor
  • Only studied in a very small number of patients with virologic failure
  • Requires IV therapy
  • High cost
MVC
CCR5 Antagonist
  • Requires testing for CCR5 tropism before initiation of therapy
  • No virologic benefit when compared with other recommended regimens
  • Requires twice-daily dosing
T20
Fusion Inhibitor
  • Only studied in patients with virologic failure
  • Twice-daily subcutaneous injections
  • High rate of injection site reactions
Key: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; CAB = cabotegravir; CD4 = CD4 T lymphocyte; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DLV = delavirdine; DRV = darunavir; DTG = dolutegravir; ECG = electrocardiogram; EFV = efavirenz; ETR = etravirine; FPV = fosamprenavir; FPV/r = fosamprenavir/ritonavir; FTC = emtricitabine; FTR = fostemsavir; GI = gastrointestinal; IBA = ibalizumab; IDV = indinavir; IDV/r = indinavir/ritonavir; IM = intramuscular; IV = intravenous; LPV = lopinavir; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PO = oral; RPV = rilpivirine; RTV = ritonavir; SJS = Stevens Johnson Syndrome; SQV = saquinavir; SQV/r = saquinavir/ritonavir; T20 = enfuvirtide; TDF = tenofovir disoproxil fumarate; TEN = toxic epidermal necrolysis; TPV = tipranavir; TPV/r = tipranavir/ritonavir; ZDV = zidovudine

Table 10. Antiretroviral Components or Regimens Not Recommended as Initial Therapy

ARV Components or Regimens Reasons for Not Recommending as Initial Therapy
Combination INSTI + NNRTI
CAB plus RPV (PO or IM)
  • This regimen only is approved for people who have achieved viral suppression on another ARV regimen. It has not been studied as initial ARV regimen.
DTG plus RPV
  • This regimen only is approved for people who have achieved viral suppression on another ARV regimen. It has not been studied as initial ARV regimen.
NRTIs
ABC/3TC/ZDV (Coformulated)
As triple-NRTI combination regimen
  • Inferior virologic efficacy
ABC/3TC/ZDV plus TDF
As quadruple-NRTI combination regimen
  • Inferior virologic efficacy
d4T plus 3TC
  • Significant toxicities (including lipoatrophy and peripheral neuropathy) and hyperlactatemia (including symptomatic and life-threatening lactic acidosis, hepatic steatosis, and pancreatitis)
ddI plus 3TC (or FTC)
  • Inferior virologic efficacy
  • Limited clinical trial experience in ART-naive patients
  • ddI toxicities, such as pancreatitis and peripheral neuropathy
ddI plus TDF
  • High rate of early virologic failure
  • Rapid selection of resistance mutations
  • Potential for immunologic nonresponse/CD4 cell decline
  • Increased ddI drug exposure and toxicities
ZDV/3TC
  • Greater toxicities (including bone marrow suppression, GI toxicities, skeletal muscle myopathy, cardiomyopathy, and mitochondrial toxicities, such as lipoatrophy, lactic acidosis, and hepatic steatosis) than recommended NRTIs
NNRTIs
DLV
  • Inferior virologic efficacy
  • Inconvenient (three times daily) dosing
ETR
  • Insufficient data in ART-naive patients
NVP
  • Associated with serious and potentially fatal toxicity (hepatic events and severe rash, including SJS and TEN)
  • When compared to EFV, NVP did not meet noninferiority criteria
PIs
ATV (Unboosted)
  • Less potent than boosted ATV
DRV (Unboosted)
  • Use without RTV or COBI has not been studied
FPV (Unboosted) or FPV/r
  • Virologic failure with unboosted FPV-based regimen may result in selection of mutations that confer resistance to FPV and DRV
  • Less clinical trial data for FPV/r than for other RTV-boosted PIs
IDV (Unboosted)
  • Inconvenient dosing (3 times daily with meal restrictions)
  • Fluid requirement
  • IDV toxicities, such as nephrolithiasis and crystalluria
IDV/r
  • Fluid requirement
  • IDV toxicities, such as nephrolithiasis and crystalluria
LPV/r
  • Higher pill burden than other PI-based regimens
  • Higher RTV dose than other PI-based regimens
  • GI intolerance
NFV
  • Inferior virologic efficacy
  • Diarrhea
RTV as sole PI
  • High pill burden
  • GI intolerance
  • Metabolic toxicity
SQV (Unboosted)
  • Inadequate bioavailability
  • Inferior virologic efficacy
SQV/r
  • High pill burden
  • Can cause QT and PR prolongation; requires pretreatment and follow-up ECG
TPV/r
  • Inferior virologic efficacy
  • Higher rate of adverse events than other RTV-boosted PIs
  • Higher dose of RTV required for boosting than other RTV-boosted PIs
Entry Inhibitors
FTR
gp120 Attachment Inhibitor
  • Only studied in a very small number of patients with virologic failure
IBA
CD4 Post-Attachment Inhibitor
  • Only studied in a very small number of patients with virologic failure
  • Requires IV therapy
  • High cost
MVC
CCR5 Antagonist
  • Requires testing for CCR5 tropism before initiation of therapy
  • No virologic benefit when compared with other recommended regimens
  • Requires twice-daily dosing
T20
Fusion Inhibitor
  • Only studied in patients with virologic failure
  • Twice-daily subcutaneous injections
  • High rate of injection site reactions
Key: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; CAB = cabotegravir; CD4 = CD4 T lymphocyte; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DLV = delavirdine; DRV = darunavir; DTG = dolutegravir; ECG = electrocardiogram; EFV = efavirenz; ETR = etravirine; FPV = fosamprenavir; FPV/r = fosamprenavir/ritonavir; FTC = emtricitabine; FTR = fostemsavir; GI = gastrointestinal; IBA = ibalizumab; IDV = indinavir; IDV/r = indinavir/ritonavir; IM = intramuscular; IV = intravenous; LPV = lopinavir; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PO = oral; RPV = rilpivirine; RTV = ritonavir; SJS = Stevens Johnson Syndrome; SQV = saquinavir; SQV/r = saquinavir/ritonavir; T20 = enfuvirtide; TDF = tenofovir disoproxil fumarate; TEN = toxic epidermal necrolysis; TPV = tipranavir; TPV/r = tipranavir/ritonavir; ZDV = zidovudine

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