Updated
Reviewed
Jun. 03, 2021

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

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 + 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 + 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

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 + 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 + 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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