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ABC/3TC+EFV is a regimen containing two NRTIs and an NNRTI, classified as an “other regimen by the DHHS and not recommended by the IAS. It consists of two pills taken once daily. It has interactions with many other medications, and possible CNS side effects. This regimen should only be used in patients who are HLA-B*5701 negative.

Recommendations for treatment-naïve patients

DHHS: ABC/3TC+EFV is classified as an “other” regimen (neither recommended nor alternative), as a result of virologic and pharmacogenetic parameters that limit its use in some patients, and should only be used in patients who are HLA-B*701 negative and have a pre-ART HIV RNA <100,000 copies/mL. A different NNRTI + 2 NRTI regimen (EFV + Tenofovir/FTC) is listed as a recommended initial regimen in certain clinical situations.

IAS: ABC/3TC+EFV is not discussed in the IAS guidelines, but the guidelines discuss that a regimen containing ABC/3TC should only be used in patients who are HLA-B*5701 negative. Additionally, a regimen of 2 NRTIs + 1 NNRTI is a recommended initial regimen for individuals in whom an INSTI is not an option.

Recommendations for treatment-experienced patients

DHHS: The DHHS does not mention use of this regimen for treatment-experienced patients. There are mentions of switches to an NNRTI-based regimen in virally suppressed patients, advise considering a switch from EFV to RPV in certain circumstances. In cases of confirmed virologic failure, the DHHS does not currently discuss switching to an NNRTI + 2 NRTI regimen. 

IAS: There is no explicit recommendation to switch to this type of regimen (2 NRTI + 1 NNRTI) in the IAS guidelines in the setting of treatment failure or for those that are virally suppressed. However, they suggest that when virally suppressed, switching patients on older regimens to a variety of single-pill regimens, including RPV/FTC/TAF, can be considered. Situations in which patients should be recommended a switch include use of old NRTIs as they have long-term toxic effects, or older drugs that have higher pill burdens and are more metabolically toxic.

Other Considerations


  • May see hypersensitivity reaction in patients who are not HLA-B*5701 negative
  • Dosing does not need to be adjusted for patients with renal insufficiency


  • Can induce CNS toxicity (i.e. insomnia, abnormal dreams, nervousness)
  • Possible side effects include skin symptoms, fatigue, elevated transaminase levels, hypertriglyceridemia
  • Consider avoiding EFV in patients with QTc prolongation


Efficacy in Clinical Trials

Trial Name

Drugs Compared


Study Results

ACTG 5202

2 NRTIs plus EFV or ATV/r

463 tx-naive patients

EFV was comparable to ATV/r with respect to virological response when each was given with either TDF/FTC or ABC/3TC [1].

GS 102

FTC/TDF/EFV was non-inferior to EVG/c/TDF/FTC

700 tx-naive

At 144 weeks, EFV was non-inferior with respect to study discontinuation [2].


2 NRTIs plus RPV or EFV

1368 tx-naive

EFV was noninferior to RPV, with less virologic failure. EFV caused more discontinuations due to adverse events. The virologic advantage of EFV was most notable in participants with pre-ART viral loads >100,000 copies/mL, and NRTI and NNRTI resistance was more frequent with RPV failure [3].



833 tx-naive

At 48 weeks, a DTG-based regimen was superior to EFV with regards to viral suppression [4].



566 tx-naive

At 48 weeks, RAL was noninferior to EFV. At 4 and 5 years, RAL was superior to EFV, in part because of more frequent discontinuations due to adverse events in the EFV group [5][6][7].



786 tx-naive

Participants with baseline viral loads ≤100,000 copies/mL had higher rates of treatment success on RPV than on EFV [8].


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