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RAL+3TC

Overview

3TC+RAL is a regimen containing an NRTI and an INSTI, not formally recommended by either the DHHS or the IAS for treatment initiation in treatment-naïve patients. Although there isn't clinical evidence supporting RAL+3TC, there is evidence for the closely related regimen of DTG+3TC. There is emerging evidence on using this regimen for treatment simplification in virologically suppressed patients. There has also been some consideration of this regimen for treatment-naïve patients, as the regimen may offer some cost and toxicity advantages over 3-drug regimens.

Recommendations for treatment-naïve patients

DHHS: This regimen is not described among the recommended initial treatment regimens for patients with HIV. However, given the promising results of the PADDLE study, a regimen of 1 NRTI + 1 INSTI, specifically with 3TC + DTG, can be considered[1]. However, although there is a clinical trial underway to fully evaluate the efficacy of this type of regimen, currently there is insufficient evidence to fully support this regimen. The more complete regimen, RAL + ABC/3TC is a recommended initial regimen in certain clinical situations for patients with an HIV RNA <100,000 copies/mL and who are HLA-B*5701 negative.

IAS: Initial 2-drug regimens should only be considered in the rare situations in which a patient cannot take ABC, TAF, or TDF; given that there are not any adequately-powered studies of initial therapy for this regimen, efficacy of these regimens is inferred from other clinical trials. IAS does acknowledge the promising PADDLE trial results, but considers the trial to be too small to make a formal recommendation of this regimen for treatment-naïve patients. IAS recommends DTG over RAL among INSTI drugs, as DTG has been found to be noninferior to RAL in treatment-naïve patients, whereas it was found to be superior to RAL in treatment-experienced patients.

Recommendations for Treatment-Experienced Patients

DHHS: In virally suppressed patients, the DHHS does not specifically discuss this regimen. However, the guidelines discuss the promising results of the PADDLE study and the clinical trial that is currently underway testing the possibility of this type of regimen, specifically with 3TC + DTG, for use as a maintenance regimen in virally suppressed patients who have no NRTI, INSTI, or PI resistance. In cases of confirmed virologic failure, the DHHS recommends that patients be put on a regimen with at least two to three active drugs and does not discuss a regimen of 1 INSTI + 1 NRTI in the guidelines.

IAS: The IAS does not specifically discuss this regimen for treatment-experienced patients in cases of confirmed virologic failure. However, in virally suppressed patients, they recommend to consider switching patients on older regimens to a variety of simplified regimens (i.e. from use of old NRTIs as they have long-term toxic effects, or older PIs that have higher pill burdens and are more metabolically toxic), but do not specifically recommend any 2 drug regimens.

Other Considerations

RAL

  • Must be taken twice daily. A once daily dose has shown similar efficacy in a recent trial but there is not enough data to recommend this[2][3].
  • Should not be taken with polyvalent cations, which may be found in antacids, laxatives, and mineral supplements
  • Possible side effects include creatine kinase elevation, myositis, rhabdomyolysis, and (rarely) severe skin reactions and systemic hypersensitivity reactions

 

Efficacy in Clinical Trials

Trial Name

Drugs Compared

Participants

Study Results

PADDLE

3TC+DTG (1 arm)

20 tx-naive

At week 48, 90% (18 of 20) achieved viral suppression. The combination was well tolerated through week 48, and all adverse events were reported in the first week of therapy [1].

ANRS 167 LAMIDOL

DTG+3TC

104 tx-experienced

101/104 (97%) of patients who switched from triple ART to DTG+3TC maintained therapeutic success through 40 weeks of dual therapy [unpublished; Joly V, et al CROI 2017 Abstract 458][4]  

 

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References

  1. Citekey 152 not found
  2. Citekey 122 not found
  3. Citekey 151 not found
  4. Citekey 192 not found