You are here

DRV/c+3TC

 Overview

In specific circumstances, DRV/c+ + 3TC (lamivudine) regimens have been shown to maintain viral suppression in ART naïve patients without baseline resistance as well as patients with viral suppression. The most commonly studied regimens, LPV/r + 3TC and ATV/r + 3TC have been shown to be noninferior to 1 PI + 2 NRTI regimens in studies. However, some experts recommend a regimen of DRV/r or DRV/c + 3TC because it has a more favorable safety profile due to the reduced pill burden, higher efficacy, and better tolerance of DRV as compared to LPV or ATV. Some experts recommend DRV/c over DRV/r because of the reduced pill burden of DRV/c.

+DRV/c was found to be bioequivalent to DRV/r in healthy volunteers[1]. Based on the results of the study, efficacy of DRV/c has been extrapolated from DRV/r data. Therefore, many experts may consider use of DRV/c despite the limited supporting data from clinical trials due to the reduced pill burden. Use of DRV/c is discussed in both the DHHS and IAS guidelines for use in treatment-naïve and treatment-experienced patients. Cobicistat inhibits active tubular secretion of creatinine, which can increase serum creatinine without an effect on renal glomerular function.

 Recommendations for treatment-naïve patients

DHHS: DRV/c + 3TC is considered to be a reasonable option when regimens containing TDF, TAF, or ABC are either contraindicated or cannot be used, based on success with a regimen of LPV/r + 3TC, which is recommended by the DHHS as a "recommended regimen in certain clinical situations" when TDF, TAF, and ABC cannot be used. These regimens have achieved virologic suppression in ART-naïve individuals without baseline mutations as well as maintain virologic suppression in virally suppressed patients in studies[2]. Generally speaking, regimens containing DRV are recommended over those containing LPV/r, given that LPV/r is poorly tolerated.

IAS: 2-drug regimens have limitations and are only recommended in cases where they offer cost or toxicity advantages over 3-drug regimens. LPV/r + 3TC (lamivudine) was found to be noninferior to LPV/r + 2 NRTIs in one study and can be considered as a possible regimen[3].

 Recommendations for treatment-experienced patients

DHHS: In virally suppressed patients, the DHHS notes that switching to a regimen of a boosted PI plus 3TC should be considered as it has been seen to maintain viral suppression in virally suppressed patients who cannot be on regimens containing TDF, TAF, or ABC. A regimen of DRV/r + 3TC is thought to be promising, given the positive results of recently completed study[2]. In cases of virologic failure, the DHHS does not currently recommend a regimen of a single NRTI with a boosted PI.

IAS: The IAS does not specifically recommend any regimens for treatment-experienced patients in cases of both virologic failure or suppression. However, 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 than DRV or ATV).

 Other Considerations

DRV/c

  • Must be taken with food
  • High barrier to resistance
  • PI booster (cobicistat) interacts with many other drugs 
  • Cobicistat inhibits active tubular secretion of creatinine, which can increase serum creatinine without an effect on renal glomerular function
  • Possible side effects include diarrhea, nausea, and headache

 

Efficacy in Clinical Trials

Trial

Regimens

Participants

Results

Study 115

DRV/c vs.DRV/r

62

DRV/c is bioequivalent to DRV/r in healthy volunteers [1].

IV ATLASM

ATV/r+3TC vs ATV/r+2NRTI

266 virally suppressed

90% of patients who switched to ATV/r + 3TC maintained virologic suppression vs. 80% of patients who remained on ATV/r +2NRTI[4].

SALT

ATV/r+3TC vs ATV/r+2NRTI

286 virally suppressed

The dual-treatment regimen was found to be noninferior to the triple-treatment regimen. At week 48, 112 (84%) of the dual-treatment group had virological response versus 105 (78%) in the triple-treatment group. Treatment discontinuations were also less frequent in the dual-treatment group as compared to the triple-treatment group [5].

GARDEL

LPV/r+3TC vs 2NRTI+LPV/r

426 treatment naive

At week 48, 189 patients (88.3%) in the dual-therapy group and 169 (83.7%) in the triple-therapy group had viral suppression[6]

OLE

LPV/r+3TC vs LPV/r+2NRTI

250 virally suppressed

The dual-treatment group was found to be noninferior to the triple-treatment group as 110 (86.6%) of triple-treatment patients responded to treatment versus 108 (87.8%) of dual-treatment patients[3].

 N/A

DRV/r+3TC

94 tx-experienced

In a retrospective analysis of patients with at least six months of virological suppression switched to 3TC plus DRV/r demonstrated continued virological suppression with a favorable safety profile[2]

ANDES

DRV/r+3TC vs DRV/r+3TC/TDF

145 naive

Prospective randomized trial, 93% vs 94% virologic suppressionat 48 weeks.(Figueroa MI CROI 2018. Abstract 489)

  DUAL GESIDA

DRV+r+2NRTI vs. DRV/r+3TC

249 Tx suppressed, no hx of resistance

At 48 weeks, 89% vs 92% were virally suppressed in the dual vs triple therapy arms, respectively. Switching to dual therapy was associated with increases in total, LDL, and HDL cholesterol, but not in total to HDL ratio.  There were similar rates of drug discontinuation due to adverse effects in both arms.[7] 

 

 

 

Did we forget a study or make an error?  If so, please click on the "feedback" tab and provide details and comments.

 


References

  1. Citekey 149 not found
  2. Citekey 142 not found
  3. Citekey 143 not found
  4. Citekey 235 not found
  5. Citekey 141 not found
  6. Citekey /180 not found
  7. Citekey 296 not found