This is a generic educational information sheet for 1 NRTI + 1 PI regimens.


1 NRTI + 1 PI regimens have been shown to achieve viral suppression in ART naïve patients without baseline resistance as well as maintain viral suppression in treatment-experienced. There are several possible combinations that have been studied: LPV/r + 3TC, ATV/r + 3TC, DRV/r or DRV/c + 3TC. When these regimens are considered, some experts recommend a regimen of DRV/r or DRV/c + 3TC because they have a reduced pill burden, higher efficacy, and better tolerance as compared to LPV or ATV-based regimens.

Recommendations for treatment-naïve patients

DHHS: This is not recommended as an initial regimen for most patients with HIV, however it is recommended in certain clinical situations.  Specifically, among patients who cannot take ABC, TAF, or TDF, the DHHS lists LPV/r + 3TC as a regimen to consider. This type of regimen is thought to be able to achieve virologic suppression in ART-naïve individuals without baseline mutations as well as patients with sustained viral suppression.  Given the poor tolerability of LPV/r and its removal from the guidelines in other circumstances, we extrapolate the evidence to be supportive of other PI+NRTI combinations.

IAS: Initial 2-drug regimens have limitations and are only recommended in cases where they offer cost or toxicity advantages over 3-drug regimens. The IAS mentions that 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[1].

Recommendations for treatment-experienced patients

DHHS: In virally suppressed patients, the DHHS notes that switching to a regimen of a boosted PI plus 3TC can be considered as it has been seen to maintain viral suppression in patients with sustained viral suppression. Specifically, they recommend considering regimens of LPV/r + 3TC and ATV/r + 3TC, and consider a regimen of DRV/r + 3TC to be promising, as there is a recently completed study[2]. In cases of virologic failure, the DHHS does not currently discuss a regimen of a single NRTI with a boosted PI. However, the guidelines recommend considering a regimen of 1 boosted PI with 2 NRTIs.

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


  • Relatively high rates of gastrointestinal adverse effects and hyperlipidemia
  • Higher pill burden than other PI-based regimens


  • Must be taken with food
  • High barrier to resistance
  • PI booster (ritonavir) interacts with many other drugs
  • Possible side effects include rash, severe rash with fever, and elevated transaminases
  • Caution advised when administering to patients with severe sulfonamide allergy


  • 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






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

266 tx-experienced

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


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

286 tx-experienced

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[4].


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

426 tx-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[5].


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

250 tx-experienced

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[1].



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].


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

145 treatment naive

Prospective randomized trial. 93% vs 95% virologically supressed at week 48 (Gueroa M CROI 2018 Abstract 489)


 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[6].





1.         Arribas JR, Girard P-M, Landman R, Pich J, Mallolas J, Martínez-Rebollar M, et al. Dual treatment with lopinavir-ritonavir plus lamivudine versus triple treatment with lopinavirritonavir plus lamivudine or emtricitabine and a second nucleos(t)ide reverse transcriptase inhibitor for maintenance of HIV-1 viral suppression (OLE): a random. Lancet Infect Dis. 2015;15(7):785-92.

2.         Borghetti A, Mondi A, Piccoli B, Gagliardini R, Lamonica S, Ciccarelli N, et al. Switching to lamivudine plus darunavir/r dual therapy in a cohort of treatment-experienced HIV-positive patients: the experience of an Italian centre. J Int AIDS Soc. 2014;17(4 Suppl 3):19817.

3.         Fabbiani M, Di Giambenedetto S, Quiros-Roldan E, Latini A, Vullo V, Antinori A, et al. Simplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV-infected patients: 24-weeks interim analysis from ATLAS-M trial. J Int AIDS Soc. 2014;17(4 Suppl 3):19808.

4.         Perez-Molina JA, Rubio R, Rivero A, Pasquau J, Suarez-Lozano I, Riera M, et al. Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015;15(7):775-84.

5.         Cahn P, Andrade-Villanueva J, Arribas JR, Gatell JM, Lama JR, Norton M, et al. Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir

and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviraltherapy-

naive adults with HIV-1 infection: 48 week results of the randomise. Lancet Infect Dis. 2014;14(7):572-80.

6.         Pulido F, Ribera E, Lagarde M, Perez-Valero I, Palacios R, Iribarren JA, et al. Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial. Clin Infect Dis. 2017;65(12):2112-8.