, Volume 46, Issue 5, pp 599–605 | Cite as

Dual antiretroviral therapy with tenofovir (TDF) and darunavir/ritonavir (DRV/RTV) in an HIV-1 positive patient: a case report, review, and meta-analysis of the literature on dual treatment strategies using protease inhibitors in combination with an NRTI

  • S. HöringEmail author
  • B. Löffler
  • M. W. Pletz
  • S. Rößler
  • S. Weis
  • B. T. Schleenvoigt



Here, we report the case of an HIV positive patient under a dual antiretroviral drug regimen with tenofovir disoproxil and darunavir/ritonavir with stable clinical, virological, and immunological response over 126 weeks. Dual antiretroviral therapy has the advantage of reduced toxicity and lower health care costs, treatment failure and fostering drug resistance are perceived risks. Optimal drug combinations and indication criteria for dual treatment remain controversial. Nevertheless, first clinical trials indicate non-inferiority for combinations of nucleoside reverse transcriptase inhibitors and protease inhibitors. This case presents the combination of tenofovir disoproxil in combination with a protease inhibitor as a new potential dual treatment regimen.


We performed a systematic literature search and meta-analysis of trials comparing dual to triple ART.


Literature review revealed nine studies in which dual therapy with a protease inhibitor and an NRTI was compared to triple therapy. We performed a meta-analysis of six trials that reported a 48-week follow-up. In treatment-naïve patients as well when ART switch was assessed, there was no difference in the treatment success in patients with dual ART versus triple.


We conclude that dual therapy with a protease inhibitor and NRTI is safe and effective. The use of tenofovir in dual treatment as described in our case needs to be assessed in future clinical trials.


Dual therapy HIV Antiretroviral therapy Tenofovir Lamivudine Protease inhibitor 



This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. BTS and MWP were supported by grants from the German Federal Ministry of Education and Research (BMBF), Grant numbers 01KI1501 and 03ZZ0820D. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

SH, BL, SW, and MP declare no conflicts of interest. BS received research funding from Gilead, funding for attending congresses by MSD, Janssen-Cilag and Gilead, gave talks for MSD, Janssen-Cilag, Gilead, AIDS-Hilfe Potsdam and AIDS-Hilfe Dresden and worked as a consultant for Gilead, Janssen and ViiV. SR gave talks for Gilead and ViiV and received financial support for attending conferences from Gilead, ViiV, MSD, and Hexal.


  1. 1.
    Deutsche AIDS Gesellschaft. Leitlinien zur antiretroviralen Therapie der HIV-Infektion. 2015.Google Scholar
  2. 2.
    Madeddu G, Rusconi S, Cozzi-Lepri A, Di Giambenedetto S, Bonora S, Carbone A, et al. Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤ 50 cp/mL. Infection. 2017;45:521–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Filippas-Ntekouan S, Liberopoulos E, Elisaf M. Lipid testing in infectious diseases: possible role in diagnosis and prognosis. Infection. 2017;45:575–88.CrossRefPubMedGoogle Scholar
  4. 4.
    Zeder AJ, Hilge R, Schrader S, Bogner JR, Seybold U. Medium-grade tubular proteinuria is common in HIV-positive patients and specifically associated with exposure to tenofovir disoproxil Fumarate. Infection. 2016;44:641–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Andrade R, Villarreal-Williams E, Mall M, Shillington A, Pasley M, Trinh R, et al. A pilot study: lopinavir/ritonavir (LPV/r) plus lamivudine (3TC) as dual agents in antriretroviral (ARV) naive HIV-infected subjects (the LOREDA study). In: 6th International AIDS society (IAS) conference on HIV pathogenesis, treatment and prevention, Rome 2011.Google Scholar
  6. 6.
    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 antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial. Lancet Infect Dis. 2014;14:572–80.CrossRefPubMedGoogle Scholar
  7. 7.
    Cai W, He H, Li L, Hu F, Lan Y, Tang X. Simplified dual therapy (LPV/r plus 3TC) for ART-naive patients is a viable alternative in resource-limited settings in China: 48-week results from a randomized, open-label, non-inferiority trial. In: 9th International AIDS society (IAS) conference on HIV science, Paris 2017.Google Scholar
  8. 8.
    Sued O, Figueroa MI, Gun A, Belloso W, Gecchini D, Lopardo G, et al. Dual therapy with darunavir/ritonavir plus lamivudine for HIV-1 treatment initiation: week 24 results of the randomized ANDES study. In: 9th International AIDS society (IAS) conference on HIV science, Paris 2017.Google Scholar
  9. 9.
    Arribas JR, Girard PM, Landman R, Pich J, Mallolas J, Martinez-Rebollar M, et al. Dual treatment with lopinavir–ritonavir plus lamivudine versus triple treatment with lopinavir–ritonavir plus lamivudine or emtricitabine and a second nucleos(t)ide reverse transcriptase inhibitor for maintenance of HIV-1 viral suppression (OLE): a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015;15:785–92.CrossRefPubMedGoogle Scholar
  10. 10.
    Lombardi F, Belmonti S, Quiros-Roldan E, Latini A, Castagna A, D’Ettorre G, et al. Evolution of blood-associated HIV-1 DNA levels after 48 weeks of switching to atazanavir/ritonavir + lamivudine dual therapy versus continuing triple therapy in the randomized AtLaS-M trial. J Antimicrob Chemother. 2017;72:2055–9.CrossRefPubMedGoogle Scholar
  11. 11.
    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;15:775–84.CrossRefPubMedGoogle Scholar
  12. 12.
    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;65:2112–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Pinola M, Lazzarin A, Antinori A, Carosi G, Di Perri G, Moroni M, et al. Lopinavir/ritonavir + tenofovir dual therapy versus lopinavir/ritonavir-based triple therapy in HIV-infected antiretroviral naive subjects. the kalead study. J Antivir Antiretrovir. 2010;2:056–62.CrossRefGoogle Scholar
  14. 14.
    Di Giambenedetto S, Fabbiani M, Quiros Roldan E, Latini A, D’Ettorre G, Antinori A, et al. Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M). J Antimicrob Chemother. 2017;72:1163–71.PubMedGoogle Scholar
  15. 15.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMedGoogle Scholar
  16. 16.
    The Nordic Cochrane Centre. Review manager. 5.2 edn. Copenhagen: The Cochrane Collaboration; 2012.Google Scholar
  17. 17.
    Ryom L, Boesecke C, Bracchi M, Ambrosioni J, Pozniak A, Arribas J, et al. Highlights of the 2017 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons version 9.0. HIV Med. 2018;19:309–15.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Johnson VA, Calvez V, Gunthard HF, Paredes R, Pillay D, Shafer R, et al. 2011 update of the drug resistance mutations in HIV-1. Top Antivir Med. 2011;19:156–64.PubMedGoogle Scholar
  19. 19.
    Campbell TB, Shulman NS, Johnson SC, Zolopa AR, Young RK, Bushman L, et al. Antiviral activity of lamivudine in salvage therapy for multidrug-resistant HIV-1 infection. Clin Infect Dis. 2005;41(2):236–42.CrossRefPubMedGoogle Scholar
  20. 20.
    Castagna A, Danise A, Menzo S, Galli L, Gianotti N, Carini E, et al. Lamivudine monotherapy in HIV-1-infected patients harbouring a lamivudine-resistant virus: a randomized pilot study (E-184V study). AIDS. 2006;20:795–803.CrossRefPubMedGoogle Scholar
  21. 21.
    Llibre JM, Bonjoch A, Iribarren J, Galindo MJ, Negredo E, Domingo P, et al. Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study. HIV Med. 2008;9:508–13.CrossRefPubMedGoogle Scholar
  22. 22.
    Trottier B, Galanakis C, Longpré D, D H, V S. S. L, et al. Removing inactive NRTIs in a salvage regimen is safe, maintains virological suppression and reduces treatment costs: results from the VERITAS study (TMC114HIV4054). HIV Clin Trials. 2015;16:111–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Tashima KT, Smeaton LM, Fichtenbaum CJ, Andrade A, Eron JJ, Gandhi RT, et al. HIV salvage therapy does not require nucleoside reverse transcriptase inhibitors: a randomized, controlled trial. Ann Intern Med. 2015;163:908–17.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Arribas JR, Girard PM, Paton N, Winston A, Marcelin AG, Elbirt D, et al. Efficacy of protease inhibitor monotherapy vs. triple therapy: meta-analysis of data from 2303 patients in 13 randomized trials. HIV Med. 2016;17:358–67.CrossRefPubMedGoogle Scholar
  25. 25.
    Taiwo B, Swindells S, Berzins B, Acosta E, Ryscavage P, Lalerazi J, et al. Week 48 results of the maraviroc plus darunavir/ritonavir study (MIDAS) for treatment-naive patients infected with R5-tropic HIV-1. In: 19th International AIDS conference (AIDS 2012), Washington, D.C. 2012.Google Scholar
  26. 26.
    Stellbrink H, Pulik P, Szlavik J, Murphy D, Lazzarin A, Portilla J, et al. Maraviroc (MVC) dosed once daily with darunavir/ritonavir (DRV/r) in a 2 drug-regimen compared to emtricitabine/tenofovir (TDF/FTC) with DRV/r; 48-week results from MODERN (Study A4001095). In: 20th International AIDS conference (AIDS 2014), Melbourne 2014.Google Scholar
  27. 27.
    Harris M, Cote H, Ochoa C, Allavena C, Negredo E, Thorne A, et al. A randomized, open-label study of a nucleoside analogue reverse transcriptase inhibitor-sparing regimen in antiretroviral-naive HIV-infected patients. J Acquir Immune Defic Syndr. 2009;50:335–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Ryom L, Mocroft A, Kirk O, Worm SW, Kamara DA, Reiss P, et al. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study. J Infect Dis. 2013;207:1359–69.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    van Leeuwen R, Katlama C, Kitchen V, Boucher CA, Tubiana R, McBride M, et al. Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study. J Infect Dis. 1995;171:1166–71.CrossRefPubMedGoogle Scholar
  30. 30.
    Hall AM. Update on tenofovir toxicity in the kidney. Pediatr Nephrol. 2013;28:1011–23.CrossRefPubMedGoogle Scholar
  31. 31.
    Sax PE, Zolopa A, Brar I, Elion R, Ortiz R, Post F, et al. Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. J Acquir Immune Defic Syndr. 2014;67:52–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • S. Höring
    • 1
    Email author
  • B. Löffler
    • 1
  • M. W. Pletz
    • 2
  • S. Rößler
    • 2
    • 5
  • S. Weis
    • 2
    • 3
    • 4
  • B. T. Schleenvoigt
    • 2
  1. 1.Institute of Medical MicrobiologyJena University HospitalJenaGermany
  2. 2.Institute for Infectious Diseases and Infection ControlJena University HospitalJenaGermany
  3. 3.Center for Sepsis Control and Care (CSCC)Jena University HospitalJenaGermany
  4. 4.Department of Anesthesiology and Intensive CareJena University HospitalJenaGermany
  5. 5.Department of Internal Medicine IIKlinikum ChemnitzChemnitzGermany

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