Skip to main content

Advertisement

SpringerLink
Log in

Nucleoside-Sparing Antiretroviral Regimens

  • HIV/AIDS (R MacArthur, Section Editor)
  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs approved for use as antiretroviral therapy in patients infected with HIV. Despite the introduction of other classes of antiretroviral drugs, they remain an important component of combination regimens as recommended by many treatment guidelines. They also continue to be used in prevention of disease from mother to child, postexposure prophylaxis, and more recently for preexposure prophylaxis. Unfortunately, the toxicities associated with this class of drugs can limit their use. Although NRTI-sparing regimens are not currently recommended for first-line therapy there is an increasing amount of data supporting their use in both treatment-naive and in treatment-experienced patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as follows: • Of importance •• Of major importance

  1. AIDSinfo. Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Washington, DC: Department of Health and Human Services. 2013. Available from: http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.

  2. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013. Geneva: World Health Organization. Available from: http://www.who.int/hiv/pub/guidelines/.

  3. Williams I, Churchill D, Anderson J, et al. British HIV Association guidelines for the treatment of HIV-1 positive adults with antiretroviral therapy 2012. HIV Med. 2012;13 Suppl 2:1–85.

    Google Scholar 

  4. Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society – USA Panel. JAMA. 2012;308(4):387–402.

    Article  CAS  PubMed  Google Scholar 

  5. Tressler R, Godfrey C. NRTI backbone in HIV treatment: will it remain relevant? Drugs. 2012;72(16):2051–62.

    Article  CAS  PubMed  Google Scholar 

  6. Cote HC, Brumme ZL, Craib KJ, et al. Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients. New Engl J Med. 2002;346(11):811–20.

    Article  CAS  PubMed  Google Scholar 

  7. Cossarizza A, Moyle G. Antiretroviral nucleoside and nucleotide analogues and mitochondria. AIDS. 2004;18(2):137–51.

    Article  CAS  PubMed  Google Scholar 

  8. Lonergan JT, Behling C, Pfander H, et al. Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus-infected patients receiving nucleoside analogue combination regimens. Clin Infect Dis. 2000;31(1):162–6.

    Article  CAS  PubMed  Google Scholar 

  9. Bonnet F, Bonarek M, Morlat P, et al. Risk factors for lactic acidosis in HIV-infected patients treated for nucleoside reverse-transcriptase inhibitors: a case control study. Clin Infect Dis. 2003;36(10):1324–8.

    Article  CAS  PubMed  Google Scholar 

  10. Boubaker K, Sudre P, Flepp M, et al. Hyperlactemia and antiretroviral therapy: the Swiss HIV cohort study. Clin Infect Dis. 2001;33(11):1931–7.

    Article  CAS  PubMed  Google Scholar 

  11. Ter Hofstede H, De Marie S, Foudraine N, Danner S, Brinkman KI. Clinical features and risk factors of lactic acidosis following long-term antiretroviral therapy: 4 fatal cases. Int J STD AIDS. 2000;11(9):611–6.

    Article  PubMed  Google Scholar 

  12. Riddler SA, Haubrich R, DiRenzo G, et al. Class sparing regimens for initial treatment of HIV-1 infection. N Engl J Med. 2008;358(20):2095–106.

    Article  CAS  PubMed  Google Scholar 

  13. Duvivier C, Ghosn J, Assoumou L, et al. Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippopcampe-ANRS 121 Trial. J Antimicrob Chemother. 2008;62(4):797–808.

    Article  CAS  PubMed  Google Scholar 

  14. Reynes J, Lawal A, Pulido, et al. Examination of noninferiority, safety, and tolerability of lopinavir/ritonavir and raltegravir compared with lopinavir/ritonavir and tenofovir/emtricitabine in antiretroviral naïve subjects: the PROGRESS study, 48 week results. HIV Clin Trials. 2011;12(5):255–67. This study demonstrated that the efficacy rates with a protease inhibitor plus an integrase inhibitor are comparable to those with a protease inhibitor plus an NRTI in treatment-naive patients.

    Article  CAS  PubMed  Google Scholar 

  15. Taiwo B, Gallien S, Matining R, et al. Efficacy of a nucleoside sparing regimen of darunavir/ritonavir plus raltegravir in treatment naïve HIV-1 infected patients (ACTG A5262). AIDS. 2011;25(17):2113–22. This study demonstrated that a protease inhibitor plus an integrase inhibitor regimen may be associated with higher rates of virological failure and integrase resistance in treatment-naive patients with baseline HIV-1 viral loads >100,000 copies/mL.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Markowitz M, Nguyen BY, Gotuzzo E, et al. Rapid and durable antiretroviral effects of the HIV-1 integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with hIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007;46:125–33.

    Article  CAS  PubMed  Google Scholar 

  17. Gulick RM, Ribaudo HJ, Shikuma CM, et al. Three vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial. JAMA. 2006;296:769–81.

    Article  CAS  PubMed  Google Scholar 

  18. Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naïve HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008;372:646–55.

    Article  CAS  PubMed  Google Scholar 

  19. Johnson M, Grinsztejn B, Rodriguez C, et al. Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS. 2005;19:685–94.

    Article  CAS  PubMed  Google Scholar 

  20. Kozal MJ, Lupo S, DeJesus E, et al. A nucleoside and ritonavir sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment naïve HIV infected patients: SPARTAN study results. HIV Clin Trials. 2012;13(3):119–30.

    Article  CAS  PubMed  Google Scholar 

  21. Taiwo B, Acosta EP, Ryscavage P, et al. Virologic response, early HIV-1 decay, and maraviroc pharmacokinetics with the nucleos(t)ide-free regimen of maraviroc plus darunavir/ritonavir in a pilot study. J Acquir Immune Defic Syndr. 2013;64(2):167–73.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Mills A, Mildvan D, Podzamczer D, et al. Maraviroc once daily nucleoside analog sparing regimen in treatment naïve patients: randomized open label pilot study. J Acquir Immune Defic. 2013;62(2):164–70.

    Article  CAS  Google Scholar 

  23. Bedimo R, Drechlser H, Turner, et al. RADAR study: raltegravir combined with boosted darunavir has similar safety and antiviral efficacy as tenofovir/emtricitabine combined with boosted darunavir in antiretroviral-naive patients. Abstract MOPE214. Presented at 6th IAS Conference 2011. Rome, Italy.

  24. ClinicalTrials.gov. Study of darunavir/r + tenofovir/emtricitabine vs. darunavir/r + raltegravir in HIV-infected antiretroviral naïve subjects. NCT01066962. www.clinicaltrials.gov. Accessed 26 Apr 2014.

  25. Calmy A, Petoumenos K, Lewden C, et al. Combination antiretroviral therapy without a nucleoside reverse transcriptase inhibitor: experience from 335 patients in three cohorts. HIV Med. 2007;8(3):171–80.

    Article  CAS  PubMed  Google Scholar 

  26. Negredo E, Moltó J, Burger D, Côté H, et al. Lopinavir/ritonavir plus nevirapine as a nucleoside-sparing approach in antiretroviral-experienced patients (NEKA study). J Acquir Immune Defic Syndr. 2005;38(1):47–52.

    Article  CAS  PubMed  Google Scholar 

  27. Allavena V, Ferré V, Brunet-Françoise C, et al. Efficacy and tolerability of a nucleoside reverse transcriptase inhibitor-sparing combination of lopinavir/ritonavir and efavirence in HIV-1-infected patients. J Acquir Immune Defic Syndr. 2005;39(3):300–6.

    Article  CAS  PubMed  Google Scholar 

  28. Valantin MA, Lanoy E, Bentata M, et al. Recovery of fat following a switch to nucleoside reverse transcriptase inhibitor-sparing therapy in patients with lipoatrophy: results from the 96-week ANRS 108 NoNuke trial. HIV Med. 2008;9(8):625–35.

    Article  CAS  PubMed  Google Scholar 

  29. Nozza S, Galli L, Visco F, et al. Raltegravir, maraviroc, etravirine: an effective protease inhibitor and nucleoside reverse transcriptase inhibitor-sparing regimen for salvage therapy in HIV-infected patients with triple-class experience. AIDS. 2010;24(6):924–8.

    Article  CAS  PubMed  Google Scholar 

  30. Katlama C, Valantin MA, Algarte-Genin M, et al. Efficacy of arunavir/ritonavir maintenance monotherapy in patients with HIV-1 suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136. AIDS. 2010;24(15):2365–74.

    CAS  PubMed  Google Scholar 

  31. Arribas JR, Horban A, Gerstoft J, et al. The MONET trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/mL. AIDS. 2010;24(2):223–30.

    Article  CAS  PubMed  Google Scholar 

  32. Clumeck N, Rieger A. Banhegyi, et al. 96 week results from the MONET trial: a randomized comparison of darunavir/ritonavir with versus without nucleoside analogues, for patients with HIV RNA <50 copies/mL at baseline. J Antimicrob Chemother. 2011;66(8):1878–85.

    Article  CAS  PubMed  Google Scholar 

  33. Arribas JR, Clumeck N, Nelson M, et al. The MONET trial: week 144 analysis of the efficacy of darunavir/ritonavir (DRV/r) monotherapy versus DRV/r plus two nucleoside reverse transcriptase inhibitors, for patients with viral load <50 HIV-1 RNA copies/mL at baseline. HIV Med. 2012;13(7):398–405.

    Article  CAS  PubMed  Google Scholar 

  34. Ofotokun I, Sheth AN, Sanford SE, et al. A switch in therapy to a reverse transcriptase inhibitor sparing combination of lopinavir-ritonavir and raltegravir in virologically suppressed HIV-infected patients: a pilot randomized to assess efficacy and safety profile: the KITE study. AIDS Res Hum Retroviruses. 2012;28(10):1196–206.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Tashima K, Smeaton L, Andrage A, et al. Omitting NRTI from ARV regimens is not inferior to adding NRTI in treatment-experienced HIV+ subjects failing a protease inhibitor regimen: the ACTG OPTIONS Study. Proceedings of the 20th Conference on Retroviruses and Opportunistic Infections. Atlanta, GA, USA, 3–6 March 2013. This study showed that if more than two active drugs are part of a new ART regimen in patients with viral resistance and/or three-drug class experience, virologic efficacy is not compromised by omitting an NRTI.

Download references

Compliance with Ethics Guidelines

Conflict of Interest

John Baxter has served as a consultant for Quest Diagnostics and Siemens Healthcare Diagnostics. Pola de la Torre declares no conflicts of interest. Jomy George received payment for development of educational presentations from Mid-Atlantic Chapter American College of Clinical Pharmacy.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the authors.

Author information

Authors and Affiliations

  1. Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ, USA

    Pola de la Torre & John D. Baxter

  2. Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA

    Jomy George

  3. Cooper Medical School of Rowan University, 401 Haddon Avenue, Camden, NJ, 08103, USA

    Pola de la Torre

Authors
  1. Pola de la Torre
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jomy George
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John D. Baxter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pola de la Torre.

Additional information

This article is part of the Topical Collection on HIV/AIDS

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de la Torre, P., George, J. & Baxter, J.D. Nucleoside-Sparing Antiretroviral Regimens. Curr Infect Dis Rep 16, 410 (2014). https://doi.org/10.1007/s11908-014-0410-4

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11908-014-0410-4

Keywords

Search

Navigation