The online version of this article (doi:10.1186/s12879-017-2311-2) contains supplementary material, which is available to authorized users.
Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients.
In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA <50 copies/ml for 6 months or longer, negative for HBsAg and on a stable (>6 months) cART.
Ninety-four individuals were included. They were mostly men (77.7%) with a mean age of 53 years. They presented 159 co-morbidities including cardiovascular, bone, hepatic, kidney, and CNS diseases. Because of these pathologies, they took 207 non-ARV drugs (mean 2.2 per patient). Median duration of viral suppression was 77.5 months (IQR 61). All subjects were prospectively followed up to week 24 and all remained on dual therapy during the whole period. Neither virological failure, nor viral blip was detected.
The median CD4 count rose from 658 cells/mcl (IQR 403) to 724 cells/mcl (IQR 401) (P = 0.006) without a significant (P = 0.44) change in the CD4/CD8 ratio. A significant (P < 0.0001) increment of median creatinine from 0.87 mg/dl (IQR 0.34) to 0.95 mg/dl (IQR 0.29) was observed in the first 2 months but thereafter leveled on these values (1.00 mg/dl; IQR 0.35) (P = 0.111 compared to 2 months). The lipid profile slightly improved. The daily cost of cART was significantly (P < 0.0001) reduced of 6.89 euros (SD 6.10).
Switching to a dual cART regimen based on lamivudine + dolutegravir maintains virological efficacy up to week 24, and is associated to slight improvements of the immunologic and metabolic status. The strategy allows to freely using concomitant medications for associated pathologies. The dual therapy is less expensive in economic terms.
Although still limited evidence exists, a dolutegravir-based dual therapy in combination with lamivudine shows promising results to be confirmed in larger controlled trials.
Additional file 1: DTG-3TC Anonymous db for paperR1. (XLSX 82.1 kb)12879_2017_2311_MOESM1_ESM.xlsx
Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2015 Available: http://www.aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed 22 Sept 2016.
European AIDS Clinical Society (2014) Guidelines: Clinical management of treatment of HIV infected adults in Europe. 2014 version 7.1. Available: http://www.eacsociety.org/files/guidelines_english_71_141204.pdf. Accessed 22 Sept 2016.
Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, Dabis F, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. 2008;371:1417–26. doi: 10.1016/S0140-6736(08)60423-7. CrossRefPubMed
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 trial to assess efficacy and safety profile: the KITE study. AIDS Res Hum Retroviruses. 2012;28:1196–206. CrossRefPubMedPubMedCentral
Nishijima T, Gatanaga H, Shimbo T, et al. Switching tenofovir/emtricitabine plus lopinavir/r to raltegravir plus darunavir/r in patients with suppressed viral load did not result in improvement of renal function but could sustain viral suppression: a randomized multicenter trial. PLoS One. 2013;8:e73639. CrossRefPubMedPubMedCentral
Arribas JR, Girard P-M, Landman R. 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. Available at: http://dx.doi.org/ 10.1016/S1473-3099(15)70129-5. Accessed 1 Oct 2016
Di Giambenedetto S, Fabbiani M, Colafigli M, et al. Safety and feasibility of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients on stable treatment with two nucleos(t)ide reverse transcriptase inhibitors + atazanavir/ritonavir with virological suppression (Atazanavir and Lamivudine for Treatment Simplification, ATLAS pilot study). J Antimicrob Chemother. 2013;68:1364–72. CrossRefPubMed
Perez-Molina J, Rubio R, Rivero A, 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 randomized, open label, non inferiority trial. Lancet Infect Dis. 2015;15:775–84. CrossRefPubMed
Maggiolo F, Di Filippo E, Valenti D, Ortega PS, Callegaro A. NRTI sparing therapy in virologically controlled HIV-1 infected subjects: results of a controlled randomized trial (Probe). JAIDS. 2016;72:46–51. PubMed
Linee Guida Italiane sull’utilizzo dei farmaci antiretrovirali e sulla gestione diagnostico-clinica delle persone con infezione da HIV-1. 22 novembre 2016. Available at http://www.salute.gov.it/imgs/C_17_pubblicazioni_2545_allegato.pdf. Accessed Jan 2017.
Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidemia, and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998;12:FS1–8. CrossRef
Mulligan K, Grunfeld C, Tai VW, et al. Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV-1 infection. JAIDS. 2000;23:35–43. PubMed
Cohen C, Green J, Olivet H, et al. A randomized pilot study of tenofovir/emtricitabine (TDF/FTC) + boosted atazanavir (ATV/r) vs. raltegravir (RALBID) + ATV/r vs. RAL BID + ATV BID. J Int AIDS Soc. 2012;15 suppl 4:18279.
Negredo E, Molto J, Burger D, et al. Lopinavir/ritonavir plus nevirapine as a nucleoside-sparing approach in antiretroviral-experienced patients (NEKA study). JAIDS. 2005;38:47–52. PubMed
Lennox JL, Landovitz RJ, Ribaudo HJ, et al. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014;161:461–71. CrossRefPubMedPubMedCentral
Rockstroh JK, DeJesus E, Lennox JL, et al. Durable efficacy and safety of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: final 5-year results from STARTMRK. JAIDS. 2013;63:77–85. PubMed
Oldenbuettel C, Wolf E, Ritter A, et al. Dolutegravir monotherapy as treatment de-escalation in HIV-infected adults with virological control: DoluMono cohort results. Antiviral therapy 2016; doi: 10.3851/IMP3082
Reynes J, Meftah N, Montes B. Dual therapy with dolutegravir and lamivudine maintains virologic suppression in HIV-infected HAART-treated patients: DOLULAM pilot study. Fifteenth European AIDS Conference, Barcelona, 2015. Abstract PE8/81.
Borghetti A, Baldin G, Ciccullo A, et al. Virological control and metabolic improvement in HIV-infected, virologically suppressed patients switching to lamivudine/dolutegravir dual therapy. J Antimicrob Chemother 2016; doi: 10.1093/jac/dkw147
Figueroa MI, Sued O, Patterson P et al. Dolutegravir-lamivudine as initial therapy in HIV-infected, ARV naive patients: first results of the PADDLE trial. Fifteenth European AIDS Conference, Barcelona, 2015. Abstract LBPS4/1.
Sued OG, Figueroa MI, Rolon MJ, et al. Comparable Viral Decay in Dual and Triple Dolutegravir-Based Antiretroviral Therapy. Conference on Retroviruses and Opportunistic Infections, Boston 2016. Abstract 947.
De Boer M, Van den Berk G, Van Holten N, Oryszczyn J, Dorama W, Moha DA, et al. Intolerance of dolutegravir containing cART regimens in real life clinical practice. AIDS 2016; doi: 10.1097/QAD.0000000000001279
Shah BM, Schafer JJ, DeSimone, JA Jr. Dolutegravir: A New Integrase Strand Transfer Inhibitor for the Treatment of HIV. Pharmacotherapy 2013; doi: 10.1002/phar.1386
Post FA, Tebas P, Clarke A, et al. Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Adults With Renal Impairment: 96-Week Results From a Single Arm, Multicenter, Open-Label Phase 3 Study. JAIDS 2016; doi: 10.1097/QAI.0000000000001186
- Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients
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