DOLAMA study: Effectiveness, safety and pharmacoeconomic analysis of dual therapy with dolutegravir and lamivudine in virologically suppressed HIV-1 patients.
Adult
Anti-HIV Agents
/ administration & dosage
CD4 Lymphocyte Count
Cost-Benefit Analysis
Drug Therapy, Combination
Economics, Pharmaceutical
Fees, Pharmaceutical
/ statistics & numerical data
Female
HIV Infections
/ drug therapy
HIV-1
Heterocyclic Compounds, 3-Ring
/ administration & dosage
Humans
Lamivudine
/ administration & dosage
Male
Middle Aged
Oxazines
Piperazines
Pyridones
Retrospective Studies
Viral Load
Journal
Medicine
ISSN: 1536-5964
Titre abrégé: Medicine (Baltimore)
Pays: United States
ID NLM: 2985248R
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
entrez:
9
8
2019
pubmed:
9
8
2019
medline:
4
9
2019
Statut:
ppublish
Résumé
Dolutegravir (DTG) has shown effectiveness in combination with rilpivirine in with experience of antiretroviral therapy (ART) and with 3TC in naïve patients (GEMINI trial). The main objectives of this real-life study were to analyze the effectiveness and safety of 3TC plus DTG in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic analysis.We conducted an observational, retrospective and multicenter study of HIV+ patients pretreated for at least 6 months with ART that was then simplified to 3TC + DTG for any reason. We gathered data on viral loads (VLs) during exposure to the DT, calculating the rate with VL < 50 copies/mL at week 48, and on associated adverse effects.The 177 HIV+ patients were collected, 77.4% male, with average age of 48.5 years and mean count of 252.2cell/μL CD4+ nadir lymphocytes; 96.6% had VL < 50 copies/mL and 674 cells/μL CD4+ lymphocytes. Median time since HIV diagnosis was 15 years, and median ART duration was 13 years, and 34.5% of patients were on mono- or dual-therapy before the switch. At week 48, 82.4% of patients had VL < 50 cop/μL using an intention-to-treat (ITT) analysis, 89.6% according to mITT, and 96.7% according to Per-Protocol analysis. 3.3% patients had virological failure (VF). These effectiveness data and costs were compared with those for 2 reference triple therapies (DTG/ABC/3TC and EVG/cobi/FTC/TAF) in a cost minimization analysis, showing cost savings with administration of DTG+3TC (2741 &OV0556;/year vs DTG/ABC/3TC and 4164 &OV0556;/year vs EVG/cobi/FTC/TAF) and in a cost-effectiveness analysis, finding the DT to be the most cost-effective approach (ICER = -548 vs DTG/ABC/3TC and ICER = -4,627&OV0556; vs EVG/cobi/FTC/TAF)The combination of 3TC with DTG appears to be a safe and effective option for the simplification of ART in pretreated and virologically stable HIV-positive patients, being cost-effective and offering the same effectiveness as the triple therapy it replaces.
Identifiants
pubmed: 31393412
doi: 10.1097/MD.0000000000016813
pii: 00005792-201908090-00072
pmc: PMC6708975
doi:
Substances chimiques
Anti-HIV Agents
0
Heterocyclic Compounds, 3-Ring
0
Oxazines
0
Piperazines
0
Pyridones
0
Lamivudine
2T8Q726O95
dolutegravir
DKO1W9H7M1
Types de publication
Journal Article
Multicenter Study
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16813Références
Samji H, Cescon A, Hogg RS, et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS One 2013;8:e81355.
Documento de consenso de GESIDA/plan nacional sobre el SIDA respecto al tratamiento antirretroviral en adultos infectados por el virus de la inmunodeficiencia humana. gesida-seim.org. Update January 2019.
Pasquau J, Hidalgo-Tenorio C. Nuke-sparing regimens for the long-term care of HIV infection. AIDS Rev 2015;17:220–30.
Arribas JR, Girard PM, Landman R, 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.
Perez-Molina JA, 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 randomised, open-label, non-inferiority trial. Lancet Infect Dis 2015;15:775–84.
Di Giambenedetto S, Fabbiani M, Quiros Roldan E, 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.
Pulido F, Ribera E, Lagarde M, 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.
Cucchetto G, Lanzafame M, Nicole S, et al. Raltegravir plus lamivudine as ’maintenance therapy’ in suppressed HIV-1-infected patients in real-life settings. J Antimicrob Chemother 2017;2138-40.
Yendewa GA, Salata RA. Hot news: ready for HIV dual therapy? – New data from International HIV/AIDS Society 2017. AIDS Rev 2017;19:167–72.
Llibre JM, Hung CC, Brinson C, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet 2018;391:839–49.
Cahn P, Rolon MJ, Figueroa MI, et al. Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study. J Int AIDS Soc 2017;20:21678.
Cahn P, Sierra Madero J, Arribas J, et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet 2019;393:143–55.
Wertz RT. Intention to treat: once randomized, always analyzed. Clin Aphasiol 1995;23:57–64.
Abraha I, Montedori A. Modified intention to treat reporting in randomised controlled trials: systematic review. BMJ 2010;340:c2697.
Day S. Analysis Issues, ITT, Post-Hoc, and Subgroups. Johns Hopkins University. 2008 Available from: http://ocw.jhsph.edu/courses/Biostat- MedicalProductRegulation/biomed_lec7_day.pdf.
Trottier B, Lake JE, Logue K, et al. Dolutegravir/abacavir/lamivudine versus current ART in virally suppressed patients (STRIIVING): a 48-week, randomized, non-inferiority, open-label, phase IIIb study. Antivir Ther 2017;22:295–305.
Mills A, Arribas JR, Andrade-Villanueva J, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis 2016;16:43–52.
Joly V, Burdet C, Landman R, et al. Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: results of the ANRS 167 trial (LAMIDOL). J Antimicrob Chemother 2019;74:739–45.
Tau L, Ziv-Baran T, Cohen-Poradosu R, et al. Switch to dolutegravir in HIV patients responding to a first line antiretroviral treatment- 96 weeks of experience. In: 16th EACS Milan, Italy. 2017;26 Abstract: PE9/.
Maggiolo F, Gulminetti R, Pagnucco L, et al. Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients. BMC Infect Dis 2017;17:215.
Reynes J, Meftah N, Montes B. Dual regimen with dolutegravir and lamivudine maintains virologic suppression even in heavily treatment-experienced HIV-infected patients: 48-week results from a pilot study (DOLULAM). In: Abstracts of the International Congress of Drug Therapy in HIV Infection, Glasgow, UK. 2016;Abstract 080.
Taiwo BO, Zheng L, Stefanescu A, et al. ACTG A5353: a pilot study of dolutegravir plus lamivudine for initial treatment of human immunodeficiency virus-1 (HIV-1)-infected participants with HIV-1 RNA <500000 Copies/Ml. Clin Infect Dis 2018;66:1689–97.
Borghetti A, Lombardi F, Gagliardini R, et al. Efficacy and tolerability of lamivudine plus dolutegravir compared with lamivudine plus boosted PIs in HIV-1 positive individuals with virologic suppression: a retrospective study from the clinical practice. BMC Infect Dis 2019;19:59.
Baldin G, Ciccullo A, Borghetti A, et al. Virological efficacy of dual therapy with lamivudine and dolutegravir in HIV-1-infected virologically suppressed patients: long-term data from clinical practice. J Antimicrob Chemother 2019;74:1461–3.
Blanco JL, Rojas J, Paredes R, et al. Dolutegravir-based maintenance monotherapy versus dual therapy with lamivudine: a planned 24 week analysis of the DOLAM randomized clinical trial. J Antimicrob Chemother 2018;73:1965–71.
Taiwo BO, Marconi VC, Berzins B, et al. Dolutegravir plus lamivudine maintains human immunodeficiency virus-1 suppression through week 48 in a pilot randomized trial. Clin Infect Dis 2018;66:1794–7.
Jenks JD, Hoenigl MJ. CD4:CD8 ratio and CD8+ cell count for prognosticating mortality in HIV-infected patients on antiretroviral therapy. Lab Precis Med 2018;3: pii:8.
pii: 8
Osterholzer DA, Goldman M. Dolutegravir: a next-generation integrase inhibitor for treatment of HIV infection. Clin Infect Dis 2014;59:265–71.
Elzi L, Erb S, Furrer H, et al. Adverse events of raltegravir and dolutegravir. AIDS 2017;31:1853–8.
Girouard MP, Sax PE, Parker RA, et al. The cost-effectiveness and budget impact of 2-drug dolutegravir-lamivudine regimens for the treatment of HIV infection in the United States. Clin Infect Dis 2016;62:784–91.
Perez-Molina JA, Martinez E, Blasco AJ, et al. Analysis of the costs and cost-effectiveness of the guidelines recommended by the 2018 GESIDA/Spanish National AIDS Plan for initial antiretroviral therapy in HIV-infected adults. Enferm Infecc Microbiol Clin 2018;37:151–9. pii: S0213-005X (18) 30185-X.
pii: s0213-005x