Real Life Study of Dolutegravir Plus Lamivudine in HIV-1-Infected Treatment-Naive Patients

NCT04002323 | Completed FDA Drug

• 1 other identifier: DOLAVI
• Study Type: observational
• Target: 88
• Locations: 1 country
• Sites: 24

Brief Summary

Thanks to the actual highly active antiretroviral therapy (HAART) patients living with HIV have a better life expectancy, becoming chronical patients. Today's antiretroviral treatment (ART) must be maintained for life to prevent disease progression until a cure is reached. Given this need, ARTs are becoming safer and more effective but are still toxic. Cause of that simplification therapies are real, reducing the number of different Antiretrovirals involved controlling the infection. This strategies include from monotherapy using/with protease inhibitors (PI), which was investigated with treatment-experienced patients and virologically suppressed, to dual therapies which recently were investigated in treatment-naïve and treatment-experienced patients with combinations such as dolutegravir (DTG) plus lamivudine (3TC), Dolutegravir plus rilpivirine or rilpivirine plus darunavir/ritonavir boosted. Nowadays dual therapy in real life (not into the context of a clinical trial) with dolutegravir plus lamivudine is largely studied in treatment-experienced patients who are virologically suppressed and got nearly a 100% efficacy results. Recently published results from clinical trials in treatment-naïve patients GEMINI 1 \&2, where efficacy of the dual therapy with DTG 50mg plus 3TC 300mg/QD was compared versus the efficacy of triple therapy with tenofovir disoproxil fumarate, emtricitabine and dolutegravir (TDF/FTC+ DTG) (QD). Both trials show similar efficacy results, with virologic suppression higher than 90% at week 48. Clinical trials are the gold standard to approve and add to the clinical practice new drugs and new therapies, but is also known that have some inconvenient like strict inclusion-exclusion criteria which put the study population far from being a real sample. Studies with real world data (RWD) have several strengths such as quality in medical attention and works like a bridge between clinical trials and standard clinical care, reducing/lowering general costs, improving results and accelerating the generation of knowledge. For all the reasons above, the primary objective of this study is to analyze in treatment-naïve HIV patients the effectiveness in real life of 3TC (300 mg p.o. q 24 h) plus DTG (50 mg p.o. q 24 h). Secondary objectives are: to describe the patient who receive this dual therapy, to quantify the time gap between the clinic visit and the first dose of dual therapy administrated evaluating this dual therapy as candidate to "test and treat" therapies; to analyze the viral load drop and the increase of cluster of differentiation 4 (CD4) T lymphocytes levels; To analyze virological failures and previous mutations influence in basal resistance tests; and finally a pharmacoeconomic analysis, safety of the treatment and adherence to the healthcare system.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects with plasma HIV 1 RNA <50 copies/milliliter at week 48

  The proportion of subjects with viral suppression (HIV-1 RNA \<50 copies/mL) among subjects who received at least one dose of study medication

  48 weeks

Secondary Outcomes (3)

• Changes from baseline in lymphocytes cell counts at week 24 and 48

  Baseline, 24 weeks and 48 weeks

• Number of Participants With Any Adverse Event (AE)

  48 weeks

• Number of Participants Who Discontinue Treatment

  48 weeks

Study Arms (1)

HIV-1 ART-Naive

Lamivudine (300 mg p.o. q 24 h) plus Dolutegravir (50 mg p.o. q 24 h)

Drug: Dolutegravir 50mg Tab; Drug: Lamivudine 300 mg

Interventions

Dolutegravir 50mg Tab DRUG

The subjects starts their ART with this drugs, once a day

HIV-1 ART-Naive

Lamivudine 300 mg DRUG

The subjects starts their ART with this drugs, once a day

HIV-1 ART-Naive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study will be conducted in approximately 139 HIV-1 infected, ART-naive adults who began their ART with DTG 50mg plus 3TC 300mg , without limits of viral load or CD4 lymphocytes recount at screening. The following population will be assessed: Intent-to-treat (ITT) Population: This population will consist of all randomized subjects who receive at least one dose of study medication. Intent-to-treat modified (ITT-m) Population: this population will consist of subjects in the ITT Population with the exception of mild protocol violators, those who discontinue for reasons other than those related to treatment (such as adverse events, tolerability or lack of efficacy). Per protocol (PP) Population: This population will consist of subjects in the ITT Population with exception of major protocol violators, such as violations which could affect the assessment of antiviral activity.

You may qualify if:

• HIV-1 infected adults (\<17 y.o.)
• Antiretroviral-naïve.
• Be able to comply with protocol requirements and instructions.
• Subject or the subject's representative capable of giving signed informed consent.

You may not qualify if:

• Women who are breastfeeding or plan to become pregnant during the study.
• Patients who in the investigator's judgment, poses a significant drop out risk or life expectancy inferior to study ending.
• Patients with anticipated need to change the ART before study ending.

Sponsors & Collaborators

• University Hospital Virgen de las Nieves: lead

Study Sites (24)

Hospital Marina Baixa

Villajoyosa, Alicante, 03570, Spain

Location

Hospital Universitario Virgen de Las Nieves

Granada, Andalusia, 18008, Spain

Location

Hospital San Pedro

Logroño, La Rioja, 26006, Spain

Location

Hospital Clínico Universitario "Virgen de la Arrixaca"

El Palmar, Murcia, 30120, Spain

Location

Hospital Reina Sofía

Murcia, Murcia, 30003, Spain

Location

Hospital Universitario Torrecárdenas

Almería, Spain

Location

Hospital de Jerez

Cadiz, Spain

Location

Hospital Universitario Puerto Real

Cadiz, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Spain

Location

Hospital Campus de la Salud

Granada, 18014, Spain

Location

Hospital Comarcal Santa Ana de Motril

Granada, Spain

Location

Hospital de Jaen

Jaén, Spain

Location

Hospital Universitario de Gran Canaria Doctor Negrín

Las Palmas de Gran Canaria, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Costa del Sol

Málaga, Spain

Location

Hospital Comarcal de Melilla

Melilla, Spain

Location

Hospital Universitario de melilla

Melilla, Spain

Location

Hospital General Universitario Santa Lucía

Murcia, Spain

Location

Hospital de Son Llàtzer

Palma de Mallorca, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Hospital Universitario y Politécnico de La Fe

Valencia, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Location

Related Publications (13)

• Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013 Nov 2;382(9903):1525-33. doi: 10.1016/S0140-6736(13)61809-7. Epub 2013 Oct 23.

  PMID: 24152939 BACKGROUND

• Zicari S, Sessa L, Cotugno N, Ruggiero A, Morrocchi E, Concato C, Rocca S, Zangari P, Manno EC, Palma P. Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART. Viruses. 2019 Feb 27;11(3):200. doi: 10.3390/v11030200.

  PMID: 30818749 BACKGROUND

• Pasquau J, Hidalgo-Tenorio C. Nuke-Sparing Regimens for the Long-Term Care of HIV Infection. AIDS Rev. 2015 Oct-Dec;17(4):220-30.

  PMID: 26679853 BACKGROUND

• Pasquau J, Hidalgo-Tenorio C, Montes ML, Romero-Palacios A, Vergas J, Sanjoaquin I, Hernandez-Quero J, Aguirrebengoa K, Orihuela F, Imaz A, Rios-Villegas MJ, Flores J, Farinas MC, Vazquez P, Galindo MJ, Garcia-Merce I, Lozano F, de Los Santos I, de Jesus SE, Garcia-Vallecillos C; QoLKAMON STUDY GROUP. High quality of life, treatment tolerability, safety and efficacy in HIV patients switching from triple therapy to lopinavir/ritonavir monotherapy: A randomized clinical trial. PLoS One. 2018 Apr 12;13(4):e0195068. doi: 10.1371/journal.pone.0195068. eCollection 2018.

  PMID: 29649309 BACKGROUND

• Taiwo BO, Zheng L, Stefanescu A, Nyaku A, Bezins B, Wallis CL, Godfrey C, Sax PE, Acosta E, Haas D, Smith KY, Sha B, Van Dam C, Gulick RM. 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 May 17;66(11):1689-1697. doi: 10.1093/cid/cix1083.

  PMID: 29253097 BACKGROUND

• Cahn P, Rolon MJ, Figueroa MI, Gun A, Patterson P, Sued O. 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 May 9;20(1):21678. doi: 10.7448/IAS.20.01.21678.

  PMID: 28537061 BACKGROUND

• Palacios R, Mayorga M, Gonzalez-Domenech CM, Hidalgo-Tenorio C, Galvez C, Munoz-Medina L, de la Torre J, Lozano A, Castano M, Omar M, Santos J. Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study. J Int Assoc Provid AIDS Care. 2018 Jan-Dec;17:2325958218760847. doi: 10.1177/2325958218760847.

  PMID: 29529910 BACKGROUND

• Pasquau J, de Jesus SE, Arazo P, Crusells MJ, Rios MJ, Lozano F, de la Torre J, Galindo MJ, Carmena J, Santos J, Tornero C, Verdejo G, Samperiz G, Palacios Z, Hidalgo-Tenorio C; RIDAR Study Group. Effectiveness and safety of dual therapy with rilpivirine and boosted darunavir in treatment-experienced patients with advanced HIV infection: a preliminary 24 week analysis (RIDAR study). BMC Infect Dis. 2019 Feb 28;19(1):207. doi: 10.1186/s12879-019-3817-6.

  PMID: 30819101 BACKGROUND

• Borghetti A, Lombardi F, Gagliardini R, Baldin G, Ciccullo A, Moschese D, Emiliozzi A, Belmonti S, Lamonica S, Montagnani F, Visconti E, De Luca A, Di Giambenedetto S. 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 Jan 17;19(1):59. doi: 10.1186/s12879-018-3666-8.

  PMID: 30654739 BACKGROUND

• Baldin G, Ciccullo A, Borghetti A, Di Giambenedetto S. 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 May 1;74(5):1461-1463. doi: 10.1093/jac/dkz009. No abstract available.

  PMID: 30726922 BACKGROUND

• Cahn P, Madero JS, Arribas JR, Antinori A, Ortiz R, Clarke AE, Hung CC, Rockstroh JK, Girard PM, Sievers J, Man C, Currie A, Underwood M, Tenorio AR, Pappa K, Wynne B, Fettiplace A, Gartland M, Aboud M, Smith K; GEMINI Study Team. 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 Jan 12;393(10167):143-155. doi: 10.1016/S0140-6736(18)32462-0. Epub 2018 Nov 9.

  PMID: 30420123 BACKGROUND

• Berger ML, Sox H, Willke RJ, Brixner DL, Eichler HG, Goettsch W, Madigan D, Makady A, Schneeweiss S, Tarricone R, Wang SV, Watkins J, Daniel Mullins C. Good practices for real-world data studies of treatment and/or comparative effectiveness: Recommendations from the joint ISPOR-ISPE Special Task Force on real-world evidence in health care decision making. Pharmacoepidemiol Drug Saf. 2017 Sep;26(9):1033-1039. doi: 10.1002/pds.4297.

  PMID: 28913966 BACKGROUND

• Hidalgo-Tenorio C, Pasquau J, Vinuesa D, Ferra S, Terron A, SanJoaquin I, Payeras A, Martinez OJ, Lopez-Ruz MA, Omar M, de la Torre-Lima J, Lopez-Lirola A, Palomares J, Blanco JR, Montero M, Garcia-Vallecillos C. DOLAVI Real-Life Study of Dolutegravir Plus Lamivudine in Naive HIV-1 Patients (48 Weeks). Viruses. 2022 Mar 4;14(3):524. doi: 10.3390/v14030524.

  PMID: 35336931 RESULT

MeSH Terms

Interventions

dolutegravir; Lamivudine

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Target Duration: 48 Weeks
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: SPECIALIST PHYSICIAN

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: June 28, 2019
• Study Start: May 7, 2019
• Primary Completion: February 28, 2021
• Study Completion: March 31, 2022
• Last Updated: July 10, 2024

Record last verified: 2024-07

Locations

ES (24)