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

HIV-1-infection Clinical Trial

— DOLAVI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04002323
• Other study ID #: DOLAVI
• Status: Recruiting
• Start date: May 7, 2019
• Est. completion date: March 31, 2021

Study information

• Verified date: July 2019
• Source: University Hospital Virgen de las Nieves
• Contact: CARMEN HIDALGO, Dr
• Phone: +34 958 895 414
• Email: CHIDALGO72[@]GMAIL.COM
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 139
• Est. completion date: March 31, 2021
• Est. primary completion date: February 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. HIV-1 infected adults (<17 y.o.)

2. Antiretroviral-naïve.

3. Be able to comply with protocol requirements and instructions.

4. Subject or the subject's representative capable of giving signed informed consent.

Exclusion Criteria:

1. Women who are breastfeeding or plan to become pregnant during the study.

2. Patients who in the investigator's judgment, poses a significant drop out risk or life expectancy inferior to study ending.

3. Patients with anticipated need to change the ART before study ending.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• Dolutegravir 50mg Tab
The subjects starts their ART with this drugs, once a day
• Lamivudine 300 mg
The subjects starts their ART with this drugs, once a day

Locations

Country	Name	City	State
Spain	Hospital Universitario Virgen de Las Nieves	Granada	Andalucía

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Virgen de las Nieves

Country where clinical trial is conducted

Spain, 

References & Publications (12)

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 Feb 5. doi: 10.1093/jac/dkz009. [Epub ahead of print] — View Citation

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. — View Citation

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. — View Citation

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. Erratum in: Lancet. 2018 Nov 28;:. — View Citation

Cahn P, Rolón 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. — View Citation

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. Review. — View Citation

Palacios R, Mayorga M, González-Domenech CM, Hidalgo-Tenorio C, Gálvez C, Muñoz-Medina L, de la Torre J, Lozano A, Castaño 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. — View Citation

Pasquau J, de Jesus SE, Arazo P, Crusells MJ, Ríos 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. — View Citation

Pasquau J, Hidalgo-Tenorio C, Montes ML, Romero-Palacios A, Vergas J, Sanjoaquín I, Hernández-Quero J, Aguirrebengoa K, Orihuela F, Imaz A, Ríos-Villegas MJ, Flores J, Fariñas MC, Vázquez P, Galindo MJ, García-Mercé I, Lozano F, de Los Santos I, de Jesus SE, García-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. — View Citation

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. Review. — View Citation

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. — View Citation

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). pii: E200. doi: 10.3390/v11030200. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Changes from baseline in lymphocytes cell counts at week 24 and 48		Baseline, 24 weeks and 48 weeks
Secondary	Number of Participants With Any Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical investigation participant	48 weeks
Secondary	Number of Participants Who Discontinue Treatment		48 weeks