Lamivudine/Dolutegravir in Virologically Suppressed Subjects With Expected or Confirmed Resistance to Lamivudine

NCT04880785 | Completed Phase 2

• 1 other identifier: GESIDA11820
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 17

Brief Summary

Dolutegravir (DTG) plus lamivudine (3TC) is a dual regimen combination recommended for both naïve and suppressed persons with HIV-1 infection1. However, data regarding the efficacy of this regimen in suppressed persons with history of past resistance or virologic failures is currently insufficient. This is a phase IIa, open-label, single arm, multicentric study. The hypothesis is that therapy with DTG/3TC would be able to maintain viral control in HIV infected participants with prior history of 3TC resistance but without evidence of M184V/I resistance mutation in proviral DNA population sequencing at baseline. The investigators also hypothesize that archived minority 3TC resistance associated mutations detected by next-generation (NGS) sequencing prior to the switch would not have a significant impact on the efficacy of DTG/3TC.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• The efficacy of a switch to DTG/3TC for maintenance of virologic suppression, in persons with past confirmed or suspected 3TC resistance, when proviral DNA population sequencing does not detect 3TC resistance-associated mutations at baseline.

  Proportion of virologic failure (VF) defined as HIV-1 RNA viral load (VL) ≥ 50 copies per mL (in the intention-to-treatexposed population (ITT-e) using the US Food and Drug Administration (FDA) snapshot algorithm).

  Week 48

Secondary Outcomes (15)

• Estimations of virological control

  Week 48 and week 96

• Viral resistance in persons experiencing VF.

  Throughout all the study, an average of 96 weeks

• Time to VF

  Throughout all the study, an average of 96 weeks

• Proportion of VF in subgroups: Confirmed historical M184V/I vs No resistance mutations

  Throughout all the study, an average of 96 weeks

• Proportion of VF in subgroups: INSTI exposure vs No prior INSTI exposure

  Throughout all the study, an average of 96 weeks

Study Arms (1)

Dovato (Dolutegravir+lamivudine)

EXPERIMENTAL

Treatment: Dolutegravir 50 mg/Lamivudine 300 mg, one film coated-tablet once daily during 96 weeks

Drug: Dolutegravir 50 MG / Lamivudine 300 MG Oral Tablet [Dovato]

Interventions

Dolutegravir 50 MG / Lamivudine 300 MG Oral Tablet [Dovato] DRUG

change of current antiretroviral treatment to DTG 50 mg/3TC 300 mg QD

Dovato (Dolutegravir+lamivudine)

Eligibility Criteria

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

You may qualify if:

• Adults (\>=18 years old) with HIV-1 infection able to understand and give informed written consent.
• Stable ART in the 12 weeks prior to screening visit.
• \- Only switch for tolerability/convenience/access reasons to generic drugs or switch from ritonavir to cobicistat or TDF to TAF would be allowed in the 12-week window and as long as the components of the regimen are unchanged.
• Viral load \<50 copies/mL at screening and in the year prior to study entry.
• CD4 count \> 200 cel/μL at screening.
• History of 3TC resistance: either confirmed historical 3TC resistance (historical RNA Sanger or RNA NGS\>20% threshold genotype with M184V/I mutation) OR suspected historical 3TC resistance.
• Suspicion of past 3TC resistance is defined as any of the following:
• i. Previous treatment with only 2 NRTIs (1 of them being emtricitabine or 3TC \[XTC\]).
• ii. Two consecutive VL \> 200 cp/mL while on treatment including XTC. iii. One VL \> 200 cp/mL while on treatment including XTC PLUS change of ART as consequence of that elevated VL.

You may not qualify if:

• Participants with M184V/I or K65R in screening visit proviral DNA Sanger genotype.
• Prior virologic failure (VF) under integrase inhibitor (INSTI)- based regimen. defined as two consecutive VL \> 200 copies/mL while receiving INSTI regardless of genotypic test results
• INSTI resistance mutations in historical RNA genotype.
• Positive Surface Hepatitis B Ag (HBAgS) OR negative HBAgS and negative hepatitis B surface antibody (anti-HBs) with positive anti-core antibody (anti-HBc) and positive HBV DNA.
• Pregnant, breastfeeding women, women with a positive pregnancy test at the time of screening, sexually active fertile women wishing to conceive or unwilling to commit to contraceptive methods (see Appendix 1 for the accepted list of the highly effective methods for avoiding pregnancy), for the duration of the study and until 4 weeks after the last dose of study medication. All women are considered fertile unless they have undergone a sterilizing surgery or are over the age of 50 with spontaneous amenorrhea for over 12 months prior to study entry.
• Patients with active opportunistic infections or cancer requiring intravenous treatment and/or chemotherapy at screening.
• Any comorbidities or treatment with experimental drugs that according to the investigator could bias study results or entail additional risks for the participant.
• Participants receiving other medications that according to study drug label are contraindicated.
• Severe hepatic impairment (Class C) as determined by Child-Pugh classification.
• Alanine aminotransferase (ALT) over 5 times the upper limit of normal (ULN) or ALT over 3xULN and bilirubin over 1.5xULN.
• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones);
• Creatinine clearance of \<30 mL/min/1.73m2 via CKD-EPI method.
• Any verified Grade 4 laboratory abnormality that to the investigators criteria would affect the safety of the participant if included in the study.
• History or presence of allergy to dolutegravir or lamivudine.

Sponsors & Collaborators

• Fundacion SEIMC-GESIDA: lead
• ViiV Healthcare: collaborator

Study Sites (17)

H. Álvaro Cunqueiro

Vigo, Pontevedra, Spain

Location

CHUAC

A Coruña, Spain

Location

H. de Elche

Alicante, Spain

Location

H. General de Alicante

Alicante, Spain

Location

H. Bellvitge

Barcelona, Spain

Location

H. Clinic

Barcelona, Spain

Location

H. del Mar

Barcelona, Spain

Location

H. de Donosti

Donostia / San Sebastian, Spain

Location

H. Fundación Jimenez Díaz

Madrid, Spain

Location

H. Infanta Leonor

Madrid, Spain

Location

H. La Princesa

Madrid, Spain

Location

H. Príncipe de Asturias

Madrid, Spain

Location

H. Severo Ochoa

Madrid, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital General Univ. Gregorio Marañón

Madrid, Spain

Location

Hospital Univ. La Paz

Madrid, Spain

Location

H. Virgen de la Victoria

Málaga, Spain

Location

MeSH Terms

Conditions

HIV Infections

Interventions

dolutegravir; Lamivudine; Tablets

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase IIa, open-label, single arm, multicentric study

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 11, 2021
• Study Start: July 28, 2021
• Primary Completion: June 12, 2023
• Study Completion: April 9, 2024
• Last Updated: March 7, 2025

Record last verified: 2025-03

Locations

ES (17)