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

NCT ID: NCT04880785

Last Updated: 2025-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-28
• Study Completion Date: 2024-04-09

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.

Detailed Description

This is a multicentre study, and it will be conducted at different healthcare centres in Spain. 117 participants will be recruited. A minimum of 30%-50% of the study population would be required to have historical RNA population genotype with confirmed M184V/I mutation.

Conditions

HIV Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dovato (Dolutegravir+lamivudine)

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

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

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

Interventions

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

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adults (>=18 years old) with HIV-1 infection able to understand and give informed written consent.

2. 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.

3. Viral load <50 copies/mL at screening and in the year prior to study entry.

• A blip (50-500 copies/ml) would be allowed within 48 weeks prior to inclusion in the study, if preceded and followed by an undetectable VL determination.

4. CD4 count > 200 cel/μL at screening.

5. 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.

Exclusion Criteria

1. Participants with M184V/I or K65R in screening visit proviral DNA Sanger genotype.

2. 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

3. INSTI resistance mutations in historical RNA genotype.

4. 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.

5. 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.

6. Patients with active opportunistic infections or cancer requiring intravenous treatment and/or chemotherapy at screening.

7. Any comorbidities or treatment with experimental drugs that according to the investigator could bias study results or entail additional risks for the participant.

8. Participants receiving other medications that according to study drug label are contraindicated.

9. Severe hepatic impairment (Class C) as determined by Child-Pugh classification.

10. Alanine aminotransferase (ALT) over 5 times the upper limit of normal (ULN) or ALT over 3xULN and bilirubin over 1.5xULN.

11. 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);

12. Creatinine clearance of <30 mL/min/1.73m2 via CKD-EPI method.

13. Any verified Grade 4 laboratory abnormality that to the investigators criteria would affect the safety of the participant if included in the study.

14. History or presence of allergy to dolutegravir or lamivudine.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: collaborator

Fundacion SEIMC-GESIDA

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

H. Álvaro Cunqueiro

Vigo, Pontevedra, Spain

CHUAC

A Coruña, , Spain

H. de Elche

Alicante, , Spain

H. General de Alicante

Alicante, , Spain

H. Bellvitge

Barcelona, , Spain

H. Clinic

Barcelona, , Spain

H. del Mar

Barcelona, , Spain

H. de Donosti

Donostia / San Sebastian, , Spain

H. Fundación Jimenez Díaz

Madrid, , Spain

H. Infanta Leonor

Madrid, , Spain

H. La Princesa

Madrid, , Spain

H. Príncipe de Asturias

Madrid, , Spain

H. Severo Ochoa

Madrid, , Spain

Hospital 12 de Octubre

Madrid, , Spain

Hospital General Univ. Gregorio Marañón

Madrid, , Spain

Hospital Univ. La Paz

Madrid, , Spain

H. Virgen de la Victoria

Málaga, , Spain

Countries

Spain

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

GESIDA11820

Identifier Type: -

Identifier Source: org_study_id