Darunavir/Ritonavir + Lamivudine Versus Darunavir/Ritonavir +Emtricitabine/Tenofovir in Naïve HIV-1 Infected Subjects

NCT02770508 | Completed Phase 4

• 1 other identifier: FH-15
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to compare the safety and efficacy of a combination of a QD regimen consisting on ritonavir boosted darunavir (FDC) and lamivudine versus ritonavir boosted darunavir (FDC) plus co-formulated tenofovir and emtricitabine or co-formulated tenofovir/lamivudine in naïve HIV-1 infected patients. Subjects will be ARV-naïve HIV-1-infected patients eligible to start ARV therapy according to current guidelines.Subjects will be adults ≥ 18 years of age who meet all of the inclusion criteria and none of the exclusion criteria.

Conditions

HIV-1 Infection

Keywords

antiretroviral naive; dual therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with HIV-1 RNA levels of less than 50 copies/mL at week 48

  The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) \<50 c/mL at Week 48 will be assessed using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks).

  48 weeks

Secondary Outcomes (6)

• Percentage of patients with HIV-1 RNA <400 copies/mL at week 24

  24 weeks

• Number and type of resistance mutations in case of virologic failure

  from week 24 to week 48

• CD4+ lymphocyte count and change between baseline (defined as the average between screening and baseline visit values) and weeks 24 and 48

  week 24 and 48

• Frequency, type and severity of adverse events and laboratory abnormalities.

  week 24 and 48

• Clinical disease progression (CDP)

  week 24 and 48

Study Arms (2)

Darunavir/ritonavir plus lamivudine

EXPERIMENTAL

Darunavir/ritonavir 800/100 mg, 1 coformulated tablet QD and lamivudine 300 mg, 1 tablet QD

Drug: darunavir/ritonavir; Drug: Lamivudine

Darunavir/ritonavir plus emtricitabine/tenofovir(FTC/TFD)

ACTIVE COMPARATOR

Darunavir/ritonavir 800/100 mg1 coformulated tablet QD (FDC) plus FTC/TDF 200/300 mg, 1 coformulated tablet QD

Drug: darunavir/ritonavir; Drug: emtricitabine-tenofovir(FTC/TDF)

Interventions

darunavir/ritonavir DRUG

Also known as: Virontar R

Darunavir/ritonavir plus emtricitabine/tenofovir(FTC/TFD); Darunavir/ritonavir plus lamivudine

Lamivudine DRUG

Also known as: 3TC

Darunavir/ritonavir plus lamivudine

emtricitabine-tenofovir(FTC/TDF) DRUG

Also known as: TRUVADA

Darunavir/ritonavir plus emtricitabine/tenofovir(FTC/TFD)

Eligibility Criteria

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

You may qualify if:

• \> 18 years of age.
• Patient with documented HIV-1 infection defined as a positive ELISA plus a confirmatory Western Blot; or alternatively, a plasma HIV-1 RNA ≥1,000 copies/mL ever documented.
• Subject has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB) / Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject has had the opportunity to ask questions. The informed consent must be signed before any study-specific procedures are performed.
• Subject agrees not to take any medication during the study, including over the counter medicines or herbal preparations, without the approval of the trial physician.
• Documented HIV-1 RNA \>1,000 copies/mL
• Subject naïve to ARV. (Patients who had received ARV ≤ 48 hours are allowed). Subject has indication to receive an antiretroviral regimen.
• Subjects can comply with protocol requirements.
• Subject's general medical condition, in the investigator's opinion, does not interfere with assessments and completion of the trial.
• If patient is a female she must not be breastfeeding or pregnant. She must be either postmenopausal for at least one year, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or she must:
• use 2 different methods of birth control including, at least, one barrier method, and are acceptable to both the subject and investigator, and
• has a urine pregnancy test performed at the Screening Visit and on Baseline. Results of both tests must be negative.
• continue using 2 different methods of birth control including, at least, one barrier method for at least 30 days after the end of the treatment period
• For male patients, must comply with the use of a barrier birth control method during the Study and 60 days beyond the Study completion

You may not qualify if:

• Evidence of resistance to or 3TC or DRV/r, TDF, FTC o 3TC based in the results of the resistance testing done in the screening visit, such resistance being considered in accordance with IAS-USA panel, version dated March 2013.
• Any of the following mutations will be considered resistance to DRV/r :
• I47V, I50V, I54M/L, L76V, I84V or, 3 or more minor mutations : V11I, V32I, L33F, T74P, L89V.
• Any of the following mutations will be considered resistance to 3TC or FTC : M184V/I and /or K65R and / or Q151M.
• Any of the following mutations will be considered resistance to TDF: K65R, K70E, double insertion 69 or 3 TAMS including M41L or L210W.
• Prior HIV-2 documented infection.
• The use of disallowed concomitant therapy (see Appendix C).
• Active Hepatitis B infection (at any stage).
• The patient was diagnosed with acute active hepatitis by any cause, or chronic hepatitis C WITH levels of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 5 higher than the upper limit of normal (ULN) AND/OR may require one-year treatment.
• Any clinical significant active disease (for instance, tuberculosis, heart failure, pancreatitis) or any medical history or physical examination findings that, according to the investigator's opinion, may risk the patient's safety, the results of the study or adherence to the rules of the protocol.
• The patient has an active AIDS-associated opportunistic disease (Category C according to the CDC classification system for HIV infection as of 1993) within 30 days after the screening. Stabilized patients under treatment for AIDS-associated opportunistic disease may be included in the study.
• Life expectancy \< 1 year according to the investigator
• Laboratory tests performed during the screening visit show any of the following alterations:
• Hemoglobin \<8.0 gm/dL
• Absolute neutrophil count (ANC) \< 750 cells/µL

Sponsors & Collaborators

• Fundación Huésped: lead
• Ministry of Science and Technology,Argentine: collaborator
• National AIDS and STD programme,Argentine: collaborator
• Richmond Laboratories: collaborator

Study Sites (5)

Consultorio Infectológico Dr. Pryluka

CABA, Buenos Aires, 1121, Argentina

Location

Hospital Cosme Argerich

CABA, Buenos Aires, 1155ADP, Argentina

Location

Hospital Italiano

CABA, Buenos Aires, 1199ABB, Argentina

Location

Fundacion huesped

CABA, Buenos Aires, C1202ABB, Argentina

Location

Centro de Estudios Infectologicos SA (CTD Stamboulian)

CABA, Buenos Aires, C1425AWK, Argentina

Location

Related Publications (1)

• Figueroa MI, Sued O, Cecchini D, Sanchez M, Rolon MJ, Lopardo G, Ceschel M, Mernies G, De Stefano M, Patterson P, Gun A, Fink V, Ortiz Z, Cahn P; ANDES Study Group. Dual therapy based on co-formulated darunavir/ritonavir plus lamivudine for initial therapy of HIV infection: The ANDES randomized controlled trial. Int J Antimicrob Agents. 2024 Oct;64(4):107301. doi: 10.1016/j.ijantimicag.2024.107301. Epub 2024 Aug 14.

  PMID: 39151647 DERIVED

MeSH Terms

Interventions

Darunavir; Ritonavir; Lamivudine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Tenofovir; Organophosphonates; Organophosphorus Compounds; Emtricitabine; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Pedro Cahn, PhD, MD

  Fundacion Huesped

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, MD

Study Record Dates

• First Submitted: November 16, 2015
• First Posted: May 12, 2016
• Study Start: November 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: October 1, 2017
• Last Updated: August 3, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share

Locations

AR (5)