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RESIST-2: 2nd-line ART for HIV-2 Infection (RESIST-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03394196
Recruitment Status : Active, not recruiting
First Posted : January 9, 2018
Last Update Posted : January 22, 2020
Sponsor:
Collaborators:
Clinique des Maladies Infectieuses, CHNU de Fann, Dakar, Senegal
Centre de Sante de Ziguinchor, Casamance, Senegal
Janssen Pharmaceutica
Merck Sharp & Dohme Corp.
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Geoffrey S. Gottlieb, University of Washington

Brief Summary:
Prospective, longitudinal, open label, HIV-2 viral load and antiretroviral resistance informed 2nd-line ARV implementation study.

Condition or disease Intervention/treatment Phase
HIV-2 Infection Diagnostic Test: HIV-2 Genotypic Drug Resistance Testing using DBS Drug: 2nd line ART ( Zidovudine 300mg BID + Lamivudine 150mg BID or Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID) Drug: 2nd line ART (Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID + Raltegravir 400mg BID ) Drug: 2nd line ART (Tenofovir DF 300mg QD + Lamividine 300mg QD or Tenofovir DF 300mg QD + Emtricitabine 200mg QD + Darunavir 600mg BID-Ritonavir 100mg BID +Raltegravir 400mg BID) Not Applicable

Detailed Description:

Prospective, longitudinal, open label, HIV-2 viral load and antiretroviral resistance informed 2nd-line ARV implementation study.

DURATION

Up to 3 years

SAMPLE SIZE

150

POPULATION

HIV-2-infected adults (≥18 years old); ARV-experienced, with virologic failure on 1st-line 2NRTI+LPV/r in the ISAARV program.

STRATIFICATION

By ARV resistance

REGIMEN OR INTERVENTION

Intervention: Implement real time ARV resistance testing using rapid DBS/CS ARV Regimens: Based on ARV resistance testing

  1. No resistance: Current ART: Zidovudine 300mg BID + Lamivudine 150mg BID or Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID (AZT/3TC or TDF/3TC or TDF/FTC + LPV/r) +Enhanced Adherence Counseling
  2. NRTI resistance only: Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID + Raltegravir 400mg BID (TDF/FTC or TDF/3TC + LPV/r + RAL) + Enhanced Adherence Counseling
  3. NRTI-PI resistance: Tenofovir DF 300mg QD + Lamividine 300mg QD or Tenofovir DF 300mg QD + Emtricitabine 200mg QD + Darunavir 600mg BID-Ritonavir 100mg BID + Raltegravir 400mg BID (TDF/FTC or TDF/3TC +DRV/r2 + RAL) + Enhanced Adherence Counseling

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Implementation and Evaluation of an HIV-2 Viral Load and ARV Resistance Informed Algorithm for 2nd-line ART in HIV-2 Infected Patients in the Initiative Sénégalaise d'Accès Aux Antirétroviraux (ISAARV) Program
Actual Study Start Date : July 4, 2018
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: No HIV-2 resistance Diagnostic Test: HIV-2 Genotypic Drug Resistance Testing using DBS
Real time HIV-2 genotypic drug resistance testing using dried blood spots and consensus sequencing.

Drug: 2nd line ART ( Zidovudine 300mg BID + Lamivudine 150mg BID or Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID)
1. No resistance: Continue Current ART: Zidovudine 300mg BID + Lamivudine 150mg BID or Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID (AZT/3TC or TDF/3TC or TDF/FTC + LPV/r) + Enhanced Adherence Counseling

Experimental: HIV-2 NRTI resistance only Diagnostic Test: HIV-2 Genotypic Drug Resistance Testing using DBS
Real time HIV-2 genotypic drug resistance testing using dried blood spots and consensus sequencing.

Drug: 2nd line ART (Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID + Raltegravir 400mg BID )
2. NRTI resistance only: Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID + Raltegravir 400mg BID (TDF/FTC or TDF/3TC + LPV/r + RAL) + Enhanced Adherence Counseling

Experimental: HIV-2 NRTI and PI resistance Diagnostic Test: HIV-2 Genotypic Drug Resistance Testing using DBS
Real time HIV-2 genotypic drug resistance testing using dried blood spots and consensus sequencing.

Drug: 2nd line ART (Tenofovir DF 300mg QD + Lamividine 300mg QD or Tenofovir DF 300mg QD + Emtricitabine 200mg QD + Darunavir 600mg BID-Ritonavir 100mg BID +Raltegravir 400mg BID)
3. NRTI-PI resistance: Tenofovir DF 300mg QD + Lamividine 300mg QD or Tenofovir DF 300mg QD + Emtricitabine 200mg QD + Darunavir 600mg BID-Ritonavir 100mg BID +Raltegravir 400mg BID (TDF/FTC or TDF/3TC +DRV/r2 + RAL) + Enhanced Adherence Counseling




Primary Outcome Measures :
  1. Death [ Time Frame: up to 3 years ]
    all cause mortality

  2. Loss to follow up [ Time Frame: 1 year ]
    no contact with study for 1 year

  3. Virologic Failure on 2nd line ART [ Time Frame: up to 3 years ]
    VL >250 copies/ml

  4. HIV-2 ARV resistance on 2nd line ART [ Time Frame: up to 3 years ]
    by DBS genotyping


Secondary Outcome Measures :
  1. New WHO stage 3 or 4 event > 6 months after starting ART [ Time Frame: up to 3 years ]
    BY WHO criteria

  2. Grade 3 or 4 adverse events [ Time Frame: up to 3 years ]
    DAIDS definitions

  3. CD4 T-cell count trajectory [ Time Frame: up to 3 year after starting 2nd-line ART ]
    delta CD4 count per year



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV-2 infection: confirmed by Determine (Alere, Inc.) & Immunocomb II (Alere, Inc.) or equivalent
  2. Failing 1st line antiretroviral therapy (e.g. AZT/3TC or TDF/XTC + LPV/r; previous 3 NRTI or 2 NRTI regimens; previous Indinavir (IDV) use, current or previous Atazanavir (ATV) use; previous NNRTI use)
  3. For females of reproductive potential: negative serum or urine pregnancy test
  4. Men and women age >/=18 years
  5. Ability and willingness of subject to provide informed consent

Exclusion Criteria:

  1. HIV-1 or HIV-1/HIV-2 dual infection
  2. Pregnancy or Breast-feeding
  3. Lab Abnormalities

    • AST/ALT >2.5 X ULN
    • CrCl <30
  4. Current or previous use of Integrase Inhibitors or Darunavir

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03394196


Locations
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Senegal
Centre de Sante de Ziguinchor
Ziguinchor, Casamance, Senegal
Clinique des Maladies Infectieuses Ibrahima DIOP Mar/CRCF, Centre Hospitalier Universitaire de Fann
Dakar, Senegal
Sponsors and Collaborators
University of Washington
Clinique des Maladies Infectieuses, CHNU de Fann, Dakar, Senegal
Centre de Sante de Ziguinchor, Casamance, Senegal
Janssen Pharmaceutica
Merck Sharp & Dohme Corp.
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Geoffrey S Gottlieb, MD PhD University of Washington
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Responsible Party: Geoffrey S. Gottlieb, Professor, University of Washington
ClinicalTrials.gov Identifier: NCT03394196    
Other Study ID Numbers: STUDY00000228
R01AI120765 ( U.S. NIH Grant/Contract )
First Posted: January 9, 2018    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD shared on request with ORB approval on final cleaned dataset
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: at end of study
Access Criteria: IRB approval

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Infection
Ritonavir
Lopinavir
Darunavir
Tenofovir
Lamivudine
Zidovudine
Emtricitabine
Raltegravir Potassium
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Antimetabolites
HIV Integrase Inhibitors
Integrase Inhibitors