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

NCT03394196 — Not applicable, Terminated, 152 participants, University of Washington
ClinicalTrials Daily  ·  Areas  ·  Conditions  ·  Drugs  ·  Sponsors  ·  

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

RegistryNCT03394196, acronym RESIST-2
StatusTerminated - COVID-19 and Funding
PhaseNot applicable
Study typeInterventional; non randomized, parallel, masking: none, treatment
Enrollment152 (Actual)
SponsorUniversity of Washington (Other); collaborators: Clinique des Maladies Infectieuses, CHNU de Fann, Dakar, Senegal, Centre de Sante de Ziguinchor, Casamance, Senegal, Janssen Pharmaceutica, Merck Sharp & Dohme LLC, National Institute of Allergy and Infectious Diseases (NIAID)
ConditionsHIV-2 Infection
InterventionsHIV-2 Genotypic Drug Resistance Testing using DBS, 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), 2nd line ART (Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID + Raltegravir 400mg BID ), 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) (Diagnostic test, drug)
Datesstart 2018-07-04, primary completion 2020-05-31, completion 2020-05-31, first posted 2018-01-09, last updated 2021-01-25
Locations2 sites in Senegal

Related Papers Related Patents Related Grants Related Experts
All trials for HIV-2 Infection All trials of HIV-2 Genotypic Drug Resistance Testing using DBS All trials of 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)

-Summary

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

Expand all sections  ·  Collapse all

+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

+Arms and interventions

ArmTypeInterventionsDescription
No HIV-2 resistanceExperimentalDiagnostic 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)
HIV-2 NRTI resistance onlyExperimentalDiagnostic Test: HIV-2 Genotypic Drug Resistance Testing using DBS; Drug: 2nd line ART (Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID + Raltegravir 400mg BID )
HIV-2 NRTI and PI resistanceExperimentalDiagnostic Test: HIV-2 Genotypic Drug Resistance Testing using DBS; 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)
  • HIV-2 Genotypic Drug Resistance Testing using DBS (Diagnostic test): Real time HIV-2 genotypic drug resistance testing using dried blood spots and consensus sequencing.
  • 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): 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
  • 2nd line ART (Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID + Raltegravir 400mg BID ) (Drug): 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
  • 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) (Drug): 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

+Outcome measures

Primary outcomes

  • Death [up to 3 years]: all cause mortality
  • Loss to follow up [1 year]: no contact with study for 1 year
  • Virologic Failure on 2nd line ART [up to 3 years]: VL >250 copies/ml
  • HIV-2 ARV resistance on 2nd line ART [up to 3 years]: by DBS genotyping

Secondary outcomes

  • New WHO stage 3 or 4 event > 6 months after starting ART [up to 3 years]: BY WHO criteria
  • Grade 3 or 4 adverse events [up to 3 years]: DAIDS definitions
  • CD4 T-cell count trajectory [up to 3 year after starting 2nd-line ART]: delta CD4 count per year

+Eligibility

Sex: All, ages: 18 Years to any

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

+Locations (2)

FacilityCityCountryStatus
Centre de Sante de ZiguinchorZiguinchor, CasamanceSenegal
Clinique des Maladies Infectieuses Ibrahima DIOP Mar/CRCF, Centre Hospitalier Universitaire de FannDakarSenegal

+Publications

  • Results publication: Raugi DN, Diallo K, Diallo MB, Faye D, Cisse O, Smith RA, Sall F, Sall EHI, Faye K, Diatta JP, Diaw B, Sambou J, Malomar JJ, Hawes SE, Seydi M, Gottlieb GS; University of Washington-Senegal HIV-2 Study Group. Resource and infrastructure challenges on the RESIST-2 Trial: an implementation study of drug resistance genotype-based algorithmic ART switches in HIV-2-infected adults in Senegal. Trials. 2021 Dec 18;22(1):931. doi: 10.1186/s13063-021-05902-5. PMID 34922614

+Investigators

+Funding

NIH grants: R01AI120765