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

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

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

Study Overview

• Status: Terminated
• Conditions: HIV-2 Infection
• Intervention / Treatment: 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)

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

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Senegal
  • Dakar, Senegal
    • Clinique des Maladies Infectieuses Ibrahima DIOP Mar/CRCF, Centre Hospitalier Universitaire de Fann
  • Casamance
    • Ziguinchor, Casamance, Senegal
      • Centre de Sante de Ziguinchor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New WHO stage 3 or 4 event > 6 months after starting ART	BY WHO criteria	up to 3 years
Grade 3 or 4 adverse events	DAIDS definitions	up to 3 years
CD4 T-cell count trajectory	delta CD4 count per year	up to 3 year after starting 2nd-line ART

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Merck Sharp & Dohme LLC; Janssen Pharmaceutica; Clinique des Maladies Infectieuses, CHNU de Fann, Dakar, Senegal; Centre de Sante de Ziguinchor, Casamance, Senegal

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 4, 2018
• Primary Completion (ACTUAL): May 31, 2020
• Study Completion (ACTUAL): May 31, 2020

Study Registration Dates

• First Submitted: December 14, 2017
• First Submitted That Met QC Criteria: January 5, 2018
• First Posted (ACTUAL): January 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 20, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Raltegravir Potassium; Ritonavir; Lopinavir; Lamivudine; Zidovudine; Darunavir
• Other Study ID Numbers: STUDY00000228; R01AI120765 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD shared on request with ORB approval on final cleaned dataset
• IPD Sharing Time Frame: at end of study
• IPD Sharing Access Criteria: IRB approval
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• 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