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

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

Detailed Description
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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 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 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 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

Official Title
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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

Conditions
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HIV-2 Infection

Intervention / Treatment
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* 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)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-2 infection: confirmed by Determine (Alere, Inc.) & Immunocomb II (Alere, Inc.) or equivalent 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) For females of reproductive potential: negative serum or urine pregnancy test Men and women age >/=18 years Ability and willingness of subject to provide informed consent Exclusion Criteria: HIV-1 or HIV-1/HIV-2 dual infection Pregnancy or Breast-feeding Lab Abnormalities AST/ALT >2.5 X ULN CrCl <30 Current or previous use of Integrase Inhibitors or Darunavir

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No HIV-2 resistance<br> | Diagnostic Test: HIV-2 Genotypic Drug Resistance Testing using DBS<br>* Real time HIV-2 genotypic drug resistance testing using dried blood spots and consensus sequencing.<br>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)<br>* 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<br>|
| Experimental: HIV-2 NRTI resistance only<br> | Diagnostic Test: HIV-2 Genotypic Drug Resistance Testing using DBS<br>* Real time HIV-2 genotypic drug resistance testing using dried blood spots and consensus sequencing.<br>Drug: 2nd line ART (Tenofovir DF 300mg QD + Lamividine 300mg QD or Emtricitabine 200mg QD + Lopinavir/Ritonavir 400/100mg BID + Raltegravir 400mg BID )<br>* 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<br>|
| Experimental: HIV-2 NRTI and PI resistance<br> | Diagnostic Test: HIV-2 Genotypic Drug Resistance Testing using DBS<br>* Real time HIV-2 genotypic drug resistance testing using dried blood spots and consensus sequencing.<br>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)<br>* 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<br>|

What is the study measuring?
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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 |