Oligonucleotide Ligation Assay (OLA) Resistance Study

Study Overview
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Brief Summary
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The investigators propose to gauge improvements in the rate of durable suppression of viral replication by ART when OLA is used to guide clinical decisions at the PEPFAR Coptic Hope Center in Kenya, and to determine the cost-effectiveness of implementing this strategy at Coptic Hope Center.

Detailed Description
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Durable suppression of HIV replication is critical to (1) improving the health of infected individuals, (2) to reducing HIV transmission to sexual partners and from mothers to their infants, and (3) to maintaining the effectiveness of the current 1st-line non-nucleoside reverse transcriptase inhibitors (NNRTI)- based ART. Across multiple trials, individuals with NNRTI-resistance, even at low-concentrations, have substantially greater virologic failure when treated with NVP- vs PI-ART. A cost-effective strategy is needed to detect and manage ARV-resistant HIV infections. A simple low-cost innovative assay the investigators developed and successfully transferred to Asian and African countries (oligonucleotide ligation assay (OLA)) can detect NNRTI+lamivudine (3TC) resistant HIV using reagents that costs <$7.00/person. Furthermore, detection of NNRTI-resistance by OLA is highly (P<0.001) associated with virologic failure of nevirapine (NVP)-ART in two retrospective studies; one of Thai women who had been previously randomized to single-dose NVP and the second of ARV-naïve Kenyan adults. The investigators hypothesize that implementation of OLA into routine care will allow Kenyan clinicians to appropriately target protease inhibitor (PI)-based ART and improve rates of durable suppression of viral replication, and thus improve CD4 cell gains and individuals' health, reduce the transmission of ARV-resistant HIV within the community, and maintain the utility of NNRTI-ART. In addition, the investigators hypothesize that programmatically OLA-guided ART will be more cost-efficient compared to the current strategy of empiric use of NNRTI-ART as initial treatment.

Official Title
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Drug-resistance Testing in Kenya to Improve ART Suppression of HIV Replication

Conditions
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HIV Positive

Intervention / Treatment
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* Other: Pre-ART Oligonucleotide Assay (OLA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed HIV infection >2 years of age Qualifying for 1st-line ART based on Kenyan Guidelines Plan to reside in area for >1 year Adult patient or parent of minor agrees to study and provides informed consent Exclusion Criteria: Received ART previously from Hope Center Ongoing ART Plan to start 2nd-line ART

Ages Eligible for Study
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Minimum Age: 2 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-ART Oligonucleotide Assay (OLA)<br>Pre-ART OLA will be tested for resistance at 5 pol codons conferring high-level resistance to NNRTI and 3TC (K103N, V106M, Y181C, G190A and M184V) | Other: Pre-ART Oligonucleotide Assay (OLA)<br>* Block randomization (1:1) to pre-ART OLA testing or OLA testing after 12mo on ART<br>* Other names: Pre-ART OLA;|
| No Intervention: No OLA (Standard of Care [SOC])<br>The participants will receive standard of care as per Kenya guidelines but will be offered OLA resistance testing after 12 months | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Overall Difference in Rates of Virologic Failure With OLA-guided ART vs. Standard of Care | The primary endpoint will be a comparison of the rates of viral non-suppression >400 copies/mL between study arms at 12 months | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Difference in Virologic Failure Among the Subgroup of ARV-naïve Participants With Transmitted Drug-resistance (TDR) Associated With Use of OLA-guided ART vs. SOC |  | 15 months | 
| The Difference in Virologic Failure Among the Subgroup of Participants Referred to Hope Center With Previous or Ongoing ARV Use Associated With Use of OLA-guided ART vs. SOC |  | 15 months | 
| Prevalence of TDR by Consensus Sequencing and OLA |  | 15 months | 
| Proportion of Subgroup With TDR With Virologic Failure by Randomization Arm |  | 15 months | 
| Prevalence of TDR Increase in the Coptic Clinic |  | 15 months | 
| Estimates of Medical Resource Utilization During the One-year Trial Period |  | 15 months | 
| An Assessment the Short-term Cost-effectiveness of OLA-guided Testing |  | 15 months | 
| An Assessment of the Potential Long-term Cost-effectiveness of OLA-guided Testing Over a Patient's Lifetime |  | 15 months | 
| Determination of Whether Low-level ARV Resistance (<5%) Detected by PYRO But Not by OLA is Associated With Virologic Failure |  | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transmitted Drug Resistance