Oligonucleotide Ligation Assay (OLA) Resistance Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Washington
Sponsor:
Collaborators:
Seattle Children's Hospital
University of Nairobi
Information provided by (Responsible Party):
Michael Chung, University of Washington
ClinicalTrials.gov Identifier:
NCT01898754
First received: July 9, 2013
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
HIV Positive
Other: Pre-ART Oligonucleotide Assay (OLA)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Drug-resistance Testing in Kenya to Improve ART Suppression of HIV Replication

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • The overall difference in rates of virologic failure with OLA-guided ART vs. Standard of care [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The primary endpoint will be a comparison of the rates of viral non-suppression >1000 copies/mL between study arms at 12 months


Secondary Outcome Measures:
  • 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 [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 15 months ] [ Designated as safety issue: Yes ]
  • Prevalence of TDR by consensus sequencing and OLA [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • Proportion of subgroup with TDR with virologic failure by randomization arm [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • Prevalence of TDR increase in the Coptic Clinic [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • Estimates of medical resource utilization during the one-year trial period [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • An assessment the short-term cost-effectiveness of OLA-guided testing [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • An assessment of the potential long-term cost-effectiveness of OLA-guided testing over a patient's lifetime [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • Determination of whether low-level ARV resistance (<5%) detected by PYRO but not by OLA is associated with virologic failure [ Time Frame: 15 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Descriptions of technology transfer of OLA to the Hope Center Laboratory, including intra- and inter-assay the reproducibility, and discussion of obstacles and possible solutions [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • A comparison of OLA results obtained using DBS in Kenya to retesting of same specimens with input of viral templates measured in Seattle [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • A comparison of rates of resistance detected across codons by OLA vs. consensus sequencing in Seattle [ Time Frame: 15 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 1000
Study Start Date: May 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pre-ART Oligonucleotide Assay (OLA)
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)
Block randomization (1:1) to pre-ART OLA testing or OLA testing after 12mo on ART
Other Name: Pre-ART OLA
No Intervention: No OLA (Standard of Care [SOC])
The participants will receive standard of care as per Kenya guidelines but will be offered OLA resistance testing after 12 months

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed HIV infection
  2. >2 years of age
  3. Qualifying for 1st-line ART based on Kenyan Guidelines
  4. Plan to reside in area for >1 year
  5. Adult patient or parent of minor agrees to study and provides informed consent

Exclusion Criteria:

  1. Received ART previously from Hope Center
  2. Ongoing ART
  3. Plan to start 2nd-line ART
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01898754

Locations
Kenya
Coptic Hospital Recruiting
Maseno, Kenya
Contact: Nelly J Yatich, DrPH    +254728234771    yatich@u.washington.edu   
Principal Investigator: Michael H Chung, MD, MPH         
Coptic Hospital Recruiting
Nairobi, Kenya
Contact: Nelly J Yatich, DrPH    +254728234771    yatich@u.washington.edu   
Contact: Catherine Kiptinness, MPH       cathykiptiness@gmail.com   
Principal Investigator: Michael H Chung, MD, MPH         
Sponsors and Collaborators
University of Washington
Seattle Children's Hospital
University of Nairobi
Investigators
Principal Investigator: Lisa Frenkel, MD University of Washington, Seattle Children's Research Institute
Principal Investigator: Michael H Chung, MD, MPH Department of Global Health, University of Washington
  More Information

No publications provided

Responsible Party: Michael Chung, Associate Professor, University of Washington
ClinicalTrials.gov Identifier: NCT01898754     History of Changes
Other Study ID Numbers: 14124-SCH
Study First Received: July 9, 2013
Last Updated: March 11, 2014
Health Authority: Kenya: Ethical Review Committee
United States: Federal Government

Keywords provided by University of Washington:
Transmitted Drug Resistance

Additional relevant MeSH terms:
HIV Seropositivity
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on September 16, 2014