Oligonucleotide Ligation Assay (OLA) Resistance Study (OLA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01898754
Recruitment Status : Completed
First Posted : July 12, 2013
Last Update Posted : November 6, 2017
Seattle Children's Hospital
University of Nairobi
Information provided by (Responsible Party):
Michael Chung, University of Washington

Brief Summary:
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 or disease Intervention/treatment Phase
HIV Positive Other: Pre-ART Oligonucleotide Assay (OLA) Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 990 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Drug-resistance Testing in Kenya to Improve ART Suppression of HIV Replication
Actual Study Start Date : May 2013
Actual Primary Completion Date : December 2016
Actual Study Completion Date : February 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. The overall difference in rates of virologic failure with OLA-guided ART vs. Standard of care [ Time Frame: 12 months ]
    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 :
  1. 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 ]
  2. 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 ]
  3. Prevalence of TDR by consensus sequencing and OLA [ Time Frame: 15 months ]
  4. Proportion of subgroup with TDR with virologic failure by randomization arm [ Time Frame: 15 months ]
  5. Prevalence of TDR increase in the Coptic Clinic [ Time Frame: 15 months ]
  6. Estimates of medical resource utilization during the one-year trial period [ Time Frame: 15 months ]
  7. An assessment the short-term cost-effectiveness of OLA-guided testing [ Time Frame: 15 months ]
  8. An assessment of the potential long-term cost-effectiveness of OLA-guided testing over a patient's lifetime [ Time Frame: 15 months ]
  9. Determination of whether low-level ARV resistance (<5%) detected by PYRO but not by OLA is associated with virologic failure [ Time Frame: 15 months ]

Other Outcome Measures:
  1. 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 ]
  2. 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 ]
  3. A comparison of rates of resistance detected across codons by OLA vs. consensus sequencing in Seattle [ Time Frame: 15 months ]

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01898754

Coptic Hospital
Maseno, Kenya
Coptic Hospital
Nairobi, Kenya
Sponsors and Collaborators
University of Washington
Seattle Children's Hospital
University of Nairobi
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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Michael Chung, Associate Professor, University of Washington Identifier: NCT01898754     History of Changes
Other Study ID Numbers: 14124-SCH
First Posted: July 12, 2013    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Michael Chung, 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