Oligonucleotide Ligation Assay (OLA) Resistance Study

HIV Positive Clinical Trial

— OLA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01898754
• Other study ID #: 14124-SCH
• Status: Completed
• Phase: N/A
• Start date: May 2013
• Est. completion date: February 2017

Study information

• Verified date: October 2021
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 991
• Est. completion date: February 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Positive
• HIV Seropositivity

Intervention

Other:
• Pre-ART Oligonucleotide Assay (OLA)
Block randomization (1:1) to pre-ART OLA testing or OLA testing after 12mo on ART

Locations

Country	Name	City	State
Kenya	Coptic Hospital	Maseno
Kenya	Coptic Hospital	Nairobi

Sponsors (3)

Lead Sponsor	Collaborator
University of Washington	Seattle Children's Hospital, University of Nairobi

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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		15 months
Other	A Comparison of OLA Results Obtained Using DBS in Kenya to Retesting of Same Specimens With Input of Viral Templates Measured in Seattle		15 months
Other	A Comparison of Rates of Resistance Detected Across Codons by OLA vs. Consensus Sequencing in Seattle		15 months
Primary	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	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
Secondary	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
Secondary	Prevalence of TDR by Consensus Sequencing and OLA		15 months
Secondary	Proportion of Subgroup With TDR With Virologic Failure by Randomization Arm		15 months
Secondary	Prevalence of TDR Increase in the Coptic Clinic		15 months
Secondary	Estimates of Medical Resource Utilization During the One-year Trial Period		15 months
Secondary	An Assessment the Short-term Cost-effectiveness of OLA-guided Testing		15 months
Secondary	An Assessment of the Potential Long-term Cost-effectiveness of OLA-guided Testing Over a Patient's Lifetime		15 months
Secondary	Determination of Whether Low-level ARV Resistance (<5%) Detected by PYRO But Not by OLA is Associated With Virologic Failure		15 months