Oligonucleotide Ligation Assay (OLA) Resistance Study

University of Washington

Status: Completed

Conditions: HIV Positive

Treatments: Other: Pre-ART Oligonucleotide Assay (OLA)

Study type: Interventional

Funder types: Other

Identifiers

NCT01898754

14124-SCH

Details and patient eligibility

About

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.

Full 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.

Enrollment: 991 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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991 participants in 2 patient groups

Pre-ART Oligonucleotide Assay (OLA)

Experimental group

Description:

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)

Treatment:

Other: Pre-ART Oligonucleotide Assay (OLA)

No OLA (Standard of Care [SOC])

No Intervention group

Description:

The participants will receive standard of care as per Kenya guidelines but will be offered OLA resistance testing after 12 months