Clinical trial NCT01898754: Oligonucleotide Ligation Assay (OLA) Resistance Study
Official title: Drug-resistance Testing in Kenya to Improve ART Suppression of HIV Replication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Positive
Keywords: Transmitted Drug Resistance
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Seattle Children's Hospital
name: University of Nairobi
First posted: 2013-07-12
Enrollment: 991
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Number of Participants With Virologic Failure With OLA-guided ART vs. Standard of Care
timeFrame: 12 months
Secondary outcomes:
measure: The Difference in Virologic Failure Among Participants With Transmitted Drug-resistance (TDR) ≥10% Associated With Use of OLA-guided ART vs. SOC
timeFrame: 15 months
measure: Difference in Virologic Failure in the Subgroup of Participants With Prior or Ongoing ART Use Associated With Use of OLA-guided ART vs. SOC
timeFrame: 15 months
measure: Prevalence of TDR by Consensus Sequencing and OLA
timeFrame: 15 months
measure: Proportion of Subgroup With TDR With Virologic Failure by Randomization Arm
timeFrame: 15 months
measure: Estimates of Medical Resource Utilization During the One-year Trial Period
timeFrame: 15 months
measure: An Assessment of the Potential Long-term Cost-effectiveness of OLA-guided Testing Over a Patient's Lifetime
timeFrame: 15 months
measure: Determination of Whether Low-level ARV Resistance (<5%) Detected by PYRO But Not by OLA is Associated With Virologic Failure
timeFrame: 24 months
Other outcomes:
measure: 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
timeFrame: 15 months
measure: A Comparison of OLA Results Obtained Using DBS in Kenya to Retesting of Same Specimens With Input of Viral Templates Measured in Seattle
timeFrame: 15 months
measure: Detection of Resistance Mutations at OLA Codons by OLA vs. Consensus Sequencing
timeFrame: Enrollment
Locations:
city: Maseno
country: Kenya
facility: Coptic Hospital
city: Nairobi
country: Kenya
facility: Coptic Hospital
Study officials:
affiliation: University of Washington, Seattle Children's Research Institute
name: Lisa Frenkel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Global Health, University of Washington
name: Michael H Chung, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chung MH, McGrath CJ, Beck IA, Levine M, Milne RS, So I, Andersen N, Dross S, Coombs RW, Chohan B, Yatich N, Kiptinness C, Sakr SR, Kiarie JN, Frenkel LM. Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial. Lancet HIV. 2020 Feb;7(2):e104-e112. doi: 10.1016/S2352-3018(19)30337-6. Epub 2019 Dec 7.
citation: Silverman RA, Beck IA, Kiptinness C, Levine M, Milne R, McGrath CJ, Bii S, Richardson BA, John-Stewart G, Chohan B, Sakr SR, Kiarie JN, Frenkel LM, Chung MH. Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014. J Infect Dis. 2017 Dec 19;216(12):1569-1578. doi: 10.1093/infdis/jix544.