Drug Resistance Testing in Kenya to Improve ART Suppression of HIV Replication

 

The Challenge
Viral suppression of HIV is critical to improving the health of HIV-positive individuals, reducing HIV transmission to sexual partners and from mothers to their infants, and maintaining the effectiveness of the first-line antiretroviral therapy. Individuals with resistance to antiretroviral (ARV) drugs have substantially greater virologic failure when treated with certain treatment regimens. A cost-effective strategy is needed to detect and manage ARV-resistant HIV infections in routine HIV care and treatment programs in resource-limited settings.

Project Goals
A sensitive and specific oligonucleotide ligation assay (OLA), developed as a low-cost assay to detect HIV drug-resistance, can accurately quantify mutant genotypes and predict virologic failure among individuals prescribed NVP-based ART. If implemented in routine HIV care and treatment programs, the OLA could allow Kenyan clinicians to appropriately target protease inhibitor (PI)-based ART and increase rates of HIV viral suppression, potentially improving the outcome and reducing the cost of ART, and in doing so reduce the incidence of HIV infection. Furthermore, successful implementation of the OLA would give our bioengineering colleagues impetus to transform the OLA into a point of care assay.

Our Approach
This NIH-funded randomized controlled trial evaluated the implementation of OLA testing among HIV-infected individuals initiating ART at the Coptic Hope Center with an overall goal of improving rates of HIV viral suppression and validating whether OLA testing is cost effective in Kenya.

Personnel
This study was led by Dr. Michael Chung and Dr. Lisa Frenkel of Seattle Children’s Research Institute.

Recent Publications

1. Chung MH, McGrath CJ, Levine M, Milne RS, Kiarie JN, So I, Andersen N, Dross S, Coombs RW, Chohan B, Yatich N, Kitpinness C, Sakr SR, Beck IA, Frenkel LM. Randomized Clinical Trial Detecting Pre-Treatment HIV Drug Resistance by Oligonucleotide Ligation Assay in Kenya. 2019. Lancet HIV. doi: 10.1016/S2352-3018(19)30337-6. [original work]

2. Beck IA, Levine M, McGrath CJ, Bii S, Milne RS, Kingoo JM, So I, Andersen N, Dross S, Coombs RW, Kiarie J, Chohan B, Sakr SR, Chung MH, Frenkel LM. Pre-treatment HIV-Drug Resistance Associated with Virologic Outcome of First-Line NNRTI-Antiretroviral Therapy: A Cohort Study in Kenya. 2019. EClinicalMedicine. doi.org/10.1016/j.eclinm.2019.100239. [original work]

3. Panpradist N, Beck IA, Vrana J, Higa N, McIntyre D, Ruth PS, So I, Kline ECE, Milne R, Kanthula R, Wong-On-Wing A, Lim J, Ko D, Rossouw T, Feucht UD, Chung MH, Jourdain G, Ngo-Giang-Huong N, Laomanit L, Soria J, Lai J, Klavins E, Frenkel LM, Lutz BR. Development and Evaluation of OLA-Simple 1.0: A Software-Guided Test Kit for Low-Resource Laboratories to Detect Drug Resistance in HIV-1 subtypes A, B, C, D and AE. 2019. EBioMedicine. doi: 10.1016/j.ebiom.2019.11.002. [original work]

Research Title: 
Drug Resistance Testing in Kenya to Improve ART Suppression of HIV Replication