Oligonucleotide Ligation Assay (OLA) Resistance Study (OLA)

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.

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.

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)

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

The primary endpoint will be a comparison of the rates of viral non-suppression >400 copies/mL between study arms at 12 months

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

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

An Assessment of the Potential Long-term Cost-effectiveness of OLA-guided Testing Over a Patient's Lifetime

Determination of Whether Low-level ARV Resistance (<5%) Detected by PYRO But Not by OLA is Associated With Virologic Failure

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

A Comparison of OLA Results Obtained Using DBS in Kenya to Retesting of Same Specimens With Input of Viral Templates Measured in Seattle

A Comparison of Rates of Resistance Detected Across Codons by OLA vs. Consensus Sequencing in Seattle

Inclusion Criteria: Confirmed HIV infection >2 years of age Qualifying for 1st-line ART based on Kenyan Guidelines Plan to reside in area for >1 year Adult patient or parent of minor agrees to study and provides informed consent Exclusion Criteria: Received ART previously from Hope Center Ongoing ART Plan to start 2nd-line ART

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.

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.