Oligonucleotide Ligation Assay (OLA) Resistance Study

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

We did not analyze and report outcome of people with TDR ≥10%, instead we reported pretreatment drug resistance (PDR) as this parameter could be determined but antiretroviral history was not reliably available. Thus, PDR ≥10% is considered below in place of TDR ≥10%.

Chung et al. Lancet HIV 2020; 7: e104-12.

The primary outcome was virologic failure defined as plasma HIV RNA of at least 400 copies per mL after initiation of antiretroviral therapy (ART).

We did not analyze and report outcome of people with TDR, instead we reported pretreatment drug resistance (PDR) as this parameter could be determined but antiretroviral history was not reliably available. Thus, PDR is considered below in place of TDR. PDR was assessed by OLA and confirmed by consensus sequence or next-generation sequencing.

We did not analyze and report outcome of people with TDR, instead we reported pretreatment drug resistance (PDR) as this parameter could be determined but antiretroviral history was not reliably available. Thus, PDR is considered below in place of TDR. The primary outcome for this analysis was the difference in virologic failure, defined as plasma HIV-1 RNA of at least 400 copies per mL following ART initiation, by PDR. [Chung et al. Lancet HIV 2020; 7: e104-12]

Estimates of medical resource utilization during was not calculated. No data available (data on medical resource utilization was not collected during the one-year trial)

This was not calculated as the model could not test for a period longer than 15 years due to computing limitations.

The prespecified outcomes of this study included differences in the rate of virologic failure over 24 months of efavirenz-based ART between participants by frequency of drug-resistant variants detected by next-generation sequencing at enrollment. Drug-resistance frequency was defined as the proportion of a nucleotide variant encoding a drug-resistant codon in specimens with at least 100 viral templates sequenced. Virologic failure was defined as plasma HIV RNA of at least 400 copies/ml in sequential specimens or at the final study visit in participants prescribed efavirenz-based ART. [Milne et al. AIDS 2022 Nov 15;36(14):1949-1958]

Technology transfer of OLA to the Hope Center Laboratory in Kenya is described, including intra- and inter-assay the reproducibility, and discussion of obstacles and possible solutions.

Duarte et a. AIDS 2018, 32:2301-2308

DBS were not tested in Kenya and thus, the comparison of OLA results obtained using DBS in Kenya to retesting of same specimens with input of viral templates measured in Seattle was not evaluated.

Rates of pre-treatment drug resistance among all study participants in the study were assessed by OLA but not by consensus sequencing (CS) due to the high cost of sequencing the entire population. However, all mutations detected by OLA were confirmed by CS in Seattle, and if not detected by CS were confirmed by next generation Illumina sequencing. Participants with any indeterminate OLA results were also sequenced to determine the genotype at the indeterminate codon.