CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

of resistance was estimated using robust Poisson regression with general estimated equations to account for repeated visits by some participants. Results: 109,328 participant visits were contributed, including 20,383 (26.9%) from PLHIV. Using deep-sequencing data from 4,253 visits, we estimated that the prevalence of NNRTI resistance among pre-treatment viremic participants increased 3.51 (95% CI 2.1–5.9)-fold between the 2012 and 2022 surveys, reaching 16.9 (11.8%–24.2%, Figure 1A). INSTI, NRTI, and PI resistance among pre-treatment viremic participants remained stable and below 2.5% throughout the study. We observe a 3.6 (2.2–6.0)-fold and 7.1 (3.2–15.5)-fold decrease in the prevalence of NNRTI and NRTI resistance among treatment experienced viremic PLHIV, falling to below 25% in the 2022 survey (Figure 1B). The majority (80.2%, 69.3%–87.3%) of treatment-experienced viremic PLHIV were not resistant to any drug classes in the 2022 survey. INSTI resistance among treatment-experienced viremic PLHIV was minimal throughout, including the 2022 survey (2.9%, 1.0%–8.9%). We observe the inS153Y mutation, which confers 2-fold resistance to DTG, in 5.8% (n=8/139) and 7.4% (n=6/81) of pre treatment and treatment-experienced viremic participants in the 2022 survey. This mutation was not observed previously. Conclusions: The roll-out of DTG has not yet reduced the prevalence of NNRTI resistance among pre-treatment PLHIV. However, NNRTI and NRTI resistance among treatment-experienced viremic PLHIV has decreased significantly, potentially due to DTG initiation. Most viremia among treatment-experienced PLHIV is not due to resistance, owing to the importance of engaging PLHIV in care. The sudden recent emergence of inS153Y is concerning and warrants continued monitoring to ensure sustained efficacy of DTG-based therapy. Plasma DTG Exposure Test as Objective Tool to Identify People With HIV at Highest Risk of Resistance Kim Steegen 1 , Jeremy Nel 2 , Chijioke N. Umunnakwe 3 , Karabo Mophiring 4 , Erin H. Smeijsters 5 , Wouter M. Tiel Groenestege 5 , Matthijs van Luin 6 , Sean Currin 1 , Lucas E. Hermans 7 , Hugo A. Tempelman 3 , Lucia Hans 1 , Francois Venter 8 , Monique Nijhuis 5 , Annemarie M. J. Wensing 5 1 National Health Laboratory Service, Johannesburg, South Africa, 2 University of Witwatersrand, Johannesburg, South Africa, 3 Ndlovu Care Group, Groblersdal, South Africa, 4 Hillbrow Community Health Care Centre, Johannesburg, South Africa, 5 University Medical Center Utrecht, Utrecht, Netherlands, 6 Meander Medical Center, Amersfoort, Netherlands, 7 University of Cape Town, Cape Town, South Africa, 8 Ezintsha, Johannesburg, South Africa Background: Second-generation integrase inhibitors are the cornerstone of antiretroviral therapy (ART) worldwide. Recently, WHO reported higher levels of dolutegravir (DTG) resistance in some low and middle-income countries compared to clinical trial data. As resources for resistance testing remain limited, we implemented a prospective reflex testing strategy (ITREMA-2) to prioritize resistance testing to those most likely to benefit. Methods: All individuals with viral loads (VL) ≥400 c/mL from two hospitals in Johannesburg were offered participation. Plasma DTG (pDTG) levels were determined using a semi-quantitative enzyme immunoassay (ARK Diagnostics). Samples with pDTG ≥20 ng/mL were classified as detectable. Resistance testing was performed on all samples with detectable pDTG levels and on a random subset with undetectable pDTG. Mutations were assessed with Stanford HIVdb v9.6. Results: Between April 2023 and September 2024, 208 out of 210 eligible individuals with ≥12 weeks DTG exposure and VL≥400 cp/mL participated (288 samples). Most were female (57%), mean age of 42 years (SD +/- 13), median log10 VL of 4.1 cp/mL (IQR: 3.1-4.9), median duration of ART was 89 months (IQR: 46-155), including DTG for 11 months (IQR: 6-24 months). pDTG was below detection limits in 175 samples (60%), indicating non-adherence. Only 33% of individuals with VL≥1000 c/mL had detectable pDTG levels versus 64% of those with VL 400-1000 c/mL (p<0.001). Detectable pDTG levels were not associated

with sex, age, regimen, facility, duration of DTG, total ART duration, prior PI or NNRTI exposure. As part of the reflex strategy, 96 sequences were generated from 75 individuals with detectable pDTG levels. DTG resistance was detected in 13% (10/75) of individuals showing diverse mutation profiles. Accumulation of integrase mutations was observed in 3 individuals within 7 months of follow-up (Table). At least eight individuals with DTG resistance had prior NNRTI and/or PI exposure. DTG resistance was not detected in the 17 randomly selected virally unsuppressed individuals with undetectable pDTG levels. Conclusions: Prevalence of DTG resistance in virally unsuppressed individuals with detectable pDTG levels was 13%; higher than reported from unselected individuals in routine care. Reflex pDTG exposure testing offers an objective and easily implementable measure to identify virally unsuppressed individuals with non-adherence, optimizing the allocation of limited resources for those most likely to benefit.

Poster Abstracts

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Plasma Dolutegravir Exposure as a Triaging Tool for HIV Drug Resistance Testing by ONT Sequencing Hendrik J. Coetser 1 , Dieketseng Magubane 2 , Lucinda Gaelejwe 2 , Esrom Letsoalo 3 , Derryn Legg-E’Silva 4 , Lucia Hans 2 , Sean Currin 2 , Kim Steegen 2 1 University of the Witwatersrand, Johannesburg, South Africa, 2 National Health Laboratory Service, Johannesburg, South Africa, 3 WITS Health Consortium, Johannesburg, South Africa, 4 National Health Laboratory Service, Cape Town, South Africa Background: South African antiretroviral therapy (ART) guidelines recommend dolutegravir (DTG) based regimens. Although DTG resistance is infrequently reported, it is paramount to identify individuals at risk for resistance. We assessed the use of plasma DTG (pDTG) drug-exposure (DE) testing as a triaging tool to identify individuals at highest risk for DTG resistance. Additionally, we assessed the use of Oxford Nanopore Technologies (ONT) sequencing in a public health setting for HIVDR testing. Methods: Sanger sequences were available for 97 individuals who had resistance tests requested when failing DTG-based treatment in South Africa. Remnant specimens were used to qualitatively assess pDTG DE using an LC-MS/ MS method. Nanopore sequences were obtained for 55 specimens using the ONT native barcoding kit for amplicons (SQK-NBD114.96). Nanopore and Sanger sequences were analysed with NanoRecall and Recall respectively at a 25% threshold and submitted to Stanford HIVdb V9.6. Results: Most individuals were female (70.1%) with a median age of 35 (IQR: 20-44) and log10 viral load of 4.8 (IQR: 3.2-5.7). The median time of DTG treatment was 13.8 months (IQR: 6.1-26.3). DTG resistance was detected in 19.5% (19/97) individuals by Sanger sequencing (Table). Individuals with detectable pDTG (45.4%), were more likely to have DTG resistance (OR: 9.01; 95% CI 2.41 – 35.59, p=0.001). Undetectable pDTG predicted the absence of DTG resistance with high accuracy (NPV: 94.2%, 95% CI: 85.1-97.9). Multivariate logistic regression demonstrated there was no association between pDTG DE results and VL, sex, duration on DTG, and prior PI exposure. However, individuals with prior ART (OR: 15.9; 95% CI: 1.8-141.7, p=0.013) and specially NNRTI exposure (OR: 0.14; 95% CI: 0.03-0.59, p=0.008) were more likely to have detectable pDTG, as were older individuals (OR: 1.04; 95% CI: 1.0-1.1, p=0.019). Resistance mutations detected by Sanger and ONT had a 96.4% (95% CI: 98.3-100) and 97.1% (95% CI: 98.3-100) pairwise identity for integrase and protease-reverse transcriptase respectively. Conclusions: We demonstrated that pDTG DE testing can accurately predict the absence of DTG resistance and can therefore be considered an adequate screening method to identify individuals who do not require HIVDR testing, decreasing the financial burden associated with HIVDR testing. Additionally,

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