CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

731

Rilpivirine Drug Resistant Mutations in Experienced Patients in Mexico: Impact on Long-Acting ART Angel J. Granados-Gomez, Elsa Y. Vidal Laurencio, Juan P. Ramírez-Hinojosa, Gilbert Perez-Rodriguez, Juan J. Calva-Mercado, Luis E. Soto-Ramirez Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico Background: Baseline rilpivirine drug resistance mutations (DRMs) are a risk factor for virological failure in patients treated with long-acting cabotegravir and rilpivirine (CAB/RPV LA). We investigated rilpivirine cross-resistance in experienced patients in Mexico, where Efavirenz (EFV) was the preferred initial ARV drug for more than 10 years. Methods: Genotypic sequence data from 2442 patients experiencing at least two treatment failures were included for analysis. Pol sequences were submitted to Stanford HIVdb v9.6 to identify rilpivirine DRMs. The following mutations were included as rilpivirine DRMs (Stanford HIVdb penalty score ≥10): A98G, V100IV, K101EPH, V106I, E138AGKQR, V179DEFL, Y181CFGISV, Y188FL, G190ACEQSTV, H221Y, F227C, and 230IL. Resistance profiles were categorized as susceptible (including potential low-level resistance), intermediate (including low-level resistance), or high-level resistance. Results: Patients failing two or more ART combinations (n=2442) were included, all belonging to subtype B virus. All patients have experienced one treatment failure to NNRTIs, mostly to EFV. Of those, 1644 (67.3%) presented with at least one NNRTI DRM, including 619 (25.3%) with at least one rilpivirine DRM and 361 (21.9%) with at least two rilpivirine DRMs. Rilpivirne DRMs or combinations with more than 5% frequency are presented in Figure. DRMs related to EFV failure were the most frequent found. More than three quarters of patients with NNTRI-DRMs, showed intermediate (25.3%; n =416) and high-level rilpivirine resistance (44.2%; n =727). Considering all the genotypes studied (n=2442), we found intermediate rilpivirine resistance in 415 cases (17.0%) and high-level resistance in 728 (29.8%). Conclusions: This retrospective analysis indicates that rilpivirine DRMs are common in a setting wherein NNRTI-based treatment was widely implemented, and has implications for operational implementation of CAB/RPV LA. Screening for existing DRMs is logistically and technically challenging in Mexico and could be a barrier to use of CAB/RPV LA.

the proportion of INI users among the total number of ARV-treated PLWHIV increased from 3.3% (n=102/3 100) to 72.2% (n=3 152/4 364). For the whole cohort, there was an increase (3.2% in 2007 to 21.5% in 2013) followed by a decrease (to 4.4% in 2023) in the use of RAL (Figure 1A). The same usage profile was observed for EVG (0.03% in 2007 to 15.7% in 2019 and 2.4% in 2023). Over the period of their use, DTG and BIC continued to increase (0.03% in 2007 to 39.3% for DTG and 2.0% in 2019 to 28.1% in 2023 for BIC). The use of CAB is reported in 2017 (0.07%) and represents 3.8% in 2023. The number of HIV RNA integrase genotypic resistance tests increased from 97 at the start of testing in 2008 up to 365 in 2023. During the first 3 years of INI use, a dramatic level of resistance was observed. The resistance rate decreased significantly over time from 45-50% in 2008 for all INIs, with similar resistance rates in 2023 for DTG, CAB and BIC (5.1%), but remained high for RAL (10.3%) and EVG (11.0%), respectively (Figure 1B). Conclusions: The INI class of ARVs is now widely used and, finally, large increase in use within this class do not increase the resistance over time in ARV-treated PLWHIV with virological failure. The very high level of INI resistance at the beginning of INI use was probably due to the use of RAL in combination with other ARVs that were not fully sensitive during the first 3 years. The INIs used today have a higher genetic barrier that limits the emergence of resistance mutations. Daniele Armenia 1 , Claudia Alteri 2 , Valeria Micheli 3 , Bianca Bruzzone 4 , Isabella Bon 5 , Celestino Bonura 6 , Tiziano Allice 7 , Romina Corsini 8 , Federica Novazzi 9 , Marialinda Vatteroni 10 , Ada Bertoli 11 , Gabriele Ibba 12 , Antonia Bezenchek 13 , Maurizio Zazzi 14 , Maria Mercedes M. Santoro 15 , for the Italian NGS Network 1 Saint Camillus International University of Health Sciences, Rome, Italy, 2 University of Milan, Milan, Italy, 3 Fatebenefratelli Sacco Hospital, Milan, Italy, 4 San Martino Hospital, Genoa, Italy, 5 IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, 6 University Hospital of Palermo, Palerno, Italy, 7 Amedeo di Savoia Hospital, Torino, Italy, 8 Azienda Unita Sanitaria Locale di Reggio Emilia, Reggio Emilia, Italy, 9 University of Insubria, Varese, Italy, 10 Azienda Ospedaliero Universitaria Pisana, Pisa, Italy, 11 Hospital of Rome Tor Vergata, Rome, Italy, 12 AOU di Sassari, Sassari, Italy, 13 EuResist Network, Rome, Italy, 14 University of Siena, Siena, Italy, 15 University of Rome Tor Vergata, Rome, Italy Background: The aim of this study was to characterize subtypes circulation and transmitted drug resistance (TDR) in Italy by next-generation sequencing (NGS). Methods: Routine plasma HIV-1 RNA NGS genotyping data were collected from newly diagnosed individuals over 2021-2024. TDR for PI, NRTI, NNRTI and INI, and genotypic susceptibility were evaluated through HIVdb (ver.9.6) with NGS set at 10% and 20%. Subtype and transmission clusters (TC) were determined through the Maximum Likelihood phylogeny based on the GTR+F+R9 model. Results: 473 PLWH (median age 41 [31-51], 77.6% males) were included; 56.2% of them harboured non-B strains (CRF02_AG [15.6%]; CRFs BF [13.1%]; F1 [5.1%]; A1/A6 [7.4%]; Others [15.0%]). TDR prevalence to any class was 12.3% at Sanger like NGS-setting (>20%) and slightly increased (15.9%) at 10% setting. PI-TDR was low regardless of NGS-settings (2.7% and 2.3%); NRTI-TDR and NNRTI-TDR was 4.0% and 6.8% at 20% NGS-setting and slightly increased at 10% NGS setting (5.9% and 7.6%). INI-TDR was very low at both NGS-setting (20%: 0.2%; 10%: 1.1%). TDR was higher in B compared to non-B subtypes, particularly for NRTI (Figure 1A). Concerning genotypic susceptibility, the currently recommended first-line regimens based on high genetic barrier drugs showed full activity in >97% of individuals, regardless of NGS-setting and subtypes. These proportions were lower for rilpivirine- (≥86%) and raltegravir-based (≥95%) regimen regardless NGS-setting. Rilpivirine susceptibility was lower in the B-subtype subset, while raltegravir was predicted less active in non-B subtypes (Figure 1B). Concerning transmission networks, a total of 35 TC were detected: 27 pairs, 7 small clusters (3-8 sequences), and 1 large cluster (9 sequences). Among them, 23 were found in non-B subtypes (60%). Six TC had RTI-TDR including: 3 subtype B and 2 CRF02_AG TC with thymidine analogue mutations; 1 CRF31_BC TC with the NNRTI mutation K103N. Of note, TDR was detected as minority mutations in three out of six TC. Conclusions: A high proportion of HIV-1 non-B subtypes circulate in Italy. TDR prevalence is around 16% using NGS set at 10%. However, the impact of the detected TDR on the susceptibility to currently recommended first-line regimens is negligible. NGS genotyping can improve the characterization of The figure, table, or graphic for this abstract has been removed. Molecular Epidemiology of HIV-1 Transmitted Drug-Resistance Among Subtypes Circulating in Italy

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Poster Abstracts

732

Despite Increasing Use of INIs to Treat HIV Infection, Resistance to This Class Remains Stable Vincent Calvez 1 , Rachid Agher 1 , Basma Abdi 1 , Marc Wirden 1 , Elisa Teyssou 1 , Karen Zafilaza 1 , Christine Katlama 1 , Marc-Antoine Valantin 1 , Roland Tubiana 1 , Luminita Schneider 1 , Antoine Faycal 1 , Romain Palich 1 , Valerie Pourcher 1 , Anne-Geneviève Marcelin 1 , Cathia Soulié 2 1 Assistance Publique – Hôpitaux de Paris, Paris, France, 2 Institut national de la santé et de la recherche médicale (Inserm), Paris, France Background: Since the beginning of HIV treatment, changes in the use of antiretroviral (ARV) drugs have often led to changes in HIV resistance mutation patterns. The integrase inhibitor (INI) class has benefited from many developments: first raltegravir (RAL) and elvitegravir (EVG), followed by dolutegravir (DTG), cabotegravir (CAB) and bictegravir (BIC). The aim of this study was to evaluate changes in resistance levels and profiles to INIs in relation to changes in the use of different INIs over 17 years in people living with HIV (PLWHIV) treated with ARVs and in virological failure. Methods: We analyzed in parallel the use of the different INIs in ARV-treated PLWHIV in an academic center (Pitié Salpêtrière Hospital, Paris, France, 2007 2023) and the HIV INI resistance profiles in RNA (2008-2023; analyzed using the latest ANRS-MIE algorithm v33). Results: The total number of PLWHIV on ARV treatment was 3 100 people in 2007 and has increased to 4 364 people in 2023. During this period (2007-2023),

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