CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: In a cohort of participants from KwaZulu-Natal, the presence of majority DRMs increased the risk of VF, an effect largely driven by the presence of dual-class resistance. The detection of drug-resistant minority variants alone did not significantly increase the risk of VF, but their inclusion with majority DRMs affected the sensitivity/specificity of predicting VF. 520 TENOFOVIR DIPHOSPHATE IN DRIED BLOOD SPOTS PREDICTS VIROLOGIC FAILURE AND RESISTANCE Jose R. Castillo-Mancilla 1 , Yuan Zhao 2 , Jaysingh Brijkumar 3 , Brent Johnson 4 , Alex Edwards 2 , Pillay Selvan 3 , Melendhran Pillay 3 , Pravi Moodley 3 , Mahomed- Yunus Moosa 3 , Daniel R. Kuritzkes 5 , Henry Sunpath 3 , Lane R. Bushman 1 , Lucas Ellison 1 , Peter L. Anderson 1 , Vincent C. Marconi 2 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 Emory University, Atlanta, GA, USA, 3 University of KwaZulu-Natal, Durban, South Africa, 4 University of Rochester, Rochester, NY, USA, 5 Brigham and Women's Hospital, Boston, MA, USA Background: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a measure of cumulative adherence and exposure to TFV-based antiretroviral therapy (ART). This adherence biomarker has been associated with viral suppression and found to predict future viremia in persons living with HIV (PLWH) receiving tenofovir disoproxil-fumarate (TDF)-based ART. However, little is known about its utility in the context of virologic failure (VF) and drug resistance in resource-limited settings. Methods: Participants within a prospective clinical cohort of PLWH who initiated TDF-based ART in 2 clinical sites in KwaZulu-Natal, South Africa, were evaluated. DBS samples were collected from participants who received at least 6 months of ART and developed VF, defined as an HIV VL >1000 copies/mL (cases), and in a selected group of participants who had an HIV VL <1000 copies/mL (controls, matched by site, age, gender, race and duration of ART). Cases were categorized as having VF without resistance or having VF with resistance using genotypic resistance testing. Concentrations of TFV-DP in DBS were quantified using a validated LC-MS/MS method. One-way ANOVA was used to compare the concentrations of TFV-DP in DBS at the time of the last study visit between controls, participants with VF without resistance and participants with VF with resistance. Data are presented as mean [SD] or median (IQR). Results: A total of 1000 participants (500 at each site) were enrolled in the cohort. Of these, 288 (45 cases) had available DBS samples, which were included in the analysis. Median age was 31 (26, 38) years and 170 (59%) were women. TFV-DP concentrations in DBS in controls were higher than in participants with VF with resistance and VF without resistance (808 [503] vs. 589 [495] vs. 527 [555] fmol/punch; P<0.01; Table), respectively. Conclusion: TFV-DP in DBS was associated with VF and drug resistance in South African PLWH on TDF-based ART. Participants with VF who developed drug resistance had TFV-DP concentrations in the mid-range of cumulative exposure, but higher than those who did not develop resistance. These results suggest that moderate cumulative drug exposure is required to develop ART resistance. Future research on the clinical utility of TFV-DP in DBS to prevent the development of VF and drug resistance is needed.

[protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and integrase strand transfer inhibitors (INSTIs)] between July 1, 2012 and June 30, 2018 were analyzed. All samples were collected as part of routine clinical care and evaluated using Monogram Biosciences GenoSure PRIme assay. Results: Of 84,611 samples evaluated, 27,911 (33.0%) demonstrated reduced susceptibility to at least one ARV. Between 2012 and 2018, resistance to NRTIs (54.8% to 40.8%) and PIs (14.7% to 8.3%) steadily declined. The proportion of samples with reduced susceptibility to at least one INSTI decreased between 2012 and 2015 (20.3% to 14.0%), stabilizing from 2015 to 2018. Multiclass (≥2 ARV classes) resistance declined between 2012 and 2018. The proportion of resistant samples with 2-, 3-, and 4-class resistance, respectively, decreased from 33.5% to 21.9%, 11.3% to 5.5%, and 3.1% to 1.1%. (Figure) This trend corresponds to increasing proportions of samples with resistance to NNRTIs in the absence of NRTI, PI, and INSTI resistance (2012-2018: 36.2% to 52.6%). Among samples with multiclass resistance, 78.7%were still susceptible to at least 1 ARV in the NNRTI class, 93.4% to ≥1 NRTI, 97.9% to ≥1 PI, and 93.7% to ≥1 INSTI; of these, 29.1%were susceptible to a single INSTI. The proportion of resistant samples with reduced susceptibility to multiple ARV classes increased with older age (21-30 yrs: 21.5%; 31-40: 30.4%; 41-50: 38.1%; 51-60: 41.4%; >60: 42.4%). No associations between degree of resistance and gender or geographic region were observed. Conclusion: Decreasing prevalence of multiclass ARV resistance was observed in testing data, in addition to declines in NRTI, PI, and INSTI resistance. These trends correspond with the availability of newer treatment options with favorable cross-resistance profiles, improved efficacy, and more convenient formulations leading to better adherence.

Poster Abstracts

522 PREVALENCE OF RESISTANCE AND LIMITED THERAPEUTIC OPTIONS IN PATIENTS VIREMIC ON ART Olivier Robineau 1 , Elisabeth André-Garnier 2 , Lise Cuzin 3 , Solène Sécher 2 , Félicie Dewulf 1 , Fanny Taudière 3 , Laurence Bocket 4 , Raymond Césaire 3 , Virginie Ferré 2 , Clotilde Allavena 2 , André Cabié 3 , François Raffi 2 1 Centre Hospitalier de Tourcoing, Tourcoing, France, 2 CHU de Nantes, Nantes, France, 3 CHU Fort de France, Fort de France, Martinique, 4 CHU de Lille, Lille, France Background: Although current ART has led to improved rates of prolonged virologic suppression, some patients remain viremic under ART. We evaluated the prevalence of resistance and therapeutic options among viremic subjects on ART in a large multicentric study. Methods: All HIV infected adults on ART for ≥6 months on Oct 1, 2018 at 3 French sites from the Dat’AIDS cohort (NCT02898987) were included. We compared individuals with last confirmed HIV RNA >50 c/mL vs ≤50c/mL. For each viremic subject, mutations were analyzed to assess cumulative ARV resistance genotype [ANRS algorithm (version 29; 2018)], genotype sensitivity score (GSS) and the number of active drugs (AD). Limited therapeutic options (TO) was defined as resistance to 3 of 4 ARV classes (maraviroc and enfuvirtide were not considered) and ≤2 AD among 5 specified drug groups (3TC or FTC, ABC or TDF, ≥1 NNRTI, ≥1 PI/r, ≥1 INSTI), based on cumulative genotype. χ 2 and Mann-Whitney tests were used for comparisons. Results: Of 5,429 individuals under follow-up, 215 (3.97%) had HIV RNA >50 c/mL. Excluding 7 subjects with no available genotype, characteristics of the 208 viremic vs virologically suppressed subjects are shown in Table. Adherence issues and social problems were found in 64.9% and 49.5% of viremic individuals, respectively. On cumulative genotype, 8.2% of viremic subjects had resistance to 3 or 4 ARV classes and 50.4 % to none; susceptibility to TDF,

521 TRENDS AND CHARACTERISTICS OF HIV-1 DRUG RESISTANCE IN THE UNITED STATES (2012-2018) Cassidy E. Henegar 1 , Mark Underwood 1 , Leigh Ragone 1 , Harmony Garges 2 , Vani Vannappagari 1 1 ViiV Healthcare, Research Triangle Park, NC, USA, ViiV Healthcare, London, UK Background: The prevalence of transmitted and acquired HIV-1 drug resistance impacts effectiveness of antiretroviral therapy in both treatment-naïve and treatment-experienced people living with HIV. This analysis utilized data from a large, representative commercial patient testing database to assess trends in HIV-1 resistance prevalence in the modern treatment era. Methods: Samples from HIV-1-infected individuals in the United States submitted for genotypic resistance testing to 4 antiretroviral (ARV) classes

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