CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

523 PRETREATMENT HIV DRUG RESISTANCE SPREAD WITHIN TRANSMISSION CLUSTERS IN MEXICO CITY Margarita Matías-Florentino 1 , Antoine Chaillon 2 , Santiago Avila-Rios 1 , Verónica Ruiz 3 , Silvia del Arenal 1 , Manuel A. Becerril-Rodríguez 1 , Alicia Piñeirúa 3 , Florentino Badial Hernandez 3 , Andrea Gonzalez Rodriguez 3 , Sanjay R. Mehta 2 , Gustavo Reyes-Terán 1 1 National Institute of Respiratory Diseases, Mexico City, Mexico, 2 University of California San Diego, San Diego, CA, USA, 3 Clinica Especializada Condesa, Mexico City, Mexico Background: Baseline screening for HIV drug resistance mutations (DRM) for all individuals starting antiretroviral treatment (ART) has been proposed as a public health action in Mexico in response to rising non-nucleoside reverse transcriptase inhibitor (NNRTI) pretreatment drug resistance (PDR). Here we performed full-length pol deep sequencing (MiSeq, Illumina) for DRM screening in all persons diagnosed at Clinica Especializada Condesa (CEC), the largest HIV clinic in Mexico, to estimate prevalence and transmission of PDR. Methods: All individuals diagnosed with HIV at CEC from April 2016 to July 2017 who agreed to participate in the study were enrolled, and blood was obtained for sequencing. Sequences were assembled using HyDRA (Public Health Agency of Canada). ART resistance was defined as presence of any surveillance DRM at a sensitivity threshold 5%. Genetic network analyses were performed to infer relationships between HIV sequences (<1.5% genetic distance), and we looked for DRM shared between genetically linked sequences. Results: Full-length pol sequences were generated from 987 individuals. The median read coverage for DRM sites was 1,620 (IQR 944-2548). Using the 5% sensitivity threshold, 14.9% (147/987) of sequences contained surveillance DRM to any antiretroviral, 11.3% (74/987) to NNRTI, 4.3% (42/987), to nucleoside RT inhibitors (NRTI), 4.9% to protease inhibitors (PI) (48/987), and 0.7% (6/987) to integrase strand transfer inhibitors (INSTI). K103N was the most frequent surveillance DRM (5.3%). A total of 295/987 (31.5%) sequences had a putative linkage with at least one other sequence forming 109 clusters (range: 2-14 individuals, 28 non-dyad clusters). 36 sequences within clusters had DRMs. From these, 22/36 (61.1%) shared the same DRM with a linked sequence in 9 distinct clusters, including one cluster of 7 individuals in which 6/7 sequences shared K103N (Figure). The most frequently transmitted DRMs were K103N (10/22 individuals sharing DRMs, 3 clusters), T215S (6/22, 3 clusters), Y188L (4/22, 2 clusters and M46L (4/22, 2 clusters). None of 6 low-frequency DRMs (<20% sensitivity threshold) were shared between genetically linked individuals. Conclusion: Network analysis demonstrated frequent cases of shared DRMs among linked individuals, especially K103N, revealing the potential for spread of pretreatment DRM. No cases of transmission of low-frequency DRMs were observed. These results highlight the need to obtain and rapidly deliver HIV DR results to treating clinicians in Mexico.

524 SPREAD OF HIV-1 PRE-TREATMENT DRUG RESISTANCE IN THE COLOGNE- BONN REGION, GERMANY Melanie Stecher 1 , Martin Hoenigl 2 , Anna-Maria Eis-Huebinger 3 , Clara Lehmann 1 , Gerd Fätkenheuer 1 , Jan-Christian Wasmuth 3 , Rolf Kaiser 1 , Sanjay R. Mehta 2 , Joerg Janne Vehreschild 1 , Antoine Chaillon 2 1 Cologne University Hospital, Cologne, Germany, 2 University of California San Diego, San Diego, CA, USA, 3 Bonn University Hospital, Bonn, Germany Background: In Germany, the prevalence of HIV-1 drug resistance mutations (DRM) remains high, affecting treatment failure and the choice of antiretroviral therapy (ART). We sought to understand the molecular epidemiology of HIV and DRM transmission in the metropolitan region of Cologne-Bonn, one of the regions with the highest rate of new infections, using a combined phylogenetic and geospatial approach. Methods: We included 714 HIV-1 infected ART naïve individuals, followed at the University Hospital Cologne (n=558;78.2%) and Bonn (n=156;21.9%) between 1999 and 2016. Phylogenetic and network analyses were performed to infer putative relationships between HIV partial pol sequences obtained by routine genotype testing. Sociodemographic and geographic data were used to characterize transmission clusters. Geospatial dispersal of the clusters was determined by calculating the average distance between reported residence (centroids of 3-digit zipcode, ArcGIS®). Transmission of DRM was estimated between genetically linked individuals. Results: HIV-1 infected participants were predominantly male (81.9%) and had a median age of 39 years (IQR: 31-47). Drug resistance screening found 7% and 13.6% of sequences contained nucleoside or non-nucleoside reverse transcriptase inhibitor (NRTI/NNRTI) DRM. Putative transmission links were inferred in 177/714 (24.8%) sequences forming a total of 63 clusters (size ranging from 2-8, Figure). Clustering individuals were significantly younger (median age 36 vs 39, p=0.0014), men (92.1% vs 78.5%, p<0.001) reporting sex with men (MSM) as main risk factor (69.5% vs 53.1%, p<0.001). DRM frequency was comparable in clustering and not clustering individuals (18.1% vs 17.1%, p=0.91). Most clustering individuals were found in the city center of Cologne 43/177 (47.5%). The distance between centroids was significantly lower for genetically linked- than non-linked sequences (18.6km [IQR 11.7-30.7] vs 36.2km [IQR 22.5-53.8]; p<0.001). Of the 51 putative links including sequences harboring any DRM, 20 (39%) were shared by genetically-linked partners (Figure, red edges), suggesting DRM transmission among ART Naïve individuals. Conclusion: In our study sample, we found evidence of transmitted DRM located especially in the city center of Cologne, well known for its districts with strong gay community. Phylogenetic and geospatial characterization of HIV revealed close/dense hotspots of HIV transmission that could help identifying targets for treatment and interventions.

Poster Abstracts

CROI 2018 191