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IntroductionThe Robert Koch Institute (RKI) aimed to assess a molecular surveillance strategy based on filter‐dried serum spots (DSS) of all newly diagnosed HIV infections in Germany. In 2013, diagnostic laboratories sent DSS to the RKI representing 55% of the newly diagnosed HIV infections reported to the RKI (protection against infection act). DSS were first tested serologically to identify recently acquired infections (<140 days duration of infection); those classified as "recent infection" were processed for HIV‐1 genotyping. The aim of this study was to assess the level of TDR and the current HIV‐1 subtypes in the main HIV transmission group categories (TrGrpC) in 2013: men who have sex with men (MSM), women/men with heterosexual contacts (HET) and injecting drug users (IDUs).Materials and MethodsDSS were tested for recency of infection using the BED capture EIA. Viral RNA from "recent infections" was amplified by HIV‐1 group M generic pol‐RT‐PCR covering all resistance‐associated positions in the HIV‐1 protease (AS1‐99) and reverse transcriptase (AS1‐252) if viral loads were ≥6,500 copies/mL. PCR amplicons were sequenced (Sanger) to analyze genotypic resistance and the HIV‐1 subtype. Results were merged to data from the HIV report, i.e. the TrGrpC.ResultsIn 2013, 1027 DSS were classified as recent HIV infections (506 MSM, 118 HET, 31 IDUs, 6 others, 366 unknown). RNA was extracted from 703 recent cases and 389/503 samples with sufficient viral load were PCR‐positive. By June 2014, 276/389 samples were sequenced: TDR was identified in 13% (35/276) of the recent infections including single (PI, NRTI, NNRTI) and dual drug class resistant strains (NRTI/NNRTI; NNRTI/PI). 18% (51/276) of recent HIV‐1 infections were caused by non‐B subtypes (A1, C, CRF01_AE, CRF02_AG, D, F, G, URFs). TDR was observed at comparable levels in all TrGrpC. Proportions of non‐B infections were significantly higher in HET (78%; 14/18) and IDUs (60%; 3/5) compared to MSM (8%; 14/169) (p<0.01).ConclusionsThe proportion of TDR was similar but the proportion of HIV‐1 subtype non‐B infections was higher as previously described for Germany based on results from the German HIV‐1 Seroconverter Cohort [1,2]. This difference could be the result of a broadened inclusion of HET and IDUs due to the sampling method used making this study representative for molecular surveillance of HIV‐1 in Germany.

Background A steady increase in HIV drug resistance (HIVDR) has been demonstrated globally in individuals initiating first-line antiretroviral therapy (ART). To support effective use of ART and prevent spread of HIVDR, monitoring is essential. Aim We piloted a surveillance system for transmitted HIVDR to assess the feasibility of implementation at the European level. Method All 31 countries in the European Union and European Economic Area were invited to retrospectively submit data on individuals newly diagnosed with HIV in 2015 who were tested for antiviral susceptibility before ART, either as case-based or as aggregate data. We used the Stanford HIV database algorithm to translate genetic sequences into levels of drug resistance. Results Nine countries participated, with six reporting case-based data on 1,680 individuals and four reporting aggregated data on 1,402 cases. Sequence data were available for 1,417 cases: 14.5% of individuals (n = 244) showed resistance to at least one antiretroviral drug. In case-based surveillance, the highest levels of transmitted HIVDR were observed for non-nucleoside reverse-transcriptase inhibitors (NNRTIs) with resistance detected in 8.6% (n = 145), followed by resistance to nucleoside reverse-transcriptase inhibitors (NRTI) (5.1%; n = 85) and protease inhibitors (2.0%; n = 34). Conclusion We conclude that standard reporting of HIVDR data was feasible in the participating countries. Legal barriers for data sharing, consensus on definitions and standardisation of interpretation algorithms should be clarified in the process of enhancing European-wide HIV surveillance with drug resistance information. ; Peer Reviewed

BACKGROUND: A steady increase in HIV drug resistance (HIVDR) has been demonstrated globally in individuals initiating first-line antiretroviral therapy (ART). To support effective use of ART and prevent spread of HIVDR, monitoring is essential. AIM: We piloted a surveillance system for transmitted HIVDR to assess the feasibility of implementation at the European level. METHOD: All 31 countries in the European Union and European Economic Area were invited to retrospectively submit data on individuals newly diagnosed with HIV in 2015 who were tested for antiviral susceptibility before ART, either as case-based or as aggregate data. We used the Stanford HIV database algorithm to translate genetic sequences into levels of drug resistance. RESULTS: Nine countries participated, with six reporting case-based data on 1,680 individuals and four reporting aggregated data on 1,402 cases. Sequence data were available for 1,417 cases: 14.5% of individuals (n = 244) showed resistance to at least one antiretroviral drug. In case-based surveillance, the highest levels of transmitted HIVDR were observed for non-nucleoside reverse-transcriptase inhibitors (NNRTIs) with resistance detected in 8.6% (n = 145), followed by resistance to nucleoside reverse-transcriptase inhibitors (NRTI) (5.1%; n = 85) and protease inhibitors (2.0%; n = 34). CONCLUSION: We conclude that standard reporting of HIVDR data was feasible in the participating countries. Legal barriers for data sharing, consensus on definitions and standardisation of interpretation algorithms should be clarified in the process of enhancing European-wide HIV surveillance with drug resistance information.

Background. Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping. Methods. We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load. Results. Multiple single variants within the major histocompatibility complex (MHC) region were observed to be strongly associated with HIV-1 outcome, consistent with the known impact of classical HLA alleles. However, no single variant or gene located outside of the MHC region was significantly associated with HIV progression. Set-based association testing focusing on genes identified as being essential for HIV replication in genome-wide small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) studies did not reveal any novel associations. Conclusions. These results suggest that exonic variants with large effect sizes are unlikely to have a major contribution to host control of HIV infection. ; This study has been financed in part within the framework of the Swiss HIV Cohort Study (www.shcs.ch) project #651 and supported by the Swiss National Science Foundation (www.snf.ch) grant #148522 (J.F.). The International HIV Controllers Study was made possible through a generous donation from the Mark and Lisa Schwartz Foundation and a subsequent award from the Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation (www.cavd.org). This work was also supported in part by the Harvard University Center for AIDS Research (cfar.globalhealth.harvard.edu) grant P-30-AI060354; University of California San Francisco (UCSF) Center for AIDS Research (cfar.ucsf.edu) grant P-30 AI27763; UCSF Clinical and Translational Science Institute (https://ctsi.ucsf.edu) grant UL1 RR024131; Center for AIDS Research Network of Integrated Clinical Systems (http://cfar.globalhealth.harvard.edu) grant R24 AI067039; and the National Institutes for Health (www.nih.gov) grants AI28568 and AI030914 (B.D.W.). The AIDS Clinical Trials Group was supported by NIH grants AI069513, AI34835, AI069432, AI069423, AI069477, AI069501, AI069474, AI069428, AI69467, AI069415, Al32782, AI27661, AI25859, AI28568, AI30914, AI069495, AI069471, AI069532, AI069452, AI069450, AI069556, AI069484, AI069472, AI34853, AI069465, AI069511, AI38844, AI069424, AI069434, AI46370, AI68634, AI069502, AI069419, AI068636, RR024975, AI077505, AI110527, and TR000445 (D.W.H.). For the CASCADE Consortium, the research leading to these results has received funding from the European Union Seventh Programme (FP7/2007–2013) under EuroCoord (www.eurocoord.net) grant agreement no. 260694 (K.P.) and the Spanish Network of HIV/AIDS grant nos. RD06/006, RD12/0017/0018 and RD16CIII/0002/0006 (J.DA.). A portion of the data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS). MACS (Principal Investigators): Johns Hopkins University Bloomberg School of Public Health (Joseph Margolick, Todd Brown), U01-AI35042; Northwestern University (Steven Wolinsky), U01-AI35039; University of California, Los Angeles (Roger Detels, Oto Martinez-Maza, Otto Yang), U01-AI35040; University of Pittsburgh (Charles Rinaldo, Lawrence A. Kingsley, Jeremy J. Martinson), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson, Gypsyamber D'Souza), UM1-AI35043. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR, or NCATS. The MACS website is located at http://aidscohortstudy.org/ ; Sí