Ambrosioni, Juan

Miró Meda, José M.

Mosquera, Maria Mar

JAMA

English

Diposit Digital de la Universitat de Barcelona

The difference in MACE numbers was 15 between the pla-cebo group (n = 61) and escitalopram group (n = 46), in linewith the differences in depression remission. The differencein MACE occurrence appearing beyond 1 year after random-ization is a reasonable concern. However, a meta-analysis of16 studies of depression following ACS found that differ-ences in MACE occurrence became prominent after 1 yearand over longer follow-up intervals4; this is in keeping withour findings, although we agree that further replicationshould be sought.Dr Zimmermann and colleagues raise concerns about thecumulative incidence figures in the article. The data in Figure2 have been rechecked, and we found that the cumulativeevent curves were matched erroneously to the numbers atrisk. This was our mistake and an error that arose during therevision process after the original submission and uncon-nected to other analyses. The article has been correctedonline, and we apologize for the oversight. In addition, num-bers at risk have also been revised for Figures 2 and 3, takinginto account the censoring date as well as end points. Regard-ing mortality definitions, all-cause mortality was chosen as acomponent of the MACE outcome at an early stage of proto-col development, was recorded in the body of the protocol,and was used in a prior publication2 as well as in the currentanalysis. However, the change was not applied in the synop-sis by mistake.We appreciate Dr Rust’s concerns about placebo controls.Because of the lack of evidence for the effect of depressiontreatment shortly following ACS at the time the study wasdesigned, the EsDEPACS trial was judged both by fundersand by an independent ethics review panel to be addressingan issue of clinical equipoise.5 In addition to providing studydrugs, research psychiatrists met with all participantsfor at least 30 minutes at every visit and addressed psycho-logical symptoms through supportive intervention as well aspromoting cardiac treatment. Participants could withdrawfrom the trial for any reason. For participants without remis-sion after the trial, further treatment was facilitated whenrequested. All participants were approached for evaluation ofpsychiatric outcomes 1 year after baseline evaluation.6 Weagree that findings from our studies3,5 support further activecontrol and stepwise intensification trials.Jae-Min Kim, MD, PhDRobert Stewart, MD, FRCPsychJin-Sang Yoon, MD, PhDAuthor Affiliations:Department of Psychiatry, ChonnamNational UniversityMedical School, Republic of Korea (Kim, Yoon); Institute of Psychiatry,Psychology and Neuroscience, King’s College London, London, England(Stewart).Corresponding Author: Jae-Min Kim, MD, PhD, Department of Psychiatry,ChonnamNational University Medical School, 160 Baekseoro, Dong-gu,Gwangju 61669, Republic of Korea (jmkim@chonnam.ac.kr).Conflict of Interest Disclosures: The authors have completed and submittedthe ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Stewartreported receiving grants from Janssen and Roche and co-supervision of a PhDcandidate with GlaxoSmithKline. No other disclosures were reported.1. Kim JM, Bae KY, Kang HJ, et al. Design andmethodology for the Koreanobservational and escitalopram treatment studies of depression in acutecoronary syndrome: K-DEPACS and EsDEPACS. Psychiatry Investig. 2014;11(1):89-94. doi:10.4306/pi.2014.11.1.892. Kim JM, Stewart R, Kim JW, et al. Serotonin transporter gene associationbetween anxiety and long-term cardiac outcomes in acute coronary syndromes.J Am Coll Cardiol. 2018;71(23):2706-2707. doi:10.1016/j.jacc.2018.04.0063. Kim JM, Stewart R, Lee YS, et al. Effect of escitalopram vs placebo treatmentfor depression on long-term cardiac outcomes in patients with acute coronarysyndrome: a randomized clinical trial. JAMA. 2018;320(4):350-358. doi:10.1001/jama.2018.94224. Meijer A, Conradi HJ, Bos EH, et al. Adjusted prognostic association ofdepression followingmyocardial infarction with mortality and cardiovascularevents: individual patient data meta-analysis. Br J Psychiatry. 2013;203(2):90-102. doi:10.1192/bjp.bp.112.1111955. Kim JM, Bae KY, Stewart R, et al. Escitalopram treatment for depressivedisorder following acute coronary syndrome: a 24-week double-blind,placebo-controlled trial. J Clin Psychiatry. 2015;76(1):62-68. doi:10.4088/JCP.14m092816. Kim JM, Stewart R, Bae KY, et al. Effects of depression co-morbidity andtreatment on quality of life in patients with acute coronary syndrome: theKorean Depression in ACS (K-DEPACS) and the Escitalopram for Depression inACS (EsDEPACS) study. Psychol Med. 2015;45(8):1641-1652. doi:10.1017/S003329171400275XBaseline Genotype Testing to Assess DrugResistance Before BeginningHIV TreatmentTo the Editor In theupdatedRecommendations of the Interna-tional Antiviral Society–USA Panel for the treatment and pre-vention of human immunodeficiency virus (HIV) infection inadults,1 the recommendations for laboratorymonitoringhavebeen revised to include the use of baseline HIV genotype toassess transmitted drug resistance. The panel recommendedtesting only for nucleoside reverse transcriptase inhibitors,nonnucleoside reverse transcriptase inhibitors, and proteaseinhibitors, and reserved testing for integrase strand-transferinhibitor (InSTI) resistance to cases of suspected exposure toa partner with InSTI resistance. All preferred regimens areInSTI-based, favoringdolutegravir andbictegravir and,whenthosearenot available, raltegravir andelvitegravir/cobicistat.1Although the transmission of signature mutations forInSTIs (such as Y143R/C, N155H, or Q148K/R/H) is extremelyinfrequent—henceweagree there is generallynoneed tomoni-tor for these mutations prior to treatment initiation—there isno rarity of InSTI polymorphisms that can reduce InSTI activ-ity. Casadellà et al2 reported a 14% prevalence of such substi-tutions in Europe on the basis of samples collected in treat-ment-naive patients between 2006 and 2007. In our owninstitution, prevalence was also 14% in treatment-naivepatients with acute or recent (<6 months postinfection) HIVinfection diagnosed in 2015 and 2016. The most frequentlyfound substitution was the E157Q polymorphism, and all pa-tientswere infectedwith subtype B strains, suggesting that itis unrelated to specific recombinant forms or subtypes.3Antiretroviral-naivepatients carryingviruseswith suchapoly-morphism have been reported to experience virologic failurewith raltegravir-4 and elvitegravir/cobicistat5–based regi-mens. In fact, Charpentier et al5 reported that 2 of 8 antiret-roviral-naivepatients startingelvitegravir/cobicistat–basedan-tiretroviral treatment had experienced virologic failure.In this context,webelieve that testingbaseline InSTIgeno-typemight be considered inparticular epidemiologic settingsif such polymorphisms are reported to be frequent in a givenLettersjama.com (Reprinted) JAMA November 27, 2018 Volume 320, Number 20 2153© 2018 American Medical Association. All rights reserved.Downloaded From: https://jamanetwork.com/ by a Universidad de Barcelona User  on 05/25/2020population, region, or HIV risk group, particularly if raltegra-vir or elvitegravir/cobicistat are the available or chosen In-STIs. Regimenswith bictegravir or dolutegravir would not beaffected by such polymorphisms.Juan Ambrosioni, MD, PhDMar Mosquera, MDJosé M. Miró, MD, PhDAuthor Affiliations: Infectious Diseases Service, Hospital Clinic of Barcelona,Barcelona, Spain (Ambrosioni, Miró); Service of Microbiology, Hospital Clinic ofBarcelona, Barcelona, Spain (Mosquera).Corresponding Author: JoséM. Miró, MD, PhD, Infectious Diseases Service,Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain (jmmiro@ub.edu).Conflict of Interest Disclosures: The authors have completed and submittedthe ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Miróreported receiving personal fees and academic and research grants fromAbbvie, Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen,Medtronic, Merck, Novartis, Pfizer, and ViiV Healthcare. No other disclosureswere reported.1. SaagMS, Benson CA, Gandhi RT, et al. Antiretroviral drugs for treatment andprevention of HIV infection in adults: 2018 recommendations of theInternational Antiviral Society–USA Panel. JAMA. 2018;320(4):379-396. doi:10.1001/jama.2018.84312. Casadellà M, van Ham PM, Noguera-Julian M, et al; SPREAD Programme.Primary resistance to integrase strand-transfer inhibitors in Europe.J Antimicrob Chemother. 2015;70(10):2885-2888. doi:10.1093/jac/dkv2023. Ambrosioni J, Nicolás D, Manzardo C, et al. Integrase strand-transfer inhibitorpolymorphic and accessory resistance substitutions in patients withacute/recent HIV infection. J Antimicrob Chemother. 2017;72(1):205-209. doi:10.1093/jac/dkw3764. Charpentier C, Descamps D. Resistance to HIV integrase inhibitors: aboutR263K and E157Qmutations. Viruses. 2018;10(1):E41. doi:10.3390/v100100415. Charpentier C, Malet I, Andre-Garnier E, et al. Phenotypic analysis of HIV-1E157Q integrase polymorphism and impact on virological outcome in patientsinitiating an integrase inhibitor–based regimen. J Antimicrob Chemother. 2018;73(4):1039-1044. doi:10.1093/jac/dkx511In Reply As stated in the panel’s report,1 the relative absenceof resistance-conferringmutations for InSTIdrugssupports therecommendation to not test routinely for InSTI resistance be-fore start of HIV treatment. A summary of existing data re-garding the relative lack of transmission of InSTI resistance–conferring mutations was published this year.2As discussed by Dr Ambrosioni and colleagues, the rela-tively high prevalence of InSTI polymorphisms is of someconcern. We agree that it is worth monitoring the effect ofInSTI polymorphisms over time, especially as they maypotentially affect the efficacy of 2-drug, InSTI-basedtherapy. To date, however, there are few data indicating thatthese mutations have meaningful clinical effect on virologicresponse, especially to InSTI agents recommended for ini-tial therapy.One of the main reasons the recommendations are up-dated every 2 years is to incorporate new data that emerge re-garding treatment of patients with and at risk for HIV infec-tion. Since relevant and important data often emerge quicklyin this dynamic field, we are grateful to Ambrosioni and col-leagues for putting this issue on the “watch list” for future rec-ommendations.Michael S. Saag, MDHuldrych F. Günthard, MDDavey M. Smith, MDAuthor Affiliations: School of Medicine, University of Alabama at Birmingham(Saag); University Hospital Zurich, Zurich, Switzerland (Günthard); University ofCalifornia, San Diego, La Jolla (Smith).Corresponding Author:Michael S. Saag, MD, School of Medicine, University ofAlabama at Birmingham, 845 19th St S, BBRB 256, Birmingham, AL 35294(msaag@uabmc.edu).Conflict of Interest Disclosures: The authors have completed and submitted theICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Saag reportedreceiving grants and personal fees fromMerck, Gilead, andViiV.Dr Günthard reported receiving grants from theNational Institutes of Health, SwissNational Science Foundation, Swiss HIV Cohort Study, University of Zurich, YvonneJacob Foundation, SystemsX, Gilead, andRoche and receiving personal fees fromMerck, Gilead, Sandoz, and Teva. No other disclosureswere reported.1. SaagMS, Benson CA, Gandhi RT, et al. Antiretroviral drugs for treatment andprevention of HIV infection in adults: 2018 recommendations of theInternational Antiviral Society–USA panel. JAMA. 2018;320(4):379-396. doi:10.1001/jama.2018.84312. Günthard HF, Calvez V, Paredes R, et al. Human immunodeficiency virus drugresistance: 2018 recommendations of the International Antiviral Society–USApanel. Clin Infect Dis. 2018;67:1-11.CORRECTIONIncorrect Data in Figures: In the Original Investigation entitled “Effect of Escit-alopramvsPlaceboTreatment forDepressiononLong-termCardiacOutcomes inPatientsWith Acute Coronary Syndrome: A Randomized Clinical Trial,” publishedin the July 24/31, 2018, issue of JAMA,1 errors occurred in figures. In Figure 2, in-correct data curveswere published in the graph, and in Figures 2 and 3, incorrectnumbers at risk were shown. This article has been corrected online.1. Kim JM, Stewart R, Lee YS, et al. Effect of escitalopram vs placebo treatmentfor depression on long-term cardiac outcomes in patients with acute coronarysyndrome: a randomized clinical trial. JAMA. 2018;320(4):350-358. doi:10.1001/jama.2018.9422Unclear Sentence and Incorrect Number in Figure: The Research Letter en-titled “Lethality of Civilian Active Shooter Incidents With andWithout Semiauto-matic Rifles in the United States,”1 published in the September 11, 2018, issue ofJAMA, contained an unclear sentence. The second sentence should have beenworded as follows: “Many weapons were banned in 1994 under the federal as-sault weapons ban but were reintroduced to the public marketplace in 2004.” Inaddition, the Figure should have reported the number of active shooter incidentswith a semiautomatic rifle as n = 61. This article was corrected online.1. de Jager E, Goralnick E, McCarty JC, Hashmi ZG, JarmanMP, Haider AH.Lethality of civilian active shooter incidents with and without semiautomaticrifles in the United States. JAMA. 2018;320(10):1034-1035. doi:10.1001/jama.2018.11009Letters2154 JAMA November 27, 2018 Volume 320, Number 20 (Reprinted) jama.com© 2018 American Medical Association. All rights reserved.Downloaded From: https://jamanetwork.com/ by a Universidad de Barcelona User  on 05/25/2020

Baseline genotype testing to assess drug resistance before beginning HIV treatment

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Baseline genotype testing to assess drug resistance before beginning HIV treatment

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