Mark A Wainberg Elly Katabira PUBLISH OR PERISH Strengthening the Skills of Developing World Investigators to Publish their Research/Project Findings Skills Building Workshop

Workshop Objectives Increase knowledge of the role of eJIAS in supporting research from the developing world Increase knowledge of the role of eJIAS in supporting research from the developing world Increase understanding of ms requirements and peer review process for scientific journals Increase understanding of ms requirements and peer review process for scientific journals Strengthen skills in manuscript preparation Strengthen skills in manuscript preparation

Mark A Wainberg Elly Katabira electornic Journal of the International AIDS Society (eJIAS) Skills Building Workshop

eJIAS Objectives 1. To provide a prominent, accessible, and prestigious forum for the publication of original, peer-reviewed articles that advance the field of HIV/AIDS in developing countries 2. To encourage and facilitate publication by scientists and clinicians working in developing countries 3. To improve the dissemination of high-quality medical evidence from research conducted in a diversity of geographic, cultural, socioeconomic, and clinical settings 4. To enable scientists and healthcare personnel to remain informed about research, analysis and opinion relevant to the delivery of HIV/AIDS prevention, treatment, and care in developing countries

eJIAS  publishing platform for high quality medical information that uses the internet as its medium because it is better, faster, and cheaper than any other medium  Articles published in eJIAS are available at no cost to readers or authors

eJIAS Publishes Research study results Research study results Review articles Review articles Case reports Case reports Editorials Editorials Letters to the editor Letters to the editor

eJIAS Readership Readership (up to 2008) PhysiciansNurses Other HCPs Total Unique Users 10,2721,20612,87924,357 Page Views 25,4772,58431,09927,302

Workshops/ Mentoring Training workshops are aimed at strengthening the conceptualization, manuscript development and peer-review skills of young investigators from resource-limited settings Training workshops are aimed at strengthening the conceptualization, manuscript development and peer-review skills of young investigators from resource-limited settings 3rd IAS Conference on HIV Pathogenesis and Treatment3rd IAS Conference on HIV Pathogenesis and Treatment Eastern European and Central Asian AIDS ConferenceEastern European and Central Asian AIDS Conference XVI International AIDS Conference (AIDS 2006) (Toronto)XVI International AIDS Conference (AIDS 2006) (Toronto) 4 th IAS Conference on HIV Pathogenesis and Treatment (Sydney, 2007)4 th IAS Conference on HIV Pathogenesis and Treatment (Sydney, 2007) IXVII International IADS Conference (Mexico City, 2008)IXVII International IADS Conference (Mexico City, 2008) Online abstract mentoring programme: new investigators linked to experienced researchers in the developed and developing world Online abstract mentoring programme: new investigators linked to experienced researchers in the developed and developing world

Skills Building Workshop: How to Write a Paper for Publication 1st AIDS Conference of Central Europe 5 -8 June 2008

Study Design The most important factors affecting manuscript publication are the design and implementation of the research or study and the analysis of the data The most important factors affecting manuscript publication are the design and implementation of the research or study and the analysis of the data

Title Page  Write the paper’s title  List study authors (including highest degrees attained)  List the institution of each author (using footnotes to list institutional affiliation)

Abstract A brief summary of the manuscript A brief summary of the manuscript No information appears in the abstract that does not also appear in the body No information appears in the abstract that does not also appear in the body See specific formatting requirements for each journal See specific formatting requirements for each journal

Introduction  Provide a brief discussion of the general topic (why is it important?)  Provide a brief discussion of prior work by you and/or others  Provide an explicit statement of your study question/hypothesis

Group Work Title Page, Abstract, Introduction Identify the components of the title page, abstract and introduction Identify the components of the title page, abstract and introduction Are they all there?Are they all there? What is missing?What is missing? Is there information that belongs in another section? Is there information that belongs in another section? Identify the objectives of the study Identify the objectives of the study How could these sections be improved? How could these sections be improved? Identify what the authors have done particularly well Identify what the authors have done particularly well

Methods  Describe your study site  Describe your study population (source, inclusion, and exclusion criteria)  Describe your recruitment methods in detail  Describe your intervention (if an interventional study)  Describe the data that you collected and how it was collected  Describe your data analysis in detail (dependent variables, independent variables, comparisons, primary and secondary analysis, statistical methods used, P-value accepted as significant, etc.)

Group Work Methods Identify the components of the materials/ methods section Identify the components of the materials/ methods section Are they all there?Are they all there? What is missing?What is missing? Is there information that belongs in another section? Is there information that belongs in another section? Identify areas of the study design that were innovative and areas that could be improved Identify areas of the study design that were innovative and areas that could be improved

Results  Describe main analysis results: (Do not repeat table data – describe the table data in qualitative terms, where possible)  Provide relevant statistical information: report statistical significance or lack thereof (again, do not repeat table data)  Describe secondary analysis results (again, do not repeat table data)

Group Work Results Identify the components of the results section Identify the components of the results section Are they all there?Are they all there? What is missing?What is missing? Is there information that belongs in another section? Is there information that belongs in another section? How could this section be improved? How could this section be improved? What have the authors done particularly well? What have the authors done particularly well?

Discussion  Write down the most important take-home point that you want the reader to remember  Write down the second most important take- home point and discuss it  Write down the third most important take-home point and discuss it  List and discuss the study’s limitations  Write down your conclusions (usually a version of the first take-home point that you want the reader to remember)  Give future directions (often the next study you want to do following this one)

Group Work Discussion Identify all components of the discussion Identify all components of the discussion Are they all there?Are they all there? What is missing?What is missing? Is there information that belongs in another section? Is there information that belongs in another section? Do the authors use different headings for this section? Do the authors use different headings for this section? How could this section be improved? How could this section be improved? What have the authors done particularly well? What have the authors done particularly well?

Figures and Tables

Group Work Figures and Tables Identify different components of the figures and tables Identify different components of the figures and tables Are they labeled adequately?Are they labeled adequately? Are the figures and tables described in the text? Are the figures and tables described in the text? Is there numerical information in the text that is not summarized in a figure or table? Is there numerical information in the text that is not summarized in a figure or table? How could these sections be improved? How could these sections be improved? What have the authors done particularly well? What have the authors done particularly well?

Peer-Review Process 1. Editors-in-chief and Executive Editor 2. Reviewers 3. Comments and suggestions to author (rejection or revision) 4. Revised manuscript to reviewers 5. Copyediting 6. Author 7. Production 8. Posting

Peer Review Experience Group Discussion Problems with manuscript submission? Problems with manuscript submission? Feedback from peer reviewers? Feedback from peer reviewers? Group discussion/problem solving Group discussion/problem solving

Advice from Peer Reviewers Are there fatal flaws? Are there fatal flaws? Is there sufficient technical content? Is there sufficient technical content? Is it new? Is it new? Is it sufficiently important? Is it sufficiently important? Is there balanced and proper use of references? Is there balanced and proper use of references? Is this article suitable for this journal? Is this article suitable for this journal? Should we suspect conflict of interest? Should we suspect conflict of interest? Technical merit (and can it be saved, if flawed?) Technical merit (and can it be saved, if flawed?) What do you suggest to improve the manuscript? What do you suggest to improve the manuscript? New experimentsNew experiments New dataNew data New technical informationNew technical information Re-writingRe-writing

Final Recommendation [ ] Accept as is [ ] Accept if suitably revised [ ] Revise and reconsider [ ] Reject

Top 10 Reasons for Failure to Publish* 1. Poor study design 2. Picking the wrong journal 3. Incorrect format for journal 4. Not following manuscript preparation guide 5. Poor writing 6. Unnecessary information in discussion 7. Suboptimal results reporting 8. Inadequate description of methods 9. Failure to revise/resubmit after peer review 10. Failure to write/submit full manuscript after abstract presentation *Adapted from: The Top 10 Reasons Why Manuscripts Are Not Accepted for Publication Pierson DJ, Respiratory Care, Oct. 2004, 49:10.

Resources Cetin S, Hackman D. An Approach to the Writing of a Scientific Manuscript Cetin S, Hackman D. An Approach to the Writing of a Scientific Manuscript Journal of Surgical Research 128, (2005) Reporting Randomized Clinical Trials Reporting Randomized Clinical Trials Moher D. Schultz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials BMC Medical Research Methodology 2001, 1:2 Translation of CONSORT statement into Russian and other languages: Translation of CONSORT statement into Russian and other languages: Ioannidis JPA, Evans SJW, Gotzsche PC, et al, for the CONSORT Group. Better reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement Ioannidis JPA, Evans SJW, Gotzsche PC, et al, for the CONSORT Group. Better reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement Annals of Internal Medicine: 2004; 141:

DefectiveHIV Viruses Can Play a Role in Pathogenesis Defective HIV Viruses Can Play a Role in Pathogenesis Authors: Same Background: To assess if defective viruses can be rescued by recombination. Methods: We infected cell lines with defective drug-resistant viruses and rescued them by super-infection and recombination. Results: A cell line that produced non-infectious particles was super-infected with either wild-type viruses or complementary drug-resistant viruses. We found that the cultures went on to produce viruses containing drug-resistance mutations. Conclusions: The clinical significance of our findings will be discussed.

HIV Subtypes Differ in Regard to Drug Resistance Authors: Same Background: Subtypes of HIV may differ in regard to drug resistance. We wanted to test if this was true. test if this was true. Methods: Viruses of different subtypes were grown in the presence of various drugs. Mutations were analyzed by sequencing. Results: We showed that subtype C viruses were more prone to develop K65R than were subtype B viruses. This was shown in multiple experiments. Many drugs were capable of yielding this result including tenofovir. Conclusions: These results show that subtype C viruses can develop the K65R mutation faster than those of subtype B. The clinical significance of this observation will be discussed.

Biological Basis for Preferential Selection of the K65R Mutation in HIV Subtype C C Invernizzi, D Coutsinos, B Brenner, M Oliveira, D Moisi, and MA Wainberg McGill University AIDS Centre, Jewish General Hospital, Montreal, Canada Background: We have shown that subtype C HIV-1 selects more rapidly for K65R than does Subtype B under nucleoside drug pressure in cell culture. However, biochemical studies that compared the reverse transcriptase (RT) enzymes of these subtypes did not reveal major differences. This study was performed to determine whether differences between the subtypes in regard to RNA template might be responsible for the differences observed. Methods: NL4-3 (C 64/65) plasmid (subtype B with subtype C nucleotide sequence at residues ) was generated from NL4-3 (wt) plasmid (subtype B) by site-directed mutagenesis. MT2 cells were infected with viruses harvested from 293T cells (multiplicity of infection, 0.01) over 2 hours. Infected MT2 cells were seeded and selections for drug resistance performed in the presence of various drugs, e.g. TNF, ABC, 3TC. Culture fluids were collected for genotypic analysis. Results: Biochemical results showed increased pausing at the 65 position in RT when reactions were performed with subtype C as opposed to subtype B templates. In contrast, NL4-3 (wt) acquired K65R after >15 passages in the presence of TNF and M184I/V after 7 to 13 passages in the presence of TNF plus either 3TC or ABC. In contrast, NL4-3 (C 64/65) developed K65R after as few as 7 passages with any of TNF or TNF + 3TC. As expected, exposure to 3TC alone led to M184I/V in both cases after only 7 passages. Single mutations in NL4-3 (wt) that yielded either NL4-3 (C 64) or NL4-3 (C 65) did not increase the probability for K65R acquisition. Conclusion: These results, together with our previous mechanistic data, demonstrate that nucleotide sequence changes at both positions 64 and 65 within subtype C, distinct from subtype B, redirect the selection pattern with a variety of N(t)RTIs toward the K65R resistance mutation pathway. Hence, the 64/65 changes in subtype C are required in tandem and represent signature polymorphisms for the development of K65R in this subtype in regard to N(t)RTI selective pressure.

Superinfection and Recombination Can Rescue Replication-Deficient Multiply Drug-Resistant Variants of HIV-1 Y Quan, BG Brenner, C Liang and MA Wainberg McGill University AIDS Centre, Jewish General Hospital Montreal, Quebec, Canada Background: To assess whether replication-defective HIV variants, that harbor drug-resistance (DR) mutations, can potentially be rescued by superinfection and recombination. Methods: Cell lines were infected with DR viruses and cells were isolated that contained defective provirus, as confirmed by sequencing. We then super-infected the cells with other complementary defective viruses to try to rescue the DR mutations. Results: A clonal cellular outgrowth, derived from MT2 cells that were infected with a multiply drug-resistant (MDR) variant, was shown to produce non-infectious particles. Superinfection of these cells by wild-type (wt) HIV-1 led to production of replication-competent MDR viruses. In addition, superinfection also was achieved using a replication-defective, non-revertant virus, mutated in capsid, also leading to production of infectious viral progeny. Sequencing confirmed the results and that the producer cells initially contained two copies of different defective proviral genomes and were presumably able to produce functional virions through complementation and assembly of viral proteins produced from the two differently defective proviral genomes. This was then followed by recombination between the complementary HIV genomes during a second round of infection. Sequencing also showed that the majority of the rescued viruses were wild-type when the cells were passaged in the absence of RT inhibitors, but that MDR viruses dominated the cultures if even single RT inhibitors were present. Conclusions: Cells that harbor defective viruses can produce infectious progeny after superinfection by another defective virus, because of probable recombination during second rounds of infection. Defective HIV variants may represent an important component of the HIV-1 reservoir in terms of both wt and drug-resistant viral progeny.

Submitting Manuscripts to eJIAS See Instructions to Authors: See Instructions to Authors: Or submit directly to: Or submit directly to: Mark Wainberg Elly Katabira Shirin Heidari Shirin Heidari

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