{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T06:57:01Z","timestamp":1778914621630,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.14683.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T00:00:00Z","timestamp":1554249600000}}],"reference-count":29,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T00:00:00Z","timestamp":1554249600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002992","name":"Department for International Development, UK Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002992","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["095778"],"award-info":[{"award-number":["095778"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"\n Background:<\/ns4:bold>\n It has been hypothesised that\n Schistosoma<\/ns4:italic>\n co-infection exacerbates HIV progression, and hence anthelminthic intervention in co-infected individuals will delay it. We evaluated effects of high-intensity versus low-intensity praziquantel treatment of schistosomiasis on HIV disease progression among co-infected patients from fishing populations around Lake Victoria, Uganda.\n <\/ns4:p>\n \n Methods<\/ns4:bold>\n : Between August 2012 and September 2015, we conducted an open-label randomised, controlled trial. Adults, antiretroviral therapy-na\u00efve, CD4 counts \u2265350 cells\/\u03bcl, HIV and\n S. mansoni<\/ns4:italic>\n co-infected, were randomised 1:1 to praziquantel (40mg\/kg) given quarterly (starting at enrolment) or annually (starting 12 weeks after enrolment; such that low-intensity participants were still untreated when sampled at 12 weeks). A non-randomised HIV-positive\n S. mansoni-<\/ns4:italic>\n negative comparison group was recruited. The primary outcome was mean change in plasma viral load at 12 and 60 weeks.\n <\/ns4:p>\n \n Results:<\/ns4:bold>\n In total 363 participants (high-intensity 113, low-intensity 113, comparison group 137) were recruited; 96 (85.0%), 97 (85.8%) and 107 (78.1%) completed 60 weeks of follow up, respectively. Adjusting for baseline age and viral load, the geometric mean ratio (aGMR [95%CI]) viral load for high-intensity vs low-intensity groups at 12 weeks was 0.90 [0.65, 1.25] p=0.55 and at 60 weeks 1.88 [0.78, 4.53] p=0.16. Results in the comparison group were similar to trial arms. High-intensity, compared to low-intensity, treatment resulted in substantially lower\n S. mansoni<\/ns4:italic>\n prevalence at all follow up visits (p<0.05).\n <\/ns4:p>\n \n Conclusions:<\/ns4:bold>\n In communities with a high burden of both\n S. mansoni<\/ns4:italic>\n and HIV infection, high-intensity treatment of\n S. mansoni<\/ns4:italic>\n does not delay HIV progression despite relevant benefit for parasite clearance.\n <\/ns4:p>\n \n Trial registration:<\/ns4:bold>\n ISRCTN15371662<\/ns4:ext-link>\n (17\/11\/2016)\n <\/ns4:p>","DOI":"10.12688\/wellcomeopenres.14683.2","type":"journal-article","created":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T11:15:08Z","timestamp":1554290108000},"page":"81","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of high-intensity versus low-intensity praziquantel treatment on HIV disease progression in HIV and Schistosoma mansoni co-infected patients: a randomised controlled trial"],"prefix":"10.12688","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6770-5588","authenticated-orcid":false,"given":"Andrew","family":"Abaasa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9966-1153","authenticated-orcid":false,"given":"Gershim","family":"Asiki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8255-8822","authenticated-orcid":false,"given":"Andrew","family":"Obuku Ekii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josephine","family":"Wanyenze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2334-0684","authenticated-orcid":false,"given":"Pietro","family":"Pala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Govert","family":"J. van Dam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0004-0526","authenticated-orcid":false,"given":"Paul L.A.M.","family":"Corstjens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8069-1056","authenticated-orcid":false,"given":"Song","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Pantaleo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pontiano","family":"Kaleebu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2818-9549","authenticated-orcid":false,"given":"Alison M.","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anatoli","family":"Kamali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2019,4,3]]},"reference":[{"key":"ref-1","first-page":"249-51","article-title":"[Bilharziasis and human immunodeficiency virus infection in Congo].","volume":"55","author":"M N'Zoukoudi-N'Doundou","year":"1995","journal-title":"Med Trop (Mars)."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"431-5","DOI":"10.4269\/ajtmh.1998.58.431","article-title":"Intestinal parasitic infections in human immunodeficiency virus (HIV)-positive and HIV-negative individuals in San Pedro Sula, Honduras.","volume":"58","author":"J Lindo","year":"1998","journal-title":"Am J Trop Med Hyg."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"269-78","DOI":"10.1080\/00034983.2000.11813539","article-title":"Epidemiology of infections with intestinal parasites and human immunodeficiency virus (HIV) among sugar-estate residents in Ethiopia.","volume":"94","author":"A Fontanet","year":"2000","journal-title":"Ann Trop Med Parasitol."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"777-82","DOI":"10.4269\/ajtmh.2005.73.777","article-title":"Prevalence and predictors of intestinal helminth infections among human immunodeficiency virus type 1-infected adults in an urban African setting.","volume":"73","author":"K Modjarrad","year":"2005","journal-title":"Am J Trop Med Hyg."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"315-33","DOI":"10.1016\/S0001-706X(03)00063-9","article-title":"Could control of soil-transmitted helminthic infection influence the HIV\/AIDS pandemic.","volume":"86","author":"J Fincham","year":"2003","journal-title":"Acta Trop."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"1012-30","DOI":"10.1128\/CMR.17.4.1012-1030.2004","article-title":"Chronic immune activation associated with chronic helminthic and human immunodeficiency virus infections: role of hyporesponsiveness and anergy.","volume":"17","author":"G Borkow","year":"2004","journal-title":"Clin Microbiol Rev."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"605-12","DOI":"10.1111\/j.1365-3024.2006.00918.x","article-title":"HIV and helminth co-infection: is deworming necessary?","volume":"28","author":"G Borkow","year":"2006","journal-title":"Parasite Immunol."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"483-96","DOI":"10.1111\/j.1365-3024.2006.00909.x","article-title":"Immune modulation by helminthic infections: worms and viral infections.","volume":"28","author":"S Kamal","year":"2006","journal-title":"Parasite Immunol."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"113-9","DOI":"10.1046\/j.1365-2249.2003.02106.x","article-title":"Role of incidental and\/or cured intestinal parasitic infections on profile of CD4+ and CD8+ T cell subsets and activation status in HIV-1 infected and uninfected adult Ethiopians.","volume":"132","author":"A Kassu","year":"2003","journal-title":"Clin Exp Immunol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"56-62","DOI":"10.1097\/00126334-200209010-00008","article-title":"Treatment of intestinal worms is associated with decreased HIV plasma viral load.","volume":"31","author":"D Wolday","year":"2002","journal-title":"J Acquir Immune Defic Syndr."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"e102","DOI":"10.1371\/journal.pntd.0000102","article-title":"Treatment of helminth co-infection in individuals with HIV-1: A systematic review of the literature.","volume":"1","author":"J Walson","year":"2007","journal-title":"PLoS Negl Trop Dis."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"307-13","DOI":"10.1097\/QAI.0b013e3182511e42","article-title":"The effect of anthelmintic treatment during pregnancy on HIV plasma viral load: results from a randomized, double-blind, placebo-controlled trial in Uganda.","volume":"60","author":"E Webb","year":"2012","journal-title":"J Acquir Immune Defic Syndr."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"925-32","DOI":"10.1016\/S1473-3099(12)70207-4","article-title":"Empiric deworming to delay HIV disease progression in adults with HIV who are ineligible for initiation of antiretroviral treatment (the HEAT study): a multi-site, randomised trial.","volume":"12","author":"J Walson","year":"2012","journal-title":"Lancet Infect Dis."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"CD006419","DOI":"10.1002\/14651858.CD006419.pub4","article-title":"Antihelminthics in helminth-endemic areas: effects on HIV disease progression.","volume":"4","author":"A Means","year":"2016","journal-title":"Cochrane Database Syst Rev."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"733-44","DOI":"10.1038\/nri1183","article-title":"Immune regulation by helminth parasites: cellular and molecular mechanisms.","volume":"3","author":"R Maizels","year":"2003","journal-title":"Nat Rev Immunol."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"13-6","DOI":"10.1590\/S0074-02761987000800004","article-title":"Immunological aspects of host-schistosome relationships.","volume":"82 Suppl 4","author":"R Damian","year":"1987","journal-title":"Mem Inst Oswaldo Cruz."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s13063-015-0702-5","article-title":"The Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA): study protocol for a randomised controlled trial.","volume":"16","author":"M Nampijja","year":"2015","journal-title":"Trials."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"511-5","DOI":"10.1136\/sti.2010.046805","article-title":"HIV and syphilis prevalence and associated risk factors among fishing communities of Lake Victoria, Uganda.","volume":"87","author":"G Asiki","year":"2011","journal-title":"Sex Transm Infect."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"2437-43","DOI":"10.1097\/00002030-200011100-00004","article-title":"The effect of treatment of schistosomiasis on blood plasma HIV-1 RNA concentration in coinfected individuals.","volume":"14","author":"S Lawn","year":"2000","journal-title":"AIDS."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"1648-57","DOI":"10.1086\/429668","article-title":"Treatment of Schistosoma mansoni infection increases helminth-specific type 2 cytokine responses and HIV-1 loads in coinfected Ugandan adults.","volume":"191","author":"M Brown","year":"2005","journal-title":"J Infect Dis."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"1956-61","DOI":"10.1086\/497696","article-title":"Schistosomiasis and HIV-1 infection in rural Zimbabwe: effect of treatment of schistosomiasis on CD4 cell count and plasma HIV-1 RNA load.","volume":"192","author":"P Kallestrup","year":"2005","journal-title":"J Infect Dis."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"1311-20","DOI":"10.1086\/428907","article-title":"Schistosomiasis and HIV-1 infection in rural Zimbabwe: implications of coinfection for excretion of eggs.","volume":"191","author":"P Kallestrup","year":"2005","journal-title":"J Infect Dis."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"1190-5","DOI":"10.1111\/tmi.12531","article-title":"Schistosoma mansoni and HIV acquisition in fishing communities of Lake Victoria, Uganda: a nested case-control study.","volume":"20","author":"A Ssetaala","year":"2015","journal-title":"Trop Med Int Health."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"1201-8","DOI":"10.1111\/tmi.12545","article-title":"Schistosoma mansoni and HIV infection in a Ugandan population with high HIV and helminth prevalence.","volume":"20","author":"R Sanya","year":"2015","journal-title":"Trop Med Int Health."},{"key":"ref-25","first-page":"397-400","article-title":"A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni.","volume":"14","author":"N Katz","year":"1972","journal-title":"Rev Inst Med Trop Sao Paulo."},{"key":"ref-26","article-title":"Report of the WHO Informal Consultation on Hookworm Infection and Anaemia in Girls and Women","year":"1995"},{"key":"ref-27","first-page":"145-63","article-title":"Schistosomiasis and soil-transmitted helminth infections--preliminary estimates of the number of children treated with albendazole or mebendazole.","volume":"81","year":"2006","journal-title":"Wkly Epidemiol Rec."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"433-9","DOI":"10.1097\/OLQ.0b013e318251555d","article-title":"High HIV incidence and socio-behavioral risk patterns in fishing communities on the shores of Lake Victoria, Uganda.","volume":"39","author":"J Seeley","year":"2012","journal-title":"Sex Transm Dis."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"103-8","DOI":"10.1016\/S0035-9203(03)90040-X","article-title":"Associations between helminth infection and CD4+ T cell count, viral load and cytokine responses in HIV-1-infected Ugandan adults.","volume":"97","author":"A Elliott","year":"2003","journal-title":"Trans R Soc Trop Med Hyg."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-81\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-81\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-81\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T02:22:14Z","timestamp":1554949334000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-81\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,3]]},"references-count":29,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.14683.2","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.16601.r35215","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.16601.r35215","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,3]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-81\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.16601.r35215, Judd L. Walson, Departments of Global Health, Medicine (Infectious Disease), Pediatrics and Epidemiology, University of Washington, Seattle, WA, USA, 04 Apr 2019, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-81\/v2#referee-response-35215","order":0,"name":"referee-response-35215","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.15987.r33727, Paul Garner, Liverpool School of Tropical Medicine\u00a0(LSTM), Liverpool, UK, 19 Oct 2018, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-81\/v1#referee-response-33727","order":1,"name":"referee-response-33727","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Andrew Abaasa<\/b>; \nPosted: 26 Mar 2019<\/i>; \nEffect of high-intensity versus low-intensity praziquantel treatment on HIV disease progression in HIV and Schistosoma mansoni <\/i>co-infected patients: a randomised controlled trial<\/b> \n <\/b> \nAbaasa et al<\/b> \n <\/b> \nResponse to the reviewer\u2019s comments <\/u><\/b> \n <\/b> \nReviewer Three<\/b> \nPaul Garner<\/b>, Liverpool School of Tropical Medicine (LSTM), Liverpool, UK  Approved 1.     The authors examine the question of whether helminth infection-with Schistosomiasis-exacerbates HIV infection. The authors give PZ to S mansoni infected people, and those on the low intensity schedule were untreated at 12 weeks so a direct comparison of no treatment with PZ 40 dose was possible in terms of mean change in geometric mean of viral load. The treatment reduced S mansoni but did not show any impact on mean viral load change. 2.     This is an important study and is highly relevant in a research question where there seem to be strong beliefs there is an effect, yet effects to date have been mixed but always quite small, and as such the evidence base is at risk of selective publication and selective reporting. The authors have therefore done a service to science in ensuring this study, which does not demonstrate an effect, has been published. They also appear to have adhered to the protocol and not sought secondary outcomes or subgroup analyses that risk generating spurious results. 3.     It is a fascinating also because the authors were able to evaluate the effect of PZ and treating the infection in people with HIV that was not suppressed by ARVs. This was because it was conducted prior to the WHO recommendation to treat all people living with HIV with ARVs irrespective of CD counts. So this study is \u201cas good as it will ever get\u201d in testing whether treatment has any influence on HIV progression. 4.     The study is well-written. The background explains studies to date and the gap in the literature leading to this study. Whilst this is a basic expectation of the background section, so many authors do not do this or do it badly, surprisingly; I will use this as an example of good practice in our teaching!  and the methods are clearly explained. The follow up is good and the results well presented. 5.     It is appropriately reported without any attempt to overinterpret the results. Given the complexity of the study the authors have good numbers recruited. Very few people were started on ARVs during the course of the study and the sensitivity analysis showed this did not, by chance, influence the results, which might have happened if there was chance imbalance in the numbers treated in comparator groups. 6.     The one point that would really help understand the context-and this is a broader concern with these studies of this kind around treating helminths in HIV (including the studies of albendazole used for soil transmitted helminth infection in people with HIV) is the ambiguity around the purpose of the study: is it truly believed by the authors that this could be potentially important component of treatment by delaying progression of the disease as stated in the first sentence of the discussion? Or that treatment of schisto could have some public health impact on transmission as outlined at the end of paragraph 3 in the introduction? Or is it simply a randomised explanatory trial to elucidate immune mechanisms with helminth infection? This is the only strongly recommended change I would want to see in the amended version. \nResponse<\/u>: Much as we are fascinated by the immunomodulating effects of helminths, and the wider implications of this for human health, we confirm that our intention in conducting this relatively large trial was to obtain conclusive information (to the extent possible) on whether treating schistosomiasis has significant benefit for controlling HIV replication and progression.  Therefore we believe that the statements in the introduction reflect our true position prior to conducting the trial.<\/i><\/b> 7.     With the absence of any demonstrable effect in this study, it seems most unlikely, given the dramatic effectiveness of ARVs in viral suppression, that further studies would be worthwhile. Indeed, given patients would need to be on ARVS, with such small putative possible effects of the treatment, the studies would have to be extremely large, probably so large that no-one would fund them. I think it would be extremely worthwhile reporting in their discussion.  \nResponse<\/u>: This is a thought provoking comment.  We agree that it is not likely to be worth testing the effects of treatment of S. mansoni on HIV progression any further.  However, although antiretroviral treatment is recommended on a \u201ctest and treat\u201d basis in high HIV transmission settings, such as fishing communities, this is not easy to implement. So complementary interventions which may be easier to implement would be worth consideration.<\/i><\/b>","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-81\/v2#referee-comment-3833","order":2,"name":"referee-comment-3833","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.15987.r34261, Birgitte\u00a0Jyding\u00a0 Vennervald, Section for Parasitology and Aquatic Pathobiology (PAP), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, 15 Nov 2018, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-81\/v1#referee-response-34261","order":3,"name":"referee-response-34261","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Andrew Abaasa<\/b>; \nPosted: 26 Mar 2019<\/i>; \nEffect of high-intensity versus low-intensity praziquantel treatment on HIV disease progression in HIV and Schistosoma mansoni <\/i>co-infected patients: a randomised controlled trial<\/b> \n <\/b> \nAbaasa et al<\/b> \n <\/b> \nResponse to the reviewer\u2019s comments <\/u><\/b> \n <\/b> \nReviewer Two<\/b> \nBirgitte Jyding  Vennervald<\/b>, Section for Parasitology and Aquatic Pathobiology (PAP), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark  Approved   This is a very interesting paper reporting the results of an open-label Randomised Controlled Trial (RCT) on the effect of intensive, 4 times per year vs. standard once yearly PZQ treatment on viral load among HIV and \nSchistosoma mansoni <\/i>co-infected people living in fishing communities near lake Victoria. A non-randomised HIV-positive \nS. mansoni-<\/i>negative comparison group was recruited as well.   The primary study outcome was viral load at 12 and 60 weeks of follow up. Secondary outcomes were CD4 counts and the clinical progression of the HIV infection and reduction of \nS. mansoni<\/i> infection prevalence and intensity.   The results showed no statistically significant diffrences in viral load between the high-intensity vs low-intensity treatment groups at 12 weeks and 60 weeks and the overall conclusion of the paper is that in fishing communities with high \nS. mansoni <\/i>and HIV infection prevalences, high-intensity treatment of S. mansoni does not delay HIV progression. The paper is clearly and well written. Overall the study is well conducted; the results described in a clear and concise manner and the conclusions drawn based on the results are sound and justified. I am very pleased to see that the authors report their results findings despite the fact that they found no significant differences between the two arms. This is highly important for the scientific community and generally for society that negative results are published. Well done. We should see more of that. I have some minor questions or comments to various sections of the paper: 1.     The parasitological diagnosis was based on Kato-Katz technique with preparation of two slides per stool sample. I would have liked the authors to state the amount of stool used for a slide, since this may vary (25mg to 50 mg) and have an impact of the overall sensitivity of the method. \nResponse<\/u>: Thank you for this observation, the amount of the stool used for slides was 41.7 mg.  This has been included in the manuscript.  <\/i><\/b> 2.     At the baseline examination and randomisation participants were providing three stool samples on three consecutive days. However, as far as I can see, parasitological results at follow-up time points are all based on a single stool. This has implications for the sensitivity of the test. Kato-Katz is not a very sensitive test and sensitivity is very low with just a single stool sample post treatment. This is why the CAA assay is very useful and important to include as an additional diagnostic measure. It would have been good to include these points in the discussion. \nResponse<\/u>: In our second paragraph of the discussion section, we allude to this<\/i><\/b>.   3.     I do not really see the point in having the group of \nS. mansoni <\/i>negatives. Parasitological and CAA analysis reveal that some of them are in fact infected at 12 weeks and they are treated with PZQ just like the low-intensity PZQ group. Furthermore, since they are \nS. mansoni <\/i>negative or very slightly infected despite living in a high transmission fishing community means that they may differ from the two randomisation groups with respect to parameters, which have not been investigated but which may be of importance. \nResponse<\/u>:  It is plausible that an infection such as schistosomiasis exacerbates HIV progression and that the effect is not reversible by treatment - because of persistence of helminth antigen, for example, and\/or lasting impact on the immune system.  As indicated in the discussion, we consider the results from the comparison group useful to address this possibility \u2013 there was no substantial difference in progression between the comparison group and either treatment arm.  We do agree, however, that there were important (and largely inevitable) differences between the comparison group and the infected groups and we acknowledge that all comparisons with that group should be taken with caution and as secondary results. We draw our major findings from the two randomized arms.<\/i><\/b> 4.     I am amazed to see that despite very intense PZQ treatment (every 12 weeks) it is not possible to bring \nS. mansoni <\/i>infection down to almost nothing in this group of adults. \nS. mansoni <\/i>is a tough parasite to treat. I am wondering if \nSchistosoma haematobium <\/i>is easier and if this may play a role when comparing with the Zimbabwean \nS. haematobium <\/i>study? \nResponse<\/u>: We thank the reviewer for this interesting comment.<\/i><\/b>   5.     I do not quite understand figure 2 based on the figure legend. Maybe the legend could be expanded. \nResponse<\/u>: The legend has been expanded to align PZQ with high-intensity not to give an impression it is with the comparison arm. <\/i><\/b>   6.     Could this maybe be re-phrased: \u201cproducing the type 2 bias of responses to worm antigens\u201d. Maybe just remove \u201cbias of\u201d. Whenever I read it I stumble on type 2 bias and try to figure out how statistics come into this. \nResponse<\/u>:  \u201cbias of\u201d has been removed <\/i><\/b>","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-81\/v2#referee-comment-3834","order":4,"name":"referee-comment-3834","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust through a Wellcome Trust Senior Fellowship grant [095778] to AME.\nThis work was also supported by European Community's Seventh Framework Programme [FP7\/2007-2013] under EC-GA n\u00b0 241642, and the UK Medical Research Council (MRC) and Department for International Development (DFID) as part of the MRC-DFID Concordat agreement. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}