Student: Frendalie Aurelia Marchena. Course: Clinical Research, International Health track. Institution: ISGlobal & University of Barcelona .... Research timeline.
Systematic review protocol: Outcome of HIV test and treat protocol in primary health care setting. The effect of combination antiretroviral therapy in people with HIV -1 infection after starting cART in test and treat programs.
(“Study looks into HIV virus spread in Dutch Caribbean - Curaçao Chronicle,” 2017)
Student:
Frendalie Aurelia Marchena
Course:
Clinical Research, International Health track
Institution:
ISGlobal & University of Barcelona
Supervisor:
Dr. Hermanides MD PhD, AMC Universiteit van Amsterdam
Document:
Master’s Thesis Protocol
Word count:
1252
Summary: More than 70 million people worldwide have been infected by human immunodeficiency virus (HIV). A strong decrease in the morbidity and mortality due to HIV type1 has been registered since the introduction of combination Antiretroviral therapy (cART). Under the Globalized test and treat program every HIV positive person receives treatment regardless of their CD4+ count, as the model predicted to improve live expectancy and stop HIV transmission. With increasing numbers of people eligible for cART, treatment strategies are essential. The goal of this research is to investigate the outcome the HIV test and treat protocol in primary health care setting.
Table of Contents 1.
Background............................................................................................................................ 3
2. Objectives .................................................................................................................................. 3 3. Methodology ............................................................................................................................. 4 3.1 Search Strategy ................................................................................................................... 4 3.2 Inclusion & exclusion criteria .............................................................................................. 4 3.3 Study selection .................................................................................................................... 5 3.4 Data Analysis ....................................................................................................................... 5 4. Study Limitations ....................................................................................................................... 6 5. Research timeline ..................................................................................................................... 6 Bibliography .................................................................................................................................. 7
2
1.Background More than 70 million people worldwide have been infected by human immunodeficiency virus (HIV) since the start of the epidemic, with approximately 35 million deceased (“WHO | HIV/AIDS,” 2017). Nonetheless, a strong decrease in the morbidity and mortality due to HIV type-1 has been registered since the introduction of combination Antiretroviral therapy (cART). This in turn has increased the life expectancy of people infected with HIV-1 (van den Dries, Claassen, Groothuismink, van Gorp, & Boonstra, 2017). After initiating cART a substantial amount of people with HIV-1 infection achieve an immeasurably low level of HIV-RNA that leads to HIV replication suppression by an increase of CD4+ T cells, and minimizes the chance of transmission to an extreme low. Being that people with HIV-1 are currently dependent on suppression medication and given that HIV-1 RNA is capable to develop antiviral resistance, Is cART absolutely essential in the Health care system (Liu, Ma, Liu, Chen, & Zhang, 2015). Conventional treatment plans indicated that a HIV positive person would have to register a CD4+ count pf 500 or less to be eligible for medicinal treatment until 2012 (World Health Organization., World Health Organization. Department of HIV/AIDS., & International Conference on AIDS (19th : 2012 : Washington, 2012). This is when the World Organization Bank (WHO) published strategic guidelines containing the ¨test and treat¨ approach, followed by the Universal ¨treat all¨ strategy (Sorensen et al., 2012). Under the Globalized test and treat program every HIV positive person receives medicinal treatment regardless of their CD4+ count, as the model was predicted to improve live expectancy and stop HIV transmission (Ortega, Brier, & Ances, 2015). Although this strategy was predicted to be the best approach, scientist were concerned about drug availability for the massive number of people now eligible for treatment, resources to sustain lifelong treatment and the rise of drug resistance as a potential problem (Michaeleen Doucleff, 2012). The aim of this systematic review is to investigate the outcome of the HIV test and treat protocol in primary health care setting (Kulkarni, Shah, Sarma, & Mahajan, 2013).
2. Objectives As there is a major increase in the number of people eligible for cART under the new WHO guidelines, strategies on treatment delivery without long waiting periods or multiple clinic visits are essential. The goal of this research is to investigate and analyze the outcome the HIV test and treat protocol in primary health care setting. The primary focus objective is to assess the effectivity of combination antiretroviral therapy in people with HIV-1 infection after starting cART in test and treat programs. Other research focus are as follow: 1. The Virologic response of cART after implementing HIV test and treat (in primary health care setting). 2. The Immunological response of cART after implementing HIV test and treat. 3. The Clinical response of cART after implementing HIV test and treat. 4. The Retention in care after implanting HIV test and treat.
3
3. Methodology This Systematic review will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, as it is the basis for systematic reviews by reputable Journals (“Guidelines for Systematic Reviews,” 2017).
3.1 Search Strategy Using a query combination of the key words plus synonyms such as ¨Test and Treat¨ AND HIV1¨ AND NOT ¨HIV-2¨ AND ¨Health care¨, The online databases listed below will be searched for relevant studies: ▪ ▪ ▪ ▪ ▪ ▪ ▪ ▪
MEDLINE (www.nlm.nih.gov) EMBASE (https://www.elsevier.com) ScienceDirect (www.sciencedirect.com) The Cochrane Library (accessible databases) Pubmed (www.ncbi.nlm.nih.gov/pubmed) POPLINE (www.popline.org) Google Scholar (scholar.google.nl) World Health Organization and other UN agencies (www.who.int)
If time permits, Unpublished studies will be investigated through the databases that follow: ▪ ▪
ISI Web of Knowledge (includes Conference Proceedings, BIOSIS Previews, and Journal Citation Reports) Databases of ongoing studies (http://www.who.int/trialsearch/)
Other search strategies include: ▪ ▪
Analysis of reference lists from relevant studies or literature reviews Citation searching from news articles
3.2 Inclusion & exclusion criteria All articles where the test and treat program is being used in a primary setting will be considered. All studies included in the research will be from the year 2011 and onwards, as the test and treat program and the treat all program model initiated in 2012. All articles where data was collected from test and treat programs will be considered. The list that follows are the studies eligible for inclusion: • • • • •
Observational studies with a comparison group Prospective longitudinal before and after studies Cohort studies Clinical trials (Randomized) controlled studies
The list that follows are the studies excluded from the research: • • • • •
Book reviews Editorial / commentary articles Studies targeting HIV-2 Studies outside of the primary care setting Studies not in Dutch, German, English or Spanish
4
Where relevant systematic reviews are identified, these will be analyzed and eligible references of interest will be included in the analysis.
3.3 Study selection • Screening phase 1: The titles and abstracts of identified studies will be analyzed for relevance to the subject, where studies defined as irrelevant will be excluded. Studies involving the topic, but not prissily targeted objectives will be considered with supervisor. • Screening phase 2: Hereby Full text articles/documents will be sought for all studies who passed phase 1 and indicate to meet the inclusion criteria. The Final selection will be made by consideration with supervisor. The Prisma flow-diagram that follows gives a schematic overview of the process.
Figure 1 Prisma Systematic review Flow-diagram (Liberati et al., 2009).
3.4 Data Analysis All studies and documents collected from manual and electronic searches will be scanned by first and second authors to rule out research bias. Studies will be included according to the criteria’s above and will then be analyzed according to the PRISMA guidelines checklist (Moher et al., 2015). A log of all searches and articles will be logged manually in a MS World document file organized by database, query, author, title and abstract. Full copies of the identified relevant studies will be retrieved in a Mendeley folder to be organized for data extraction. The data will be extracted, categorized and synthesized from included studies yet to be define with supervisor. 5
4. Study Limitations Potential limitations in contexts of this systematic review could be: • • • •
The number of articles that would only centered in the region of Africa, hereby not being representative of the HIV-1 community on a global scale. Autor bias by many articles being produced by the same researchers. One investigator reviewing the searches. Language of the publications.
5. Research timeline The schedule of the research stages and their expected periods are in the table that follows.
Milestone
Expected Date
MFP complete proposal
18 February
Proposal presentation (orally)
22 February
Database and sources research
1 January – 20 February
Literature collection
1 February – 20 March
All literature reviewed
20 March – 20 April
Data analysis
Done by 1 May
Writing article
1 May – 30 May
First draft to be circulated
1 June
Final version reviewed + abstract
20 June
Presentation article (orally)
27-29 June
Figure 2 Research Timeline.
6
Bibliography Guidelines for Systematic Reviews. (2017). Retrieved from http://ajot.submit2aota.org/journals/ajot/forms/systematic_reviews.pdf Kulkarni, S. P., Shah, K. R., Sarma, K. V, & Mahajan, A. P. (2013). Clinical uncertainties, health service challenges, and ethical complexities of HIV "test-and-treat": a systematic review. American Journal of Public Health, 103(6), e14-23. https://doi.org/10.2105/AJPH.2013.301273 Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gøtzsche, P. C., Ioannidis, J. P. A., … Moher, D. (2009). The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Medicine. https://doi.org/10.1371/journal.pmed.1000100 Liu, C., Ma, X., Liu, B., Chen, C., & Zhang, H. (2015). HIV-1 functional cure: will the dream come true? BMC Medicine, 13(1), 284. https://doi.org/10.1186/s12916-015-0517-y Michaeleen Doucleff. (2012). “Test And Treat” Strategy For Curbing HIV Draws Questions : Shots - Health News : NPR. Retrieved February 18, 2018, from https://www.npr.org/sections/health-shots/2012/09/05/160630263/test-and-treatstrategy-for-curbing-hiv-draws-questions Moher, D., Shamseer, L., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M., … Whitlock, E. (2015). Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews, 4(1). https://doi.org/10.1186/20464053-4-1 Ortega, M., Brier, M. R., & Ances, B. M. (2015). Effects of HIV and combination antiretroviral therapy on cortico-striatal functional connectivity. AIDS (London, England), 29(6), 703– 712. https://doi.org/10.1097/QAD.0000000000000611 Sorensen, S. W., Sansom, S. L., Brooks, J. T., Marks, G., Begier, E. M., Buchacz, K., … Kilmarx, P. H. (2012). A mathematical model of comprehensive test-and-treat services and HIV incidence among men who have sex with men in the United States. PLoS ONE, 7(2). https://doi.org/10.1371/journal.pone.0029098 Study looks into HIV virus spread in Dutch Caribbean - Curaçao Chronicle. (2017). Retrieved February 18, 2018, from http://curacaochronicle.com/local/study-looks-into-hiv-virusspread-in-dutch-caribbean/ van den Dries, L., Claassen, M. A. A., Groothuismink, Z. M. A., van Gorp, E., & Boonstra, A. (2017). Immune activation in prolonged cART-suppressed HIV patients is comparable to that of healthy controls. Virology, 509, 133–139. https://doi.org/10.1016/J.VIROL.2017.06.014 WHO | HIV/AIDS. (2017). WHO. Retrieved from http://www.who.int/gho/hiv/en/ World Health Organization., World Health Organization. Department of HIV/AIDS., & International Conference on AIDS (19th : 2012 : Washington, D. C. . (2012). The strategic use of antiretrovirals to help end the HIV epidemic. World Health Organization.
7
