Promoting HIV indicator condition-guided testing in hospital settings (PROTEST 2.0): study protocol for a multicentre interventional study
Authors: Bogers Saskia J. , Schim van der Loeff Maarten F. , Davidovich Udi , Boyd Anders , van der Valk Marc , Brinkman Kees , de Bree Godelieve J. , Reiss Peter , van Bergen Jan E. A. M. , Geerlings Suzanne E. ,   on behalf of the HIV Transmission Elimination AMsterdam (H-TEAM) Consortium, van Bergen J. E. A. M. , Brokx P. , Deug F. , Heidenrijk M. , Prins M. , Reiss P. , van der Valk M. , de Bree G. J. , Brokx P. , Davidovich U. , Geerlings S. E. , Hoornenborg E. , Oomen A. , van Sighem A. , Zuilhof W. , Schat N. , Achterbergh R. C. A. , van Agtmael M. , Ananworanich J. , Van de Beek D. , van den Berk G. E. L. , Bezemer D. , van Bijnen A. , Blok W. L. , Bogers S. , Bomers M. , Boucher C. A. B. , Brokking W. , Burger D. , Brinkman K. , Brinkman N. , de Bruin M. , Bruisten S. , Coyer L. , van Crevel R. , Daans C. G. , Dellemann L. , Dijkstra M. , van Duijnhoven Y. T. , van Eeden A. , Elsenburg L. , van den Elshout M. A. M. , Ester C. , Ersan E. , Felipa P. E. V. , Frissen P. H. J. , Geijtenbeek T. B. H. , Godfried M. H. , van Gool J. , Goorhuis A. , Groot M. , Hankins C. A. , Heijnen A. , Hillebregt M. M. J. , Hogewoning A. , Hommenga M. , Hovius J. W. , Janssen Y. , de Jong K. , Jongen V. , Kootstra N. A. , Koup R. A. , Kroon F. P. , van de Laar T. J. W. , Lauw F. , van Leeuwen M. M. , Lettinga K. , Linde I. , Loomans D. S. E. , van der Meer J. T. , Mouhebati T. , Mulder B. J. , Mulder J. , Nellen F. J. , Nijsters A. , Nobel H. , Oostvogel P. , Op de Coul E. L. M. , Peters E. , Peters I. S. , van der Poll T. , Ratmann O. , Rokx C. , van Rooijen M. S. , van der  Loeff M. F. Schim , Schouten W. E. M. , Sonder G. J. , Veenstra J. , Verbon A. , Verdult F. , de Vocht J. , de Vries H. J. , Vrouenraets S. , van Vugt M. , Wiersinga W. J. , Wit F. W. , Woittiez L. R. , Zaheri S. , Zantkuijl P. , van Zelm M. C. , Żakowicz A. , Zimmermann H. M. L. 
Published: June 2021

Abstract
Background
Late presentation remains a key barrier towards controlling the HIV epidemic. Indicator conditions (ICs) are those that are AIDS-defining, associated with a prevalence of undiagnosed HIV > 0.1%, or whose clinical management would be impeded if an HIV infection were undiagnosed. IC-guided HIV testing is an effective strategy in identifying undiagnosed HIV, but opportunities for earlier HIV diagnosis through IC-guided testing are being missed. We present a protocol for an interventional study to improve awareness of IC-guided testing and increase HIV testing in patients presenting with ICs in a hospital setting.

Methods
We designed a multicentre interventional study to be implemented at five hospitals in the region of Amsterdam, the Netherlands. Seven ICs were selected for which HIV test ratios (proportion of patients with an IC tested for HIV) will be measured: tuberculosis, cervical/vulvar cancer or high-grade cervical/vulvar dysplasia, malignant lymphoma, hepatitis B and C, and peripheral neuropathy. Prior to the intervention, a baseline assessment of HIV test ratios across ICs will be performed in eligible patients (IC diagnosed January 2015 through May 2020, ≥18 years, not known HIV positive) and an assessment of barriers and facilitators for HIV testing amongst relevant specialties will be conducted using qualitative (interviews) and quantitative methods (questionnaires). The intervention phase will consist of an educational intervention, including presentation of baseline results as competitive graphical audit and feedback combined with discussion on implementation and opportunities for improvement. The effect of the intervention will be assessed by comparing HIV test ratios of the pre-intervention and post-intervention periods. The primary endpoint is the HIV test ratio within ±3 months of IC diagnosis. Secondary endpoints are the HIV test ratio within ±6 months of diagnosis, ratio ever tested for HIV, HIV positivity percentage, proportion of late presenters and proportion with known HIV status prior to initiating treatment for their IC.

Discussion
This protocol presents a strategy aimed at increasing awareness of the benefits of IC-guided testing and increasing HIV testing in patients presenting with ICs in hospital settings to identify undiagnosed HIV in Amsterdam, the Netherlands.

Trial registration
Dutch trial registry: NL7521. Registered 14 February 2019.