Published guidelines have a limited impact on the first prescription of antiretroviral therapy for HIV-1-infected patients in Lyon, France.

Abstract

In France, the first antiretroviral therapy (ART) guidelines were released in 1990, and were then updated regularly [1]. Observational studies [2] have since provided an opportunity to establish whether these national guidelines are applied in practice. Our aim was to determine if ‘first ART prescriptions’ are consistent with guidelines published in 1993, 1996 and 1998. We designed a before–after study with data derived from the Lyon HIV-1 hospital database [3], which enrolled 2158 adult patients who received medical care between 1 July 1992 and 31 December 1998. Quarterly compliance rates were obtained by dividing the number of prescriptions that fulfilled the criteria of the given recommendations based on the clinical, virological and immunological status of the patients by the total number of prescriptions dispensed within that period. Fig. 1 relates to the guidelines published in 1993 and 1996, showing breaks associated with prescription changes. The most striking feature of these breaks is that they occurred many months before the release of the guidelines. Two simultaneous breaks were seen between September and November 1995, shortly after the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, at which the results of AIDS Clinical Trial Group (ACTG) Protocol 175 were presented for the first time [4]. This clinical trial showed the benefits in terms of mortality after ART combination of two nucleoside analogues versus zidovudine alone. Maximum compliance with the guidelines published in 1996 was obtained between June and September 1996, just before their release. The rate then decreased sharply, and once again began a staggering increase before the guidelines published in 1998. This increase commenced in the fourth quarter of 1996, simultaneously with the availability of the first protease inhibitor. The impact of the recommendations published in 1998 is difficult to determine. Although compliance increased after the upgrade of the guidelines, the results showed a deceleration in the rate of change, with a compliance rate already at 70%.Fig. 1.: Quarterly rates of compliance according to the series of guidelines. Arrows indicate the time of the 35th Interscience Conference on Antimicrobial Agents and Chemothrapy (ICAAC) when the AIDS Clinical Trial Group Protocol 175 was published for the first time, the date of the 3rd Conference on Retroviruses and Opportunistic Infections when the efficacy of highly active antiretroviral therapy was reported for the first time, and the date of availability of protease inhibitors (PI) on the French market. 1993, Solid grey line; 1996, broken line; 1998, solid black line.The graphs clearly illustrate that hospital physicians anticipated the recommendations because they changed their drug prescription behaviours before the release of the guidelines. This change occurred as soon as a major clinical trial produced evidence of the efficacy of a new therapy, or as soon as new drugs became available outside the context of clinical trials. Such a rapid change in practice had already been reported after the publication of ACTG Protocol 076, which saw a reduction with zidovudine treatment of mother–infant HIV-1 transmission [5]. This ‘on real time’ overreactivity of health practitioners is a particularity of HIV care [6]. In France, HIV care is mostly provided by public teaching hospitals, in departments whose referring physicians probably have the opportunity to be well informed of the latest scientific progress. Therefore, they are able to apply new therapies before the release of guidelines based on the same information. This adaptability is stimulated by patient organizations fighting AIDS, which act as an added incentive. The changes in prescription practice occurred a long time before the release of the guidelines, as though they were confirming already-existing clinical practice. One might ask: why are the recommendations released so late? The elaboration of useful guidelines, based on a critical appraisal of scientific evidence, requires time for the critical appraisal and synthesis of clinical trials to be conducted on a sufficient number of patients. This study revealed that clinicians in France anticipated the national guidelines. However, published guidelines will probably have different impacts in medical specialities other than HIV medicine. Acknowledgements R. Fayet, E. Garcia, C. Delorme. Muriel Dhenaina Philippe Vanhemsab Cyrille Colinc Dominique Peyramondd Christian Chidiacd Jean-Louis Tourained Christian Trépobd Jacques Fabryab