Differences in HIV cure clinical trial preferences of French people living with HIV and physicians in the ANRS‐APSEC study: a discrete choice experiment

Abstract

Introduction Despite the advent of HIV cure‐related clinical trials (HCRCT) for people living with HIV (PLWH), the risks and uncertainty involved raise ethical issues. Although research has provided insights into the levers and barriers to PLWH and physicians' participation in these trials, no information exists about stakeholders' preferences for HCRCT attributes, about the different ways PLWH and physicians value future HCRCT, or about how personal characteristics affect these preferences. The results from the present study will inform researchers' decisions about the most suitable HCRCT strategies to implement, and help them ensure ethical recruitment and well‐designed informed consent. Methods Between October 2016 and March 2017, a discrete choice experiment was conducted among 195 virally controlled PLWH and 160 physicians from 24 French HIV centres. Profiles within each group, based on individual characteristics, were obtained using hierarchical clustering. Trade‐offs between five HCRCT attributes (trial duration, consultation frequency, moderate (digestive disorders, flu‐type syndrome, fatigue) and severe (allergy, infections, risk of cancer) side effects (SE), outcomes) and utilities associated with four HCRCT candidates (latency reactivation, immunotherapy, gene therapy and a combination of latency reactivation and immunotherapy), were estimated using a mixed logit model. Results Apart from severe SE – the most decisive attribute in both groups – PLWH and physicians made different trade‐offs between HCRCT attributes, the latter being more concerned about outcomes, the former about the burden of participation (consultation frequency and moderate SE). These different trades‐offs resulted in differences in preferences regarding the four candidate HCRCT. PLWH significantly preferred immunotherapy, whereas physicians preferred immunotherapy and combined therapy. Despite the heterogeneity of characteristics within the PLWH and physician profiles, results show some homogeneity in trade‐offs and utilities regarding HCRCT. Conclusions Severe SE, not outcomes, was the most decisive attribute determining future HCRCT participation. Particular attention should be paid to providing clear information, in particular on severe SE, to potential participants. Immunotherapy would appear to be the best HCRCT candidate for both PLWH and physicians. However, if the risk of cancer could be avoided, gene therapy would become the preferred strategy for the latter and the second choice for the former.

Characterization of Physicians That Might Be Reluctant to Propose HIV Cure-Related Clinical Trials with Treatment Interruption to Their Patients? The ANRS-APSEC Study

“…These results can be linked to those observed for PLWH in other studies, including previous studies from ANRS-APSEC. First, HCRCT-related burdens-in particular, in terms of consultation frequency and, more generally, in terms of the deterioration of their quality of life [30,31]-have been found to be more decisive criterions than HCRCT outcomes in PLWH's decisions to participate or not in HCRCT [27,29]. Second, financially precarious PLWH have been shown to be more reluctant to participate in HCRCT, perhaps because they may anticipate difficulties regarding hospital visits in terms of time and economic burden [36].…”

“…In those that have, it was not always possible to disentangle physicians' perspectives from those of PLWH. When possible, results showed that PLWH and physicians did not have the same preferences regarding several HCRCT strategies [27]. Furthermore, qualitative and mixed-method studies have shown that some physicians were reluctant about HCRCT [19,[29][30][31][32].…”

“…Surprisingly, in quantitative studies, the majority of physicians (from 59% to 97.5%) declared they would propose HCRCT to their patients [27,30]. This counter-intuitive disparity in results has also been found among PLWH, who expressed more reluctance in qualitative surveys [19,29,30,[32][33][34] than in quantitative surveys [18,23,27,30,35,36]. Besides discrepancies between declared intentions of interest in participation and actual behavior [37], other possible explanations for this disparity were differences in methodology and in the questions asked regarding willingness to propose HCRCT [27].…”

“…However, in the current context of modern, well-tolerated cART, where new treatment regimens reducing administration frequency are being introduced, clinical and biological-related issues to HCRCT cannot be disconnected from associated ethical questions or, indeed, from the consequences on the daily lives of PLWH who will participate in HCRCT [17][18][19][20][21][22][23][24][25][26][27][28]. The limited direct benefits for participants and the risk of HIV transmission during ATI might negatively impact physicians' motivations to propose participation in HCRCT with ATI to their patients [21].…”

“…Furthermore, qualitative and mixed-method studies have shown that some physicians were reluctant about HCRCT [19,[29][30][31][32]. Surprisingly, in quantitative studies, the majority of physicians (from 59% to 97.5%) declared they would propose HCRCT to their patients [27,30]. This counter-intuitive disparity in results has also been found among PLWH, who expressed more reluctance in qualitative surveys [19,29,30,[32][33][34] than in quantitative surveys [18,23,27,30,35,36].…”