Authors' Reply to Letter to the Editor Regarding ‘Effectiveness, safety, and patient‐reported outcomes of emtricitabine/tenofovir alafenamide‐based regimens for the treatment of HIV‐1 infection: Final 24‐month results from the prospective German TAFNES cohort study’

The letter by Borrás-Blasco et al. [1] praises the high efficacy and treatment persistence of F/TAF therapy as reported in the published TAFNES study [2] but notes that, in the absence of precise adherence measurements, the results might be subject to bias. The analytical approach distinguishes between treatment persistence and adherence. The authors argue that a real-world evidence (RWE) study design—such as that employed by the German subgroup of the TAFNES study—should ideally capture both aspects in order to generate valid and practice-relevant conclusions about treatment effectiveness. The analysis also highlights the practical challenges inherent in such an assessment: objective adherence measurement is costly and logistically demanding, whereas subjective methods lack accuracy. Consequently, the authors call for the routine inclusion of adherence assessment in HIV studies to improve clinical decision-making and guideline development. The letter by Borrás-Blasco et al. [1] thus represents a valuable contribution to the ongoing scientific discussion regarding the clinical relevance of real-world evidence studies in the context of HIV therapy. From the German TAFNES subgroup analysis authors' perspective, the combination of virological efficacy (96% achieved suppression) and treatment persistence (81%) already provides a robust basis for interpretation—additional adherence measurements would likely not alter the overall positive outcome. HIV infection holds an outstanding position, as it belongs to a type of disease where treatment effects can be measured in such a direct way that they can serve as surrogate markers for treatment adherence. Moreover, the continuous monitoring of the surrogate marker HIV viral load allows for direct and reliable assessment of antiretroviral therapy (ART) adherence and clinical success [3]. However, besides maladherence, other factors may affect HIV viral loads [4], for example, pharmacokinetic drug–drug interactions. The immunological benefit for patients directly results from the effectiveness of ART. From a clinical and practical standpoint, the key determinant of success is that patients remain on therapy and maintain sustained viral suppression. These metrics are reflected both in routine clinical care and in the analysis of the German TAFNES data. Objective adherence assessments (e.g., therapeutic drug monitoring, electronic adherence tracking) are costly and labour-intensive, and in large real-world HIV cohorts, the substantial additional effort may not be justified by a proportional gain in information. Finally, it should be noted that intensive adherence monitoring may alter natural patient behaviour (“Hawthorne effect” [5]), thereby undermining the real-world nature of such studies. In conclusion, the strength of the German TAFNES subgroup analysis lies in its integration of clinical data with patient-reported outcomes (PROs), assessed through the 36-Item Short Form Health Survey (SF-36) and the HIV Treatment Satisfaction Questionnaire (HIVTSQ). The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.