Reply to Chen et al.

To the  Editor—We appreciate the opportunity to respond to the comments by Dr. Chen and colleagues related to our manuscript “Interleukin 6 Blockade With Tocilizumab Diminishes Indices of Inflammation That Are Linked to Mortality in Treated Human Immunodeficiency Virus Infection.” Understanding the potential mediators of age-related comorbidities in people with human immunodeficiency virus (HIV, PWH) is an important area of clinical research and interventional studies aimed at improving the lifespans and healthspans of this population are needed. We agree with many of the important considerations brought up by Chen et al. This was a small, short-term pilot study examining the safety and tolerability of tocilizumab (TCZ) treatment in PWH, the first study of interluekin-6 (IL-6) receptor blockade in PWH. Increasing the number of participants would give us greater power to detect differences in immune profiles during treatment and placebo and would make our results more generalizable to the global population. Taking greater account of lifestyle factors that may contribute to inflammation and lipid levels will be important in future studies. A longer duration of TCZ treatment may provide insights into the sustainability of the reductions of inflammatory and immune activation markers we identified in our study. Furthermore, a longer treatment period with TCZ may enable future studies to determine the long-term effects of TCZ on lipid levels, on CD4+ T-cell counts, immune cell function, and potentially, on clinical endpoints. Future intervention studies, using TCZ or another immunomodulatory treatment, should try to enroll participants at more advanced age and a greater proportion of women, as these factors also contribute to inflammatory profiles and age-related comorbidities in PWH. Although our enrollment criteria included individuals between 18 and 60 years old, the actual age range of participants was 26–60 years. We did collect information on other medication use among participants and included the proportion of statin users in Table 1 [1]; again, with a trial that enrolled 34 total individuals, the numbers of participants on certain medications were insufficient for stratification. We also considered several other comorbid conditions in our inclusion and exclusion criteria, including cancer, active infections, and liver disease. Without performing this initial study assessing the safety of TCZ in this population and the immune and metabolic profiling described in our study, we would not have been able to justify a long-term study with a larger enrollment.

Notes

Financial support. This work was supported by the National Institutes of Health (NIH) (grant number U01AI105937 to M. M. L.), the Fasenmeyer Foundation, and VA CRR&D to C. L. S. (grant number CDA2 CX001471).