LAUSR

TO THE EDITOR—We thank Lombardi and colleagues for their thoughtful observations about our case and appreciate the opportunity to respond. We fully agree with the authors that the high PD-1 expression on T cells in this case was mainly attributed to human immunodeficiency virus (HIV) infection [1]. The patient had reached HIV viral suppression after 6 months of antiretroviral therapy. He was hospitalized and his adherence was good. It is reasonable to infer that he maintained viral suppression when determining PD-1 expression on T cells. Therefore, the high PD-1 expression on T cells in this case was not because of uncontrolled HIV infection. However, in HIV infection, the PD-1 expression on T cells persists in blood despite prolonged viral suppression, which may be associated with the HIV reservoir size [2, 3]. In our case, PD-1 expression on both CD4 T cells and CD8 T cells was comparable to that measured previously by us in virologically suppressed people with HIV (PWH) without opportunistic infections [4]. Lombardi et al reported that in individuals with normal immune system with ongoing Mycobacterium avium complex (MAC) lung disease, only small proportions of T cells express PD-1. It is still unknown whether subjects with uncontrolled disseminated MAC disease have higher PD-1 expression on T cells than those with MAC lung disease. In another 6 cases of PWH with disseminated MAC disease, 39.9% ± 20.3% of CD4 T cells in peripheral blood expressed PD-1 (unpublished data), which is slightly lower than that of the current case. The PD-1 expression on both CD4 and CD8 T cells decreased significantly after immune checkpoint inhibitor (ICI) treatment in our patient. As MAC-specific T cells account for only a small proportion of T cells, the PD-1 expression on other T cells including HIV-specific T cells should also be decreased. Therefore, we agree with Lombardi et al that ICI treatment ameliorates the exhaustion of general T cells, which may have a synergistic effect and boost MAC-specific response. We did not measure PD-1 expression on regulatory T cells (Tregs). It is well known that PD-1 expression on Tregs is also increased in PWH [5, 6]. The effects of PD-1/PD-L1 blockade on Tregs in PWH depend on plasma viremia [5, 6]. Proliferation of Tregs and increased viral production are observed in viremic individuals while the proliferative capacity of Tregs is unchanged in virologically suppressed PWH after PD-L1 blockade [5]. We also did not measure other immunological markers including T-cell activation, maturation, exhaustion, and senescence, as targeted treatments for the immune imbalances abovementioned are lacking currently. However, monitoring the dynamics of these markers before and after ICI treatment may help to further decipher the success of the case and provide insights for future research. Overall, this unique case provides clues that ICI treatment as a hosttargeted therapy may play a role in treating infectious diseases in the selected population. Further studies are warranted to determine the population most likely to benefit and to validate the efficacy of ICI treatment.