Mpox in People With HIV: Prioritizing Interventions for Those Without HIV Viral Suppression

To the  Editor—We thank Sakuraia et al [1] for their interest in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) cohort study of mpox among people with human immunodeficiency virus (HIV; PWH) [2]. While we agree that there are limitations to our data, as in any study and as noted in our discussion, here we offer additional context for the CNICS cohort to address the concerns expressed by Sakuraia et al.

The CNICS cohort includes all PWH in clinical care at 10 academic medical centers across the United States and standardized, well-validated data to define predictors and outcomes [3]. We would reframe the concern about selection bias, which is not occurring here, to a valid question about the external validity of CNICS data beyond PWH engaged in care. While our findings may not be generalizable to all PWH, CNICS is representative of the epidemiology of mpox among PWH in care in the United States.

The rate of virologic suppression in clinics supported by the federally funded Ryan White HIV/AIDS Program in the United States, which includes all CNICS sites, is 90.6%, and the proportion of PWH in care with a CD4 cell count <200 cells/mL is proportionately low [4]. As Sakuraia et al point out, only 6% of the total 19 177 participants, including only 26 with an mpox diagnosis, had a CD4 cell count <200 cells/mL, and the findings for this group had wide 95% confidence intervals; 4 people with mpox had a CD4 cell count <50 cells/mL. Thus, further stratification was not appropriate.

Comparison of PWH with or without mpox in our study allows a stronger conclusion in support of the known importance of antiretroviral therapy and virologic suppression in preventing symptomatic mpox and in demonstrating vaccine effectiveness. Hospitalization is the most objective hard outcome of severity of mpox in the United States, unlike in countries in Central Africa and other places where hospitalization was also used for containment or treatment monitoring, as in the PALM-007 study. Clinical manifestations of mpox have been described elsewhere [5], and we agree that further study would be of interest.

Finally, given the disparities in treatment found in our study, we suggested consideration of expanding effective interventions beyond the narrow groups recommended by the US Centers for Disease Control from 2022 to 2024 [6]. We have since been contacted by public health entities in other countries seeking to use our CD4 cell count­– and viral load–stratified analyses of MVA-BN vaccine effectiveness to prioritize for the highest-risk populations the limited MVA-BN vaccine available. Subsequently, reports of preliminary results from 2 randomized clinical trials (PALM-007 in August 2024 [7] and STOMP in December 2024 [8]) suggested no overall benefit of tecovirimat. Formal analyses from both studies are pending, and it remains unclear whether people with advanced immunosuppression or severe disease (who received nonrandomized open label treatment in STOMP) or those treated early after symptom onset would have some benefit. Regardless, expansion of treatment to people with unsuppressed HIV is warranted even at higher CD4 counts should effective therapeutics be identified. The most important messaging that can emerge from our data is in prioritizing pharmacoequity in vaccine distribution and in removing barriers, such that PWH with mpox exposure risk can achieve HIV viral suppression [9, 10].

Note

Financial support. The Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) is supported by the National Institute of Allergy and Infectious Diseases (grant R24 AI067039). The CFAR sites involved in CNICS include the University of Alabama at Birmingham (grant P30 AI027767), the University of Washington (grant P30 AI027757), the University of California, San Diego (grant P30 AI036214), the University of California, San Francisco (grant P30 AI027763), Case Western Reserve University (grant P30 AI036219), Johns Hopkins University (grant P30 AI094189, U01 DA036935), Fenway Health/Harvard (grant P30 AI060354), the University of North Carolina, Chapel Hill (grant P30 AI50410), Vanderbilt University (grant P30 AI110527), and the University of Miami (grant P30 AI073961). Additional CFAR funding was obtained to support this work (grant P30 AI027757 to M. M.).