BackgroundRestricted mean survival time (RMST) is an underutilized estimand in time-to-event analyses. Herein, we highlight its strengths by comparing time to (1) all-cause mortality and (2) initiation of antiretroviral therapy (ART) for HIV-infected persons who inject drugs (PWID) and persons who do not inject drugs.MethodsRMST to death was determined by integrating the Kaplan-Meier survival curve to 5 years of follow-up. To account for the competing risks of death and loss-to-clinic when estimating time to ART, we calculated RMST to ART initiation by estimating the area between the survival curve for ART initiation and the cumulative incidence curve for death or loss-to-clinic. We standardized all curves using inverse probability of exposure weights.ResultsWe followed 3044 HIV-positive, ART-naive persons from enrollment into the Johns Hopkins HIV Clinical Cohort from 1996 to 2014. PWID had a − 0.19 year (95% confidence interval (CI): − 0.29, − 0.10) difference in survival over 5 years of follow-up compared to persons who did not inject drugs. There was no difference between the two groups in time not on ART while alive and in clinic (RMST difference = 0.08, 95% CI: -0.10, 0.36).ConclusionsPWID have similar expected time to ART initiation after properly accounting for their greater risk of death and loss-to-clinic.Electronic supplementary materialThe online version of this article (10.1186/s12874-018-0484-z) contains supplementary material, which is available to authorized users.

IMPORTANCE Immunologic decline associated with cancer treatment in people with HIV is not well characterized. Quantifying excess mortality associated with cancer treatment-related immunosuppression may help inform cancer treatment guidelines for persons with HIV.OBJECTIVE To estimate the association between cancer treatment and CD4 count and HIV RNA level in persons with HIV and between posttreatment CD4 count and HIV RNA trajectories and all-cause mortality. DESIGN, SETTING, AND PARTICIPANTSThis observational cohort study included 196 adults with HIV who had an incident first cancer and available cancer treatment data while in the care of The Johns Hopkins HIV Clinic from January 1, 1997, through March 1, 2016. The study hypothesized that chemotherapy and/or radiotherapy in people with HIV would increase HIV RNA levels owing to treatment tolerability issues and would be associated with a larger initial decline in CD4 count and slower CD4 recovery compared with surgery or other treatment. An additional hypothesis was that these CD4 count declines would be associated with higher mortality independent of baseline CD4 count, antiretroviral therapy use, and risk due to the underlying cancer. Data were analyzed from December 1, 2017, through April 1, 2018.EXPOSURES Initial cancer treatment category (chemotherapy and/or radiotherapy vs surgery or other treatment). MAIN OUTCOMES AND MEASURESPost-cancer treatment longitudinal CD4 count, longitudinal HIV RNA level, and all-cause mortality.RESULTS Among the 196 participants (135 [68.9%] male; median age, 50 [interquartile range, 43-55] years), chemotherapy and/or radiotherapy decreased initial CD4 count by 203 cells/μL (95% CI, 92-306 cells/μL) among those with a baseline CD4 count of greater than 500 cells/μL. The decline for those with a baseline CD4 count of no greater than 350 cells/μL was 45 cells/μL (interaction estimate, 158 cells/μL; 95% CI, 31-276 cells/μL). Chemotherapy and/or radiotherapy had no detrimental association with HIV RNA levels. After initial cancer treatment, every 100 cells/μL decrease in CD4 count resulted in a 27% increase in mortality (hazard ratio, 1.27; 95% CI, 1.08-1.53), adjusting for HIV RNA level. No significant increase in mortality was associated with a unit increase in log 10 HIV RNA after adjusting for CD4 count (hazard ratio, 1.24; 95% CI, 0.94-1.65). CONCLUSIONS AND RELEVANCEIn this study, chemotherapy and/or radiotherapy was associated with significantly reduced initial CD4 count in adults with HIV compared with surgery or other treatment. Lower CD4 count after cancer treatment was associated with an increased hazard of mortality. Further research is necessary on the immunosuppressive effects of cancer treatment in adults with HIV and whether health care professionals must consider the balance of cancer treatment efficacy against the potential cost of further immunosuppression. Monitoring of immune status may also be helpful given the decrease in CD4 count after treatment and the already immunocompromised state of patients with HIV.

COMPLIANCE WITH ETHICAL STANDARDS: Disclosure of potential conflicts of interest • Anthony T. Fojo declares that he has no conflict of interest • Catherine R. Lesko declares that she has no conflict of interest • Keri L. Calkins declares that she has no conflict of interest • Richard D. Moore declares that he has no conflict of interest • Mary E. McCaul declares that she has no conflict of interest • Heidi E. Hutton declares that she has no conflict of interest • William C. Mathews declares that he has no conflict of interest • Heidi Crane declares that she has no conflict of interest • Katerina Christopoulos has been scientific advisory board member for Roche Pharmaceuticals and a community advisory board member for Gilead Sciences Inc.• Karen Cropsey declares that she has no conflict of interest • Michael J. Mugavero declares that he has no conflict of interest • Kenneth Mayer declares that he has no conflict of interest • Brian W. Pence declares that he has no conflict of interest • Bryan Lau declares that he has no conflict of interest • Geetanjali Chander declares that she has no conflict of interest Research involving human participants and/or animals: This article does not contain any studies with animals performed by any of the authors. Informed consent Informed consent was obtained from all individual participants included in the study.

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