Cancer outcomes among people with HIV in North America in the era of antiretroviral therapy
CALKINS-DISSERTATION-2018.pdf (4.296Mb) (embargoed until: 2020-08-01)
Calkins, Keri Lee
MetadataShow full item record
Background: Poorer cancer outcomes have been observed for people with HIV (PWH) including more advanced stage at diagnosis, lower uptake of cancer treatment, and higher mortality. However, these results have not been consistent. Methods: We compared stage at diagnosis, treatment rates, and 5 year restricted mean survival time (RMST) between 254 PWH with cancer in the Johns Hopkins HIV Clinical Cohort (JHHCC) and similar HIV negative individuals in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program from 1997-2014. Probability differences (PD) and RMST differences due to HIV were calculated using G-computation with random forest methods. Among the JHHCC, we analyzed the effect of cancer treatment on CD4 and viral load trajectories and the association between longitudinal CD4 and viral load with all-cause mortality and the competing events of AIDS defining illness (ADI) and non-AIDS death (NAD) using joint longitudinal survival models. Results: PWH were more likely to be diagnosed at localized stage (PD= 0.24; 95% CI= 0.18, 0.30) and at distant stage (PD=0.36; 95% CI= 0.30, 0.43) than those without HIV. HIV did not affect the probability of receiving cancer treatment (PD= -0.04 [95% CI= -0.09, 0.02]). RMST differences by HIV status were accounted for by stage, except among women with HIV and CD4 ≤200 (-11.2 months; 95% CI=-25.6, -2.6). Immunosuppressive cancer treatment ([IT]; chemotherapy and/or radiation) resulted in an initial decline of 200 CD4 cells (95% CI= 95, 301). IT had no effect on viral load among PWH who were suppressed at baseline but was associated with a reduced viral load among unsuppressed PWH. A 100 CD4 cell increase reduced mortality in PWH (HR=0.81; 95% CI= 0.70, 0.93). A 100 CD4 cell increase resulted in a csHR of 0.84 (95% CI 0.60-1.13) and an sdHR of 0.91 (95% CI= 0.69-1.18) for ADI. A 100 CD4 cell increase was significantly protective for the hazard of NAD (csHR=0.77, 95%CI= 0.64-0.91; sdHR=0.73, 95%CI= 0.61-0.85). Conclusions: Interventions are needed to address disparities in stage at diagnosis by HIV status. CD4 cell count prior to and following cancer treatment is an important predictor of mortality, including non-AIDS mortality, in PWH.