NHL and HL are common in HIV+ people. Previous research has described significant declines in NHL and, to a lesser extent, HL after cART, but data on individual risk factors is limited. We sought to determine the role of demographic factors, and cumulative time spent with immunodeficiency (CD4 <200) and viral suppression (HIV RNA<400) on NHL and HL across Europe.
EuroSIDA participants with follow-up after 1/1/2001 and without NHL or HL at baseline were included and followed to first NHL or HL diagnosis, last visit or death. Risk factors for NHL and HL were assessed separately using Poisson regression including current and cumulative measures of HIV RNA (% of time with HIV RNA<400 copies/ml) and immunosuppression (% of time with CD4<200 cells/mm3).
14820 people contributed 101281 person years of follow-up (PYFU), 117 developed NHL (incidence rate 1.2/1000 PYFU, 95%CI 1.0-1.5) and 45 developed HL (0.5/1000 PYFU, 95%CI 0.3–0.6). Crude incidence of NHL and HL declined by 12% (95%CI: 7–16%) and 9% (95% CI: 1–15%) per year, however, no trend remained after adjustment (figure). In adjusted analyses, NHL incidence was lower in North and West and HL incidence in North and East compared to south Europe (figure). Lower current CD4 cell count (Figure), but not cumulative exposure to immunodeficiency (P>0.05), was associated with higher incidence of both NHL and HL. NHL incidence was strongly associated with current HIV RNA in univariate analyses (incidence rate ratio [IRR]: 3.35 95%CI: 2.33,4.83), but after adjustment, a history of poor control of HIV infection were more strongly associated with NHL, such as a prior diagnosis of AIDS-defining malignancies and lower % of time with controlled HIV RNA (figure). Other risk factors included older age (NHL only) and region of follow-up (both), whereas nadir CD4 was not associated with either HL or NHL (P>0.05).
Incidence of NHL and HL vary significantly by region, possibly reflecting differences in long term virological suppression through access to and availability of cART. NHL incidence was associated with lower CD4 and cumulative exposure to viral replication over time, suggesting that exposure to uncontrolled viral replication may play a part in NHL development in addition to current immunodeficiency. Conversely, HL incidence was elevated in those with current severe immunodeficiency (CD4<200), but cumulative exposure to uncontrolled HIV replication or immunodeficiency were not found to be significant risk factors.