INTRODUCTION:: poor CD4 response to antiretroviral treatment (HAART) is associated with increased mortality. We analyzed the impact of CD4 increase on non-AIDS related morbidity and on mortality in HIV patients and their parents. METHODS:: mortality rates were estimated among 1,758 virally suppressed patients in the Danish HIV Cohort Study after two years on HAART and among their parents (n=1,603). Analyses were stratified by pre-HAART CD4 count and CD4 increase. Incidence rate ratios of non-AIDS-related morbidity and mortality rate ratios (MRR) were analyzed using Poisson regression. RESULTS:: CD4 increases 100 cells/μL was associated with increased mortality (MRR 3.5 (95%CI 1.8-6.8)) even in individuals with pre-HAART CD4>250 cells/μ (MRR 3.2 (95%CI 1.3-7.8). Mortality of parents of patients with poor CD4 response was also increased (MRR 1.5 (95%CI 1.1-2.1)). There was a trend towards association between poor CD4 response and increased risk of cardiovascular disease and cancer (IRR 1.6 (95%CI 0.8-3.2) and 1.6 (95%CI 0.6-4.8)). CONCLUSIONS:: poor CD4 increase after HAART is associated with adverse prognosis even in absence of severe immunosuppression. CD4 response in HIV patients is associated with mortality among their parents, thus poor CD4 response may be caused by genetic factors, which might also affect morbidity and mortality in the HIV negative population.