Background HIV-infected patients who fail to normalize CD4 T cells despite suppressive antiretroviral therapy have impaired immune homeostasis: diminished naïve T cell numbers, elevated T cell turnover, senescence and inflammation. Methods Blood samples from immune failures (n=60), immune successes (n=20) and healthy controls (n=20) were examined for plasma IL-7 levels, for cellular expression of the IL-7Rα chain (CD127), for the exhaustion and senescence markers PD-1 and CD57, and for the survival factor Bcl2. As both inflammatory and homeostatic cytokines can induce T cell cycling, we also examined the effects of these mediators on exhaustion and senescence markers. Results Plasma levels of IL-7 were elevated and both CD4 and CD8 T cell CD127 expression was decreased in immune failure. Plasma levels of IL-7 correlated directly with naïve CD4 T cell counts in immune success and inversely with T cell cycling (Ki67) in healthy controls and immune success, but not in immune failure. CD4 T cell density of PD-1 was increased and Bcl2+ CD4 T cells were decreased in immune failure but not in immune success, while the proportion of T cells expressing CD57 was increased in immune failure. PD-1 and CD57 were induced on CD4 but not CD8 T cells by stimulation in vitro with inflammatory (IL-1β) or homeostatic (IL-7) cytokines. Conclusions Perturbation of the IL-7/IL-7 receptor axis, increased T cell turnover, and increased senescence may reflect dysregulated responses to both homeostatic and inflammatory cytokines in immune failure patients.