Long-term mortality in HIV-positive Individuals virally suppressed for >3 years with incomplete CD4 recovery

Background.\u2003Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/\ub5L after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. Methods.\u2003We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression ( 64500 HIV type 1 RNA copies/mL) for >3 years with CD4 count 64200 cells/\ub5L at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery ( 64200 cells/\ub5L) and Cox regression to identify associations with mortality. Results.\u2003Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/\ub5L after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/\ub5L. Individuals with CD4 64200 cells/\ub5L after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/\ub5L. The increased mortality was seen across different patient groups and for all causes of death. Conclusions.\u2003Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/\ub5L have substantially increased long-term mortality