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

Abstract

Background: Some 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/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality.

Methods: We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality.

Results: Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL 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/µL. Individuals with CD4 ≤200 cells/µL 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/µL. The increased mortality was seen across different patient groups and for all causes of death.

Conclusions: Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.

Keywords: CD4 cell recovery; HIV; mortality; risk factors; sustained viral suppression.

Figure 1.

Flowchart and study timeline. *Of the 41 081 patients who were not on combination antiretroviral therapy for >3 years, 4677 (11.3%) died. Among these individuals, 1020 (12.8%) had an available viral load measurement within 3 months from date of death, and 44 (4.3%) were virally suppressed at time of death. Abbreviations: ART-CC, Antiretroviral Therapy Cohort Collaboration; cART, combination antiretroviral therapy; COHERE, Collaboration of Observational HIV Epidemiological Research Europe; HIV-1, human immunodeficiency virus type 1; VL, viral load.

Figure 2.

Cumulative probability of survival stratified by CD4 count at the end of the virally suppressed period: ≤200 cells/µL (full line); 201–350 cells/µL (broken line); 351–500 cells/µL (dotted line); and >500 cells/µL (broken and dotted line).