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Low CD4 Count Despite Viral Suppression Linked to Higher Risk of Death


HIV positive people who have poor CD4 T-cell recovery on antiretroviral therapy (ART) had higher mortality than those with good immunological response, even if they reached undetectable viral load, according to a study published in the January 22 advance edition of Clinical Infectious Diseases.

Modern ART is usually able to suppress HIV replication, but even when viral load becomes undetectable some people do not experience good CD4 cell recovery and may remain at risk for opportunistic illness and other adverse outcomes.

Frederik Engsig from Rigshospitalet Copenhagen University Hospital and colleagues with the Antiretroviral Therapy Cohort Collaboration (ART-CC) and the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord aimed to identify risk factors for failure to achieve a CD4 count greater than 200 cells/mm3 after 3 years of sustained viral suppression, as well as the association between CD4 cell recovery and subsequent mortality.

This analysis included 5550 HIV positive adults on ART in 2 large international collaborations with more than 50 cohorts in Europe and North America. They had viral load suppressed to <500 copies/mL for more than 3 years, with a CD4 count of <200 cells/mm3 at the start of the suppressed period. The median follow-up period was about 3 years.


  • 835 study participants (15%) did not reach a CD4 count >200 cells/mm3 after 3 years of viral suppression.
  • Older participants, heterosexual men, and people infected through injection drug use were less likely to achieve a CD4 count >200 cells/mm3 despite viral suppression.
  • Lower initial CD4 count, combination ART initiation after 1998, and longer time from ART initiation to the start of viral suppression were also risk factors for not reaching >200 cells/mm3.
  • A total of 175 participants (3%) died during follow-up.
  • Mortality rates were 8% for people who had <200 cells/mm3 after 3 years of viral suppression compared with 2% for those with good CD4 cell recovery.
  • People who still had <200 cells/mm3 after 3 years had substantially increased mortality relative to those with good CD4 cell recovery (adjusted hazard ratio 2.60, or nearly 3 times the risk of death).
  • Increased mortality was seen across different patient groups and for all causes of death, including all-cause mortality (adjusted HR 2.75), non-AIDS mortality (adjusted HR 2.61), and death related to hepatitis (adjusted HR 6.76) and non-AIDS cancers (2.89). 

Based on these findings, the researchers concluded, "Virally suppressed HIV-positive individuals on combination ART who do not achieve a CD4 count >200 [cells/mm3] have substantially increased long-term mortality."

They added that these findings support efforts to expand early diagnosis and initiation of antiretroviral treatment before severe immune system damage occurs. They also advised that people with persistently low CD4 counts should be monitored for opportunistic illnesses and other conditions such as non-AIDS cancers.



FN Ensig, R Zangerle, O Katsarou, et al. Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery,