January 31, 2014
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Incomplete CD4 recovery increased mortality despite viral suppression

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New data suggest that patients with HIV who do not reach a CD4 cell count of more than 200 cells/mcL despite achieving viral suppression have increased long-term mortality.

“Our data underline the importance of early diagnosis of HIV and treatment with [combination antiretroviral therapy] before patients have a low CD4 count,” researchers wrote in Clinical Infectious Diseases. “Although we have identified risk factors for poor CD4 recovery, no interventions to increase CD4 count in virally suppressed patients have been demonstrated to have beneficial effects on clinical endpoints and mortality.”

The researchers used data from two international collaborations of HIV cohorts: the Antiretroviral Therapy Cohort Collaboration (ART-CC) and the Collaboration of Observation HIV Epidemiological Research Europe (COHERE). They evaluated risk factors for not having a CD4 count of more than 200 cells/mcL among 5,550 patients who achieved viral suppression for 3 years and had a low CD4 count at the start of viral suppression. The median follow-up time was 3.4 years.

Most of the patients (85%) had a CD4 count of more than 200 cells/mcL after 3 years of viral suppression. The risk of not reaching this CD4 count increased with age and with lower CD4 counts at start of viral suppression. Men who were infected via heterosexual sex, injection drug use or other unknown transmission had a higher risk of incomplete CD4 recovery compared with men who have sex with men. Patients who started ART after 1998 and those who took more than 1 year to reach viral suppression also had a higher risk of incomplete CD4 recovery.

Within the cohort, 175 (3.2%) of the patients died. Of those who died, 66 did not have a CD4 count of more than 200 cells/mcL. Patients who did not have a CD4 count of more than 200 cells/mcL after 3 years of viral suppression had a higher mortality (HR=2.6; 95% CI, 1.86-3.81). The estimated 5-year mortality for these patients was 11.8%. Mortality was 4.1% for patients who reached a CD4 count of 201 cells/mcL to 500 cells/mcL, 2.2% for those who reached a count of 351 cells/mcL to 500 cells/mcL and 2.2% for those who reached a count of more than 500 cells/mcL.

“Our study demonstrated an increased risk of non-AIDS causes of death in immunological nonresponders,” the researchers wrote. “Further research is needed to elucidate the mechanisms that lead to persistently low CD4 counts despite viral suppression.”

Disclosure: See the study for a full list of researchers’ financial disclosures.