Pantazis, N et al; on behalf of the Athens Multicenter AIDS Cohort Study (AMACS)
Long-term evolution of CD4⁺cell count in patients under combined antiretroviral therapy
AIDS: August 1, 2019 – Volume 33 – Issue 10 – p 1645–1655
Doi: 10.1097/QAD.0000000000002248

Antiretroviral therapy (ART) results in substantial immunologic improvement for most patients infected with HIV. However, many studies have found variability in the extent of immune recovery after viral suppression is attained. Common factors predictive of sub-optimal recovery include a low baseline CD4+ nadir and advanced age. This study from Greece (AMACS) looked at long-term CD4 cell count recovery and any associations with baseline CD4 nadir, pre-ART viral load, sex, risk group, and type of ART. The study included 3,405 treatment naive patients of whom 86% were male. The median age at ART initiation was 36 years and the median follow-up of almost four years. Among individuals who started ART with a baseline CD4 count of less than 200 cells/μl, only 43% had normalized their counts after seven years of treatment. The likelihoodof CD4 normalization after seven years of viral suppression was only 24% for those starting ART with < 200 cells/μl, and 46% for those starting treatment with 200-349 CD4 cells/μl, respectively. For the majority of patients, any CD4+ cell count increases after four years of ART were insignificant. Having a lower pre-treatment viral load was also associated with faster CD4+ recover. These findings underline the importance of early HIV diagnosis and ART initiation to decrease the risk of AIDS and non-AIDS-related morbidity and mortality. Those patients with incomplete CD4 recovery may require prophylaxis against opportunistic infections and closer monitoring than patients with normal CD4 counts.

Author’s Commentary:

This study adds to data from other U.S. and international HIV cohorts that have consistently found older age, male sex, and lower pre-ART CD4+ cell count are all associated with sub-optimal immune recovery, even with complete and sustained suppression of HIV-RNA. This has been one of the key drivers for starting patients on ART as soon as possible after HIV diagnosis. Although we monitor CD4 counts less often in our “stable” patients, those with incomplete immune recovery remain at higher risk for HIV-related complications. Current DHHS guidelines recommend that during the first 2 years of ART, for patients with a CD4 count < 300 or who develop viremia while patient on ART, a CD4 count should be checked every 3 to 6 months. For patients with a CD4 count of 300 to 500, yearly monitoring is recommended and if > 500 then CD4 monitoring is considered to be “optional.” My personal preference (and that of many of my stable patients) is to check CD4 counts once per year.