Long-term evolution of CD4+ cell count in patients under combined antiretroviral therapy

Objective Combined antiretroviral treatment (cART) results in profound immunologic improvement, but it is unclear whether CD4 cell counts return to levels similar to those of HIV-negative individuals. We explore long-term CD4 cell count evolution post-cART and its association with baseline levels, virologic suppression, pre-cART cumulative viremia and other factors. Design Data were derived from the AMACS. Included individuals were adults who started cART, at least 2003, while previously ART-naive. Methods Changes in CD4 cell counts were modeled through piecewise linear mixed models. Results A total of 3405 individuals were included. The majority was male (86.0%), homosexual (58.8%) with median (IQR) age at cART initiation 36 (31-44) years and a median (IQR) follow-up of 3.9 (2.0-6.9) years. Most persons (57%) starting cART with less than 200 cells/μl did not reach 600 cells/μl after 7 years of treatment. Those starting cART with 200-349 CD4 cells/μl could reach 600 cells/μl within less than 2 years of fully suppressive treatment. Probability of CD4 normalization (i.e. >800 cells/μl) after 7 years of suppressive treatment was 24 and 46% for those starting treatment with less than 200 or 200-349 CD4 cells/μl, respectively. Lower pre-cART cumulative viremia was associated with faster CD4 recovery. CD4 cell count increases after 4 years were either insignificant or very slow, irrespectively of baseline levels. Conclusion cART initiation before CD4 cell count drops below 350 cells/μl is crucial for achieving normal CD4 levels. These findings underline the importance of timely diagnosis and cART initiation as the risk of both AIDS and non-AIDS-related morbidity/mortality remains increased in patients with incomplete CD4 recovery.