Decrease in CD4 T-Cell Count and Risk of Severe Morbid Conditions in People With Human Immunodeficiency Virus Infection With Controlled Viral Load After Initiating Combination Antiretroviral Therapy Between 2006 and 2018.

Background: A previous study showed an association between CD4 T-cell count decline in people with human immunodeficiency virus infection (PWH) with viral suppression and an increased risk of severe morbid conditions. We aimed to assess the risk of CD4 T-cell count decline (hereafter, CD4 decline), determine associated factors, and evaluate the association of this decline with the risk of severe morbid conditions (cardiovascular disease and cancer) or death.
Methods: From the Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) CO4 French Hospital Database on HIV cohort, we selected PWH >18 years old who had been followed up for ≥2 years after viral suppression following the initiation of combination antiretroviral therapy (cART) between 2006 and 2018. CD4 decline was defined as 2 consecutive relative differences ≥15%. Among participants with such decline, we modeled CD4, CD8, and total lymphocyte counts before and after CD4 decline, using spline regression. The remaining objectives were assessed using Poisson regression, with the association between CD4 decline and the risk of severe morbid conditions or death evaluated during or after 6 months of decline.
Results: Among 15 714 participants (75 417 person-years), 181 presented with CD4 decline (incidence rate, 2.4/1000 person-years (95% confidence interval, 2.1-2.8). CD8 and total lymphocyte counts also showed a similar decline. Older current age and lower viral load at treatment initiation were associated with the risk of CD4 decline. The risk of severe morbid conditions or death was 11-fold higher during the first 6 months for participants who presented with CD4 decline versus those who did not (incidence rate ratio, 10.8 [95% confidence interval, 5.1-22.8]), with no significant difference after 6 months.
Conclusions: In PWH with viral suppression, CD4 decline was rare and related to global lymphopenia. It was associated with a higher risk of severe morbid conditions or death during the first 6 months.
Competing Interests: Potential conflicts of interest. L. W. reports grants to his institution from Gilead (observational study tenofovir alafenamide fumarate/emtricitabine/bictegravir) and Pfizer (phase IV A4001067 POEM 207740), and personal fees for educational events from MSD, outside the submitted work. A. M. reports a grant from MSD, lecture fees from ViiV, Janssen, MSD, and Gilead, and support for attending meetings from Gilead, MSD, Janssen, and ViiV. J. M. L. reports support for attending meetings and/or travel from MSD for Conference on Retroviruses and Opportunistic Infections 2020 (registration). V. P. reports consulting and lecture fees from Gilead, ViiV, and MSD, outside the submitted work. G. M. reports lecture fees from Pfizer, Astellas, and Gilead, outside the submitted work, and support for attending meetings from Astellas and Gilead. V. P., J. P. V., and S. G. report participation as data and safety monitoring board (DSMB) members for the ANRS VRI06 trial (EudraCT no. 2020-001814-40), and S. G. reports participation as a DSMB member for the Institut Pasteur trial Magtrivacsein (EudraCT no. 2013-004970-90). D. C. reports an HIV grant from Janssen (2019–2020), and personal fees from Gilead (2020) and Pfizer (2022) for lectures outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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