The clinical impact of immunodeficiency and viraemia in the era of combined antiretroviral therapy for HIV-1 infection

S. Zhang

Research output: PhD ThesisPhD-Thesis – Research external, graduation internal


Despite treatment with combined antiretroviral therapy (cART), patients may experience viraemia at different levels and for varying periods of time, and CD4 count recovery, even in patients with sustained virus suppression, frequently remains suboptimal.
We studied the characteristics of episodes of low- and high-level viraemia, including during cART interruption, and evaluated their immunologic, virologic and clinical impact in patients enrolled in the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. We found that, in patients on cART, low-level viraemia, including isolated viral blips, had limited clinical significance, while high-level viraemia was associated with both a worse immunologic response and clinical outcome.
Inspired by the results of the Strategies for Management of Antiretroviral Therapy (SMART) trial, we extended the analyses to also investigate the impact on non-AIDS-associated morbidity and mortality, particularly major cardiovascular disease, chronic renal failure, liver fibrosis/cirrhosis, non-AIDS-associated malignancy and a composite of these outcomes.
In a subset of patients who had achieved virological suppression on treatment, patients experiencing viraemia to above 400 copies/ml during treatment were at higher risk of developing cardiovascular disease, and patients experiencing persistently lower peripheral blood CD4+ T-cell levels were more likely to develop the other non-AIDS diseases studied. Given that the association between viraemia, CD4 cells and non-AIDS diseases in the treated population may have been confounded by adverse effects of cART, a similar analysis was performed among patients not yet on treatment. We found that the risk of non-AIDS morbidity generally appeared to be accentuated by more severe immunodeficiency.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Reiss, Peter, Supervisor
  • de Wolf, F., Co-supervisor, External person
Award date10 Feb 2015
Publication statusPublished - 2015

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