What is the role of poor CD4 response in antiretroviral therapy in treatment-experienced patients with HIV infection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Previous versions of the DHHS guidelines have included immunologic failure and disease progression as types of treatment failure. The failure to achieve or maintain CD4 cell recovery despite virologic suppression was considered immunologic failure; however, no standard definition of target values ever existed. The current guidelines address this as poor CD4 cell response and/or persistent inflammation despite viral suppression.

CD4 cell recovery generally continues for years in the setting of virologic suppression, with most patients achieving CD4 cell counts >500 cells/mm3. [8] There are some patients, however, that plateau at an unexpectedly low CD4 count and others that even experience a decline in count despite continuous viral suppression. Patient’s starting ART at very low baseline CD4 levels (< 200 cells/mm3) are more likely to experience a suboptimal CD4 recovery. [8] Early diagnosis and initiation of therapy is the best way to support maximal CD4 recovery.

Patients who experience suboptimal CD4 recovery or those with a declining CD4 count should be investigated to see if there are any underlying causes or contributing factors such as medications, co-infections, or malignancy. [8] Many times, no cause can be identified. Currently there are no recommended interventions to assist in CD4 recovery. Changing antiretroviral classes or adding additional agents to a suppressive regimen has shown no consistent benefit in increasing CD4 counts and is not recommended. Immune-based therapies (interleukin-2, growth hormone, interleukin-7) have been and continue to be investigated, but to date, none can be recommended. [8]

More recently, research has begun to focus on the heightened immune activation and inflammation produced secondary to HIV infection. This appears to be a factor related to morbidity and mortality independent of viral suppression and CD4 count. [8] Research is ongoing into the origin and contributing factors of this immune activation and inflammation and therapies to decrease it. At this time, routine monitoring of immune/inflammatory markers as well as any therapies to decrease ongoing activation cannot be recommended. [8]

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