Immunological failure: persistent CD4+ T cell deficiency

Recovery of immune function after ART is started is variable but generally not related to the ART regimen used. Duration of the HIV infection and degree of immunodeficiency when ART is commenced (nadir CD4+ T cell count) are much more important factors. Age is another very important factor, with a slower and often blunted immune recovery as age increases. Immune recovery may also be delayed because of other factors, such as concomitant disease, including kidney disease or sarcoidosis; persistent infections by other viruses, such as cytomegalovirus and HCV; and development of malignancy and the use of chemotherapy and/or radiotherapy to treat it.

Medications that can cause cytopaenias represent one potential factor in delayed immune recovery that can be modified. Prophylaxis for Pneumocystis jirovecii infection is used when the CD4 count is <200/µL (~15%). First-line prophylaxis with trimethoprim/sulfamethoxazole may be associated with leucopaenia. Interventions to consider include reducing the dose if a relatively high dose is being used, for example, switching from cotrimoxazole DS (160/800 mg) 1 tablet daily to cotrimoxazole single strength (80/400 mg) 1 tablet daily or cotrimoxazole DS 1 tablet on three days per week.[7]

In assessing slow immune recovery, both the total CD4 count and CD4% should be considered. The possibility of a laboratory error should be considered in the case of an unexpectedly low or high result.

Illustrative case examples:

  • A 65 year-old man with a late diagnosis of HIV infection had concomitant chronic kidney disease and diabetes. Despite consistently undetectable HIV RNA levels, the CD4 count increased from 100 to only 180/µL after 10 years of ART. Late diagnosis, older age and chronic kidney disease likely contributed to the suboptimal CD4+ T cell recovery.
  • A 52-year-old man commenced ART when the CD4 count was 30/µL (3%). Three years later, his CD4 count was only 204/µL (12%). The ART regimen remained unchanged and by two years later, he had a more robust immune recovery, with a CD4 count of 670/µL (24%). Slow recovery of CD4+ T cell count likely reflected the very low nadir CD4+ T cell count and older age but recovery eventually did occur indicating that the ART regimen was not relevant.
  • A 40 year-old man with long-term well-controlled HIV infection and a usual CD4 count of ~500/µL came for monitoring when the CD4 count was found to be 210/µL with CD4% unchanged at ~30%, and HIV RNA <20 copies/ml. He had recently developed polyarthritis and had a previous diagnosis of sarcoid disease. The fall in CD4 cell count was due to a relapse of sarcoid disease and recovered after treatment. The decline in CD4 count with preservation of CD4% provided evidence that the low CD4+ T cell count was a consequence of lymphopaenia caused by sarcoidosis rather than CD4+ T cell depletion related to HIV infection.
  • An unexpectedly low CD4 count result was received. On checking the calculation of CD4 as percentage of total lymphocyte count, it was found to be due to a laboratory calculation error. An amended report was made after discussion with the laboratory staff.