People who have had very low CD4 counts in the past, even if they now have complete viral suppression due to the use of potent anti-HIV therapy, have significantly weaker immune responses according to a brief report in the August 15th issue of the Journal of Infectious Diseases.
Although potent anti-HIV treatment has significantly improved the prognosis of HIV infected people, the recovery of CD4 cells depends on when treatment is started and for how long. Doctors already knew that very low CD4 counts may be associated with immune defects which are hard to correct. Those who have the lowest counts may not recover CD4 counts to the point where they can stop taking prophylactic drugs.
But the exact relationship between the lowest CD4 cell count a person has ever had, often called the CD4 nadir, and the strength of a person’s immune response after treatment is not clear. Therefore, investigators designed a study involving 84 HIV infected individuals. All were receiving HIV treatment and all had undetectable viral loads for at least three months. There was a wide range in their lowest-ever CD4 count. For this analysis researchers divided the participants into two groups: those whose lowest CD4 count was 200 cells/mm3; and, under and those whose lowest count was over 200 cells/mm3. They then compared the strength of the patient’s immune response after successful therapy in two ways: the strength of CD4 cell response to treatment and the CD8 cell response.
The researchers confirmed that there is a very significant relationship between CD4 nadirs and current CD4 counts. Those whose lowest CD4 count dropped below 200 cells/mm3 tended to have lower CD4 counts after therapy. But they also found that those with the lowest CD4 nadirs had a weaker immune response, irrespective of their post-HIV treatment CD4 count. This suggests that those people whose CD4 counts drop very low before therapy may not have their immune responses completely reconstituted, even if their CD4 cell counts recover. But the authors stress that there is no cut off value below which immune responses cannot recover and above which they can. Their results also suggest that the longer a person takes HIV therapy the stronger the immune response becomes, contradicting other studies that suggest that the CD4 count eventually reaches a plateau after five or six years of treatment.
So even though a low CD4 cell nadir may mean immune reponses are weaker after therapy prolonged HAART helps even in people whose CD4 counts dropped below 200 cells/mm3. These new data also suggest that those with low CD4 cell nadirs might be the most appopriate people to recruit into trials of HIV immunotherapy treatments such as therapeutic vaccines.
Siddique MA et al. Low CD4+ T cell nadir is an independent predictor of lower HIV-specific immune responses in chronically HIV-1 infected subjects receiving highly active antiretroviral therapy. J of Infect Dis,194:661-665, 2006.