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CD4 Count Normalization in Patients with HIV-1 Infection and Maximum Virological Suppression Who Are

August 2007

Normalization of CD4 Counts in Patients with HIV-1 Infection and Maximum Virological Suppression Who Are Taking Combination Antiretroviral Therapy:  An Observational Cohort Study
Mocroft A Lancet 2007;370:407-413  [Abstract]

The goal of the study was to determine CD4 cell count increases in patients who have virologic suppression.

Methods:  The study used the EuroSIDA cohort which is a European study of 14,262 patients with HIV infection in 92 centers across Europe, Israel, and Argentina.  Patients were included if they had at least two consecutive HIV viral loads <50 c/mL with measurements of CD4 cell counts every 6 months since before starting HAART.  

Results:  The median CD4 cell count at initiation of HAART was 204/mm3 and the greatest yearly increase in CD4 cell count was a median 100/mm3 in the first year after starting HAART.  Nevertheless, lower but yearly increases in CD4 cell counts averaging about 50/mm3/yr were seen at 4 years in those with CD4 cell counts <350/mm3 at baseline.  The only group that did not have a significant increase was the one who initiated HAART with CD4 cell count exceeding 500/mm3.  These results are shown in the following table:

CD4 Count at Initiation
of HAART (/mm3)
 No. Yrs Rx
 No.
 Rate of CD4 Increase
Per Yr (/mm3)

 Current CD4 Count (/mm3)
          
            =200		       <1
      1-3
      3-5
      >5		 711
2124 2109
2164		              
              76
              69
              50
              32		           204
          322
          431
          497
        
          201-350		      
      <1
      1-3
      3-5
      >5		   
  539
1158 1088
1184		             
             129
               50
               47
               23		          
          374
          519
          618
          676
        
          >350		      
      <1
      1-3
      3-5
      >5		   
  343
  851
  791
  747		               
               90
               50
               17
               21		          
          580
          684
          781
          794

Multivariable analysis showed no significant effect on the yearly increase in CD4 cell count based on age, change in CD4 cell count since starting HAART, the peak HIV viral load, or CD4 cell count at baseline.

Conclusion:  The authors conclude that normal CD4 cell counts can be achieved with viral suppression if it is maintained for a sufficient period.  

Comment:  Previous studies have shown that the CD4 cell count with a viral suppression is progressively less with sequential analyses during HIV viral suppression as shown in this report.  However, some have suggested a plateau with no further increases after 4 years (Moore RD Clin Infect Dis 2007;44:441), and others have shown a subgroup of about 40% of patients who had no further increases after 4 years (Hunt PW AIDS 2003;17:1707; Smith CJ AIDS 2003;17:963).  Some of the differences may be related to the size of the cohort, failure to make these measurements with confirmed viral load suppression, and/or the use of a higher threshold for defining viral suppression.  Of note in the context of strategies for “when to start,” the results of this study showed that patients who started HAART with a CD4 cell count of >350/mm3 had CD4 cell counts approaching the levels seen in patients without HIV infection after 3 years of HAART.  However, there was no ceiling for increases with longer duration of HAART in those who started with lower CD4 cell counts.