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Normalization of CD4 Counts in Patients Taking Combination ART with Maximum Virologic Suppression
Amanda Mocroft*1, A Phillips1, J Gatell2, B Ledergerber3, M Fisher4, N Clumeck5, M Losso6, A Lazzarin7, G Fätkenheuer8, J Lundgren9, and the EuoSIDA Study Group
1Royal Free and Univ Coll London Med Sch, UK; 2Hosp Clin i Provincial, Barcelona, Spain; 3Univ Hosp, Zurich, Switzerland; 4Royal Sussex County Hosp, Brighton, UK; 5St Pierre Hosp, Brussels, Belgium; 6Hosp JM Ramos Mejia, Buenos Aires, Argentina; 7Hosp San Raffaele, Milan, Italy; 8Univ Cologne, Germany; and 9Copenhagen HIV Prgm, Hvidovre, Denmark
Background: Whether CD4 continues to increase with long-term
combination ART (cART) is unknown in patients with
maximal virologic suppression (viral load <50 copies/mL) to reach levels seen in HIV– persons.
Methods: For each ART-naïve
patient starting cART, the change in CD4 occurring
between each pair of consecutive viral load <50 copies/mL
was calculated and standardized to give the annual change in CD4. Thus a
patient with 4 consecutive viral load <50 copies/mL
would contribute data from 3 viral load pairs; change in CD4 between first and second
viral load, second and third, third and fourth. Generalized linear models,
accounting for multiple measurements within patients, were used to compare
long-term CD4 increases. Baseline was defined as the first viral load <50 copies/mL after starting cART.
Results: We included 1517 patients in analyses: 79% were male, and 23% had a diagnosis of AIDS
prior to starting cART. The median CD4 at starting cART was 210/mm3 (IQR 91 to 340), and median baseline
date was March 2001 (IQR June 1999 to January 2003). There were 12,137 pairs of
viral load <50 copies/mL; 5614 pairs were in
patients taking a protease inhibitor (PI) -based regimen (46.3%), 4923 in
patients taking an non-nucleoside reverse transcriptase inhibitor (NNRTI) -based
regimen (40.6%), and 1600 (13.1%) in patients taking a triple-nucleoside
regimen, including abacavir. The figure illustrates
the mean annual change in CD4 while viral load <50 copies/mL after stratification by time since starting cART and by current CD4. The
greatest rises in CD4 were seen in the first year after starting cART, approximately 100/mm3, and this was
consistent with different current levels of CD4. Significant, but lower,
increases in CD4 (approximately 50/mm3) continued to be observed
even at 5 years after starting cART in patients whose
current CD4 was below 500/mm3. The only group without significant
increases in annual CD4 was in patients who had taken cART
for more than 5 years with a current CD4 >500/mm3. The current
median CD4 count in this patient group was 701/mm3 (IQR 601 to 863).
Similar results were seen after adjustment for nucleoside backbone, cART regimen started, age and change in CD4 since starting cART.
Conclusions: Only patients whose CD4 count was approaching
normal levels experienced no further significant increases in CD4 while viral
load <50 copies/mL. These results suggest that
near-normal CD4 counts could be reached in all patients with maximum virologic suppression for a sufficient length of time.
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