H. Valdez*1, E. Connick2, M. Lederman1, K. Smith3, L. Fox4, M. St. Clair5, R. Bosch6, R. Kim6, M. Blanchard7, and A. Landay3for the ACTG 375 Team.
1Case Western Reserve Univ., Cleveland, OH;2Univ. of Colorado Hlth.. Sci. Ctr., Denver;3Rush-Presbyterian-St. Luke's Med. Ctr., Chicago, IL;4NIH, Bethesda, MD;5Glaxo-Wellcome, Res. Triangle Park, NC;6Harvard Sch. of Publ. Hlth., Boston, MA; and7AIDS Clin. Trials Group, Rockville, MD.
Background:Our objective was to assess the effect of long-term control of HIV replication using highly active antiretroviral therapy (HAART) on T-lymphocyte numbers and phenotype.
Methods:ACTG 375 is a prospective, open-label study of the immunologic effects of HAART on protease- inhibitor-naïve patients. T-lymphocyte phenotypes of patients with VL under 1000 c/mL at 154 weeks of HAART were analyzed. The Wilcoxon test was used for comparisons.
Results:23 patients completed 3 years of HAART and had VL <1000 c/mL (87% <100 c/mL). Before HAART, patients had a median (Med) and interquartile range (IQR) CD4 cell count of 222 (141—252)/mL and Med VL of 4.93 log10c/mL. After 3 years, Med CD4 cell count was 411/mL (Med rise 19,1 IQR 157—270 cells/mL). Most of this rise was achieved in the first year. The Med increases in CD4 cells from year 1 to 2 (5.75) and from year 2 to 3 (10.8) were not statistically significant. 30% of patients achieved a CD4 cell count >500. After 3 years, memory (CD45RA-RO+) CD4 cells rose from a Med of 114/mL to 226/mL and naive (CD45RA+/62L+) CD4 cells rose from a Med of 51 to 125/mL. Most changes occurred mainly in year 1, from 114 to 194 cells/mL) for memory and from 51 to 143 cells/mL for naive CD4 cells. The Med number of CD8 cells after 3 years was similar to baseline (Med change 24 cells). Memory CD8 cells declined over 3 years (Med 127, IQR = -315 to 2) , while naïve CD8 cells rose (Med 86, IQR = 52—146). After 3 years, the Med percentage of CD4+/CD28+l>cells increased from 80 to 87 (Med 7%), lower than in HIV seronegatives (98%). The Med percentage of CD4+/ CD38+/HLA-DR+cells decreased after 3 years from 25 to 6 (Med 20%), still greater than in HIV seronegatives (3%).
Conclusions:Most HAART-treated individuals with moderately advanced HIV infection who achieve control of HIV replication have not normalized their CD4 counts after 3 years of therapy. Most of the increase in CD4 lymphocytes occurs in the first year of therapy. Expression of CD28, a marker of the ability of T cells to respond, remains subnormal after 3 years of therapy. The clinical implications of these findings remain to be determined.© 8th Conference on Retroviruses and Opportunistic Infections