Long-term CD4+ T-cell response to highly active antiretroviral therapy according to baseline CD4+ T-cell count.
Current treatment guidelines for HIV infection recommend a relatively late initiation of highly active antiretroviral therapy (HAART). Nevertheless, there is still a concern that immune recovery may not be as complete once CD4+ T cells have decreased below a certain threshold. This study addressed the long-term response of CD4+ T-cell counts in patients on HAART and analyzed the influence of baseline CD4+ T-cell counts, baseline viral load, and age. An observational analysis of evolution of CD4+ T cells in 861 antiretroviral therapy-naive chronic HIV-1-infected patients who started treatment consisting of at least 3 drugs in or after 1996 was performed. Patients were classified in 4 groups according to baseline CD4+ T cells: <200 cells/mm3, 200-349 cells/mm3, 350-499 cells/mm3, and >or=500 cells/mm3. The main outcome measures were proportion of patients with CD4+ T cells <200/mm3 and >500/mm3 at last determination and rate of CD4+ T-cell recovery. Patients were followed-up for a median of 173 weeks (interquartile range [IQR], 100-234). There were no differences in follow-up between the 4 groups. CD4+ T cells increased in the whole cohort from a median of 214 cells/mm3 (IQR, 90-355) to 499 cells/mm3 (IQR, 312-733) (P<0.001). Compared with the group with a baseline CD4+ T-cell count of >or=500/mm3, the relative risk of having a last determination of CD4+ T-cell counts >200 cells/mm3 was 0.79 (95% CI, 0.75-0.83), 0.92 (95% CI, 0.89-0.96) and 1 for baseline CD4+ T cells <200 cells/mm3, 200-349 cells/mm3, and 350-499 cells/mm3, respectively. The relative risk of having a last determination of CD4+ T-cell counts >500 cells/mm3 was 0.32 (95% CI, 0.27-0.39, P<0.001), 0.69 (95% CI, 0.60-0.79, P<0.001), and 0.94 (95% CI, 0.83-1.06, P=0.38) for baseline CD4+ T-cell counts <200 cells/mm3, 200-349 cells/mm3, and 350-0499 cells/mm3, respectively, compared with a baseline CD4+ T-cell count of >or=500 cells/mm3. The increase in CD4+ T cells from baseline was statistically significant and was maintained for up to 4 years of follow-up. This increase seemed to slow down after approximately 3 years and reached a plateau after 4-5 years of follow-up even in patients who achieved and maintained viral suppression in plasma. Long-term immune recovery is possible regardless of baseline CD4+ T-cell count. However, patients who start therapy with a CD4+ T-cell count <200 cells/mm3 have poorer immunologic outcome as measured by the proportion of patients with CD4+ T cells <200/mm3 or >500/mm3 at last determination. It seems that the immune recovery slows down after approximately 3 years of HAART and reaches a plateau after 4-5 years of HAART.
García
Felipe
F
Clinic Institute of Infectious Diseases and Immunology, IDIBAPS, Hospital Clínic, Faculty of Medicine, University of Barcelona, Spain. fgarcia@medicina.ub.es
de Lazzari
Elisa
E
Plana
Montserrat
M
Castro
Pedro
P
Mestre
Gabriel
G
Nomdedeu
Meritxell
M
Fumero
Emilio
E
Martínez
Esteban
E
Mallolas
Josep
J
Blanco
José L
JL
Miró
José M
JM
Pumarola
Tomás
T
Gallart
Teresa
T
Gatell
José M
JM
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000401:mortality; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D012044:Regression Analysis; D013030:Spain / Q000453:epidemiology; D013997:Time Factors
D012367:RNA, Viral