Long-Term CD4+ T-Cell Response to Highly Active Antiretroviral Therapy According to Baseline CD4+ T-Cell Count

Abstract

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.

Definition of Advanced Age in HIV Infection: Looking for an Age Cut-Off

“…Other authors have not found an association between mortality and age. 19,44,54 We must recognize some limitations in our study. One of the limitations common to all cohort studies is that they may not be representative of all HIV-infected patients.…”

Início da terapia anti-retroviral em estágio avançado de imunodeficiência entre indivíduos portadores de HIV/AIDS em Belo Horizonte, Minas Gerais, Brasil

“…O achado foi superior ao encontrado por Souza Jr. et al 18 em uma amostra representativa nacional, em que 41% dos pacientes tinham indicação imediata da TARV na avaliação inicial. Da mesma forma, nossa proporção foi superior à descrita por autores internacionais, em que a proporção de início tardio da TARV variou de 36% a 60% 11,13,14,30,31 , mas foi semelhante à encontrada por Brook et al 12 (66%). Chama a atenção que 4,8% (n = 15) foram incluídos como início tardio da TARV pela definição clínica.…”

Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy

“…19 Patients initiating HAART experience substantial increases in CD4 cell counts regardless of the CD4 cell count at initiation, with slightly greater average increases in patients with low CD4 cell counts at initiation. [20][21][22] In the Swiss HIV Cohort Study 21,23 and a Spanish cohort, 24 the likelihood that patients achieved a CD4 count >500 cells/µL up to 5 years after starting HAART was inversely associated with baseline CD4 cell count, and in gay men enrolled in the Multicenter AIDS Cohort Study, the CD4 cell count increased during the first 2 years of therapy but reached a plateau thereafter. 25 Poorer outcomes in patients starting HAART at low CD4 cell counts, compared with those starting at higher CD4 cell counts, are therefore likely to be explained by the lower CD4 cell counts experienced by these patients after initiation of HAART.…”