AEGiS-14IAC: Earlier initiation of HAART better preserves functional immune competence even in persons who achieve normal CD4+ T-cell counts.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Earlier initiation of HAART better preserves functional immune competence even in persons who achieve normal CD4+ T-cell counts.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. LbOr09)

Lange C, Valdez H, Medvik K, Asaad R, Wild M, Kalayjian R, Lederman M
Center for AIDS Research, Case Western Reserve University/University Hospitals, Cleveland, United States

BACKGROUND: To ascertain whether delaying antiretroviral therapy will compromise functional immunologic recovery in HIV-1 infection we studied patients who normalized circulating CD4+ T-cell counts after HAART using responses to immunization as a measure of functional immunologic competence.

METHODS: Twenty-nine HIV-1 infected persons with CD4+ T-cell counts >450 cells/ é L and HIV-RNA <400 copies/mL for >1 year after ART and 9 HIV(-) controls were immunized at study entry and 4 weeks later with tetanus-toxoid, diphtheria-toxoid, and keyhole limpet hemocyanin. An immune-response-score (IRS) was calculated using post-immunization antibody concentration, lymphocyte proliferation, and delayed-type-hypersensitivity responses.

RESULTS: Median current CD4+ T-cell counts were comparable in patients with CD4+ T-cell nadirs below (744 cells/ é L) or above (724 cells/ é L) the median CD4+ T-cell nadir of 250 cells/ é L. The median IRS was significantly lower in patients who started HAART with CD4+T-cell counts <250 cells/ é L when compared to patients who started HAART with CD4+ T-cell counts >250 cells/ é L (0.4 vs 0.67; p<0.005) or to HIV(-) controls (0.4 vs 0.7; p<0.001). CD4+ T-cell nadirs (rho=0.5;p<0.005) and numbers (rho=0.5;p<0.005) or percentages (rho=0.4;p<0.05) of CD4+/CD28+ T-cells were positively correlated with the IRS while current CD4+ T-cell counts were not. There was a linear relationship between the IRS and the CD4+ T-cell nadir at levels between150 and 450 cells/ é L.

CONCLUSIONS: Even among persons with "normalization" of CD4+ T-cell counts and well controlled HIV replication after HAART, the CD4+ T-cell nadir predicts the immune response to vaccination while current CD4+ T-cell count does not. Delaying the initiation of HAART in chronic HIV-1 infection results in progressive impairment of functional immune competence despite normalization of circulating CD4+ T-cell numbers. The long-term clinical consequences of delaying HAART initiation remain to be determined.

Keywords: AEGIS, CD4 Lymphocyte Count, Antiretroviral Therapy, Highly Active, T-Lymphocytes, HIV-1, HIV Infections, CD4-Positive T-Lymphocytes, Antigens, CD28, Immunization, Tetanus Toxoid, Vaccination, Human, prevention & control, immunology

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