Effect of long-term highly active antiretroviral therapy in restoring HIV-induced abnormal B-lymphocyte function

Although highly active antiretroviral therapy (HAART) has been reported to restore defects in cell-mediated immunity to a significant degree, little is known of its effects in restoring HIV-induced abnormal antibody-mediated immunity. We conducted a cross-sectional study of 1) 29 HIV-infected patients on chronic HAART whose HIV viral load was undetectable and whose absolute CD4(+) T-lymphocyte count had been consistently sustained by 150 cells/muL over their pre-HAART nadir value for >1 year; and 2) 29 untreated HIV-infected patients with current CD4 counts matching the treated patients' prior nadir CD4 counts. Serum was tested for total IgG and by protein electrophoresis with immunofixation for paraproteins. Although serum IgG levels were significantly lower in patients who had received long-term virologically effective HAART than in CD4 count-matched untreated patients (1488 +/- 475 mg/dL vs. 1999 +/- 775 mg/dL, p = .004), serum IgG was still abnormally elevated in 45% of the untreated group despite a mean 28 months of HAART-induced HIV suppression and CD4 count restoration. Paraprotein spikes were confirmed by immunofixation in 7% of patients in each group. This study provides the longest reported observation to date of the effect of HAART on HIV-induced abnormal antibody-mediated immunity. Larger and longer-term studies of HAART effect on B-cell reconstitution are needed.