BACKGROUND: Highly active antiretroviral therapy (HAART) decreases viral load and increases CD4 T-cell counts in patients with advanced HIV-1 infection. Whether HAART can improve CD4 T-cell function, and the biological characteristics affecting immune reconstitution, remain unclear. We undertook an open prospective pilot study to address these issues. Both treatment-naïve and previously treated patients were included. METHODS: 20 patients (seven naïve, 13 previously treated) were treated with one protease inhibitor and two reverse-transcriptase inhibitors and followed up for 12 months. We measured CD4-cell proliferation in response to cytomegalovirus and tuberculin antigens and counted subsets of CD4 cells at baseline and months 1, 3, 6, 9, and 12. Patients who had no antigen-specific reactivity at baseline but developed it while receiving HAART were classified as immunological responders. FINDINGS: Four patients had antigen-specific reactivity at baseline compared with 14 at month 12 (p <0.001). Between month 3 and month 12 viral load fell by a median of 1.5 log copies/mL from baseline (4.6 log copies/mL) and CD4-cell count increased by a median of 63/microL (from 93/microL). Ten patients (six of seven naïve, four of 13 previously treated) were immunological responders. They differed significantly from the ten non-responders in that their viral-load reduction was sustained for 12 months, the increase in CD4 count was greater, and they showed an early increase in memory CD4 T cells with an increase of naïve T cells. INTERPRETATION: HAART can induce sustained recovery of CD4 T-cell reactivity against opportunistic pathogens in severely immunosuppressed patients. This recovery depends not on baseline values but on the amplitude and duration of viral-load reduction and the increase of memory CD4 T cells.
BACKGROUND: Highly active antiretroviral therapy (HAART) decreases viral load and increases CD4 T-cell counts in patients with advanced HIV-1 infection. Whether HAART can improve CD4 T-cell function, and the biological characteristics affecting immune reconstitution, remain unclear. We undertook an open prospective pilot study to address these issues. Both treatment-naïve and previously treated patients were included. METHODS: 20 patients (seven naïve, 13 previously treated) were treated with one protease inhibitor and two reverse-transcriptase inhibitors and followed up for 12 months. We measured CD4-cell proliferation in response to cytomegalovirus and tuberculin antigens and counted subsets of CD4 cells at baseline and months 1, 3, 6, 9, and 12. Patients who had no antigen-specific reactivity at baseline but developed it while receiving HAART were classified as immunological responders. FINDINGS: Four patients had antigen-specific reactivity at baseline compared with 14 at month 12 (p <0.001). Between month 3 and month 12 viral load fell by a median of 1.5 log copies/mL from baseline (4.6 log copies/mL) and CD4-cell count increased by a median of 63/microL (from 93/microL). Ten patients (six of seven naïve, four of 13 previously treated) were immunological responders. They differed significantly from the ten non-responders in that their viral-load reduction was sustained for 12 months, the increase in CD4 count was greater, and they showed an early increase in memory CD4 T cells with an increase of naïve T cells. INTERPRETATION: HAART can induce sustained recovery of CD4 T-cell reactivity against opportunistic pathogens in severely immunosuppressed patients. This recovery depends not on baseline values but on the amplitude and duration of viral-load reduction and the increase of memory CD4 T cells.
Authors: H Choremi-Papadopoulou; N Panagiotou; E Samouilidou; F Kontopidou; V Viglis; A Antoniadou; J Kosmidis; T Kordossis Journal: Clin Exp Immunol Date: 2000-03 Impact factor: 4.330
Authors: Barbara Lotti; Thomas Wendland; Hansjakob Furrer; Nikhil Yawalkar; Salome von Greyerz; Karin Schnyder; Marlène Brandes; Pietro Vernazza; Ralf Wagner; Thi Nguyen; Eric Rosenberg; Werner J Pichler; Christian Brander Journal: J Clin Immunol Date: 2002-09 Impact factor: 8.317