Objective: To investigate immunological changes during CD4-guided therapy interruption in HIV+ patients who suspended HAART.
Patients: Seventeen patients aged > 18 years, who had received HAART for at least 12 months, and had a pre-interruption CD4+ cell count > 500 cells/μl, interrupted treatment. Median nadir CD4+ cell count was 288 cells/μl. HIV plasma viral load at discontinuation was < 50 or > 50 copies/ml. Criteria for restarting treatment were: a CD4+ T-lymphocyte count < 350 cells/μl on two separate occasions, a clinical manifestation of AIDS, and the patient's desire to resume HAART. Eleven patients were still off therapy after 12 months (group A); according to the first criterion, six patients restarted therapy within 12 months (group B).
Methods: Haematological, viro-immunological, cytofluorimetic and molecular assays were performed at baseline and every 2 months following standard methods. Statistical analysis was performed under Stata 7.0.
Results: In the first 2 months of treatment interruption, a significant increase in viral load and CD8+ lymphocyte activation occurred. Then such parameters decreased and remained stable. In all patients, a decrease in CD4+ lymphocytes took place as well, that affected in a similar manner naive, central memory, effector memory and terminally differentiated cells. Group B always presented lower amounts of CD4+ effector memory lymphocytes. The expression of CD127 was always higher in group A.
Conclusions: The loss of CD4+ lymphocytes upon viral rebound is equal among naive and memory subsets. Patients with higher expression of CD127, who are likely to exert a better capacity to utilize endogenous interleukin-7 by T cells, could remain off therapy for longer periods.
From the aDepartment of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy
bClinic of Infectious Diseases, University of Modena and Reggio Emilia and Azienda Policlinico, Modena, Italy.
Received 26 April, 2006
Accepted 29 June, 2006
Correspondence to A.Cossarizza, Department of Biomedical Sciences, Via Campi, 287, 41100 Modena, Italy Tel: +39 059 2055415; fax: +39 059 2055426; e-mail: firstname.lastname@example.org