Evaluation of the Relationship Between Immunologic Recovery After Highly Active Antiretroviral Therapy and the Ability to Mobilize CD34+ Stem Cells Following G-CSF Administration

In HIV infection, a progressive decline and/or dysfunction of several cell types is seen. It is thought that stem cell dysfunction or destruction may contribute to the hematologic and immunologic perturbations characteristic of HIV infection and may possibly limit the extent of immunologic recovery following HAART. This study proposes to investigate whether stem cell function and reserves are important in determining the extent of immune reconstitution following HAART.

Patients are stratified according to CD4 count. On Day 0, patients receive a 7-day cycle of subcutaneous granulocyte colony-stimulating factor (G-CSF). Blood samples are collected regularly, and on Day 14 patients undergo real-time HIV-1 RNA determinations. On Day 28, or sooner if HIV RNA is at least 1 log above baseline on Day 14, HAART consisting of daily receipt of abacavir, lamivudine, amprenavir, and ritonavir is initiated and continues until Week 76. Patients who achieve viral suppression (below 400 copies/ml of plasma HIV-1 RNA) by Week 26 are eligible to receive a second 7-day cycle of G-CSF at Week 28 and, if viral suppression continues through Week 50, a third cycle of G-CSF at Week 52. Patients are followed every 8 weeks for changes in viral load. Additionally, patients are monitored at regular intervals for surrogate markers of immunologic recovery and, during each cycle of G-CSF, for measurements of stem cell mobilization. Patients may also volunteer for A5085s (Bone Marrow Aspirate Substudy) at participating sites.