Syngeneic Bone Marrow Transplantation and Adoptive Transfer of Peripheral Blood Lymphocytes Combined with Zidovudine in Human Immunodeficiency Virus (HIV) Infection

Abstract

Objective: To examine the role of syngeneic bone marrow transplantation and peripheral blood lymphocyte infusions combined with zidovudine in the treatment of patients with human immunodeficiency virus (HIV) infection. Design: A partially randomized outpatient trial. Setting: Outpatient and inpatient facility of the Clinical Center of the National Institutes of Health, a research-based referral facility. Patients: Sixteen patients with HIV infection (15 symptomatic, 1 asymptomatic). Interventions: Symptomatic patients were treated with zidovudine, 500 mg orally every 4 hours for 12 weeks, combined with six peripheral blood lymphocyte infusions (four at week 10, two at week 12) and bone marrow transplantation (at week 12) using HIV-seronegative identical twins as donors. After transplantation, patients were randomly assigned to receive either zidovudine, 100 mg every 4 hours, or placebo for 12 months. The asymptomatic patient received zidovudine for the first 12 weeks, discontinuing therapy after transplantation. Immunologic and virologic monitoring were done monthly. Measurements and Main Results: Immediately after lymphocyte infusions and bone marrow transplantation, there was an increase in the mean (.+-. SE) CD4 cell percent (19.1% .+-. 3.1% to 28.1% .+-. 3.0%), an increase in the fraction of patients with delayed-type hypersensitivity responses to tetanus toxoid (4 of 13 to 11 of 13) and the development of delayed-type hypersensitivity to keyhole-limpet hemocyanin (a primary immunogen to which only the donor had been immunized) in 8 of 12 patients tested. No significant clinical improvement was noted, however, and there was no overall sustained immunologic improvement. No differences in CD4 cell percents, delayed-hypersensitivity skin tests, HIV cultures, or p24 antigenemia were seen between patients treated with zidovudine or placebo after transplantation. Conclusions: Although they establish the feasibility of combining zidovudine with cellular immune reconstitution in treating patient with HIV infection, our results show that any benefits from such combination therapy are at best transient. Future attempts at cellular immune reconstitution may need to use improved antiretroviral regimens as well as immunization of donors with HIV-specific antigens.