Immunologic Responses Associated with 12 Weeks of Combination Antiretroviral Therapy Consisting of Zidovudine, Lamivudine, and Ritonavir: Results of AIDS Clinical Trials Group Protocol 315

TLDR

HIV‑1 infection causes progressive cell‑mediated immune deficiency and abnormal immune activation, and although HAART increases CD4 counts and reduces opportunistic risk, the extent of immune reconstitution remains unclear. The study aims to determine whether extended viral suppression with antiretroviral therapy can achieve more complete immune restoration. Twelve weeks of zidovudine, lamivudine, and ritonavir reduced plasma HIV‑1 RNA by a median 2.3 logs, increased naive and memory CD4, naive CD8, and B lymphocytes, improved antigen‑specific lymphocyte proliferation and delayed‑type hypersensitivity, and partially corrected dysregulated immune activation, though T‑cell receptor V‑region expression remained unchanged.

Abstract

Human immunodeficiency virus (HIV)-1 infection is associated with progressive cell-mediated immune deficiency and abnormal immune activation. Although highly active antiretroviral therapy regimens can increase circulating CD4 T lymphocyte counts and decrease the risk of opportunistic complications, the effects of these treatments on immune reconstitution are not well understood. In 44 persons with moderately advanced HIV-1 infection, after 12 weeks of treatment with zidovudine, lamivudine, and ritonavir, plasma HIV-1 RNA fell a median of 2.3 logs (P < .0001). Circulating numbers of naive and memory CD4 T lymphocytes (P < .001), naive CD8 T lymphocytes (P < .004), and B lymphocytes (P < .001) increased. Improved lymphocyte proliferation to certain antigens and a tendency to improvement in delayed-type hypersensitivity also were seen. Dysregulated immune activation was partially corrected by this regimen; however, the perturbed expression of T cell receptor V regions in the CD4 and CD8 T lymphocyte populations was not significantly affected. Ongoing studies will ascertain if longer durations of virus suppression will permit more complete immune restoration.