Kinetics of productive and latent HIV infection in lymphatic tissue and peripheral blood during triple-drug combination therapy with or without additional interleukin-2

Objective: To study decay rates of productively and latently infected cells in peripheral blood and lymph nodes during triple antiretroviral therapy a nd the possible impact of interleukin-2 (IL-2) on viral kinetics. Methods: in this non-randomized study, nine antiretroviral-naive HIV-positi ve patients received either saquinavir hard gel capsules 2400 mg three time s daily (group I; four patients) or saquinavir soft gel capsules 1200 mg th ree times daily and IL-2 (group II), in both cases together with two nucleo side analogues. Plasma viraemia and lymphocyte subsets were analysed. Axill ary lymph nodes were excised before and after 12 weeks of therapy. Lymph no de sections were examined by in situ hybridization far HIV RNA, and product ively infected cells were counted. Infection rates of FAGS-sorted CD3, CD4 lymph node and peripheral blood mononuclear cells were determined by nested DNA PCR. Results: Baseline plasma HIV RNA levels ranged from <25 to >1x10(6) copies/ ml and remained undetectable throughout the study in one patient in group I . Plasma viraemia became undetectable after 3 months in four patients (thre e in group I). Productively infected cells were markedly reduced in the fol low-up lymph node specimens. HIV DNA-positive CD4 T cells were reduced in l ymphoid tissue and peripheral blood in all six evaluable patients. There we re no significant differences between the groups in the clearance rates of plasma virus and of HIV DNA-positive cells. Conclusions: Combined antiretroviral therapy rapidly suppressed active HIV replication in plasma and lymphoid tissue. Latently infected cells were cle ared at a slower rate. Viral clearance did not appear to be markedly affect ed by additional IL-2 therapy.