HIV-1 induction-maintenance at the lymph node level: The "Apollo-97" study

Objective: To assess the effects of five-drug combination therapy on HIV-1 load in lymph nodes and subsequent maintenance with four and three drugs. Methods: Ten pharmacotherapeutic ally naive patients received a combination of zidovudine, lamivudine, didanosine, ritonavir, and saquinavir for 24 we eks, then zidovudine, lamivudine, didanosine, and saquinavir for the next 2 4 weeks, and finally zidovudine, lamivudine, and saquinavir for the last 24 weeks, HIV-1 RNA in lymph nodes was measured using quantitative polymerase chain reaction (PCR) at baseline, after 12, 24, 48, and 78 weeks. Plasma H IV-1 RNA, proviral DNA in peripheral blood mononuclear cells (PBMCs), circu lating lymphocyte subsets, and protease inhibitor levels in blood were also regularly measured. Genotypic resistance was assessed in the different com partments in 2 patients who were failed by therapy. Results: HIV-1 RNA decreased in lymph nodes in 9 patients and was stable in 1 despite initial control of plasma replication < 20 copies/ml in each pat ient. Lymph node levels rebounded in 1 patient at week 72 as a result of la ck of adherence and remained stable in the 8 others despite maintenance reg imens. This represents a mean drop of -3.17 log in lymph nodes for the 8 pa tients maintaining undetectable viremia at 72 weeks. In the patient with st able lymph node viral RNA, selection of the M184V mutation was demonstrated at this level before detection in plasma and low blood saquinavir levels w ere found throughout the study. Continuous improvements in immune parameter s were observed in all cases, although PBMC proviral DNA levels either show ed a continuous decrease or stabilized to a plateau. Conclusions: More complex regimens do not perform better in lymph nodes tha n classic triple therapy. The persistence of HIV-1 RNA in lymph nodes could be related with cellular resistance mechanisms rather than an insufficient potency of the regimens.