Induction-maintenance antiretroviral therapy: proof of concept

Objective: To investigate the concept of aggressive initial combination therapy followed by reduction to a less demanding maintenance regimen with respect to its potential for sustaining viral suppression. Design: Durable viral suppression to < 20 HIV RNA copies/ml plasma was achieved with zidovudine-nevirapine-didanosine (ZDV-NVP-ddI) therapy. Potential for sustained antiviral response was explored for patients who began with ZDV-NVP-ddI and subsequently interrupted ddI. Methods: Antiretroviral-naive patients were treated with ZDV-NVP, ZDV-ddI, or ZDV-NVP-ddI. Viral load was measured with the Amplicor assay (limit of quantification 400 copies/ml) and by the Ultra Direct assay (limit of quantification 20 copies/ml) when the Amplicor result was < 500 copies/ml. Treatment adherence for each drug was recorded, including all dose adjustments. Results: Five patients who had begun treatment with ZDV-NVP-ddI discontinued ddI for at least 6 weeks after achieving viral load levels below detection. All were documented to have sustained their viral load at < 20 copies/ml during the ddI interruption. Two patients permanently discontinued ddI, both with sustained viral load below detection for more than 1 year while treated with ZDV-NVP. In contrast, no patient initially receiving ZDV-NVP was able to maintain viral load below detection for sustained periods; none had viral load below detection after week 12 of treatment. Conclusions: After induction with ZDV-NVP-ddI, patients were able to sustain viral suppression with a regimen (ZDV-NVP) that was only transiently effective as initial therapy. There was no evidence of virologic escape, even with the most sensitive measure of plasma vital load. (C) 1998 Lippincott-Raven Publishers.