Reply to Keynan et al

Abstract

To the Editor—We appreciate the concerns regarding CCR5 blockade expressed by Keynan et al. While animal models may provide a rationale to proceed to human studies, they may not always predict the observations or results that human studies yield. We acknowledge the reports of symptomatic West Nile infection in persons with a Δ32 mutation of the CCR5 receptor. Although these reports are scientifically intriguing, well-controlled prospective studies would be needed to determine the association of risk of severe or fatal West Nile virus infection in persons with the Δ32 mutation. A similar argument can be made regarding the risks of vaccination with yellow fever virus vaccine or the risk of tickborne encephalitis virus that have been reported. As for a broader risk for severe flavivirus infection among persons with the Δ32 mutation, this remains a hypothetical concern. Pharmacologic blockade of the CCR5 receptor may not behave in the same manner as a genetic polymorphism in the CCR5 receptor of all cells, which could modulate the clinical outcome of the infection. These questions emphasize the need for continued follow-up of patients treated with CCR5 antagonists. Vicriviroc has been studied in over 1600 subjects, some of whom have been treated for up to 4 years. We have not observed an excess of morbidity or mortality due to severe infections or unexplained complications that would suggest an untoward risk for those receiving vicriviroc. We continue to follow up patients receiving vicriviroc on long-term extension studies and continue evaluation of the risks expressed by the authors.