Monitoring HIV vaccine trial participants for primary infection: studies in the SIV/macaque model

Whitney, James Ba,b; Luedemann, Corinnea; Bao, Saranc; Miura, Ayakoa; Rao, Srinivas Sc; Mascola, John Rc; Letvin, Norman La,b,c

AIDS:
doi: 10.1097/QAD.0b013e32832b43d9
Basic Science
Abstract

Objectives: The ability to detect and quantify acute HIV-1 infection prior to seroconversion would be an important tool for use in HIV vaccine clinical efficacy trials. We have utilized the SIV/rhesus monkey model to evaluate whether samples more easily obtained than peripheral blood might be used for intensive monitoring of vaccine trial participants.

Methods: We have evaluated viral loads in peripheral blood, saliva, feces, and urine of five rhesus monkeys during primary SIVmac251 infection by quantitative real-time PCR. As an alternative to the direct monitoring of frozen samples, we have also developed a fully quantitative viral load assay utilizing dried blood spots.

Results: Although all compartments were found to harbor viral RNA during primary infection, viral RNA could be detected in the peripheral compartments only when levels of plasma viremia exceed a threshold value of 104 RNA copies/ml. We found no direct correlation between viral burden in plasma and saliva, feces, or urine viral loads. Importantly, both dried saliva and whole blood spots can be used for viral detection. Quantitative whole blood or plasma spotting correlated well with viral burden in plasma during both the acute and set point phase of infection.

Conclusion: Dried blood spots are amenable to rapid quantitative viral load testing. Whole blood spotting has a significant logistical benefit as it requires low blood volumes and no blood processing. Saliva or dried saliva spots or both are potential candidates for acute phase diagnostic screening. These studies indicate the feasibility of intensive monitoring of HIV-1 vaccine trial participants for virus acquisition in resource-limited settings.

Author Information

aDivision of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, USA

bHarvard Medical School, Boston, Massachusetts, USA

cVaccine Research Center, National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland, USA.

Received 28 March, 2008

Revised 7 January, 2009

Accepted 23 January, 2009

Correspondence to Norman L. Letvin, MD, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Research East Room 113, 330 Brookline Avenue, Boston, MA 02215, USA. Tel: +1 617 667 2766; fax: +1 617 667 8210; e-mail: nletvin@bidmc.harvard.edu

© 2009 Lippincott Williams & Wilkins, Inc.