Monitoring HIV vaccine trial participants for primary infection: studies in the SIV/macaque model.
OBJECTIVE
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 10 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.


CONCLUSIONS
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.
Whitney
James B
JB
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Luedemann
Corinne
C
Bao
Saran
S
Miura
Ayako
A
Rao
Srinivas S
SS
Mascola
John R
JR
Letvin
Norman L
NL
D016915:AIDS Vaccines; D000818:Animals; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005243:Feces / Q000821:virology; D008253:Macaca mulatta; D008297:Male; D012367:RNA, Viral / Q000097:blood / Q000378:metabolism* / Q000652:urine; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012463:Saliva / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification*; D013048:Specimen Handling / Q000379:methods; D019562:Viral Load; D014766:Viremia / Q000821:virology
D016915:AIDS Vaccines; D012367:RNA, Viral