Impact of HIV infection and Kaposi sarcoma on human herpesvirus-8 mucosal replication and dissemination in Uganda.
BACKGROUND
Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.


METHODS
Participants were enrolled into one of four groups on the basis of HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV negative/KS positive, and HIV positive/KS positive). Participants collected oral swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase chain reaction (PCR).


RESULTS
78 participants collected a total of 2063 orals swabs and 358 plasma samples. Of these, 428 (21%) oral swabs and 96 (27%) plasma samples had detectable HHV-8 DNA. HHV-8 was detected more frequently in both the oropharynx of persons with KS (24 (57%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p = 0.002) and the peripheral blood (30 (71%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p<0.001). In a multivariate model, HHV-8 viremia was more frequent among men (IRR = 3.3, 95% CI = 1.7-6.2, p<0.001), persons with KS (IRR = 3.9, 95% CI = 1.7-9.0, p = 0.001) and persons with HIV infection (IRR = 1.7, 95% CI = 1.0-2.7, p = 0.03). Importantly, oral HHV-8 detection predicted the subsequent HHV-8 viremia. HHV-8 viremia was significantly more common when HHV-8 DNA was detected from the oropharynx during the week prior than when oral HHV-8 was not detected (RR = 3.3, 95% CI = 1.8-5.9 p<0.001). Genital HHV-8 detection was rare (9 (3%) of 272 swabs).


CONCLUSIONS
HHV-8 detection is frequent in the oropharynx and peripheral blood of Ugandans with endemic and epidemic KS. Replication at these sites is highly correlated, and viremia is increased in men and those with HIV. The high incidence of HHV-8 replication at multiple anatomic sites may be an important factor leading to and sustaining the high prevalence of KS in Uganda.
Johnston
Christine
C
Department of Medicine, University of Washington, Seattle, Washington, United States of America. cjohnsto@u.washington.edu
Orem
Jackson
J
Okuku
Fred
F
Kalinaki
Mary
M
Saracino
Misty
M
Katongole-Mbidde
Edward
E
Sande
Merle
M
Ronald
Allan
A
McAdam
Keith
K
Huang
Meei-Li
ML
Drolette
Linda
L
Selke
Stacy
S
Wald
Anna
A
Corey
Lawrence
L
Casper
Corey
C
D000293:Adolescent; D000328:Adult; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000821:virology*; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000150:complications* / Q000821:virology*; D014454:Uganda; D014773:Virology / Q000379:methods*; D014779:Virus Replication