Impact of HIV Infection and Kaposi Sarcoma on Human Herpesvirus-8 Mucosal Replication and Dissemination in Uganda

Abstract

IntroductionKaposi 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.MethodsParticipants 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).Results78 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).ConclusionsHHV-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.

Human Herpes Virus-8 Infections among Subjects with Human Immunodeficiency Virus Infection and Normal Healthy Individuals in India

“…Western and African countries also reported high frequencies of KS among HIV-infected individuals [20,21]. However, the incidence of KS is very low in our region.…”

Dynamics of Persistent Oral Cytomegalovirus Shedding During Primary Infection in Ugandan Infants

“…As previously described [10], pregnant women in Kampala were enrolled, and oral swabs were collected in a standardized manner [11] from the mother and all children for quantitative polymerase chain reaction (qPCR) analysis of CMV [12]. Blood samples were collected from the infants at 6 weeks of age and every 4 months thereafter.…”

Human Herpesviruses 6, 7, and 8 From a Dermatologic Perspective

“…Kaposi sarcoma is more common in homosexual than heterosexual persons with AIDS. 15 The high prevalence in prepubertal children in endemic areas suggests that sexual transmission is unlikely to be the sole mode of infection. A study of HHV-8 -seropositive men who had sex with men and no clinical evidence of KS showed that exposure to infectious saliva is a risk factor for HHV-8 acquisition.…”