Oral shedding of herpesviruses in HIV-infected patients with varying degrees of immune status

Abstract

Objective Herpesvirus shedding in the oral cavity was analyzed to determine if presence in the oral compartment correlates with systemic changes in HIV-associated immune deficiency as measured by CD4+ counts, plasma HIV viral load (VL) and presence of AIDS-defining events. Design A5254 is a multicenter, cross-sectional, single-visit study to evaluate oral complications of HIV/AIDS and determine the association between clinical appearance, herpesvirus shedding and immune status as ascertained by CD4 count and HIV viral load. 307 HIV infected individuals were evaluated and throat wash collected. Methods Fisher’s exact test and Kruskal-Wallis test were used to assess the association between presence of herpes viruses and the state of immunodeficiency as stratified by a combination of CD4+ count and HIV VL. Relationship between pathogens and HIV VL in plasma was modeled by logistic regression. Results The presence of cytomegalovirus CMV and Herpes Simplex Virus-1 (HSV-1) in throat wash was associated with decreased CD4 counts. By contrast Kaposi Sarcoma-associated herpes virus (KSHV) and EBV were similarly detectable across all levels of CD4 counts. One unit increase in log10(HIV VL) was associated with 1.31 times higher odds of detecting CMV in throat wash when controlling for oral candidiasis, CD4 count, and sites (95% CI 1.04 –1.65, P=0.02). Conclusions Oral CMV shedding was significantly higher in highly immunocompromised HIV+ participants. Our finding supports the recommendations to start antiretroviral therapy (ART) independent of CD4 count as this may have the added benefit to lower the risk of herpes virus transmission among persons infected with HIV and their partners.

Kaposi sarcoma-associated herpesvirus infection in HIV patients: potential role of HIV-associated extracellular vesicles

“…In this report, we demonstrate that HIV+ EVs from the saliva of HIV-positive patients and culture medium of HIV-infected T cells promote KSHV productive infection in oral epithelial cells cultured in both monolayer and 3-D models, indicating that HIV+ EVs are capable of regulating the initial steps of KSHV infection in the oral cavity. Saliva-mediated oral transmission of KSHV is considered as the most common route for spreading among homosexual people through deep kissing and “mother to child” transmission [3,4,5,6,7,8,9]. Because both saliva and peripheral blood samples [26] from HIV-infected persons contain HIV+ EVs, our findings suggest that the in HIV seropositive people bear higher risk for KSHV infection most likely through EVs in the body fluids.…”

“…The oral mucosa is the first target of KSHV infection once the virus is in the oral cavity [6,7,8,9]. To evaluate the initial infection process of oral mucosa by KSHV, we created the 3-dimentional (3-D) organotypic culture by using OKF6/TERT2 cells as described previously [35] (Fig 3A), followed by KSHV infection.…”

“…The oral mucosa has shown to be the first target of KSHV infection once the virus is in the oral cavity [5,6,7,8,9]. Although KS incidence has dramatically decreased in developed countries in the era of antiretroviral therapy (ART), KS remains the most frequent tumor in the HIV-infected population worldwide [10,11,12].…”

Current trends and new developments in HIV research and periodontal diseases

“…In particular, for chronic periodontitis, viruses in the herpesvirus family, which include cytomegalovirus, Epstein‐Barr virus, and herpes simplex virus 1 and 2, have also been detected in periodontal pockets of patients with HIV, and are found in higher numbers compared with patients without HIV . More recent research into the Epstein‐Barr virus has shown it is present in both the chronic and aggressive forms of periodontal diseases, and that they, along with other herpesviruses, are shed into the oral cavity at a greater rate, with more severe immunosuppression …”

“…92,93 More recent research into the Epstein-Barr virus has shown it is present in both the chronic and aggressive forms of periodontal diseases, 94,95 and that they, along with other herpesviruses, are shed into the oral cavity at a greater rate, with more severe immunosuppression. 96 Several mechanisms for the direct and indirect role of these viruses in the initiation and pathogenesis of periodontal diseases have been proposed. These include the role of these viruses in promoting the overgrowth of periodontal pathogens and opportunistic infections by suppressing both innate and acquired immunity to pathogenic bacteria, and by directly or indirectly promoting the production and release of a range of inflammatory mediators that result in destruction of the periodontal support.…”