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. 2017 Sep 24;31(15):2077-2084.
doi: 10.1097/QAD.0000000000001589.

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

Dirk P Dittmer  1 , Kristen Tamburro, Huichao Chen, Anthony Lee, Marcia K Sanders, Tischan A Wade, Sonia Napravnik, Jennifer Webster-Cyriaque, Mahmoud Ghannoum, Caroline H Shiboski, Judith A Aberg
Affiliations

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

Dirk P Dittmer et al. AIDS. .

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 cell counts, plasma HIV viral load 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 cell count and HIV viral load. In total, 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 herpesviruses and the state of immunodeficiency as stratified by a combination of CD4 cell count and HIV viral load. Relationship between pathogens and HIV viral load in plasma was modeled by logistic regression.

Results: The presence of cytomegalovirus (CMV) and herpes simplex virus-1 in throat wash was associated with decreased CD4 cell counts. By contrast, Kaposi sarcoma-associated herpesvirus and Epstein-Barr virus were similarly detectable across all levels of CD4 cell counts. One unit increase in log10 (HIV viral load) was associated with 1.31 times higher odds of detecting CMV in throat wash when controlling for oral candidiasis, CD4 cell count, and sites (95% confidence interval 1.04-1.65, P = 0.02).

Conclusion: Oral CMV shedding was significantly higher in highly immunocompromised HIV participants. Our finding supports the recommendations to start antiretroviral therapy independent of CD4 cell count as this may have the added benefit to lower the risk of herpesvirus transmission among persons infected with HIV and their partners.

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Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Association between very high EBV and CMV levels in throat wash. The data are separated by stratum. The three panels represent the three study strata A, B, and C/D. The top panel shows the measurements for stratum A (high HIV VL, CD4 ≤ 200 cells/μl), the middle panel stratum B (low HIV VL, CD4 ≤ 200 cells/μl), and the bottom panel stratum C/D (CD4 > 200 cells/μl). Shown in each panel is log10 EBV copies/ml on the horizontal axis compared to log10 CMV copies/ml on the vertical axis. EBV is detectable at all strata across a wide range of VL. CMV is highly enriched in stratum A (top panel). This reflects the significant association with HIV viral load as described in Table 3. To aid visualization the threshold was set at 3 × log10 so that participants with detectable VL lower than 3 × log10 were coded as 3 × log10, and participants with detectable VL higher than 6 × log10 were coded as 6 × log10. Lastly, ART status is reflected in the color. Colored in gray are participants not on ART and shown in red are participants who self-reported being on ART, though we do not know the time of therapy initiation, nor did we detect a correlation between ART usage and CMV or EBV VL.
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