It has been suggested that the loss of CD4+ T-lymphocytes and subsequent immunosuppression in HIV-infected individuals could compromise normal mucosal responses to oral micro-organisms, resulting in an elevated colonization of cariogenic and periodontal pathogens or an alteration of the oral microbial community (Patel et al., 2003
; Gonçalves et al., 2004
; Aas et al., 2007
; Saxena et al., 2012
). Those changes could be contributing factors for the development of HIV-associated oral diseases, including increased prevalence of dental caries. Previous studies also suggested that HIV+ individuals with elevated viral load experienced high caries scores (Baqui et al., 1999
). Immunocompromised women with CD4+ counts less than 200 had more DMF teeth, and the number of DMF surfaces increased more with decreasing CD4 counts (Mulligan et al., 2004
). Caries development etiologically involves a consolidated interaction among host, cariogenic microbe, and refined carbohydrate intakes. However, the effect of HIV infection on these convergence factors and the development of caries remain to be elucidated. In the meantime, an extensive literature search found either inconclusive or divergent data, suggesting more studies are required.
The present study aimed to ascertain the effect of HIV infection on S. mutans
colonization in saliva. We found that HIV+ individuals experienced significantly higher levels of S. mutans
. Interestingly, the level of S. mutans
significantly correlated with CD8+ count, but not with viral load or CD4+ counts. It has been reported by Hicks’ group that moderate to severe immunosuppression favored more cariogenic bacterial colonization and increased prevalence of caries in HIV+ children (Hicks et al., 2000
). In our study, 73% of the 46 HIV+ and HAART-naïve individuals presented CD4+ T-cell counts over 350/mL, and the mean CD4+ count was above 200 cells/mm3
, suggesting that this HIV+ cohort could have had only slight or mild dysfunction of the immune system at the time of enrollment, according to the US Centers for Disease Control and Prevention (CDC) classification system (http://www.aidsetc.org/aidsetc?page=cg-205_hiv_classification
). Therefore, the elliptically distributed scatterplot displaying the relationship between the CD4+ counts and S. mutans
level was not surprising.
Our study also revealed decreased salivary flow rate in the HIV+ group. Saliva is strongly correlated with the colonization and clearance of pathogenic micro-organisms by means of antibacterial activities or other mechanisms. In the 1990s, Beighton and Loesche documented that the amount of saliva in the oral cavity could significantly influence the colonization of cariogenic bacteria, including S. mutans
(Beighton et al., 1991
; Loesche et al., 1995
). Recently, Lin and colleagues demonstrated that HIV infection could decrease salivary flow rate and alter the salivary composition that may affect salivary antimicrobial activities (Lin et al., 2006
). Navazesh and co-workers suggested that HIV+ individuals are at a significantly higher risk for salivary gland enlargement and salivary gland hypofunction compared with HIV− control individuals (Navazesh et al., 2009
). Together, these results support the notion that HIV infection can affect salivary glands and alter salivary functions. However, additional research is needed to determine the biological implications of these HIV-associated alterations in oral microbial colonizers.
Cytotoxic CD8+ T-cells play a key role in cell-mediated immune response (Levy, 2009
). In HIV infection, decreased CD8+ counts are associated with immune deficiency (Gulzar and Copeland, 2004
), correlated with the absence of submandibular/sublingual saliva (Mulligan et al., 2000
), and the resulting opportunistic infections in the oral cavity (Fidel, 2006
). A recent study demonstrated a significant correlation between CD8+ T-cell activation levels and total bacterial 16S rDNA present in stool samples of HIV+ individuals (Ellis et al., 2011
). Our study revealed a positive correlation between CD8+ counts and S. mutans
levels and a significant difference in S. mutans
levels between the HIV+ and the HIV− groups, clearly suggesting that other HIV-associated factors mechanistically mediate S. mutans
colonization in saliva.
Our descriptive subset study revealed that the phenotypic variance of S. mutans
was greater than its genotypic variance, e.g
., 4 different colony morphologies were isolated for participant 1, but all presented with an identical fingerprint. Although morphological characteristics have proved to be a useful tool in S. mutans
identification on mitis-salivarius agar with optimal concentrations of sucrose and bacitracin, Okahashi et al
. previously illustrated that the same serotype of S. mutans
could have different phenotypes based on the variations in glucans and fructans synthesis (Okahashi et al., 1984
). The findings of our study provide new evidence to support the notion that S. mutans
morphologic characteristics on MSB agar do not necessarily correspond to genotypic variance and are therefore not a reliable means of delineating S. mutans
genotypes. Furthermore, we demonstrated that each participant had unique genotype(s) of S. mutans
, affected neither by HIV infection nor by HAART, suggesting that the genotypic characteristics of S. mutans
are individually unique with limited variation in the oral cavity, even for individuals with compromised immune systems. The findings provide valuable insight for studying the potential cariogenicity of S. mutans
, since a considerable degree of variation in virulence among different S. mutans
strains has been observed.
In summary, this is the first study to examine the effect of HIV infection on the level and genotypic characteristics of S. mutans colonization. There are sufficient data to suggest that host immune status of HIV-infected individuals may play an important role in the colonization of S. mutans and consequently affect caries outcomes. We did not find differences in genotypic characteristics of S. mutans between HIV+ individuals and HIV− control individuals. In addition, no significant changes were observed in either levels or genotypes of S. mutans over the six-month study period, not even after HAART. Although HIV infection could accelerate S. mutans colonization, HAART apparently had no significant inhibitory effects on S. mutans colonization in the oral cavity of HIV+ individuals. Since more dental caries was evidenced in HIV+ individuals from this study and others, additional studies are required to elucidate and understand the correlation between the colonization of other cariogenic microbes, including S. mutans, and the status of immunosuppression at the advanced stages of HIV infection.