Impact of perinatal HIV exposure and infection on salivary properties among Nigerian children.

BACKGROUND: There is growing evidence that perinatal HIV infection and exposure affect salivary pH and flow rate in children in most parts of the world, but not against the background of caries and the African demographic. This study aimed to evaluate the impact of HIV infection as well as exposure on salivary properties and their influence upon the dental caries experience among school-aged children in Nigeria. METHOD: This cross-sectional study assessed the salivary flow rates and salivary pH of HIV infected and exposed school-aged (4-11) children receiving care at a Nigerian tertiary hospital. A total of 266 consenting participants which comprised of three groups as follows: (1) HIV Infected (HI) (n = 87), (2) HIV Exposed and Uninfected (HEU) (n = 82) and (3) HIV Unexposed and Uninfected (HUU) (n = 97) were recruited for the study. Questionnaires completed by parents/guardians were used for data collection. Three calibrated dentists performed oral examinations for dental caries. International Caries Detection and Assessment Scores (ICDAS) was used and presented as dmft/DMFT. Salivary pH was measured using MColourpHast™ pH indicator strips, while salivary flow rate was determined by collecting unstimulated whole saliva using the suction method. Data analysis relied on comparative statistics to determine the correlation between HIV exposure and infection on salivary pH and flow rates. RESULT: Across the groups, (HI, HEU, and HUU) mean pH of the HI was significantly less than that of HEU and HUU. Similarly, there was a statistically significant difference in the SFR across the three groups (p = 0.004). Other variables such as gender, age and oral hygiene status expressed by the gingival inflammatory scores had no significant influence on the pH and SFR of study participants. There was a rather unexpected positive correlation of DMFT of HI and HEU groups with increasing salivary flow rate; though, the relationship was weak and not significant. CONCLUSION: Perinatal HIV exposure and infection significantly impact salivary pH and flow rate among school-aged children in Nigeria. The findings of this study imply that HIV infection influenced the salivary pH, while HIV maternal exposure (without infection) impacted salivary flow rates when compared to the controls.

Supragingival mycobiome of HIV-exposed-but-uninfected children reflects a stronger correlation with caries-free-associated taxa compared to HIV-infected or uninfected children.

IMPORTANCE: Globally, caries is among the most frequent chronic childhood disease, and the fungal component of the microbial community responsible is poorly studied despite evidence that fungi contribute to increased acid production exacerbating enamel demineralization. HIV infection is another global health crisis. Perinatal HIV exposure with infection are caries risk factors; however, the caries experience in the context of perinatal HIV exposure without infection is less clear. Using high-throughput amplicon sequencing, we find taxonomic differences that become pronounced during late-stage caries. Notably, we show a stronger correlation with health-associated taxa for HIV-exposed-but-uninfected children when compared to unexposed and uninfected children. This aligns with a lower incidence of caries in primary teeth at age 6 or less for exposed yet uninfected children. Ultimately, these findings could contribute to improved risk assessment, intervention, and prevention strategies such as biofilm disruption and the informed design of pro-, pre-, and synbiotic oral therapies.

Impact of HIV on the Oral Microbiome of Children Living in Sub-Saharan Africa, Determined by Using an rpoC Gene Fragment Metataxonomic Approach.

Children living with HIV have a higher prevalence of oral diseases, including caries, but the mechanisms underlying this higher prevalence are not well understood. Here, we test the hypothesis that HIV infection is associated with a more cariogenic oral microbiome, characterized by an increase in bacteria involved in the pathogenesis of caries. We present data generated from supragingival plaques collected from 484 children representing three exposure groups: (i) children living with HIV (HI), (ii) children who were perinatally exposed but uninfected (HEU), and (iii) unexposed and therefore uninfected children (HUU). We found that the microbiome of HI children is distinct from those of HEU and HUU children and that this distinction is more pronounced in diseased teeth than healthy teeth, suggesting that the impact of HIV is more severe as caries progresses. Moreover, we report both an increase in bacterial diversity and a decrease in community similarity in our older HI cohort compared to our younger HI cohort, which may in part be a prolonged effect of HIV and/or its treatment. Finally, while Streptococcus mutans is often a dominant species in late-stage caries, it tended to be found at lower frequency in our HI cohort than in other groups. Our results highlight the taxonomic diversity of the supragingival plaque microbiome and suggest that broad and increasingly individualistic ecological shifts are responsible for the pathogenesis of caries in children living with HIV, coupled with a diverse and possibly severe impact on known cariogenic taxa that potentially exacerbates caries. IMPORTANCE Since its recognition as a global epidemic in the early 1980s, approximately 84.2 million people have been diagnosed with HIV and 40.1 million people have died from AIDS-related illnesses. The development and increased global availability of antiretroviral treatment (ART) regimens have dramatically reduced the mortality rate of HIV and AIDS, yet approximately 1.5 million new infections were reported in 2021, 51% of which are in sub-Saharan Africa. People living with HIV have a higher prevalence of caries and other chronic oral diseases, the mechanisms of which are not well understood. Here, we used a novel genetic approach to characterize the supragingival plaque microbiome of children living with HIV and compared it to the microbiomes of uninfected and perinatally exposed children to better understand the role of oral bacteria in the etiology of tooth decay in the context of HIV exposure and infection.

Prevalence and associated factors of enamel developmental defects among Nigerian children with perinatal HIV exposure.

To evaluate the prevalence and pattern of developmental defects of the enamel (DDE) and their risk factors among children born infected with Human Immunodeficiency Virus (HIV) and those born to HIV-infected mothers compared with their unexposed counterparts (i.e., children born to uninfected mothers). This was an analytic cross-sectional study evaluating the presence and pattern of distribution of DDE in three groups of school-aged children (age, 4-11 years) receiving care and treatment at a Nigerian tertiary hospital, comprising: (1) HIV-infected (HI) on antiretroviral therapy (ART) (n = 184), (2) HIV-exposed but uninfected (HEU) (n = 186) and (3) HIV-unexposed and uninfected (HUU) (n = 184). Data capture forms and questionnaires were used to record the children's medical and dental history based on clinical chart review and recall from their parents/guardians. Dental examinations were performed by calibrated dentists blinded to the study grouping. CD4+ (Cluster of Differentiation) T-cell counts were assayed for all participants. The diagnosis of DDE corresponded with the codes enumerated in the World Dental Federation's modified DDE Index. Analyses relied on comparative statistics to determine risk factors associated with DDE. A total of 103 participants distributed among the three groups presented with at least one form of DDE, which indicated a prevalence of 18.59%. The HI group had the highest frequency of DDE-affected teeth (4.36%), while that of the HEU and HUU groups were 2.73% and 2.05%, respectively. Overall, the most encountered DDE was code 1 (Demarcated Opacity), accounting for 30.93% of all codes. DDE codes 1, 4 and 6 showed significant associations with the HI and HEU groups in both dentitions (p < 0.05). We found no significant association DDE and either very low birth weight or preterm births. A marginal association with CD4+ lymphocyte count was observed in HI participants. DDE is prevalent in school-aged children, and HIV infection is a significant risk factor for hypoplasia, a common form of DDE. Our results were consistent with other research linking controlled HIV (with ART) to oral diseases and reinforce advocacies for public policies targeted at infants exposed/infected perinatally with HIV.

Dental caries and its association with the oral microbiomes and HIV in young children-Nigeria (DOMHaIN): a cohort study.

BACKGROUND: This study seeks to understand better the mechanisms underlying the increased risk of caries in HIV-infected school-aged Nigerian children by examining the relationship between the plaque microbiome and perinatal HIV infection and exposure. We also seek to investigate how perinatal HIV infection and exposure impact tooth-specific microbiomes' role on caries disease progression. METHODS: The participants in this study were children aged 4 to 11 years recruited from the University of Benin Teaching Hospital (UBTH), Nigeria, between May to November 2019. Overall, 568 children were enrolled in three groups: 189 HIV-infected (HI), 189 HIV-exposed but uninfected (HEU) and 190 HIV-unexposed and uninfected (HUU) as controls at visit 1 with a 2.99% and 4.90% attrition rate at visit 2 and visit 3 respectively. Data were obtained with standardized questionnaires. Blood samples were collected for HIV, HBV and HCV screening; CD4, CD8 and full blood count analysis; and plasma samples stored for future investigations; oral samples including saliva, buccal swabs, oropharyngeal swab, tongue swab, dental plaque were collected aseptically from participants at different study visits. CONCLUSIONS: Results from the study will provide critical information on how HIV exposure, infection, and treatment, influence the oral microbiome and caries susceptibility in children. By determining the effect on community taxonomic structure and gene expression of dental microbiomes, we will elucidate mechanisms that potentially create a predisposition for developing dental caries. As future plans, the relationship between respiratory tract infections, immune and inflammatory markers with dental caries in perinatal HIV infection and exposure will be investigated.