From 2007 to 2023, 29 studies having evaluated the oral bacterial assessment in PLWH and corresponding to the inclusion criteria defined above were selected and analyzed. A summary of each of these studies is presented in Table 1 .

In the overall composition of oral microbiota, studies have pointed out similar microbiota between PLWH and controls, regarding richness, evenness, composition, or predicted functions (Mukherjee et al., 2014; Imahashi et al., 2021; Meng et al., 2023). However, when analyzing in more detail the bacterial diversity of the oral cavity, several differences can be noticed in PLWH with reference to controls. The search for understanding these differences in PLWH has been based on significant results found in the gut microbiota in HIV infection. Beta diversity of colon samples present significant differences between PLWH and controls, pointing out an association between HIV infection and gut dysbiosis. However, these significant changes have not been found in the oral microbiota when the only variable taken into consideration is HIV infection (Meng et al., 2023).

Regarding the impact of HIV-infection in the bacterial diversity of oral microbiota, conflicting results are found in the literature: while a few studies showed no significant difference between PLWH and controls (Mukherjee et al., 2014; Goldberg et al., 2015; Gonçalves et al., 2019; Meng et al., 2023), other studies found significant differences between both groups (Gonçalves et al., 2007; Silva-Boghossian et al., 2008; Iwai et al., 2012; Hegde et al., 2014; Li et al., 2014; Kistler et al., 2015; Noguera-Julian et al., 2017; Presti et al., 2018; Griffen et al., 2019; Lewy et al., 2019; Coker et al., 2020; Yang et al., 2020; Perez Rosero et al., 2021; Guo et al., 2021b; Cao et al., 2022; Ramos Peña et al., 2022; Beall et al., 2023; Kuhn et al., 2023).

In saliva samples and oral rinses, the main differences found between PLWH and controls were related to bacterial composition (Kistler et al., 2015; Presti et al., 2018; Yang et al., 2020; Perez Rosero et al., 2021), alpha and beta diversity (Li et al., 2014; Noguera-Julian et al., 2017; Mukherjee et al., 2018; Gonçalves et al., 2019; Annavajhala et al., 2020; Li et al., 2021; Guo et al., 2021b; Kuhn et al., 2023), whereas some of them reported differences in prevalence or abundance of specific genera and species (Silva-Boghossian et al., 2008; Hegde et al., 2014). These differences have been attributed mainly to the presence of HIV-infection and ART regimens.

Differences in the overall bacterial population have been found in the oral microbiota of PLWH. The reported results regarding bacterial taxonomy in PLWH differed according to the type of samples, being saliva, biofilm, oral rinses and mucosal swabs, the most common methods used to assess the oral microbiota. The main taxonomical differences found in PLWH have been related to increased abundance of genera such as Campylobacter, Granulicatella, Neisseria, Fusobacterium, and Selenomonas (Li et al., 2014, 2021; Guo et al., 2021b; Cao et al., 2022), and decreased abundance of Actinomyces, Lactobacillus, Peptostreptococcus and Treponema (Gonçalves et al., 2007; Silva-Boghossian et al., 2008; Annavajhala et al., 2020; Ramos Peña et al., 2022). On the other hand, an association with increased abundance of Lactobacillus, Lautropia and Bacteroides has been reported in controls (Li et al., 2014; Imahashi et al., 2021; Li et al., 2021) ( Table 2 and Figure 1 ).

In terms of bacterial species, oral samples of PLWH present significantly richer bacterial communities than those of controls. Micrococcus spp, species of the Spirochaetaceae family (Spirochaeta spp, Treponema spp, T. amylovorum, and T. azotonutricum), Prevotella melaninogenica and Rothia mucilaginosa have been found related to HIV infection. Additionally, a significant reduction of viridans streptococci group, Helicobacter spp, and Streptococcus pneumoniae have been found associated to HIV infection (Hegde et al., 2014; Lewy et al., 2019; Perez Rosero et al., 2021).

The main findings regarding bacterial genera and species found in PLWH by comparison to controls are shown in Table 2 .

Periodontitis has a great impact on the oral microbiota and the impact of HIV infection in periodontitis evolution has been approached by different studies. The pathogenesis of periodontitis in PLWH can be described as a reciprocal reinforcement of the two conditions, where the local dysbiosis present in the periodontal pocket leads to inflammation, bacterial translocation and destruction of the supporting tissues, which in turn enhances a pathogenic environment that perpetuates the periodontitis cycle (Hajishengallis & Chavakis, 2021). This cycle, illustrated in Figure 2 , can be enhanced by the presence of chronic immunosuppression produced by HIV infection, leading to an increased destructive potential of periodontal tissues in these individuals (Aas et al., 2007; Annavajhala et al., 2020).

PLWH with severe forms of periodontitis were shown to present higher abundance of Prevotella melaninogenica, Rothia mucilaginosa, Rothia dentocariosa, and Fusobacterium compared to individuals with non/mild periodontitis. These patients were also found to exhibit a reduced abundance of Streptococcus, Actinomyces and Granulicatella compared to non/mild periodontitis in the subgingival biofilm (Annavajhala et al., 2020). Additionally, different stages of periodontitis present subtle microbial signatures in oral microbiota of PLWH, including the enrichment of the genera Abiotrophia, Neisseria, and Kingella regardless of the periodontal status (Noguera-Julian et al., 2017). In another study, Haemophilus parainfluenzae was shown to be significantly associated with PLWH, whilst Streptococcus mitis was most significantly associated with controls. Interestingly, these differences in the abundance of the different genera were not observed in periodontal healthy sites, where the overall bacterial composition tends to be more similar between PLWH and controls with only minor differences (Kistler et al., 2015).

In subgingival biofilm samples, differences of diversity have been reported in PLWH and controls with periodontitis, with higher alpha diversity along with lower beta diversity among PLWH (Annavajhala et al., 2020; Ramos Peña et al., 2022). Additionally, changes after the periodontal treatment were also pointed out for both groups, with a higher impact on alpha diversity reduction in PLWH with periodontitis undergoing non-surgical periodontal treatment (Ramos Peña et al., 2022). The lower abundance of classically periodontitis-related pathogens in PLWH has been associated to an increased pathogenic activity of commensal and health-related bacteria when in presence of HIV infection (Aas et al., 2007; Gonçalves et al., 2007; Guo et al., 2021b).

Other variables that have been analyzed for changes in the oral microbiota include perinatally infection/exposure, smoking, and pulmonary involvement.

A study that compared the oral microbiota of perinatally HIV-infected (PHIV) and HIV-exposed uninfected (PHEU) youth found an association between PHEU and periodontitis-associated bacteria. On the other hand, the PHIV patients presented lower abundance of Corynebacterium, a health-related species (Starr et al., 2018).

Smoking is a clinical variable that directly affects the oral microbiota and has been widely studied for its influence in several oral diseases, periodontitis and even oral cancer (Ahmed et al., 2021). When comparing HIV-infected smokers and non-smokers, bacteria in HIV-infected smokers were shown to present reduced alpha diversity in saliva and more richness in oral rinses. The genera Granulicatella, Lactobacillus, Veillonella, Enhydrobacter, Streptococcus and Lactobacillus were significantly increased in HIV-infected smokers, while Neisseria, Prevotella, Pasteurella and Fusobacterium were found to be significantly decreased in this group. The ratio of the abundance of phyla Fusobacteriota:Proteobacteriota and Bacteroidota:Proteobacteriota was significantly decreased in HIV-infected non-smokers compared to HIV-infected smokers (Mukherjee et al., 2018; Yang et al., 2020).

Due to the close anatomical relationship between the mouth, the nasal cavity and the lungs, it is reasonable to search for associations in the microbiota of these three sites. In HIV-infected patients with abnormal lung function (long term ART and normal CD4+ T cell count), alterations in the oral microbial communities have been found, with increased abundance of Veillonella, Streptococcus and Lactobacillus, while Neisseria was significantly decreased; in contrast, HIV-negative individuals did not present any association related to lung function. A reduced richness of the oral microbiota in HIV-infected patients with impaired capacity of the lungs for carbon monoxide was also observed. No difference regarding ART, CD4+ T cell count or viral load was found. The authors of this study suggest that the oral microbiota may serve as a biomarker of lung function in HIV-infected patients and may be associated to the pathogenesis of chronic obstructive pulmonary disease (Yang et al., 2020).

In another study that compared oral and airway microbiota in HIV-infected patients with pneumonia, a greater bacterial burden was detected in the oral vs airway microbiota in pneumonia; however, alpha diversity was similar across both microbiotas. Additionally, the respiratory pathogens Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa and Chlamydia pneumoniae were present in the oral microbiota of HIV-infected patients. The clusters of both oral and airway microbiotas indicated a high similarity of the microbiota profiles, especially in ART-treated patients, suggesting an impact of ART in the oral and airway microbiota, and the presence of oral dysbiosis in HIV-infected patients with pneumonia (Iwai et al., 2012). The results of this study bring additional relevance to the necessity of prevention and treatment of periodontitis in HIV-infected patients.

It is known that ART is able to restore the CD4+ T cell count and suppress the HIV viremia in most PLWH; however, several manifestations of the HIV infection can still appear in these patients, especially signs related to residual inflammation, affecting the gut and oral microbiotas, contributing to dysbiosis and to the pathogenesis of related diseases (Coker et al., 2021).

The effects of ART on the oral microbiota have been considered of small to modest magnitude, and similar to other clinical variables such as periodontal status, smoking and antibiotic usage (Griffen et al., 2019; Beall et al., 2023). Bacterial composition of PLWH under ART differs from that of PLWH without ART, and of controls. ART shifts the oral microbiota to be closer to that found in controls, although, even after long-term ART, the microbiota does not reach a composition equal to that found in controls. This diversification has also been seen in the esophageal microbiota of PLWH (Saxena et al., 2016).

The comparison of the oral microbiota in PLWH and controls shows that HIV infection has a significant impact on the oral microbiota; ART produces significant changes in the core oral microbiota, with increased abundance of Neisseria and Haemophilus and enrichment of LPS-secreting bacteria in periodontitis individuals. However, even in presence of effective ART, the association of HIV infection and periodontitis continues to alter the oral microbiota (Lewy et al., 2019; Perez Rosero et al., 2021; Beall et al., 2023).

In HIV-infected untreated patients, mean alpha diversity is more variable between individuals, with high abundance of Bacteroidota, Bacillota and Proteobacteriota. After 24 weeks of effective ART, the dominant phyla remain similar to baseline, without differences in beta or alpha diversity; however, bacterial communities became more similar between individuals, with enrichment of health-related genera such as Fusobacterium, Campylobacter, Prevotella, Capnocytophaga, Selenomonas, Actinomyces, Granulicatella and Atopobium, and decrease of pathogenic genera such as Porphyromonas and Aggregatibacter (Yang et al., 2020; Li et al., 2021; Cao et al., 2022). The bacterial communities within each individual present changes before and after ART, suggesting high person-to-person variability on salivary bacterial microbiota between baseline and 24 weeks after ART (Presti et al., 2018; Cao et al., 2022) ( Figure 1 ).

While great impact on the gut microbiota has been described in PLWH under ART, especially when NRTI are used, this same impact has not been found on the oral microbiota. Likewise, ART increases the gut beta diversity of HIV-infected patients, but not the salivary beta diversity, when comparing PLWH to controls (Imahashi et al., 2021). Additionally, long-term ART has been associated to a decrease in the severity of periodontitis in PLWH (Gonçalves et al., 2007).

In addition, when comparing ART immunological responders to non-responders, taxonomic differences were noted, with higher abundance of the genus Selenomonas in the non-responder group, and higher abundances of Cd Saccharimonas and norank_p_Saccharimonas in the immunological responders; however, the overall microbiota structure was similar between both groups (Xie et al., 2021).

In patients exhibiting pneumonia, clusters of both oral and airway microbiotas were closely together, indicating a high similarity of the microbiota profiles, especially in PHLW under ART, suggesting similar impact of ART on the oral and airway microbiotas (Iwai et al., 2012).

Aging is an important variable to be taken into consideration for the oral microbiota analysis. Several alterations take place in the mouth during the human development at both extremities of life, notably with changes in the dentition and diet in young children, and senescence-related alterations in elderly, including the occurrence of systemic diseases as diabetes mellitus, Sjögren’s syndrome, cardiovascular diseases and neurodegenerative diseases, which results in an increase of the basal level of inflammation (Zapata & Quagliarello, 2015). In PLWH, the presence of chronic immunosuppression and ART are to be taken into account, in addition to the previously mentioned factors.

In adults, age has been associated with increased bacterial diversity in PLWH and controls; older HIV-chronically infected patients under long-term ART present reduced abundance of oral commensal bacteria leading to a microbiota more similar to that of HIV-negative adults over time (Lewy et al., 2019).

Supragingival biofilm samples of HIV-infected children and teenagers under ART show similar microbial diversity than in HIV-negative individuals. Indeed, ART well-controlled HIV-infected children and teenagers presented similar oral microbiota to HIV-negative counterparts (Goldberg et al., 2015). However, another study, also using samples of supragingival and subgingival biofilms from HIV-infected children and teenagers presented opposed results, with more complex bacterial communities, increased richness and genera abundances. High abundance of Bacillota, Streptococcus spp, Veillonella spp and Prevotella spp and low abundance of Fusobacteriota and Proteobacteriota were found in PLWH but not in controls. While these differences could be attributed to several clinical variables related to the dental biofilm samples, the differences found in tongue biofilm samples were attributed exclusively to the presence of HIV infection (Gonçalves et al., 2019).

Young HIV-infected children (mean age of 4 years) present significantly lower diversity of bacterial species in saliva, with high mean count of Fusobacterium periodonticum, a normal oral species that act as a bridge between colonizers in the dental plaque. In this population, high viral load has been associated with Gemella morbilorum, Staphylococcus intermedius, Streptococcus anginosus, Treponema denticola and Enterococcus faecalis; however, no significant differences have been found between untreated patients and those under ART. Furthermore, the presence of concomitant infections, such as angular cheilitis and oral herpes, has been related to high levels of Veillonella parvula. When gingivitis is present, high prevalence of Tannerella forsythia, Eikenella corrodens and Propionibacterium acnes have been found in the saliva of HIV-infected patients, contributing to the establishment of altered microbiota since early age (Silva-Boghossian et al., 2008).

In children less than 6 years of age, a low CD4+ T cell count exerts a strong impact on the oral microbiota. Perinatal exposure is considered as a transient effect on the oral microbiota; indeed, perinatally HIV-exposed children initially present altered bacterial oral microbiota, but their microbiome tends to become more similar to that of non-HIV-exposed/HIV-negative children overtime (Coker et al., 2020).

When comparing the time of initiation of ART (before or after 6 months of age) in children (median age 11 years), the HIV-infected patients presented high abundance of Granulicatella, Streptococcus, Gemella and Bulledia, while Neisseria and Haemophilus were less abundant, independently of viral load and CD4+ T cell count. Earlier ART initiation was not associated to changes in the oral microbiota; however, the type of ART regimen did present associations with shifts in the genus-level abundances, especially lopinavir/ritonavir regimens, leading to a less diverse oral microbiota. Children receiving efavirenz-based regimens presented similar alpha diversity to HIV-negative individuals. Additionally, Corynebacterium has been found more abundant in immunosuppressed children (Kuhn et al., 2023).

According to the studies presented in this section, it can be concluded that in young people the alterations in the oral microbiota are mostly linked to the individual development, with a high impact of ART, whereas in the adult age the oral dysbiosis is strongly influenced by other clinical variables, such as smoking, periodontitis and changes in ART regimens.

In HIV-negative healthy individuals, the interactions between bacteria and fungi are considered limited, notably in terms of alpha and beta diversity. While the bacteriome is strongly shaped according to age and sex, these factors have no influence on the mycobiome (Cheung et al., 2022). Nonetheless, with the introduction of immunosuppression and bacterial dysbiosis, alteration in the mycobiome can be expected in PLWH.

From 2007 to 2023, six studies that evaluated the oral mycobiome in PLWH and corresponding to the inclusion criteria defined above were selected and analyzed. A summary of each of these studies is presented in Table 3 . The main mycobial genera/species found in PLWH in comparison to controls are shown in bold characters in Table 2 .

By contrast to the oral bacteriome, the composition of the fungal mycobiome is strongly influenced by HIV infection, while other clinical variables such as periodontitis, smoking, age and antibiotic usage have no significant influence on it (Beall et al., 2023). The smaller number of variables influencing the fungal communities by comparison to bacterial communities may be related to the relative scarcity of fungal species identified in the oral cavity (Fidel et al., 2021).

Contrary to bacterial diversity, fungal diversity has not been associated to soluble or cellular biomarkers of immune stimulation or T cell dysfunction (Annavajhala et al., 2020). Fungal alpha diversity has been found reduced in the subgingival biofilm and saliva of patients with AIDS history. While periodontitis classification has not been associated with changes in mycobial diversity, Candida albicans and C. parapsilosis have been found enriched in non/mild periodontitis individuals, and lower abundance of Candida dubliniensis, Exserohilum turcicum, Guehomyces pullalans, and Debraryomyces hansenii. On the other hand, severe periodontitis has been associated to decreased abundance of Saccharomyces cerevisiae, Exseohilum, Guehomyces, and Debaryomyces in both subgingival biofilm and saliva (Annavajhala et al., 2020).

Candida spp and Penicillium spp are two genera found in PLWH and controls, however, with different abundances. In PLWH, Candida spp has been found in lower abundance with a parallel higher abundance of Pichia spp, while the inverse was observed in controls (Mukherjee et al., 2014). While C. dubliniensis has been found predominant in controls, HIV-infected samples are shifted toward the C. albicans and Malassezia restricta predominant clusters (Fidel et al., 2021). These findings show that the oral mycobiome of PLWH differs from that of controls: while the Candida genus is present in both groups, the abundance of specific species differs between groups.

When smoking is considered for the mycobial analysis, differences between HIV-infected smokers vs HIV-infected non-smokers and HIV-negative smokers has been reported. Candida spp levels are increased in HIV-infected and HIV-negative smokers. Fungal diversity has been described as increased in HIV-infected smokers compared to HIV-infected non-smokers, suggesting that smoking does induce changes in the oral mycobiome (Mukherjee et al., 2018). Although the clinical implications of these findings are still not well understood, the effects of smoking, high levels of Candida spp and chronic immunosuppression could influence the prevalence of oral candidiasis in PLWH.

Whereas the number of studies evaluating the whole oral mycobiome is limited in PLWH, oral candidiasis is considered the most common opportunistic infection in this population. Indeed, as pointed out in the previous section, Candida spp are the most frequent species colonizing the saliva of human individuals, with C. albicans as the most common species found in HIV-infected patients. The detection of high amounts of this species is associated with low CD4+ T cell count and use of long-term antibiotics, while high CD4+ T cell count and ART treatment are associated with decrease levels of C. albicans (Merenstein et al., 2013; dos Santos Abrantes et al., 2014; Jiang et al., 2014).

In PLWH, Candida spp colonization is the most important predictive factor for the development of oral candidiasis. Indeed, while in healthy individuals the presence of C. albicans in the oral microbiota represents a true commensalism, it is associated in PLWH to a higher expression of virulence factors, such as phospholipase and DNAse, that favor the evolution to candidiasis (de Paula Menezes et al., 2016). Although ART treatment is able to decrease the expression of virulence factors and the carriage rate, the latter remains higher than that found in HIV-negative controls (Jiang et al., 2014; de Paula Menezes et al., 2016). It was also shown that the ART treatment was able to correct the dysfunctions in the production of Th1/Th2/Th17 cytokines and human beta defensin 2 in HIV-infected patients with oral candidiasis (Yong et al., 2018).

Other factors that influence Candida spp carriage in PLWH are the occurrence of periodontitis in adults (Lourenço et al., 2017; Lomeli-Martinez et al., 2019), and the presence of caries in children (das Chagas et al., 2009); by contrast, carriage levels were decreased in periodontally healthy individuals and after treatment of children with caries. A mutualism relationship between periodontitis, caries and oral candidiasis has been found in healthy individuals (Hong et al., 2020); it could be valuable to investigate this association in PLWH.

In addition, the growing resistance to antifungal drugs that affects Candida strains in some HIV populations should be considered while studying the prevention and treatment of oral candidiasis (dos Santos Abrantes et al., 2014).

There are few studies documenting the oral virome of HIV-negative individuals, with or without periodontitis. In 2016, Monaco et al. investigated a cohort of HIV-negative and HIV-infected subjects and those either treated with ART or untreated. Low peripheral CD4+ T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment (Monaco et al., 2016). Girija & Ganesh (2022) reported a predominance of phages belonging to the Siphoviridae and Myoviridae families and a high abundance of streptococcus-related phages. Eukaryotic DNA viruses were dominated by members of the Herpesviridae family (Girija & Ganesh, 2022). A study developed in 20 HIV-infected men who have sex with men (MSM) exhibiting different stages of HIV infection, with 5 HIV-negative MSM as controls, three phage families and a eukaryotic DNA family were found to be the more abundant, regardless of HIV status, namely Siphoviridae, Herpesviridae, Myoviridae, and Podoviridae, respectively. Interestingly, the Lymphocryptovirus genus of Herpesviridae, to which belong human herpesvirus 8 (HHV-8) associated to Kaposi sarcoma (KS), was particularly rare in HIV-negative controls, but abundant in HIV-infected patients (Guo et al., 2021a). Another study compared the oral and anal viromes of 78 MSM and transgender women, with and without HIV infection; human papillomaviruses (HPV) were predominant in the anal area whereas phages and Herpesviridae (notably HHV-7 and HHV-8) predominated in the oral site, whatever the groups (Lacunza et al., 2023).

HIV infection commonly leads to the development of oral lesions related to reactivation of quiescent DNA viruses, including mainly members of the Herpesviridae family and different oncogenic types of the Papillomaviridae family (HPV) (Anonymous. EC-Clearinghouse on Oral Problems Related to HIV Infection and WHO Collaborating Centre on Oral Manifestations of the Immunodeficiency Virus, 1993). These viral infections in PLWH are highly correlated to their immune status as evaluated by the CD4+ T cell count and viral load, with a high increase of their frequency in case of severe immunosuppression.