Abstract
The main goals of the Sixth World Workshop on Oral Health and Disease in AIDS were to bring together clinician and laboratory scientists interested in HIV/AIDS-related oral manifestations to share global perspectives, knowledge, and understanding of oral health and disease in HIV infection and to identify research needs, taking into account worldwide perspectives and opportunities. It represented a rare opportunity for a unified global approach to the challenges of the HIV epidemic with regard to oral aspects and to the identification of key research questions of international significance.
The workshop brought together 170 participants from 25 countries. It was structured in a similar way to the Fifth World Workshop on Oral Health and Disease in AIDS with respect to multiple questions being generated by the International Scientific Committee and discussed as part of individual workshop sessions. These questions addressed a variety of topics within pathogenesis, immunopathogenesis, epidemiology, clinical research, and social/behavioral research.
Individual Workshop Sessions
Each of the 11 sessions led to a consensus summary paper on the topic discussed based on recent reviews of the literature and the workshop discussants’ research experience. In some areas, updated reviews of the literature on oral HIV research highlighted the lack of high-quality evidence and consensus for several key issues important in determining the clinical significance of oral lesions associated with HIV infection. In other areas, detailed review of the evidence in the literature resulted in recommendations of changes in current clinical practice. Perhaps one of the most important discussions leading to a consensus declaration that may have worldwide implications was that on the HIV-infected health care worker and the assessment of any risk of transmission to patients. This lead to the Beijing Declaration, which asserts evidence regarding oral health care professionals with HIV—namely, that they do not pose a risk of transmission to patients in the dental setting—as well as a recommendation—that with caveats, such professionals can continue to provide clinical care (see Workshop 1C).
Research Agenda Overview
The 11 workshop papers are all included in this issue. They form the basis of an updated, comprehensive, global, and scientific workshop agenda for oral HIV/AIDS research. Each paper identifies and appends a detailed research agenda for referral of specific questions within its topic. This research agenda overview is organized by themes discussed in the workshop, and it represents a summary of the meeting proceedings.
HIV-Related Oral Lesions as Clinical Markers of Immunodeficiency in a Changing Era of New Generation Antiretroviral Therapy
Clinical research
The workshop participants concluded that further research should explore
The role of oral lesions in detecting antiretroviral therapy (ART) failure, suboptimal therapy, and/or poor adherence to ART (in children and adolescents in particular)
HIV-related oral lesions as potential players in immune reconstitution inflammatory syndrome (IRIS) and characterization of “oral IRIS,” if such a phenomenon exists
The prevalence of oral lesions and their association with HIV disease stage and comorbidities in pediatric populations in resource-constrained settings
The development of new therapies and/or drug delivery systems, including traditional medicines, for the management of HIV-related oral lesions such as candidiasis, necrotizing periodontitis/stomatitis, and warts, which need further investigation through well-designed clinical trials
Candida and Mycotic Infections
Basic/translational research
The workshop participants concluded that further pathogenesis and immunopathogenesis research should explore
The mechanisms of pathogenicity and virulence of Candida albicans and other species in HIV disease
The mechanisms of antifungal resistance in the context of ART failure
Host-pathogen interactions and host immune responses against Candida sp. to guide the development of immunotherapies and to understand the role of Candida sp. in mucosal biofilms
The characterization of the mycobiome (fungal biofilm) and the role of other microbial organisms in clinically apparent candidiasis
Further clinical research should explore
The potential role of oral candidiasis in predicting ART failure
The potential reemergence of antifungal resistance as a result of ART failure
The efficacy and acceptability of inexpensive alternative antifungal agents in resource-constrained settings (e.g., gentian violet, “traditional medicines”)
The development and testing of topical slow-release formulations of currently available and novel antifungal agents
Prenatal preventative strategies to avert systemic neonatal candidosis
Coinfections, Immunity, and Mechanisms of Viral Infections Associated with HIV
Basic research
The workshop participants concluded that further pathogenesis and immunopathogenesis research should explore
The interaction mechanisms of oral viral opportunistic pathogens (e.g., EBV, CMV, HSV, VZV, HPV, HSV 1 and 2, and HHV-8)
The effects of infection by HIV and other opportunistic viruses on epithelial and immune cell function and the impairment of oral mucosal barrier function
Mechanisms of enhanced HPV pathogenesis in HIV-infected persons
HPV-specific T-cell responses associated with oral HPV infection and disease
The virus-host interactions and oral pathogen-induced immune responses to guide novel therapy development
Further clinical research should explore
The effect of new-generation ART on oral HPV infection and disease (oral warts)
The risk of oropharyngeal squamous cell carcinoma among HIV-infected individuals with oral HPV shedding (HPV16 in particular)
Determination of postvaccination effects with HPV vaccines on established HPV-associated diseases
Innate and Adaptive Immunity of the Oropharyngeal Mucosa in HIV/AIDS-Associated Diseases
Translational research
The workshop participants concluded that further immunopathogenesis studies should explore
The comparative structure and function of mucosal tissues (i.e., oral, vaginal, small intestine, and colorectal cavity) by using system biology approaches
The interaction of HIV and other oral opportunistic pathogens and its role in inducing dynamic changes in the oral microbiome, viriome, and mycobiome to predict disease progression
The role of the subgingival biofilm in periodontal diseases in HIV infection
The induction of human neutralizing antibodies against HIV in vivo and their function at mucosal surfaces
The mucosal responses of “elite controllers” (i.e., highly exposed, persistently seronegative populations)
The development of novel prophylactic strategies (microbicides and vaccines) for oral mucosal delivery
Mucosal Fluids and Biomarkers of Clinical Disease
Basic/laboratory research
The workshop participants concluded that further studies should explore
Sensitivity, specificity, and predictive value of HIV RNA saliva assays in comparison with plasma assays and fluids derived from oropharyngeal sources, including analysis of the effects of handling and storing
Novel point-of-care devices (e.g., microfluidic devices) and rapid tests with higher sensitivity and specificity (applicability and acceptability)
The role of oral fluid diagnostics in oral complications of HIV infections (HHV-8, HPV, TB, HCV, cancer markers)
Salivary HIV inhibitors as a marker of mucosal susceptibility or resistance to HIV infection
Social Aspects of HIV and Relationship to Oral/Craniofacial Problems
Clinical/social science research
The workshop participants concluded that further behavioral studies should explore
Use of patient-centered outcomes (e.g., quality of life) in clinical trials involving HIV/AIDS and oral disease
Cumulative risk of tobacco, alcohol, and recreational drugs in HIV infection and impact on oral disease
Impact of health promotion in resource-constrained setting
Effectiveness of auxiliaries and other partnerships in health care promotion in resource-constrained settings
The practicalities, acceptability, and legal issues surrounding oral health care workers and in-office HIV testing in different settings
Conclusions
Several of these recommendations crossed traditional basic and applied clinical boundaries. See the conclusions of the individual workshops for additional and more detailed scientific questions in each of the 11 areas addressed:
Clinical Science Workshops
1A: Coinfections associated with human immunodeficiency virus infection
2A: New approaches to Candida and mycotic infections
3A: Clinical markers of immunodeficiency and mechanisms of IRIS and HAART therapy on HIV
4A: Oral lesions, HIV phenotypes, and management of HIV-related disease
Basic Science Workshops
1B: Innate immunity, including epithelial and nonspecific host factors
2B: Mechanisms of viral infections associated with HIV
3B: Mucosal fluids and biomarkers of clinical disease
4B: HIV infection and specific mucosal immunity
Social Science Workshops
1C: HIV transmission in the dental setting and the HIV-infected health care professional
2C: Traditional medicines and HIV
4C: Social aspects of HIV and their relationship to craniofacial problems
Footnotes
Acknowledgements
We thank Dr Isaac Rodriguez-Chavez for his contribution to this article.