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The workshop considered 5 questions related to oral lesions, HIV phenotypes, and the management of HIV-related disease, with a focus on evidence and challenges in resource-poor settings. First, are oral lesions unique with respect to geographic location or phenotype? Second, how useful would an oral lesion index be to predict HIV in resource-poor countries with no access to CD4 counts or viral load? Third, what are the latest methods and delivery modes for drugs used to treat oral lesions associated with HIV? Fourth, what is the role of the oral health care worker in rapid diagnostic testing for HIV? Fifth, what ethical and legal issues are to be considered when managing the HIV patient? The consensus of the workshop was the need for additional research in 4 key areas in developing countries: (1) additional investigation of comorbidities associated with HIV infection that may affect oral lesion presentation and distribution, especially in pediatric populations; (2) the development of region-specific algorithms involving HIV oral lesions, indicating cumulative risk of immune suppression and the presence of HIV disease; (3) well-designed clinical trials to test new therapies for oral lesions, new treatments for resistant oral fungal and viral diseases, effectiveness of therapies in children, and new drug delivery systems; and (4) the role of the oral health care worker in rapid diagnostic testing for HIV in various regions of the world.

Workshop participants discussed: the role of HIV subtypes in disease; the treatment of oral candidiasis; the relationship between and among viral load, CD4+ counts, oral candidiasis and oral hairy leukoplakia, pigmentation; and the development of a reliable oral index to predict disease progression. Regarding HIV, the literature revealed that Type I (HIV-I), in particular group M, is involved in the majority (90%) of documented infections, and groups N and O to a lesser extent. Viral envelope diversity led to the subclassification of the virus into nine subtypes, or clades-A-D, F-H, J, and K-each dominating in different geographical areas. HIV-2, currently occurring mostly in West Africa, appears to be less virulent. No evidence could be produced of any direct impact of type, subtype, or clade on oral lesions, and participants believed that further research is not feasible. Oral candidiasis in patients from resource-poor countries should be prevented. When the condition does occur, it should be treated until all clinical symptoms disappear. Oral rinsing with an antimicrobial agent was suggested to prevent recurrence of the condition, to reduce cost, and to prevent the development of antifungal resistance. Lawsone methyl ether, isolated from a plant (Rhinacanthus nasutus leaves) in Thailand, is a cost-effective mouthrinse with potent antifungal activity. Evidence from a carefully designed prospective longitudinal study on a Mexican cohort of HIV/AIDS patients, not receiving anti-retroviral treatment, revealed that the onset of oral candidiasis and oral hairy leukoplakia was heralded by a sustained reduction of CD4+, with an associated sharp increase in viral load. Analysis of the data obtained from a large cohort of HIV/AIDS patients in India could not establish a systemic or local cause of oral melanin pigmentation. A possible explanation was a dysfunctional immune system that increased melanin production. However, longitudinal studies may contribute to a better understanding of this phenomenon. Finally, a development plan was presented that could provide a reliable prediction of disease progression. To be useful in developing countries, the index should be independent of costly blood counts and viral load.

The gp120 V3-encoding region of human immunodeficiency virus type 1 (HIV-1) RNA derived from the saliva and blood plasma of 11 individuals was characterized by heteroduplex tracking assay and sequence analyses. R5-like viral variants were identified in both fluids of all subjects. X4-like variants were detected in the plasma and/or saliva of three subjects, indicating that X4-like variants are not excluded from the saliva compartment. Viral subpopulations were similar in both fluids of most subjects, suggesting that HIV-1 in oral fluids and blood may stem from a common source. These findings raise the possibility of using saliva as a noninvasive fluid for evaluating and monitoring viral evolution in infected persons.

Anatomical compartments (e.g., the reproductive tract) are reservoirs of human immunodeficiency virus type-1 (HIV-1) and potential sites of residual infection in patients receiving anti-retroviral therapy (ART). Viral hyper-excretion relative to blood is a hallmark of reservoirs. To determine whether hyper-excretion can occur in the oral cavity, we compared viral loads in blood plasma and saliva of 67 adults. Salivary viral hyperexcretion was defined as a four-fold or higher viral load in saliva than in plasma. HIV-1 RNA was detected in 79% of plasma samples, in 44% of unfiltered saliva samples, in 16% of filtered saliva samples, and in 59% of saliva-derived cell pellets. Compared with non-hyper-excretors (n = 62), hyper-excretors (n = 5) had elevated levels of viral RNA in unfiltered saliva and saliva-derived cells, HIV-associated periodontal disease, gingival inflammation, and no combination ART. Morphological characterization of cell pellets identified lymphocytes as a likely HIV-1 source. These collective findings are consistent with an oral HIV-1 reservoir in selected individuals.

Objective: The purpose of this investigation was to quantify human immunodeficiency virus type-1 (HIV-1) RNA in saliva and plasma and identify factors associated with increased salivary viral load., Study Design: Forty HIV-1-seropositive adults underwent oral examinations to assess mucosal and periodontal health. Whole saliva was evaluated for HIV-1 RNA titer and occult blood. Plasma viral load, CD4 cell count, HIV-1 staging, and antiretroviral therapy data were obtained from medical records. Associations between salivary titers and oral/systemic parameters were analyzed by means of t tests, Wilcoxon signed rank tests, Pearson's correlation coefficient, and analysis of covariance., Results: Forty-two percent of the subjects had detectable salivary HIV-1 RNA. Oral titers were highly correlated with plasma viral levels (r = 0.51, P <.01). HIV-associated periodontal disease (in particular, linear gingival erythema), severe gingival inflammation, and absence of antiretroviral therapy were associated with high salivary titers (P <.01)., Conclusions: Substantial quantities of HIV-1 can be shed in the oral cavity, particularly when inflammatory conditions are present. Salivary titer may be a useful indicator of systemic viral burden.

Background: Current medical care for patients infected with the human immunodeficiency virus type 1, or HIV-1, involves monitoring laboratory assays for CD4+ lymphocyte cell count and plasma viral load., Types of Studies Reviewed: The authors reviewed recent medical and dental studies that contribute to our current understanding of these immunologic and viral markers and their relevance to systemic and oral health., Results: Dramatic reduction in plasma viral load resulting from more potent antiretroviral drug combinations is the goal of medical management for HIV. These protease inhibitor-containing regimens, although complex, expensive and associated with substantial side effects, have decreased the morbidity and mortality associated with HIV in the United States. Although reduction in viral load can result in increases in CD4+ counts, which restores some level of immune competence, a cure for AIDS has not yet been found., Clinical Implications: Patients with low CD4+ cell counts (and often high viral loads) are more likely to develop destructive periodontal infections and other oral manifestations of HIV. Partial recovery of the immune system after viral load reduction may affect both the prognosis and oral disease experience of these patients.