(A3) HIV Phenotypes, Oral Lesions, and Management of HIV-related Disease

Abstract

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.

Melanocyte Biology and Function with Reference to Oral Melanin Hyperpigmentation in HIV-Seropositive Subjects

“…HIV-induced cytokine dysregulation roughly parallels a decreasing CD4 + T cell count, 68 so that oral melanin hyperpigmentation is observed more frequently in HIV-seropositive subjects with a CD4 + T cell count of 200 cells/mm 3 or less. 66 Mucosal inflammation, as mentioned above, can promote melanin pigmentation. As there are more immunoinflammatory cells in the subepithelial connective tissue of clinically healthy oral mucosa of HIV-seropositive subjects, probably as a subclinical response to putative exogenous antigens, it is likely that in some cases HIV-OMP is brought about by inflammatory or postinflammatory states.…”

“…2 HIV-OMP may be induced by drugs such as zidovudine, Clofazimine, and ketoconazole, taken for the treatment of the HIV disease or HIVassociated conditions, may occur because of adrenocortical insufficiency that is not uncommon in AIDS, or may be idiopathic. 1,2,66,67 The onset of HIV-OMP if it arises occurs within a period of 2 years of the diagnosis of HIV infection. 3,66 It is possible that HIV-induced upregulation of IL-1, IL-6, and TNF-a promotes the production of a-MSH by oral keratinocytes and melanocytes, and induces upregulation of the expression of MC1R of melanocytes 9,63 with an increased production of melanin resulting in the development of HIV-OMP.…”

“…1,2,66,67 The onset of HIV-OMP if it arises occurs within a period of 2 years of the diagnosis of HIV infection. 3,66 It is possible that HIV-induced upregulation of IL-1, IL-6, and TNF-a promotes the production of a-MSH by oral keratinocytes and melanocytes, and induces upregulation of the expression of MC1R of melanocytes 9,63 with an increased production of melanin resulting in the development of HIV-OMP. HIV-induced cytokine dysregulation roughly parallels a decreasing CD4 + T cell count, 68 so that oral melanin hyperpigmentation is observed more frequently in HIV-seropositive subjects with a CD4 + T cell count of 200 cells/mm 3 or less.…”

Impact of highly active antiretroviral therapy on oral manifestations of patients with human immunodeficiency virus/acquired immuno deficiency syndrome in South India

“…They speculate that a dysregulation of the immune system causes increased melanin pigmentation and have concluded that further longitudinal studies are required to apprehend such a relationship. [2728]…”

Manifestaciones orales en pacientes VIH/SIDA asociadas a tratamiento antirretroviral y el estado inmunológico en dos fundaciones de la ciudad de Cartagena

“…Con relación a la carga viral donde mayormente se presentaron manifestaciones orales asociadas a VIH, fueron en valores menores a 50.000 copias representando el 65,4% donde ninguna de las patologías mostró asociación, Mellors et al y Baqui et al afirmaron que la progresión de la enfermedad es medida lo más exactamente posible por la carga viral creciente y que también se presenta un aumento en el número de lesiones orales asociadas a VIH (23, 24), Bravo IM et al, en un estudio reportaron que los pacientes con una carga viral de 30.000 copias, presentaron más lesiones bucales relacionadas con VIH independientemente del conteo de células CD4 (17), NicolatouGalitis O et al, reportaron que las lesiones orales se incrementaron significativamente en los pacientes con la carga viral mayor de 20.000 copias p<0,001 (21), da Silva CA et al, con una prevalencia de 8,3% en pacientes con cargas virales superiores a 10.000 copias (25), Baqui et al, correlacionaron la presencia de lesiones orales y carga viral en pacientes con VIH y encontró una asociación perceptible entre cargas virales superiores a 10.000 copias y enfermedad periodontal avanzada (24), Tappuni AR et al, en un estudio reportaron una prevalencia en pacientes con cargas virales superiores a 3.000 copias (13), en 2001 se realizó un estudio donde en una cohorte mexicana de pacientes con VIH/SIDA, que no recibían tratamiento antirretroviral, reveló que la aparición de candidiasis oral y leucoplasia vellosa se presento en pacientes con reducción sostenida de células CD4 y con un fuerte aumento de copias en la carga viral (26); teniendo en cuenta lo reportado por todos los autores antes mencionados se podría decir que entre más se incremente el número de copias del virus existe mayor riesgo de presentar manifestaciones orales.…”