Oral clinical markers and viral load in a prospective cohort of Mexican HIV-infected patients

Recent cross-sectional studies have suggested that oral candidosis and hairy leukoplakia could be considered as clinical markers of high viral load levels and CD4 cell depletion in HIV infection ^[1-3]. However, until now, this association has not been documented in a prospective longitudinal study. Therefore, the aim of this cohort study was to determine the association of the occurrence of oral candidosis and hairy leukoplakia with HIV-RNA plasma levels and CD4 T cell counts in Mexican HIV-infected individuals.

Data presented were obtained from an ongoing prospective cohort of HIV-infected patients started in July 1998, at the AIDS Clinic of the Instituto Nacional de Ciencias Medicas y Nutricion 'Salvador Zubiran', in Mexico City. The study was approved by the Institutional Review Board of the Instituto Nacional de Ciencias Medicas y Nutricion 'Salvador Zubiran', all participants gave their written informed consent to the study.

HIV-infected individuals without a history of and without current oral candidosis or hairy leukoplakia and not receiving highly active antiretroviral therapy (HAART) were included in the study. Patients were examined for clinical evidence of current oral candidosis or hairy leukoplakia, at baseline and monthly during follow-up. CD4 cell counts and HIV-RNA levels were determined at baseline and at 6 month follow-up visits, or at the occurrence of oral candidosis or hairy leukoplakia. Demographic data, risk factors for HIV infection, clinical stage, and antiretroviral therapy were registered.

HIV-RNA measurements were performed by a standardized reverse transcriptase polymerase chain reaction assay (Amplicor HIV-1 Monitor, Version 1.5; Roche Diagnostic Systems, Branchburg, NJ, USA), with a lower limit of detection of 50 copies/ml. CD4 cell counts were determined by flow cytometry, using an Epics XL-MCL (Coulter-Beckman, Mexico).

A Wilcoxon-Mann-Whitney rank sum test was used for comparison of the median HIV-RNA levels and CD4 cell counts between the group of patients who developed oral candidosis or hairy leukoplakia (affected) and the group of patients who did not develop oral lesions (non-affected), at equivalent intervals throughout the study. All analyses were performed using stata version 6.0 ^[4]. P values less than 0.05 were considered statistically significant.

Ninety-four individuals with HIV infection were included in the study; they had a mean age of 34 (20-57) years, and 77% were men. The main risk factor in men was sex with men (89%), and sexual transmission in women (95%). Sixty-four individuals (68%) corresponded to A1, A2, B1and B2 categories, and 30 (32%) subjects were AIDS patients (A3, B3, C1,C3) ^[5].

Sixty-three (67%) patients were drug-naive at study entry. The remainder received non-HAART: 29 patients received two nucleoside analogue reverse transcriptase inhibitors (NRTI) and two received triple NRTI. At baseline, the median CD4 cell count/mm³ was 316 (5-1183) and the median HIV viral load copies/ml was 19 883 (< 50-322 783).

The study cohort was followed during a median period of 164 days (32-784). Twenty-seven patients originally included in the cohort started HAART at some point in their follow-up; these patients were excluded from the study after the time-point at which HAART was initiated. The follow-up median time in this group was 111 (47-555) days.

During follow-up, 30 (32%) patients developed oral candidosis or hairy leukoplakia, with a median time of 163 (32-599) days; of these patients 20 (67%) were drug naive, nine (30%) received two NRTI, and one (3%) received three NRTI. Twenty-one (70%) subjects developed oral candidosis, the erythematous type (13) being the most frequent. Seven individuals (23%) presented with hairy leukoplakia, and two (7%) presented with both.

As shown in Table 1, the median viral load levels and CD4 cell counts found at baseline were similar in both groups (P = 0.29 and P = 0.24, respectively).Viral load levels at 6, 12 and 18 months of follow-up were significantly higher in the affected individuals compared with non-affected individuals (P = 0.002, P < 0.001 and P = 0.025, respectively). The affected individuals showed lower CD4 cell counts at 6, 12 and 18 months compared with non-affected individuals, but this difference was statistically significant (P = 0.003) only at 6 months.

Table 1

A preliminary analysis suggests a threshold level (approximately 30 000-40 000 viral copies), above which it is more likely that a patient will develop either oral candidosis or hairy leukoplakia. This predictive ability is not present when CD4 cell counts were analysed in similar way.

In conclusion, in HIV-infected individuals with no treatment or under non-HAART combinations, the development of oral candidosis or hairy leukoplakia appeared to be associated with higher viral load values and lower CD4 cell counts. Therefore, the presence of these lesions may be considered to be good clinical indirect markers of the status of viral replication. Considering that the diagnosis of oral candidosis and hairy leukoplakia is easy and does not require significant costs, the detection of oral lesions can be a useful tool for identifying the progression of HIV disease, especially in regions of the world where these laboratory markers are not widely available.

Velia Ramírez-Amadora

Lilly Esquivel-Pedrazab

Juan Sierra-Maderob

Luis Soto-Ramirezb

Imelda González-Ramíreza

Gabriela Anaya-Saavedraa

Roberto Rodriguez-Diazb

Rodolfo Vick-Fragosoc

Sergio Ponce-de-Leonb