Oral lesions as clinical markers of highly active antiretroviral therapy failure: a nested case-control study in Mexico City.

BACKGROUND Clinical markers that may predict virological failure during highly active antiretroviral therapy (HAART) have not been evaluated adequately. The aim of the present study was to evaluate the usefulness of human immunodeficiency virus (HIV)-related oral lesions as clinical predictors of virological failure in HIV-infected patients receiving HAART. METHODS A nested case-control study was conducted within a cohort of 1134 HIV-infected patients receiving HAART who attended the AIDS Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City during the period 1997-2005. Case patients were patients who, after achieving an undetectable viral load, had at least 1 viral load determination > or = 2000 copies/mL while receiving treatment. Control subjects were patients who, after achieving an undetectable viral load, continued to have undetectable viral loads during the follow-up period. There were 2-3 control subjects for each case patient, matched according to duration of follow-up. Oral examinations were blinded to viral loads and CD4+ lymphocyte counts. Analyses were performed with multivariate conditional logistic regression models, and associations were shown as odds ratios (ORs) with 95% confidence intervals (CI). Positive predictive values were calculated. RESULTS The target cohort consisted of 431 HIV-infected individuals; 47 case patients and 132 control subjects underwent complete oral examinations and formed the basis of the analysis. At the visit at which an undetectable viral load was determined, case patients and control subjects showed a similar frequency of HIV-related oral lesions (21.3% vs. 17.4%) (OR, 1.39; 95% CI, 0.57-3.38; P=.47). At the visit at which virological failure was determined, case patients showed a higher risk for HIV-related oral lesions (OR, 14.5; 95% CI, 4.21-49.94; P<.001) and oral candidosis (OR, 26.2; 95% CI, 3.34-205.9; P<.001) than did control subjects. The positive predictive value of HIV-related oral lesions and oral candidosis to identify patients who experienced virological failure while receiving HAART was 80% and 83%, respectively. CONCLUSIONS HIV-related oral lesions and, specifically, oral candidosis may be considered to be clinical markers of virological failure in HIV-infected patients receiving HAART.

[1]  Martin S. Hirsch,et al.  Treatment for adult HIV infection. , 2004 .

[2]  J. Limeres,et al.  Changing prevalence of human immunodeficiency virus-associated oral lesions. , 2000, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[3]  J. Margolick,et al.  Thrush and fever as markers of immune competence in the era of highly active antiretroviral therapy. , 2001, AIDS research and human retroviruses.

[4]  S. Flint,et al.  (B3) Markers of Immunodeficiency and Mechanisms of HAART Therapy on Oral Lesions , 2006, Advances in dental research.

[5]  R. Mesquita,et al.  Risk factors for oral hairy leukoplakia in HIV-infected adults of Brazil. , 2006, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[6]  V. Robison,et al.  Oral manifestations of HIV infection in relation to clinical and CD4 immunological status in northern and southern Thai patients. , 2004, Oral diseases.

[7]  S. Gange,et al.  Incidence of Oral Lesions in HIV-1-infected Women: Reduction with HAART , 2004, Journal of dental research.

[8]  J. Castilla,et al.  Oral candidiasis as a clinical marker related to viral load, CD4 lymphocyte count and CD4 lymphocyte percentage in HIV-infected patients. , 2002, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[9]  T. Axéll,et al.  Prognostic significance of HIV-associated oral lesions and their relation to therapy. , 2002, Oral diseases.

[10]  J. J. Henning,et al.  Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, January 28, 2000 , 1998, HIV clinical trials.

[11]  J. Greenspan,et al.  Oral Lesions of HIV Disease and HAART in Industrialized Countries , 2006, Advances in dental research.

[12]  S. Vesić,et al.  Oral candidiasis and seborrheic dermatitis in HIV‐infected patients on highly active antiretroviral therapy , 2004, HIV medicine.

[13]  A. Tappuni,et al.  The effect of antiretroviral therapy on the prevalence of oral manifestations in HIV-infected patients: a UK study. , 2001, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[14]  J. Greenspan Sentinels and signposts: the epidemiology and significance of the oral manifestations of HIV disease. , 1997, Oral diseases.

[15]  I. Miziara,et al.  Oral candidosis and oral hairy leukoplakia as predictors of HAART failure in Brazilian HIV-infected patients. , 2006, Oral diseases.

[16]  L. Patton Sensitivity, specificity, and positive predictive value of oral opportunistic infections in adults with HIV/AIDS as markers of immune suppression and viral burden. , 2000, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[17]  G. T. Jones,et al.  Classification and diagnostic criteria for oral lesions in HIV infection , 1994 .

[18]  M. Etminan Pharmacoepidemiology II: The Nested Case‐Control Study—A Novel Approach in Pharmacoepidemiologic Research , 2004, Pharmacotherapy.

[19]  Michael S Saag,et al.  Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society--USA panel. , 2006, Topics in HIV medicine : a publication of the International AIDS Society, USA.

[20]  L. Gaitán-Cepeda,et al.  Oral candidosis as a clinical marker of immune failure in patients with HIV/AIDS on HAART. , 2005, AIDS patient care and STDs.

[21]  J. Sobel,et al.  Longitudinal study of mucosal Candida species colonization and candidiasis among human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women. , 2003, The Journal of infectious diseases.

[22]  V. Abbadessa,et al.  HIV infection: oral lesions, CD4 + cell count and viral load in an ltalian study population , 2007 .

[23]  W. Browner,et al.  Designing Clinical Research , 2006 .

[24]  G. Slade,et al.  Incidence of oral candidiasis and oral hairy leukoplakia in HIV-infected adults in North Carolina. , 2005, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[25]  S. Hammer,et al.  Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society-USA Panel. , 1997, JAMA.

[26]  D. Vlahov,et al.  Comparison of clinical manifestations of HIV infection among women by risk group, CD4+ cell count, and HIV-1 plasma viral load. HER Study Group. HIV Epidemiology Research. , 1999, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[27]  Gary D Slade,et al.  Risk indicators for oral candidiasis and oral hairy leukoplakia in HIV-infected adults. , 2005, Community dentistry and oral epidemiology.

[28]  L. Patton,et al.  Oral hairy leukoplakia and oral candidiasis as predictors of HIV viral load. , 1999, AIDS.

[29]  S. Challacombe,et al.  Oral lesions in infection with human immunodeficiency virus. , 2005, Bulletin of the World Health Organization.

[30]  Alvan R. Feinstein,et al.  Clinical Epidemiology: The Architecture of Clinical Research , 1988 .

[31]  J. Greenspan,et al.  The epidemiology of the oral lesions of HIV infection in the developed world. , 2002, Oral diseases.

[32]  Roger Detels,et al.  Plasma Viral Load and CD4+ Lymphocytes as Prognostic Markers of HIV-1 Infection , 1997, Annals of Internal Medicine.

[33]  C. Barr,et al.  Oral mucosal lesions and HIV viral load in the Women's Interagency HIV Study (WIHS). , 2000, Journal of acquired immune deficiency syndromes.

[34]  V. Ramírez-Amador,et al.  The Changing Clinical Spectrum of Human Immunodeficiency Virus (HIV)-Related Oral Lesions in 1,000 Consecutive Patients: A 12-Year Study in a Referral Center in Mexico , 2003, Medicine.

[35]  D. Mercante,et al.  Assessment of the Association Between HIV Viral Load and CD4 Cell Count on the Occurrence of Oropharyngeal Candidiasis in HIV-Infected Patients , 2006, Journal of acquired immune deficiency syndromes.

[36]  L. Soto-Ramírez,et al.  Oral clinical markers and viral load in a prospective cohort of Mexican HIV-infected patients. , 2001, AIDS.

[37]  L. Soto-Ramírez,et al.  Synchronous kinetics of CD4+ lymphocytes and viral load before the onset of oral candidosis and hairy leukoplakia in a cohort of Mexican HIV-infected patients. , 2005, AIDS research and human retroviruses.