High Accuracy of Common HIV-Related Oral Disease Diagnoses by Non-Oral Health Specialists in the AIDS Clinical Trial Group

Objective: Many studies include oral HIV-related endpoints that may be diagnosed by non-oral-health specialists (non-OHS) like nurses or physicians. Our objective was to assess the accuracy of clinical diagnoses of HIV-related oral lesions made by non-OHS compared to diagnoses made by OHS. Methods: A5254, a cross-sectional study conducted by the Oral HIV/AIDS Research Alliance within the AIDS Clinical Trial Group, enrolled HIV-1-infected adults participants from six clinical trial units (CTU) in the US (San Francisco, New York, Chapel Hill, Cleveland, Atlanta) and Haiti. CTU examiners (non-OHS) received standardized training on how to perform an oral examination and make clinical diagnoses of specific oral disease endpoints. Diagnoses by calibrated non-OHS were compared to those made by calibrated OHS, and sensitivity and specificity computed. Results: Among 324 participants, the majority were black (73%), men (66%), and the median CD4+ cell count 138 cells/mm3. The overall frequency of oral mucosal disease diagnosed by OHS was 43% in US sites, and 90% in Haiti. Oral candidiasis (OC) was detected in 153 (47%) by OHS, with erythematous candidiasis (EC) the most common type (39%) followed by pseudomembranous candidiasis (PC; 26%). The highest prevalence of OC (79%) was among participants in Haiti, and among those with CD4+ cell count ≤ 200 cells/mm3 and HIV-1 RNA > 1000 copies/mL (71%). The sensitivity and specificity of OC diagnoses by non-OHS were 90% and 92% (for EC: 81% and 94%; PC: 82% and 95%). Sensitivity and specificity were also high for KS (87% and 94%, respectively), but sensitivity was < 60% for HL and oral warts in all sites combined. The Candida culture confirmation of OC clinical diagnoses (as defined by ≥ 1 colony forming unit per mL of oral/throat rinse) was ≥ 93% for both PC and EC. Conclusion: Trained non-OHS showed high accuracy of clinical diagnoses of OC in comparison with OHS, suggesting their usefulness in studies in resource-poor settings, but detection of less common lesions may require OHS

Cost-Effectiveness of Early Versus Standard Antiretroviral Therapy in HIV-Infected Adults in Haiti

This cost-effectiveness study comparing early versus standard antiretroviral treatment (ART) for HIV, based on randomized clinical trial data from Haiti, reveals that the new WHO guidelines for early ART initiation can be cost-effective in resource-poor settings

Diagnosis of HIV-Associated Oral Lesions in Relation to Early versus Delayed Antiretroviral Therapy: Results from the CIPRA HT001 Trial.

Oral mucosal lesions that are associated with HIV infection can play an important role in guiding the decision to initiate antiretroviral therapy (ART). The incidence of these lesions relative to the timing of ART initiation has not been well characterized. A randomized controlled clinical trial was conducted at the GHESKIO Center in Port-au-Prince, Haiti between 2004 and 2009. 816 HIV-infected ART-naïve participants with CD4 T cell counts between 200 and 350 cells/mm3 were randomized to either immediate ART initiation (early group; N = 408), or initiation when CD4 T cell count was less than or equal 200 cells/mm3 or with the development of an AIDS-defining condition (delayed group; N = 408). Every 3 months, all participants underwent an oral examination. The incidence of oral lesions was 4.10 in the early group and 17.85 in the delayed group (p-value <0.01). In comparison to the early group, there was a significantly higher incidence of candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex in the delayed group. The incidence of oral warts in delayed group was 0.97 before therapy and 4.27 post-ART initiation (p-value <0.01). In the delayed group the incidence of oral warts post-ART initiation was significantly higher than that seen in the early group (4.27 versus 1.09; p-value <0.01). The incidence of oral warts increased after ART was initiated, and relative to the early group there was a four-fold increase in oral warts if ART was initiated following an AIDS diagnosis. Based upon our findings, candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex indicate immune suppression and the need to start ART. In contrast, oral warts are a sign of immune reconstitution following ART initiation

Incident HIV-associated oral lesions in the early and delayed ART initiation groups.

<p>Incident HIV-associated oral lesions in the early and delayed ART initiation groups.</p

High Accuracy of Common HIV-Related Oral Disease Diagnoses by Non-Oral Health Specialists in the AIDS Clinical Trial Group

AbstractObjectiveMany studies include oral HIV-related endpoints that may be diagnosed by non-oral-healthspecialists (non-OHS) like nurses or physicians. Our objective was to assess the accuracyof clinical diagnoses of HIV-related oral lesions made by non-OHS compared to diagnosesmade by OHS.MethodsA5254, a cross-sectional study conducted by the Oral HIV/AIDS Research Alliance withinthe AIDS Clinical Trial Group, enrolled HIV-1-infected adults participants from six clinicaltrial units (CTU) in the US (San Francisco, New York, Chapel Hill, Cleveland, Atlanta) andHaiti. CTU examiners (non-OHS) received standardized training on how to perform an oralexamination and make clinical diagnoses of specific oral disease endpoints. Diagnoses bycalibrated non-OHS were compared to those made by calibrated OHS, and sensitivity andspecificity computed.ResultsAmong 324 participants, the majority were black (73%), men (66%), and the median CD4+cell count 138 cells/mm3. The overall frequency of oral mucosal disease diagnosed by OHSwas 43% in US sites, and 90% in Haiti. Oral candidiasis (OC) was detected in 153 (47%) byOHS, with erythematous candidiasis (EC) the most common type (39%) followed by pseudomembranouscandidiasis (PC; 26%). The highest prevalence of OC (79%) was amongparticipants in Haiti, and among those with CD4+ cell count 200 cells/mm3 and HIV-1RNA > 1000 copies/mL (71%). The sensitivity and specificity of OC diagnoses by non-OHSwere 90% and 92% (for EC: 81% and 94%; PC: 82% and 95%). Sensitivity and specificitywere also high for KS (87% and 94%, respectively), but sensitivity was < 60% for HL andoral warts in all sites combined. The Candida culture confirmation of OC clinical diagnoses(as defined by 1 colony forming unit per mL of oral/throat rinse) was 93% for both PCand EC.ConclusionTrained non-OHS showed high accuracy of clinical diagnoses of OC in comparison withOHS, suggesting their usefulness in studies in resource-poor settings, but detection of lesscommon lesions may require OHS

Frequency of HIV-related oral lesions diagnosed by oral health specialists by site (US sites versus non-US site) among 324 participants in ACTG/OHARA¹ protocol 5254.

<p>¹ The Oral HIV/AIDS Research Alliance (OHARA) is a Collaborative Science Group within the AIDS Clinical Trial Group (ACTG)</p><p>²<b>US sites</b>: Case Western Reserve University (Cleveland); Emory University (Atlanta); New York University (New York City); University of California San Francisco (San Francisco); University of North Carolina (Chapel Hill). <b>Non-US site</b>: Centre GHESKIO (Port au Prince, Haiti)</p><p>Frequency of HIV-related oral lesions diagnosed by oral health specialists by site (US sites versus non-US site) among 324 participants in ACTG/OHARA<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131001#t003fn001" target="_blank">¹</a> protocol 5254.</p

Socio-demographic characteristics and CD4+ cell count at enrollment, by recruitment site among 324 participants in ACTG/OHARA¹ protocol 5254.

<p>¹ The Oral HIV/AIDS Research Alliance (OHARA) is a Collaborative Science Group within the AIDS Clinical Trial Group (ACTG)</p><p>²<b>US sites</b>: Case Western Reserve University (Cleveland); Emory University (Atlanta); New York University (New York City); University of California San Francisco (San Francisco); University of North Carolina at Chapel Hill (Chapel Hill). <b>Non-US site</b>: Centre GHESKIO (Port au Prince, Haiti)</p><p>Socio-demographic characteristics and CD4+ cell count at enrollment, by recruitment site among 324 participants in ACTG/OHARA<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131001#t001fn001" target="_blank">¹</a> protocol 5254.</p

Sensitivity and specificity of HIV-related oral diagnoses made by ACTG Clinical Trial Unit non-dental examiners as compared to reference standard diagnoses made by oral health specialists among 324 participants in ACTG/OHARA¹ protocol 5254.

<p>¹ The Oral HIV/AIDS Research Alliance (OHARA) is a Collaborative Science Group within the AIDS Clinical Trial Group (ACTG)</p><p>²<b>US sites</b>: Case Western Reserve University (Cleveland); Emory University (Atlanta); New York University (New York City); University of California San Francisco (San Francisco); University of North Carolina (Chapel Hill). <b>Non-US site</b>: Centre GHESKIO (Port au Prince, Haiti)</p><p>³ Number of cases diagnosed by Oral Medicine specialist</p><p>⁴ Exact 95% confidence interval</p><p>Sensitivity and specificity of HIV-related oral diagnoses made by ACTG Clinical Trial Unit non-dental examiners as compared to reference standard diagnoses made by oral health specialists among 324 participants in ACTG/OHARA<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131001#t004fn001" target="_blank">¹</a> protocol 5254.</p

Proportion of participants with a positive oral rinse culture among 153 participants¹ with a clinical diagnosis of oral candidiasis in ACTG/OHARA² protocol 5254.

<p>¹ All participants in the study had an oral rinse culture, however we only report the proportion of positive cultures, defined as ≥ 1 CFU/mL, among those who had clinical features of oral candidiasis, as potential confirmation of the clinical diagnosis</p><p>² The Oral HIV/AIDS Research Alliance (OHARA) is a Collaborative Science Group within the AIDS Clinical Trial Group (ACTG)</p><p>³ Number of clinical diagnoses. Note: participants may have more than one type of oral candidiasis, so counts do not add up to 153</p><p>Proportion of participants with a positive oral rinse culture among 153 participants<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131001#t005fn001" target="_blank">¹</a> with a clinical diagnosis of oral candidiasis in ACTG/OHARA<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131001#t005fn002" target="_blank">²</a> protocol 5254.</p

Frequency of HIV-related oral lesions diagnosed by oral health specialists by CD4+ cell count and plasma HIV RNA viral load among 324 participants in ACTG/OHARA¹ protocol 5254.

<p>^<b>1</b> The Oral HIV/AIDS Research Alliance (OHARA) is a Collaborative Science Group within the AIDS Clinical Trial Group (ACTG)</p><p>^<b>2</b> CD4 cell count in cells/mm³</p><p>^<b>3</b> VL: Plasma HIV-1 viral load in copies/mL</p><p>^<b>4</b> Other oral lesions include recurrent oral herpes simplex infection, ulcerations not otherwise specified, and necrotizing ulcerative periodontitis and gingivitis</p><p>⁵ UWS: Unstimulated whole saliva</p><p>Frequency of HIV-related oral lesions diagnosed by oral health specialists by CD4+ cell count and plasma HIV RNA viral load among 324 participants in ACTG/OHARA<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131001#t002fn001" target="_blank">¹</a> protocol 5254.</p