Under its Evidence-based Practice Program, the Agency for Healthcare Research and Quality (AHRQ) is developing scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools. Contractor institutions review all relevant scientific literature on assigned clinical care topics and produce evidence reports and technology assessments, conduct research on methodologies and the effectiveness of their implementation, and participate in technical assistance activities.
Overview / Reporting the Evidence / Methodology / Inclusion/Exclusion Criteria / Reviewing and Abstracting the Articles / Findings / Conclusions / Future Research / Availability of Full Report
This is the second in a series of systematic reviews of critical oral health care issues collaboratively supported by the National Institute of Dental and Craniofacial Research (NIDCR) and the Agency for Healthcare Research and Quality (AHRQ).
Rather than focusing on a specific dental disease condition or a particular treatment approach, this report focuses on several aspects of the dental management of a special population subgroup—the estimated 900,000 persons in the United States infected with the human immunodeficiency virus (HIV) or living with the acquired immune deficiency syndrome (AIDS). These aspects include:
This report was prepared to serve as a major element of a State of the Science Workshop that NIDCR held in December 2000 on the management of dental patients with HIV/AIDS.
The key clinical questions to be addressed in this evidence report were proposed by the NIDCR staff involved in the planning of a State of the Science Workshop on this subject, and subsequently refined through discussions with the NIDCR staff and a Technical Expert Advisory Group (TEAG) assembled for this particular topic area. The questions reflect concerns that health care practitioners, and particularly dentists, may not be aware of the available research with respect to the treatment of persons who are HIV positive, and that the research may not be as comprehensive or definitive as it should be.
This report addresses three issues:
The latter two topics have been split to cover each of the aspects in parentheses separately; thus, we have five specific key questions.
Two automated databases were searched: MEDLINE and EMBASE. The contents of the Cochrane Collaboration Library were reviewed manually. We also hand-searched the contents of the most recent 12 months (through spring 2000) of the five journals most likely to contain relevant articles:
Our review of the Cochrane materials indicated related topics that were under study but not currently available as published reports. No search was made through the "gray" literature (i.e., unpublished materials).
Separate MEDLINE searches were conducted for each of the five key questions, but all five searches began with the terms "HIV" or "HIV infection" or "acquired immunodeficiency syndrome" and were limited to humans and the English language. Beyond these similarities, the searches were customized except that the search terms for Key Questions 2A and 2B were similar to each other up to a point, as were the search terms for Key Questions 3A and 3B.
We did the searches without restriction on the year of publication, but we found no relevant publications dated before 1983. All five of the MEDLINE searches started with 83,962 articles on human HIV or AIDS in the English language. Inclusion and exclusion criteria used by the reviewers are set out in the next subsection.
For Key Question 1, the search then included a list of dental procedures of interest—dental care, tooth extraction, dental procedure, gingivoplasty, periodontitis, periodontal surgery, dental implants, gingivectomy, oral surgical procedures, orthognathic surgery, dental scaling, dental prophylaxis, root scaling, root planing, root canal therapy, and pulpectomy.
We identified 145,292 articles on these topics. When cross-checked against with the English-language articles on HIV/AIDS, 767 articles were common to both search results. These were further winnowed down to 201 articles by eliminating nonresearch articles and clinical case reports. We only included studies described in such terms as controlled clinical trials, randomized controlled trials, multicenter study, epidemiologic research design, comparative study, evaluation study, outcome and process assessment, outcome assessment, or treatment outcome.
For Key Question 2A, the departure point from the first search was to specify the oral conditions of interest—mouth diseases, periodontal diseases, oral infections, hairy leukoplakia, oral leukoplakia, oral candidiasis, necrotizing ulcerative gingivitis, oral ulcers, parotid diseases, parotid gland, parotitis, or parotid swelling. This resulted in 1,719 articles when cross-checked against the English-language articles on HIV/AIDS. These were reduced further to 297 articles by restricting them to mention of HIV seropositivity, seroconversion, or AIDS serodiagnosis.
The search for Key Question 2B included searching for the same oral condition as in Key Question 2A, but restricted the studies to those mentioning immunosuppression or CD4 lymphocyte count. This yielded 133 articles.
For Key Question 3A, the search was limited to oral candidiasis and to a list of antifungal agents—fluconazole, ketoconazole, nystatin, itraconazole, clotrimazole, amphotericin B, or drug therapy. This resulted in 223 articles, a number that was further reduced to 18 studies by restricting the search with the terms primary prevention, prevention, preventive medicine, health promotion, disease prevention, dental prophylaxis, or prophylaxis.
The search strategy for Key Question 3B was similar to the search done for Key Question 3A to the point of specifying the condition and the drugs. It then restricted the articles to those dealing with drug therapy, therapy, intervention studies, intervention, treatment outcome, or treatment and yielded 143 articles.
Subsequent to the MEDLINE searches, we conducted additional searches on EMBASE. EMBASE is somewhat more limited than MEDLINE in the time period covered (only since 1988) and in the search terms available to customize queries. For this latter reason, we did only three customized searches for the five questions: Key Questions 2A and 2B were combined into a single search, as were Key Questions 3A and 3B. The vast majority of articles uncovered in these searches were duplicative of those found in the MEDLINE searches. The EMBASE searches resulted in the addition of only three articles to the bibliography.
The basic screening criteria for inclusion and exclusion that applied to articles for all of the questions were as follows:
For Key Question 1 on the differences in outcomes and complications of intra-oral procedures between HIV-positive and HIV-negative patients, the criteria used were as follows:
For Key Question 2A on the use of oral lesions as markers for seroconversion, the criteria were as follows:
The criteria for Key Question 2B addressing the use of selected oral lesions as indicators of change in immunosuppression were as follows:
For Key Question 3A, addressing the use of available antifungal agents to prevent initial or recurrent oral candidiasis, the criteria were as follows:
The criteria for Key Question 3B, on the effectiveness of available antifungal agents to treat oral candidiasis, were as follows:
Determining which articles identified in the literature searches were to be included in the review involved a number of steps:
The data from five articles were abstracted for the review of Key Question 1 comparing the complication rates associated with dental treatment in HIV-positive persons to the complication rates for similar dental treatment in individuals who are HIV negative. Only two of the seven dental procedures specifically mentioned in Key Question 1 were the objects of study in the five articles. One article examined endodontic procedures (root canal treatment), while four studies examined tooth extraction. None reported on orthognathic surgery, periodontal surgery, prophylaxis, scaling and root planing, or implants.
Nevertheless, across all studies, the postoperative complications that were experienced were rather minor, and when they occurred, were treated on an outpatient basis. Finally, based on their findings, none of the four studies called for the need to take special precautions in HIV-positive patients who do not have a coagulopathy (e.g., hemophilia, thrombocytopenia, or other known bleeding disorders) and are sufficiently healthy to be seen on an outpatient basis.
Only one study was abstracted in the review for Key Question 2A. The question asked for evidence on a set of specific oral conditions—oral candidiasis, hairy leukoplakia, necrotizing ulcerative periodontitis, oral ulcers, and parotid swelling—as markers for recent HIV seroconversion. The study investigated the prevalence of a variety of signs and symptoms (including oral candidiasis) among two groups of initially seronegative hospital patients. All of the patients received blood transfusions for a variety of reasons, but half were transfused with seropositive blood while the "matched controls" received seronegative blood.
The question uses the medical "testing" dimensions of sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of the oral conditions as a marker of recent seroconversion as the way of evaluating their usefulness. Positive enzyme-linked immunosorbent assays (ELISAs) and Western blot tests for HIV, obtained from patients who were confirmed previously seronegative for up to 3 months after the presumed time of infection/exposure, were considered evidence of recent seroconversion. No special conditions were imposed on the diagnosis of the oral conditions.
Key Question 2B involved assessing evidence supporting the use of selected oral conditions as indicators of the progression of HIV infection to the stage of severe immunosuppression and a diagnosis of AIDS. The question suggests the use of the CD4 lymphocyte cell count as a measure of immunosuppression. The question identified the following seven oral conditions of interest: hairy leukoplakia, oral candidiasis, necrotizing ulcerative periodontitis, oral ulcers, parotid swelling, linear gingival erythema, and Kaposi's sarcoma.
The data from 10 articles were abstracted and included in the review for this question. All 10 articles reported CD4 count alone as their measure of immunosuppression.
This question also uses the medical "testing" dimensions (Sn, Sp, PPV, and NPV) of the oral conditions as an indicator of immunosuppression to evaluate their usefulness. In this context, an oral condition with high sensitivity would represent a screening tool for identifying HIV disease that has progressed to the next stage.
The oral conditions on which studies reported were quite varied. None of the articles reported on parotid swelling; however, all 10 articles reported on oral candidiasis, six reported on hairy leukoplakia, and four on oral ulcers. Only two studies reported on linear gingival erythema, two on necrotizing ulcerative periodontitis, and three on Kaposi's sarcoma.
There were six clinical trials that examined the efficacy of available antifungals to prevent oral candidiasis in persons who are HIV positive. Only two of the six available antifungals were studied in this context. There were five studies of fluconazole and one of nystatin pastilles.
Twelve clinical trials evaluated the effectiveness of the six available antifungal drugs in the treatment of oral candidiasis in persons with HIV/AIDS. No studies included an evaluation of amphotericin B suspension, and fluconazole was the most studied of the five remaining.
There is limited evidence on the risks of oral procedures among persons with HIV/AIDS. Very few studies have been reported, and only two types of procedures—root canal therapy and extractions—have been investigated. From this meager base, there is little evidence of unusual rates or severity of complications for these procedures among persons with HIV/AIDS.
Evidence for the utility of selected oral lesions as markers for seroconversion is limited to a single study of a single oral condition—candidiasis. While most of the persons who had candidiasis had seroconverted (high PPV), only a small proportion of the seroconverters had candidiasis (low Sn). This review does not suggest the use of oral conditions as markers for seroconversion. While there is a greater amount of evidence with respect to using a similar set of oral conditions as indicators of progress to severe immune suppression (CD 4 counts < 200 cells/mm3), the conclusions are not dissimilar. They are generally not good to use in place of a test to detect HIV progression to the next stage, and, with the exception of Kaposi's sarcoma which has a very high PPV, are of little benefit in a clinical setting.
The evidence with respect to the efficacy of fluconazole to prevent oropharyngeal candidiasis is good, but for other antifungal agents there is no evidence. The situation is different with respect to the effectiveness of antifungals as treatments for oropharyngeal candidiasis. With the exception of amphotericin B, the evidence is good that they are all effective, although not equally.
To advance our understanding of differences in oral complication rates associated with patient HIV status, the number of studies on extractions and endodontics must be increased, and the types of dental treatments that are studied need to be expanded to include periodontal procedures, implants, orthognathic surgery, and oral prophylaxis. The study designs need to be more sophisticated, the samples large, and the analyses multivariate. Important variables that need to be better measured and reported include complications, postprocedural compliance, and antibiotic and antiretroviral use.
Furthering our knowledge of oral conditions as markers of recent seroconversion will require a large commitment of professional manpower and resources to monitor large at-risk cohorts over time. It will require that attention be given to the full range of oral conditions implicated in the seroconversion process, their consistent diagnosis, and frequent HIV testing.
As with future research on oral conditions as markers of seroconversion, more intensive study and consistent diagnosis of the suspected oral conditions (in addition to oral candidiasis and hairy leukoplakia) are needed to ascertain their value as indicators of changes in the level of immunosuppression. Additionally, the role of antiretroviral therapy—especially the newer, highly active agents—needs to be considered in future analyses, and viral load should be measured in addition to CD4 lymphocyte counts to measure changes in levels of viral replication and immunosuppression.
Large gaps remain to be filled in our knowledge with regard to the efficacy of ketoconazole, clotrimazole, itraconazole, nystatin suspension, and amphotericin B oral solution when used prophylactically against initial and recurrent oropharyngeal candidiasis in HIV patients. Studies using these drugs need to be performed, and more needs to be done using nystatin.
Future studies need to follow well-defined cohorts and control for immunological and clinical HIV status, HIV viral replication rates, prior history of oropharyngeal candidiasis, prior use of antifungals, and current antiretroviral therapy. Observations are needed of patient compliance with the drug regimen, fungal speciation, and resistance to the drug (via susceptibility testing).
Although much more research already exists regarding treatment effectiveness of available antifungals against oral candidiasis than on their prophylactic use, there is a need for studies of amphotericin B if it is to be included in the array of antifungal drugs used. The same methodological conditions mentioned in the context of research on the prophylactic use of antifungals also apply in the context of treatment.
The full evidence report from which this summary was derived was prepared for the Agency for Healthcare Research and Quality by the Research Triangle Institute-University of North Carolina at Chapel Hill Evidence-based Practice Center under contract No. 290-97-0011. Printed copies may be obtained free of charge from the AHRQ Publications Clearinghouse by calling 800-358-9295. Requestors should ask for Evidence Report/Technology Assessment No. 37, Management of Dental Patients Who Are HIV Positive.
The Evidence Report is also online on the National Library of Medicine Bookshelf, or can be downloaded as a zipped file.
AHRQ Publication No. 01-E041
Current as of March 2001
Internet Citation:
Management of Dental Patients Who Are HIV Positive. Summary, Evidence Report/Technology Assessment: Number 37. AHRQ Publication No. 01-E041, March 2001. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/epcsums/denthivsum.htm
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