BACKGROUND

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Complications may result from dental treatment in any healthy person. Risks of prolonged postoperative bleeding, delayed wound healing, oral wound or distant site infection, or alveolitis can occur whenever surgical procedures are performed. Studies reporting postoperative complication rates after the removal of third molars in patients not infected with HIV demonstrate that complication rates can vary from 3 to 10 percent.^5,6 Some evidence also suggests that the complication rates increase in patients with immunocompromising diseases.⁷ Tooth extraction is a common surgical procedure performed on thousands of people every day, many of whom are infected with HIV. Patients with underlying medical diseases, such as hemophilia, liver cirrhosis or immune dysfunction resulting from various causes, may be at higher risk than those with intact hemorrhagic and immune systems.^7–9 Thus, it seems that the HIV-infected patient also may be at increased risk.

Whether HIV-infected patients have a greater propensity for experiencing complications from dental treatment has been controversial. One retrospective review of 1,810 common invasive dental procedures (including periodontal, restorative, endodontic, prosthodontic and surgical procedures) performed mainly by general practitioners among 331 HIV-infected patients with substantially suppressed immune systems (that is, CD4 counts of less than 200 cells/cubic millimeter) demonstrated a low overall complication rate of 0.9 percent.¹⁰ Simple extractions resulted in a 4.1 percent complication rate, and surgical extractions resulted in an 11.8 percent complication rate (mainly dry sockets).¹⁰ Another study demonstrated that prophylactic socket medication may decrease the risk of dry and infected sockets among HIV-positive patients.¹¹

The question of HIV infection increasing the risk of developing serious odontogenic infection that requires inpatient hospitalization and the relative difficulty in managing these infections also are controversial. A case-control study conducted at Grady Memorial Hospital, Atlanta, from 1992 to 1995 demonstrated no significant difference in the risk of developing serious odontogenic infection between HIV-positive and -negative patients.¹² However, a recent case-control study of HIV-positive and HIV-negative patients admitted for treatment of odontogenic infection at the same hospital demonstrated a significantly more intense hospital course for patients who were HIV-positive (for example, a higher percentage required treatment in the intensive care unit), although the overall length of hospital stay was not significantly different from that for patients who were HIV-negative.¹³

Dental surgical procedures or instrumentation involving periodontal structures commonly is associated with transient bacteremias.^14,15 Expert consensus^3,16 suggests that routine antibiotic coverage to prevent septicemia from bacteremias arising from dental procedures is not indicated based solely on the patient’s HIV status, but is recommended for severely neutropenic patients with absolute neutrophil counts below 500 cells/mm³. Although neutropenia may result from use of medications to treat HIV infection or its opportunistic disease, less than 1 percent of HIV-infected dental patients are likely to develop severe neutropenia.¹⁷ However, dentists may choose to prescribe antibiotics for patients to prevent local wound or distant site infection.

A recent survey of 505 dental practitioners in British Columbia, Canada, indicated that patients with AIDS were more likely to receive antibiotic treatment before and after invasive dental procedures such as periodontal surgery, extractions, endodontic surgery and implant placement, as well as in cases in which infection was identified, than were patients without HIV or AIDS.¹⁸ Chlorhexidine antimicrobial mouthrinse has been suggested for use before dental treatment to reduce the risk of postprocedural bacterial complications.¹⁶

Any surgical procedure in a patient with an underlying bleeding disorder, such as hemophilia, thrombocytopenia or severe liver disease, places the patient at risk of experiencing bleeding complications. Patients with hemophilia now constitute less than 1 percent of all patients with HIV infection.¹⁹ HIV-related thrombocytopenia may be due to a variety of factors, including an autoimmune disorder, or may be a side effect of medications. In an evaluation of 516 outpatients with HIV infection conducted between 1995 and 1998, one of us (L.P.) reported that 80 (15.5 percent) had thrombocytopenia (20.7 percent among the 174 patients with AIDS or CD4 counts of less than 200 cells/mm³); however, only two patients had severe thrombocytopenia (that is, platelet counts below 50,000 cells/mm³), placing them at an elevated risk of developing postextraction bleeding.¹⁷ Recently, Bonacini and Puoti²⁰ reported the presence of hepatitis C in up to 33 percent of patients with HIV, thus raising the risk of liver damage and an associated reduction of coagulation factors.

Some experts have suggested that special provisions are necessary to avoid postoperative complications among HIV-infected patients receiving dental treatment.^21–23 This suggestion is based on the rationale that because patients with HIV infection are immunologically compromised, they are at increased risk of developing complications associated with dental treatment. If true, it follows then that those with substantial immunosuppression (that is, CD4 cell count < 200 cells/mm³) or severe neutropenia (that is, absolute neutrophil count < 500 cells/mm³) are at greater risk of developing complications. However, the extent to which HIV-positive and HIV-negative patients experience different rates of postoperative complications after routine dental procedures remains unclear.

This systematic literature review addresses two common concerns: health care practitioners—particularly dentists—may not be aware of the available research with respect to the treatment of HIV-positive patients, and the research may not be as comprehensive or definitive as it should be to guide practitioners in their clinical decision making. We examined published studies to compare the complication rates associated with dental treatment in HIV-positive people with the complication rates for similar dental treatment in people who are HIV-negative. We also explored any factors associated with differences in the complication rates.

	METHODS

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Topics, questions and methods used to guide this review were formulated by the Research Triangle Institute-University of North Carolina, or RTI-UNC, Evidence-based Practice Center, or EPC, Research Triangle Park and Chapel Hill, N.C., in collaboration with staff from the National Institute of Dental and Craniofacial Research,or NIDCR, Bethesda, Md., and the Agency for Healthcare Research and Quality, Rockville, Md. A Technical Expert Advisory Group, or TEAG, was assembled by NIDCR staff and us to assist in refining the key clinical question regarding the dental management of HIV-positive patients.

Clinical question. The objective of the following clinical question was to ascertain whether people who are HIV-positive are at greater risk of developing infection, excessive bleeding, delayed healing or alveolitis as a result of their HIV status: "Are HIV/AIDS patients at increased risk of complications (for example, local infection, systemic infection, increased bleeding, delayed healing or alveolitis) from intraoral dental procedures (that is, extractions, orthognathic surgery, periodontal therapy, endodontics, prophylaxis, dental implants, and scaling and root planing) as compared to similar patients without HIV/AIDS?"

Databases. We searched two databases, MEDLINE and EMBASE, for original human research articles in the English literature published through April 2000 using these two sets of search terms: HIV, HIV infection or acquired immunodeficiency syndrome and dental care, tooth extraction, dental procedures, gingivoplasty, periodontitis, periodontal surgery, dental implants, gingivectomy, oral surgical procedures, orthognathic surgery, dental scaling, dental prophylaxis, root scaling, root planing, root canal therapy or pulpectomy.

This search identified 767 articles. From these, we identified 201 articles that were described in the databases as being one or more of the following: controlled clinical trials (one article), randomized controlled trials (two articles), multicenter study (three articles), epidemiologic research design (187 articles), comparative study (33 articles), evaluation study (six articles) and outcome and process assessment, outcome assessment or treatment outcome (six articles). We then applied the inclusion and exclusion criteria (box, "Inclusion and Exclusion Criteria for Studies Reviewed").

Evidence tables. We reviewed the complete articles and entered information about the research design and results into evidence tables, which permitted salient aspects of the studies to be displayed for ease of comparison. Evidence table columns reflected aspects of the studies including number and source of patients, providers, complications and statistical analyses. We assigned a summary quality score to each article by assessing important attributes of the study.

The attributes and their respective point maximums were as follows: research design (7), data analysis (6) and measurement and validity (7). The points awarded to each attribute were summed, with totals ranging from 0 to 20. We rescaled the totals on a 0-to-100 scale for clarity of presentation, with a score of 100 representing the best or highest possible quality. Although customized to address the clinical question, many of the component items of the attributes listed above were taken directly from or represent modifications of existing rating scales used by the RTI-UNC EPC.²⁴ In developing the quality-rating item set, we were guided by the suggestions advanced by Lohr and Carey,²⁴ both investigators in the RTI-UNC EPC.

TEAG members and additional independent experts reviewed the draft evidence report. Reviewers represented six categories, including dental researchers, clinical experts, professional organization representatives, consumer representatives, potential report users and government agencies. Their comments and suggestions formed the basis for revisions to the draft evidence report, the results of which are contained in this article.

	RESULTS

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We found reports of only two of the seven dental procedures of interest in the five articles. One article examined endodontic treatment,²⁵ and four examined tooth extraction.^26–29 None reported on orthognathic surgery, periodontal surgery, implants, prophylaxis, or scaling and root planing.

Endodontic procedures. The study of postoperative complications associated with endodontic therapy used a retrospective cohort design.²⁵ The researchers reviewed patient records to determine the course of dental treatment, and related medical records confirmed HIV status. The sample included 48 adults, predominantly male, with a mean age of 34 years. The 32 HIV-positive patients (67 percent) were categorized further according to the presence or absence of AIDS-related symptoms. A total of 57 teeth in the HIV-positive and HIV-negative groups underwent endodontic treatment. Nine of the HIV-positive patients and eight of the HIV-negative control patients received antibiotic treatment for relief of symptoms (such as pain, swelling and evidence of periapical infection) before undergoing endodontic treatment. The researchers assessed complications at scheduled recall examinations for up to three months after obturation.

The immediate (one- to three-month follow-up) postoperative complication rate was exceedingly low in the HIV-positive group and nonexistent in the control group.²⁵ Only one (2 percent) of the 48 patients experienced any postoperative complications. An asymptomatic HIV-positive man was found to have pain and swelling after the initial endodontic treatment. He received local débridement and antibiotic therapy, and no further complications occurred. No other complications associated with endodontic therapy were noted in any of the patients’ records, regardless of whether or not they received prophylactic antibiotic therapy. We assigned this study a relatively low quality rating of 40, because of the potential for introduction of bias in areas of design and analysis.

Extractions. Four studies met the inclusion criteria for examining postoperative complications associated with tooth extraction.^26–29 The table summarizes these studies. Two studies used retrospective cohort designs^26,28 and two used prospective cohort designs.^27,29 The four studies followed up more than 500 patients, 238 of whom were HIV-positive and the vast majority of whom were male. Across the four studies, patients in the HIV-negative groups had low rates of prophylactic antibiotic coverage (7.7 to 13.3 percent), while preoperative antibiotic coverage in the HIV-positive groups ranged from 23.7 to 63.0 percent.

In 1997, Dodson²⁹ reported finding no difference in a prospective study of complication rates between HIV-positive and HIV-negative patients undergoing tooth extractions at Grady Memorial Hospital, Atlanta, from Nov. 1, 1993, to April 15, 1996 (relative risk, or RR, for HIV status = 1.68; 95 percent confidence interval, or CI, 0.82 to 3.62).

In contrast, a retrospective study conducted by Dodson and colleagues²⁸ in 1988 and 1989 found that postextraction complication rates among groups of HIV-positive and HIV-negative patients at the Veterans Affairs Medical Center, San Francisco, differed significantly (RR = 7.04; 95 percent CI, 2.0 to 25.0; P = .001), and that the risk increased with increased levels of immune suppression. When these results were adjusted for age, preoperative antibiotic coverage and tobacco use, the difference in complication rates was no longer statistically significant (RR = 4.3; 95 percent CI, 0.93 to 19.5; P = .06). Nevertheless, the authors suggested that biological and statistical evidence, while not overwhelming, did support the conclusion that HIV-positive patients were at increased risk of developing complications after tooth extraction. They further asserted that because the complications are generally mild and treated conservatively, special measures such as determination of the extent of immune suppression or presurgical antibiotic treatment are not recommended.

Across all studies, the postoperative complications were rather minor and patients were treated on an outpatient basis.

Three of the four studies found no significant difference between postoperative complications in the HIV-positive and HIV-negative groups, although the HIV-positive groups tended to have more complications. The fourth study found that HIV-positive patients had a statistically higher complication rate, but after adjusting for other known risk factors, the authors determined that it was no longer significant.²⁸

Postextraction complications that varied in prevalence between the studies included persistent bleeding, persistent pain, localized alveolitis, local wound infection and delayed wound healing. Nevertheless, across all studies, the postoperative complications were rather minor and patients were treated on an outpatient basis. Finally, based on the findings of the studies, none of the authors suggested a need to take special precautions for HIV-positive patients who do not have a coagulopathy (that is, hemophilia, thrombocytopenia or other known bleeding disorders) and are sufficiently healthy to be seen on an outpatient basis.

	DISCUSSION

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Our inclusion criteria required that studies examined in this review have a concurrent HIV-negative control or comparison group that received the same treatments in the same settings as the HIV-positive group. Imposition of this criterion excluded studies involving only HIV-infected populations^10,30 (which reported rather low rates of overall complications). Also excluded were studies that had a comparison group but that did not report complications separately for the two groups.³¹

We found that the quality of the studies included in this review varied. Only two studies used the stronger prospective study design. Only one study reported complication rates for subgroups receiving or not receiving preoperative antibiotic therapy, and only one study of extraction complications included substantial numbers of female patients. All studies were conducted before the clinical availability of viral load assessment and HAART. Two of the five studies reported overall complication rates, but no complication rates for individual complications (for example, delayed healing). None of the studies controlled for severity of the oral condition, and none adjusted for comorbid medical conditions, such as diabetes. Finally, unavailability of patients for follow-up was a concern in two studies.

Grading the literature. Our approach for assigning overall categorical grades to the entire collection of evidence for each dental procedure took into account the overall quality of the individual articles and the number of studies reported on the dental procedure, as well as the strength and consistency of the findings across the studies. We devised four basic grades, which are shown in the box ("Grading the Literature").

In the study of endodontic procedures, the immediate (that is, one- to three-month follow-up) postoperative complication rate was exceedingly low in the HIV-positive group and nonexistent in the control group.²⁵ The authors did not detect a significant difference in complication rates between the two groups. However, because it is only one study, we conclude that the available evidence is insufficient to determine whether differences exist between HIV-positive and HIV-negative people in regard to complication rates associated with endodontic therapy.

Postextraction complications in the four studies included persistent bleeding, persistent pain, localized alveolitis, local wound infection and delayed wound healing. Nevertheless, across all studies, the postoperative complications were rather minor and treated on an outpatient basis. Moreover, none of the four studies called for the need to take special precautions in the treatment of HIV-positive patients who do not have a coagulopathy and are sufficiently healthy to be seen on an outpatient basis. However, given the limited number of studies that addressed extractions, the low rate of complications generally and the variability in the results when analytic approaches differed, we found the evidence to be poor as a basis for ruling in or out a meaningful relationship between HIV-positive status and postoperative complications after tooth extraction.

Limitations of studies. Several limitations are apparent in the published studies. These include an inadequate amount of research, failure to address all of the elements in the clinical question, small sample size, weakness in research design and data analysis, inconsistent results and failure to regularly take into account important characteristics of the study groups. Recent changes in HIV population demographics (for example, an increased prevalence among socioeconomically disadvantaged people) and improvement in the viral and immune status among patients receiving HAART therapy may, in some way, affect the relevance of clinical studies completed earlier in the AIDs epidemic and thus weaken our ability to draw definite conclusions about dental complication risks.

To advance our understanding of differences in complication rates associated with dental patient HIV status, researchers need to consider several factors when designing and analyzing future studies. The number of studies on extractions and endodontic therapy must be increased, and studies of periodontal procedures, dental implants and orthognathic surgery must be conducted. Complication rates need to be reported according to clinical AIDS status, CD4 cell counts and level of plasma viral load.

In any analysis of complications, researchers need to routinely control for several important factors, such as administration of preoperative or postoperative antibiotics, severity of the oral condition being treated, number of dental procedures performed in a patient (for example, single vs. multiple extractions) and other known risk factors such as diabetes and tobacco use. Studies also should report the percentage of HIV-positive patients receiving antiretroviral therapy and the type of therapy administered, including HAART. Patients receiving the more highly active therapies may be receiving added protection against complications. Future studies also should report rates for each specific type of complication, not just overall rates for all complications combined, and they should document patient compliance with postprocedural instructions (such as completion of prescribed antibiotic and analgesic therapy).

In view of the relatively low prevalence rate of postoperative complications in the general population, researchers need to increase sample sizes substantially so that studies have the power to detect significant differences. Also, more sophisticated and rigorous research designs, such as prospective cohort studies, should be used to more rigorously control the criteria for, and comparability of, what is recorded as a specific type of complication. In addition, researchers need to perform more complex analyses of the complications using multivariate analytic techniques that statistically take into account potentially important differences within and between the study groups. Finally, with the changing demographic composition of the HIV-infected population, it will be increasingly important to determine whether complication outcomes differ according to sex, race or poverty status.

	CONCLUSION

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The 1996 national probability sample of the HIV Cost and Services Utilization Study estimated that 65 percent of HIV-positive patients with a regular source of dental care had seen their dentist in the previous six months.³² With increasing numbers of HIV-infected patients seeking and receiving dental care, dentists are called upon more frequently to use their clinical judgment, based on knowledge gained from the literature and their clinical experience, to provide dental care tailored to the individual circumstances of the HIV-positive patient. Although limited published scientific evidence is available to guide clinicians in regard to possible increased risks of invasive oral procedures associated with HIV status, reported complications have been mild and readily amenable to outpatient treatment.