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Human Immunodeficiency Virus (HIV) and
endodontics: a review

Edgar Schäfer
Department of Operative
Dentistry,
University of Münster,
Waldeyerstr. 30,
Key words
AIDS, CD4 cell count, HAART, infection control, Kaposi’s sarcoma, prophylactic antibiotic treatment, treatment outcome GermanyTel: +49 251 8347040Email: eschaef@uni-muen- Due to the introduction of highly active antiretroviral therapy (HAART), HIV infection has gradually become more of a chronic immunodeficiency disease. In response to HAART, the CD4 cell count, in Sebastian Bürklein
most cases, increases and thereby the HIV-infected patients are at a lower risk of developing oppor- tunistic infections; this leads to an enhanced quality of life and a reduced mortality. Therefore, nowa- days, the endodontist is more likely to encounter an HIV-infected patient in need of endodontictreatment. Unfortunately there is a lack of guidelines for the treatment of HIV-infected or AIDS pa-tients. The intention of this overview is to evaluate current knowledge regarding endodontic treat-ment and its outcome in HIV-infected patients.
Introduction
global markets and the eastward enlargement of theEuropean Union, East European and central Asian Worldwide more than 40 million people are infected states must also be included in the statistics. The es- with the human immunodeficiency virus (HIV). An- timated numbers will rise. The estimated increase is nual new infections are estimated to be 4.9 million, approximately 2.32 million HIV-infected adults with and annual deaths 3.1 million. Since the first descrip- tion of this disease to the year 2004, a total of ap- In 1981 the clinical appearance of AIDS was first proximately 27.1 million people died from AIDS (ac- described by Gottlieb as an unusual accumulation of quired immunodeficiency syndrome). In West and rare and often fatal running illness of previously Central Europe, the number amounts to 720,000 healthy young homosexual men in the USA. A com- HIV-infected people, which corresponds to a preva- bination of Pneumocystis jiroveci infections and Ka- lence of about 0.3% HIV-infected adults. For a long posi’s sarcoma (Figs 1a and 1b) were observed, a clin- time the number of new infections remained at a ical picture that up to that time was associated only constant level or was even slightly decreasing. How- with immunocompromised patients. Therefore even ever, in 2005 the Robert-Koch institute reported a at that early stage an acquired immunodeficiency substantial increase in infection of about 20% com- disease was considered to be the most probable pared with previous years. The clear indication is that cause. The lymphadenopathy virus (LAV), which was it is prudent not to play down the risk of HIV infec- thought to be the perpetrator of AIDS, was isolated tion and the importance of HIV. With the opening of in 1983 by a French group led by Luc Montagnier.
Alle R Copyrigh
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Fig 1 Patient with a Kaposi’s sarcoma, both a) extraoral, on the skin of the cheek, and b) intraoral, visible in the distal re-
gion of the right mandible.
From 1985, a test for the detection of the LAV virus been made in improving the immune status of HIV- was available. A year later, the virus was named HIV.
infected patients, leading to an enhanced quality of Nowadays, two different types of viruses (HIV I and HIV II) are recognised, with many subtypes depend-ing on regional locality.
In the first decade of the HIV epidemic, HIV in- Pathogenesis of HIV infection
fection and AIDS were described as a disease with afulminant course leading in most cases to rapid In the case of the first infection, an acute HIV syn- death. At that time, HIV-infected patients were con- drome develops, corresponding symptomatically sidered to be at a higher risk of developing oppor- to influenza. This stage can last up to three weeks.
tunistic infections than medically healthy patients. In There is an initial rise of plasma viral load with a the last 10 years this has changed dramatically. Since corresponding reduction of the number of CD4 the introduction of highly active antiretroviral thera- lymphocytes4. A humoral immunity response does py (HAART), HIV infection has gradually become not occur5, which is why a negative antibody result more of a chronic immunodeficiency disease. In re- is possible up to six weeks after the infection6. This sponse to HAART, the CD4 cell count in most cases asymptomatic stage can be followed by symptoms increases and thereby the HIV-infected patients are and are assigned to the clinical group B (Table 1)7.
at lower risk for developing the above-mentioned in- The symptoms are due to a possible disorder of the fections. On the whole, remarkable advances have cellular defence, which is normally associated with Category
CD4 cell count (cells/µl)
Clinical symptoms
persisting generalised lymphadenopathy, or acute, primary HIV-infection without presence of AIDS-defining diseases. ARC-symptoms (e.g. oral candidiasis) without AIDS-defining diseases [ARC = AIDS-related complex; a suspicion of a clinical picture justifyingAIDS] Table 1 Classification
AIDS-defining diseases: e.g. candidiasis of the oesophagus, the trachea, respiratory tract, and the lungs, Kaposi’s sarcoma, repeated pneumonia (>1 within 12 months), repeated salmonella septicaemia, Pneumocystis Alle R Copyrigh
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a secondary rise in the virus load and the continu- HIV and endodontics
ous reduction of the CD4 cells, combined with a change for the worse in the CD4/CD8-ratio. In se- Until now, there has been only limited information vere immune defect cases, the CD4 cell count is be- available about the pathology and clinical progress of low 200 cells/mm3; in patients with substantially an existing apical periodontitis or the prognosis of en- suppressed immune systems, the occurrence of dodontic treatment in HIV-infected patients. The re- AIDS-related diseases, leading to mortality after sults of immunhistological studies, case reports and differing times, must be expected in the worst basic immunological principles suggest that, in gener- al, endodontic treatment of apical periodontitis would HIV is an RNA virus and possesses a reverse tran- have a poorer prognosis in immunocompromised pa- scriptase that processes the RNA genome into com- tients, such as HIV-infected patients. It is well known plementary DNA. The virus has receptors for T lym- that T cells play an important role in the pathogene- phocytes, the primary cells to be infected. The virus sis, as well as healing, of apical periodontitis10–12.
attaches via the protein gp120 onto a specific mem- Even if treatment of HIV-infected patients is only brane protein of the host cell, the so-called CD4 pro- palliative or to avoid root canal treatment in mo- tein. After the decomposition of the nucleocapsids, lars13,14, the principles of standard root canal treatment the viral RNA is rewritten in DNA and finally inte- are applicable to HIV-infected patients, or those with grated into the DNA of the host organism. Once the AIDS. The necessity for antibiotic prophylaxis before virus establishes itself intracellularly, infected cells endodontic treatment is still a matter of debate14,15, in can then attach to other cells and the virus can then particular with regard to possible post-operative com- be transferred from cell to cell. The resultant viral plications16. Unfortunately, evidence-based recom- structure and enzyme proteins are assembled to- mendations from clinical trials on this question have gether with the RNA to form new viruses and re- been absent until now. The following recommenda- leased. The infected CD4 lymphocytes become in- tions are based on current knowledge17–20: active after weeks to months; however, this is not • During endodontic treatment, prophylactic anti- the case for the macrophages as they act as a kind biotic therapy is not indicated for patients as- of reservoir8. The affected CD4 cells (T lymphocytes, signed to categories A and B (Table 1) as long as epidermal Langerhans’ cells and macrophages) rep- the granulocytes count is less than 500 cells/µl of resent important control elements in the immune defence. If HIV reaches the body, it evokes a marked • If the granulocytes count ranges above 500 defence reaction; however, the antibodies formed cells/µl of blood, endodontic treatment should be on this occasion are not able to eliminate the virus.
performed under prophylactic antibiotic cover.
A small number of the affected T helper cells will be • The indication for the root canal treatment or the destroyed directly by the virus. Furthermore, indirect alternative of an extraction with patients with attack mechanisms can lead to restricted and mis- AIDS-defining diseases belonging to category C guided controlled defence reactions and will there- (Table 1) should be carefully evaluated with re- by reduce significantly the number of the T4 helper spect to the general health of the patient and cells. That is the reason why otherwise harmless in- their immune resistance. In this case, antibiotic fections, so-called opportunistic infections, can be prophylaxis should be obligatory prior to treat- ment. The advice of the patient’s general medical HIV infection is classified according to the CDC practitioner or haematologist should be sought classification, proposed by the American Centers prior to dental treatment. The assessment should for Disease Control and Prevention, and was last focus on the seriousness of the patient’s immune revised in 1993. The classification is based on suppression and the state of the thrombocytes.
three different categories depending on the clini- • Patients with CD4 cell counts below 200 cells/µl, cal picture of the disease (A-C) and categorised those in categories A3, B3 and C3 (Table 1), according to the status of the CD4 T helper might suffer from a disorder of blood coagulation due a thrombocytopenia. If the thrombocyte Alle R Copyrigh
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count is more than 60,000 cells/mm3, routine e at the same time the primary target of HIV, are dental treatment is normally allowable without edominant. In contrast, during the chr ssenz
the risk of massive secondary haemorrhage. Infil- CD8 cells are predominant, while simultaneously CD4 tration and/or intraligamentary anaesthesia is cells gradually decrease in number. CD8 cells are, in preferred in order to avoid complications associ- comparison to the CD4 cells, relatively unaffected by ated with mandibular or maxillary block anaes- HIV23–25. Observations from several case reports, in- thesia. If the thrombocyte count is below 60,000 cluding a report by Gerner et al22, have suggested that cells/mm3 a specialist should be consulted before the observed delayed healing of apical periodontitis planning dental treatment, or, if necessary, the after endodontic treatment of HIV-infected patients patient should be referred to a specialist.
may be due to a relative lack of T helper cells. Since • Antimicrobial mouthrinses two to three days be- CD4 T cells play an important role in activating B cells, fore planned dental treatment is recommended macrophages and other T cells, it would be reason- (e.g. chlorhexidine) in order to achieve a significant able to assume that patients with low counts of these reduction of oral microorganisms and thereby re- cells may have a compromised local immune function duce the risk of post-operative complications.
and thus show an ineffective immunological defenceagainst residual microorganisms in the root canal sys- Shortly after the discovery of AIDS, only a few case tem26. On the other hand, Gerner et al22 reported that reports could be found in the literature, but now root canal treatments of all teeth with vital pulps were many more, including retrospective studies, have been published. Nevertheless, there are still several In 1993, a retrospective study on conventional unanswered questions on HIV and endodontic treat- root canal treatment in patients with HIV infection ment. Dental practitioners are left to decide how was published20. However, the observation period in best to treat an HIV-infected patient. There is still this study was quite short, only three months (Table scarcity of data on the clinical progression of apical 2). Moreover, the criteria for success were not very periodontitis or the prognosis of endodontic treat- well described; success was defined as a lack of clin- ment in patients with HIV. The current knowledge of ical signs of apical disease at the one- and three- endodontic treatment of patients suffering from HIV month follow-up visits. The immediate post-opera- tive complication rate was exceedingly low in both Histological studies of HIV patients have revealed the HIV-positive and the control groups. There is no high concentrations of proviral HIV DNA present in significant difference in post-operative complications pulp tissue. This has important implications with re- between HIV-infected and healthy patients. The au- gard to infection control in the dental practice21.
thors concluded that as far as short-term success Moreover, HIV can also be found in the granuloma in rates are concerned, root canal therapy can be car- chronic apical periodontitis22. From the findings of ried out on HIV-infected patients using standard pro- further histological studies it is known that in the cedures without the need for antibiotic prophylaxis.
early phases of apical periodontitis, CD4 cells, which Nevertheless, due to limitations including possible Observation
Evaluation
Control:
Success: HIV-
Success:
criteria
infected pa-
infected
of healthy tients
patients
patients
patients
Table 2 Summary of
retrospective studiesevaluating the outcome Alle R Copyrigh
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bias in design, the study is of limited value23,25. More- 34 posterior teeth (32 without and 22 with periapi- int
over, this study was performed before the clinical cal lesions), and was evaluated clinically (palpation, availability of new combinations of HAART and of mobility, sinus tract, percussion, function, infection, viral load assessment. This might be of importance swelling, occlusion, and subjective symptoms) and when interpreting the study results because patients radiographically (periodontal ligament space, rar- receiving highly active therapy may be better pro- efaction, lamina dura, root resorption, and quality of tected against post-operative complications16.
obturation) at review. All root canal treatment was Recently, two studies have been published that performed over several appointments and the mean may prove more helpful for the evaluation of treat- follow-up time was 26 months. The CD4 cell counts ment outcome in HIV-positive patients (Table 2)26,28.
were in the range of 10 to 790 cells/mm3 with a In the first investigation, a retrospective study was mean cell count of 240 cells/mm3. It was reported carried out, comparing periapical healing between that treatment was judged a success clinically in 33 HIV-positive and 33 HIV-negative patients one 88%, questionable in 10%, and a failure (i.e. these year after root canal treatment of teeth with infect- patients developed an apical lesion after the thera- ed pulps and chronic apical periodontitis26. No pa- py) in only 2% of cases. When judged radiographi- tients were diabetic or immunocompromised. The cally, treatment was considered a success in 80%, CD4 counts of the HIV-infected patients were near and a failure in 5% of the cases. The results are re- normal. The primary inclusion criterion was the pres- markable since inadequate obturation was observed ence of radiographically observable apical periodon- in 31% of the treated teeth. Statistically, CD4 cell titis with a minimum lesion size of 2x2 mm associat- count, type of tooth treated, quality of obturation, ed in a non-vital tooth. All the pre-operative radi- and antibiotic therapy had no significant effect on ographs were scored by three experienced endodon- treatment. Based on these results and improved sur- tists using the periapical index (PAI)27. All root canal vival of HIV-infected or AIDS patients due to HAART, treatments were performed in at least two visits, the authors concluded that endodontic treatment of and calcium hydroxide was placed as an intracanal HIV/AIDS patients with irreversible pulpal disease dressing. No prophylactic antibiotic was prescribed.
should be as of standard treatment28.
Follow-up radiographs were taken 12 months after In a retrospective review of 2477 dental proce- root canal obturation and again scored by three en- dures performed on 331 HIV-infected patients on an dodontists using PAI. The mean change of PAI was outpatient basis, amongst others, the rate of post- used to assess the degree of healing and was statis- operative complications after root canal treatment tically analysed and compared between the two was assessed29. Only patients with a CD4 cell count groups. There was no statistically significant differ- below or equal to 200 cells/mm3 were included in ence between the two groups with regard to perapi- this study. A total of 73 endodontic procedures cal healing (Table 2). The authors concluded that were performed and in the immediate follow-up nonsurgical root canal treatment of HIV-positive pa- period, no post-operative complications were iden- tients has the same prognosis as that of medically tified, and the overall complication rate of all den- healthy patients and that there is no need for clini- tal treatment procedures was 0.9%. As the inci- cians to alter their standard endodontic treatment dence of inter-appointment flare-ups in the med- procedure; the prognosis of root canal treatment ically healthy population is reported to be about with HIV-infected patients is not reduced26.
3.2%30, this finding is somewhat surprising28.
In another retrospective study, the long-term Interestingly, with HIV-positive patients who un- outcome over a six-year period, with a minimum of derwent routine dental care on a regular basis, ap- six months follow-up of nonsurgical root canal treat- proximately 36% less endodontic procedures were ment in HIV-positive patients was evaluated (Table indicated compared with HIV-infected patients seek- 2)28. The endodontic treatment was assessed with 60 ing only occasional dental treatment31. These non- teeth from 54 patients; all of the patients were HIV- regular attendees have five-times as many anterior positive, with 12 carrying the diagnosis AIDS. Root and twice as many premolar teeth root treated when canal treatment was performed on 26 anterior and compared with regular attendees (Fig 2). Therefore a Alle R Copyrigh
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Fig 2 HIV-infected patient seeking only
occasional dental treatment. Apart from
destroyed and carious teeth, apical peri-
odontitis is also visible.
recall system should be established for HIV-positive or ed or AIDS patients on an outpatient basis. These pa- AIDS patients in order to ensure that they receive reg- tients have the same prognosis with nonsurgical root ular dental care (Figs 3a and 3b). Fortunately, the at- canal treatment as medically healthy patients (Figs 4a titude of endodontists towards HIV-infected patients and 4b). Considerable efforts should be directed in has changed dramatically over the years32. In 1986, encouraging patients to seek regular, rather than oc- only 21% of the endodontists were willing to treat HIV-infected patients, but this had increased to 93%in 199532. However, according to the same survey, in1995 only 67% of the general dentists were willing HIV infection control precautions
to treat these patients. A dentist may not ethically re-fuse to treat purely because of a patient’s HIV status! The risk of accidental HIV transmission in dental prac- According to this survey, based upon patient self- tice is estimated to be very low. The potential for sali- reporting, less than 1% of all patients in endodon- vary transmission of HIV has been investigated in de- tic practices were HIV-positive32. In fact, it is safe to tail33. Although HIV was found in half of the infected assume that some patients are unaware of their HIV 83 patients in this study, in only one case was it pos- status, so the incidence of HIV-infected patients in sible to detect HIV in saliva33. Even in this case it took daily practice is certainly higher than just 1%.
three weeks of intensive culturing to isolate the virus.
In summary, it can be stated that endodontic It seems that the virus load of saliva is very low, and treatment must be seen as standard for HIV-infect- at the same time saliva is known to inhibit HIV-1.
Fig 3a HIV-infected patient recalled for routine dental care. During this
Fig 3b Tooth 47 following root canal filling.
appointment apical periodontitis was observed radiographically withtooth 47 and mesial carious lesions in 16 and 17.
Alle R Copyrigh
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Fig 4a HIV-infected patient: post-operative
Fig 4b A 3.5 year follow-up radiograph of the root canal filling of tooth 37
showing complete apical healing. A radiographically visible apical periodon- canals of tooth 37 which is associated with titis associated with tooth 46 was discovered and root canal re-treatment is Another mode of transmission might be an ac- canal instrumentation technique using nickel-titanium cidental needle stick or other accidental injury (e.g.
instruments, not only the used instruments but also with a scalpel) with HIV-infected blood. According the handpiece must be disinfected and sterilised af- to several prospective studies, the risk of serocon- version after a needle stick with HIV-infected bloodis approximately 0.03%34,35. The risk of virus trans-mission after a needle stick with hepatitis B-infect- Clinical conclusions
ed blood, is approximately 6–8%36 and could be ashigh as 50% if the patient is hepatitis Be antigen A dentist may not ethically refuse to provide treat- (HBeAg)-positive33. In the case of deep-penetrating ment purely because of a patient’s HIV status.
injuries with accidental exposure to HIV-infected Nonsurgical endodontic therapy in HIV-positive body fluids, a prophylactic administration of a triple patients should be routine and on an outpatient ba- antiretroviral therapy regimen is advised. This sis16,28. Current knowledge supports that there is no should be a combination of two nucleoside reverse need for a routine prophylactic antibiotic treatment transcriptase inhibitors [NRTI; for instance zidovu- except for patients with a substantially suppressed dine (also known as azidothymidine, AZT), 3TC, immune system, those in category C (Table 1). There and abacavir] and either one protease inhibitor (e.g.
is some scientific evidence showing that HIV-infect- lopinavir, ritonavir) or one non-nucleoside reverse ed patients enjoy the same prognosis with nonsurgi- transcriptase inhibitor (NNRTI, e.g. nevirapine, cal root canal treatment as medically healthy pa- efavirenz)37,38. Immediate referral to a specialist is tients. In future, considerable efforts must be per- highly recommendable. The usual precautions, such formed to improve dental prophylaxis in these pa- as not putting a used injection needle back into the tients and to encourage them to seek routine dental sheath, and wearing gloves and goggles during the treatment, are regarded as adequate infection con-trol precautions39.
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Desert de danakil et erta ale

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