Oral Transmission
Oral HIV Transmission
Fariba S. Younai, DDS
Copyright 2001 Journal of the California Dental Association.
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Although transmission of HIV through casual contact with saliva has not been shown, oral exposure to HIV-infected semen, blood, and breast milk can lead to infection. Unprotected orogenital contact, especially receptive oral intercourse, is associated with greater risk of HIV transmission than previously thought. The salivary anti-HIV properties, the local and systemic immunologic responses, the local mucosal integrity, and the level of infectious HIV present at the oral mucosal site all influence the potential for HIV infection through the oral mucosa. Although more information on the exact mechanisms of oral HIV transmission are necessary, based on the current understanding of this process, educational HIV prevention methods must focus on the potential risks associated with orogenital sexual behaviors. |
Since the onset of the human immunodeficiency virus epidemic, transmission of HIV infection through the oral route has been considered a rare phenomenon. Studies conducted in the early years of the epidemic demonstrated that nonsexual, casual contact with saliva (sharing utensils, HIV in dentistry) is not associated with an increased risk of HIV transmission.1-3 As reviewed by Rothenberg et al,4 from 1983 to 1994, several epidemiologic studies focused on the specific sexual behaviors that had resulted in HIV transmission. These studies also concluded that oral exposure is not considered an independent risk factor in sexual transmission of the HIV.5-21 Despite these earlier studies, through more careful epidemiologic investigations as well as anecdotal reports of HIV transmission from orogenital contact and infection of newborns through breastfeeding, it became apparent that transmission of HIV by oral mucosal exposure to infected semen, blood, and breast milk is possible.22-51 As more information has become available in regard to the anti-HIV properties of saliva, there is now greater understanding of the factors that may influence the protective role of the oral environment against HIV transmission.52-54 Although, casual contact with saliva remains insignificant in the spread of the HIV, the impact of oral sexual behaviors on the HIV epidemic should be given greater attention.
HIV Epidemiology in the New Millennium
HIV is considered a predominantly sexually transmitted disease in the United States and worldwide. There are, however, significant variations in the demographics and exposure risk categories among various regions. In the United States, of the cumulative 733,374 cases of AIDS reported to the Centers for Disease Control and Prevention through December 1999, 47 percent are attributed to male homosexual and bisexual contacts; among women, heterosexual contact accounts for 40 percent of the cases.55 In fact, among female groups, heterosexual transmission has surpassed the rate of parenterally acquired HIV infection.55 In the second decade of the HIV epidemic, despite the enormous public educational efforts instituted at every level, surprising patterns of HIV transmission are emerging. This phenomenon may be partly related to the recent advances in the medical management of HIV infection and the steady decline in the HIV mortality rate that appear to be influencing the public’s general perception of this still deadly infection. There is epidemiologic evidence that despite the general shift in the transmission patterns of the HIV infection toward women and minority populations, high-risk sexual behaviors among younger homosexual men that was on the decline remains a serious concern (this is still the largest single exposure group);55 alcohol and illicit substances are becoming strongly influential in the rate and the type of sexual behaviors among high-risk groups;56-59 and the spread of HIV among adolescents, especially females, has assumed an upward trend (in 1999, people age 13 to 24 accounted for 15 percent of reported new HIV cases, and women accounted for 49 percent of cases in this age group).55
In addition to the continued concern over the spread of HIV infection through homosexual and heterosexual modes, oral sexual behaviors have come into focus in recent years. Because of the perceived relative safety of oral sex compared to other types of sexual behavior, unprotected oral sexual practices have been prevalent among many high-risk groups.60-61 It has recently been realized that orogenital contact -- once considered to have an extremely low potential for infection as compared to anal intercourse or the use of contaminated intravenous devices -- may play a significantly stronger role in the future of the HIV epidemic than originally thought.46,59, 62
Transmission of HIV Through the Oral Mucosa
Although oral transmission of HIV is considered a rare phenomenon, reports of such transmissions do exist. Table 1 demonstrates a comprehensive list of the documented cases of oral transmission dating to the onset of the HIV epidemic.22-51 The questionable circumstances involved with many of these cases have resulted in serious doubts concerning the true risk of HIV infection through an oral mucosal mode. For instance, the reliability of self reports of sexual practices, multiple risk behaviors, and very small numbers of seroconversions in the follow-up studies have all overshadowed the very few apparently confirmed cases of oral HIV transmission. What is common among almost all these cases is a lack of evidence for HIV transmission through saliva alone. One possible exception is a 1997 report by the CDC that described a case of potential HIV transmission between an infected man to his previously uninfected female partner through deep kissing.43 In studying this report, one must note that the HIV-infected man reportedly had severe periodontal disease and gingival bleeding during tooth brushing. He reported brushing his teeth every time before engaging in a sexual relationship with his partner who also had inflamed gingival tissues according to her dental records. Therefore, because of the potential presence of blood (of periodontal disease origin), this report also lacks strong evidence that saliva can play a significant role in HIV transmission. In fact, in terms of mode of transmission, this case is not unlike the reported cases of human bite transmission where blood contact was made by the index cases who were bitten by HIV-positive source cases.27,40
Until recently, orogenital intercourse, especially receptive oral intercourse, was believed to be associated with some but small risk of HIV transmission. In a 1993 study of the estimated risk of receptive oral intercourse, based on the HIV prevalence, sexual behaviors, and seroconversion status, the per-partner risk of seroconversion was shown to be 1 percent (range, 0.85 percent to 2.3 percent), compared to 10 percent (range, 4.2 percent to 12 percent) for receptive anal intercourse.63 Other modeling studies have shown the risk for unprotected receptive anal intercourse to be eight times higher than the risk for receptive oral intercourse.64 In a recent study conducted by researchers at the CDC, San Francisco General Hospital and the University of California San Francisco, the rate of HIV seroconversion related to oral sex was reported to be much higher (7.8 percent).46 The study presented during the Seventh Conference on Retroviruses and Opportunistic Infections held in the early part of 2000, consisted of 102 recently infected homosexual men. Through self-administered and interviewer-administered questionnaires, clinical evaluations, partners interviews, and counselor’s interventions, a process of risk assessment for six months preceding a patient’s seroconversion was accomplished. Eight seroconversions (7.8 percent) were attributed to oral sex. Although a few patients recalled oral sores or periodontal disease at the time of their exposure, most did not have an apparent break in their mucosal tissues. This newly reported rate of possible oral HIV transmission has raised serious concerns over the apparent increased frequency of unprotected oral sexual behavior, especially among young homosexual men.
In addition to the epidemiologic studies and case reports of oral HIV infection, animal studies on simian immunodeficiency virus have shown the ability of the tested virus subtypes to penetrate the oral mucosal barrier. In these studies, SIV has been successfully transmitted to neonate and adult Macaques by gently painting various viral concentrates on the dorsal aspect of the tongue.65,66 In one report, the viral concentration required for transmission through the oral mucosa was shown to be 6,000 times lower than that needed for rectal infection.
All these reports point out to the likelihood of HIV transmission across the oral mucosa and raise several questions in regard to local and systemic factors, which may facilitate or hinder the transmission process. The exact mechanism of HIV transmission after exposure of oral mucous membrane surface to HIV-infected fluids is unknown. During exposure of mucosal surfaces, HIV could be transmitted by
* Entering through epithelial lesions;
* Infecting CD4 positive cells (e.g., Langerhans’ cells, monocytes and macrophages;
* Infecting intact epithelial cells.67
Based on the evidence presented, it is clear that given the right circumstances, HIV is capable of infection across the oral mucosa, though the exact mode of entry is not yet clear. This is especially true if the oral exposure occurs with body fluids containing high levels of infectious HIV. One question remains and that is to what extent saliva plays a role in delivering viable viruses for infection across the oral mucosa.
Isolation of HIV From Whole Saliva
HIV-1 was isolated from saliva in 1984.68 Several studies have demonstrated a substantial number of HIV RNA or proviral DNA in saliva while others have yielded only a modest amount (range, 15 percent to 100 percent).54,69-73 There appear to be significant differences between various reports in terms of salivary collection techniques, viral isolation methods, and patient’s general and oral health status, which may all have contributed to the variable results among these reports. In one quantitative study of HIV RNA in serum, semen, and saliva using an in-house competitive reverse transcriptase-polymerase chain reaction assay, a significant number of HIV viral RNA copies was shown in cell-free whole unstimulated saliva of 96 percent of the HIV-seropositive patients in the study (median of 162/ml; range: 0-72080/ml), correlating with the level of HIV in blood (mean of 14,817 copies/ml and a range of 167-254,880), and increasing with HIV disease progression.73
In a recent report, by employing a highly sensitive nucleic acid sequenced-based assay that is uninhibited by salivary components, HIV-1 RNA was detected in 42 percent of the 40 subjects tested (compared with 78 percent of plasma samples).74 In that study, the mean viral load for saliva samples (2.90 log10 copies/ml) was highly correlated with the plasma viral load (3.97 log10 copies/ml). One interesting aspect of the study was that salivary viral load also significantly correlated with the presence of HIV-associated periodontal disease (linear gingival erythema and necrotizing ulcerative gingivitis and periodontitis) and severe gingival inflammation but not chronic periodontal disease, HIV-associated oral lesions, or presence of occult blood in saliva. The authors concluded that nonblood sources such as tonsils, salivary glands and gingival crevicular fluid may contribute to oral HIV shedding that reflects the systemic burden. A lack of association between the levels of HIV in the oral cavity and the presence of chronic periodontal disease had previously been demonstrated as well.71,75 Another study had demonstrated significantly higher levels of HIV RNA in saliva of patients with periodontitis compared to a matched control group with no periodontal disease (87.5 percent vs. 33 percent).72 In that study, the level of gingival inflammation was not measured; but the HIV RNA was found in 47.6 percent of gingival crevicular fluid samples of periodontitis patients, possibly related to a higher level of inflammation.
Another factor that may play a major role in the potential for oral HIV transmission is the role of oral mucosal pathology in the rate of oral viral shedding. As described before, the Shugras and colleagues 2000 report failed to show a correlation between the levels of salivary HIV viral titer and the presence of various HIV-related oral pathologies. A previous study, however, had shown that crack cocaine-induced oral ulcers were highly correlated with the rate of oral HIV transmission among the high-risk study groups.76 The discrepancies observed among these reports may be reflective of the complex mechanisms involved in oral HIV transmission. Factors influencing the likelihood of such transmission include the presence and the titer of the virus, the integrity of the oral mucosal site, mucosal and systemic immunological functions, local inhibitory factors, and the presence or absence of co-factors that are yet unknown. It must be emphasized that identification of HIV RNA in saliva is not indicative of the infectivity of the virus. Several studies have shown very low levels of infectious HIV detected in saliva (rate, 0 percent to5 percent).68,71-73,77-80 The low recovery rate of infectious HIV from saliva may be attributed to HIV inhibitory mechanisms that are endogenous to the oral environment.
Anti-HIV Activity of Saliva
Several studies dating back to 1986 have documented an anti-HIV property in human saliva.81-91 The anti-HIV-1 activity of saliva has been reported in whole saliva,81-84,88 the parotid,81,88 and submandibular saliva 81,84,85,88 and also in saliva of healthy males and females as well as HIV-infected individuals.82 Among the suggested mechanisms for the anti-HIV action of saliva are the salivary anti-HIV antibodies present in HIV-infected individuals 85,86 and aggregation of HIV-1 by large molecular-weight molecules (mucins) and thrombospondin that allow for viral clearance from the oral environment.87-89 In addition, several soluble inhibitors such as lysozyme, lactoferrin, defensins, and lactoperoxidase have been suggested to contribute to the anti-HIV action of saliva. 52,90-91 One molecule associated with the antiviral properties of saliva against HIV is the molecule secretory leukocyte protease inhibitor.52 This molecule was originally described in 1995 when McNeely and co-workers demonstrated that in vitro infection of monocytes with HIV-1 (measured by viral reverse transcriptase activity) even after one hour of exposure to saliva was suppressed for three weeks after infection. Since that original in vitro study, the in vivo effectiveness of secretory leukocyte protease inhibitor has also been demonstrated.54 The exact mechanism of the HIV-1 inhibition by the protease inhibitor is not well-understood, but it appear to interact with the host cell and inhibit the HIV cell fusion process, acting early and preventing infection of the host cells.91
HIV Transmission Through Breastfeeding
The potential for transmission of HIV by breastfeeding is well-established,47-51 although the exact mechanism by which the transmission occurs has not been characterized. Secretory leukocyte protease inhibitor levels are high in both colostrum and breastmilk, as well as the saliva of the newborn immediately postpartum; only the breastmilk shows a dramatic decrease in the protease inhibitor levels over the few weeks postpartum.4 Breastmilk has high levels of HIV as cell-free virus as well as infections within the milk monocytes and macrophages. These high levels of HIV presence coupled with the relatively low levels of the protease inhibitor in milk may facilitate the viral entry in the tonsillar and intestinal crypts of the newborn and establish the HIV infection.92 Therefore, it appears that the local inhibitory factors that are important in hindering the HIV oral mucosal transmission are not efficient in preventing infection of the newborn through breastfeeding. Clearly, more information about the mechanisms of HIV invasion through the oral mucosal surfaces and the exact mode of HIV entry are necessary.
Summary
Oral mucosal exposure to infectious HIV is associated with the risk of infection. Many local and systemic factors influence the efficiency of oral HIV transmission. Although not as efficient as other sexual behaviors, unprotected oral sexual contacts do present a risk for HIV infection.
Author
Fariba S. Younai, DDS , is an adjunct associate professor in the Section of Oral Biology and Medicine at the University of California Los Angeles School of Dentistry.
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To request a printed copy of this article, please contact/ Fariba S. Younai, DDS, UCLA School of Dentistry, 10833 Le Conte Ave., Los Angeles, CA 90095-1668, or at faribay@dent.ucla.edu.
Table 1. Case Reports and Observations on Oral Transmission
