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Int J Epidemiol. Dec 2008; 37(6): 1255–1265.
Published online Jul 29, 2008. doi:  10.1093/ije/dyn151
PMCID: PMC2638872
Systematic review of orogenital HIV-1 transmission probabilities
Rebecca F Baggaley,1* Richard G White,2 and Marie-Claude Boily1
1 Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK.
2 Infectious Disease Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
* Corresponding author. Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Campus, Norfolk Place, Paddington, London W2 1PG, UK. E-mail: r.baggaley/at/imperial.ac.uk
Accepted June 23, 2008.
Background The objective was to assess the risk of HIV transmission from orogenital intercourse (OI).
Methods Systematic review of the literature on HIV-1 infectiousness through OI conducted according to MOOSE guidelines for reviews of observational studies. The PubMed database and bibliographies of relevant articles were searched to July 2007.
Results Of the titles, 56 214 were searched from which 10 potentially appropriate studies were identified; two additional studies were identified through bibliographies and one through discussion with experts. There were 10 included studies, providing estimates of transmission probabilities per-partner (n = 5), incidence per-partner (n = 3), per-study participant (n = 3, following initially seronegative individuals whose partners are of unknown serostatus) and per-act (n = 3). Only four of 10 studies reported non-zero estimates: two per-partner estimates (20%, 95% CI: 6–51, n = 10 and a model-based estimate, 1%, range 0.85–2.3%), one per-study participant estimate (0.37%, 95% CI: 0.10–1.34%) and one per-act estimate (0.04%, 95% CI: 0.01–0.17%). Upper bounds for the 95% CI for zero estimates tended to be relatively large due to the small study sample sizes: 9.0, 12.1 and 2.8% for per-partner; 4.7, 9.6 and 1.8 per 100 person-years for incidence per-partner; 4.4% per-study participant and 0.45 and 0.02% for per-act. Given the small number of studies, a meta-analysis was not considered appropriate.
Conclusions There are currently insufficient data to estimate precisely the risk from OI exposure. The low risk of transmission evident from identified studies means that more and larger studies would be required to provide sufficient evidence to derive more precise estimates.
Keywords: HIV, oral sex, orogenital intercourse, infectivity, transmission probability
The risk of HIV transmission through orogenital intercourse (OI) has yet to be precisely quantified. Various case reports suggest that the risk of OI transmission is not nil but much lower than from vaginal and anal intercourse (AI).1 While some of these reports may have been misattributed to OI transmission through underreporting of higher risk behaviours such as AI,2 this is unlikely to be true for all cases of reported OI transmission. It is important to quantify this probability because some confusion about the risks associated with these practices remains. Based solely on the evidence from case reports, current guidelines tend to be very cautious and suggest 100% condom use and use of dental dams.3 More precise information on the actual risk would help clinicians to advise their patients on the relative risks. This may be especially important as the relative contribution of OI may have increased because other higher risk activities, such as unprotected receptive AI (URAI), have become less common. More precise transmission probability estimates would improve predictions of the contribution of OI exposure to HIV incidence that has previously been estimated to be up to 8% in some populations in industrialized countries.4–6
The risk of OI transmission is difficult to assess. Most studies focused on men who have sex with men (MSM), and since many men have varied sexual practices, risks of transmission from low-risk sexual practices such as OI have been difficult to detect. Furthermore, there is a range of OI practices that likely carry different risks, but risks for specific OI practices are difficult to quantify because many individuals practice multiple types of OI (as well as higher risk activities such as vaginal and anal sex). Here, we define OI to include both insertive and receptive penile-oral sex between males and between males and females, as well as vaginal-oral sex between females and between male and females, but to exclude oroanal contact. While Rothenberg et al. reviewed case reports and epidemiological association studies up to the beginning of 1998 reporting OI risk for HIV transmission,1 ours is the first study systematically to review the evidence on transmission probability estimates for receptive and insertive unprotected OI.
The systematic review was undertaken following MOOSE guidelines for reviews of observational studies.7
Search strategy
The PubMed database was searched to July 2007 using the following search terms and Boolean operators, for matches under any field: (HIV OR LAV OR HTLV III OR HTLV-III OR AIDS OR human immunodeficiency virus OR human T-lymphotropic virus III OR acquired immunodeficiency) AND {infectiousness OR infectivity OR probability OR contact OR contacts OR partner OR partners OR wives OR spouses OR husbands OR couples OR discordant OR [transmission AND (heterosexual OR homosexual OR risk OR female OR male OR anal)]}. Titles and available abstracts were scanned for relevance, identifying papers requiring further consideration. Bibliographies of relevant articles were checked and experts in the field were approached in order to identify additional relevant publications.
Selection criteria and data extraction
Due to the small number of studies on OI transmission probability estimates, the review included empirical studies and also statistical model-based estimates (Bernouilli models) using datasets involving partners with multiple exposure types [e.g. OI, URAI and unprotected insertive AI (UIAI)], aiming to delineate the contribution of each sexual activity to the overall transmissions observed in the sample.8,9 Four types of estimate were included: (i) per-act (one OI act); (ii) per-partner (multiple OI acts over the total duration of a sexual partnership with an infected individual); (iii) per-partner incidence (multiple OI acts over a specified duration within a sexual partnership with an infected individual) and (iv) per-seronegative study participant (studies following up initially HIV negative individuals reporting unprotected OI exposure as their sole risk factor, with one or more partners of positive or unknown serostatus). There was no other restriction by study design or language of publication. Each relevant publication was examined by two investigators (R.F.B., R.G.W.) to extract available information on estimates and study and participant characteristics. Two of the three authors contacted replied; authors of one study provided additional information.
Quantitative data synthesis
For uniformity, all confidence intervals (CIs) were recalculated using the Wilson ‘score’ method without continuity correction10,11 except for Samuel et al.8 and Vittinghoff et al.,9 which reported lowest and highest estimates from a sensitivity analysis based on various model assumptions, and the per-partner incidence estimate from de Vincenzi 1994,12 where the number of person-years exposure was not stated and, therefore, the published CI are shown.
Of the titles 56 214 were searched from which 10 potentially appropriate studies were identified; two additional studies were identified through bibliographies and one through discussion with experts. There were 10 included studies that provided five per-partner, three per-partner incidence, three per-study participant and three per-act estimates (with further estimates subdivided by direction of transmission and type of OI act). A flowchart summary of the search is shown in Figure 1. Three publications were excluded. Results from two prospective studies reported in Kingsley et al.13 and Raiteri et al.14 were superseded by Detels et al.15 and Raiteri et al.,16 respectively, which reported results with longer durations of follow-up in each case. Winkelstein et al.17 was excluded because there was no previous HIV negative test to exclude those with URAI exposure from 2 years earlier (HIV prevalence was as high as 18.2% among those with no OI or AI contact in the last 2 years).
Figure 1
Figure 1
Flowchart summarizing the results of the search on HIV-1 transmission probabilities relating to orogenital sex up to July 2007. ‘Studies’ may refer to published articles or abstracts. aCounting principal estimate by del Romero et al. 2002 (more ...)
Forest plots summarizing estimates for each transmission probability type are presented in Figure 2. Details for each study are shown in Table 1. All studies were from industrialized countries and most reported zero seroconversions (Table 1). All but two studies reported no unprotected sexual activity other than unprotected OI, but subjects often practised protected vaginal or AI. Vittinghoff et al.9 and Samuel et al.8 were able to derive model based estimates using data from MSM with various risk factors including URAI and UIAI. Samuel et al. inferred the unknown HIV status of index partners from MSM prevalence data.8 None of the MSM who exclusively reported OI as a risk factor seroconverted in Vittinghoff et al.'s study.9 Vittinghoff et al. calculated a per-act risk for infected or unknown serostatus partners because there were too few cases of OI contact with known infected partners in their dataset. Raiteri et al. followed a cohort of HIV discordant lesbian couples who reported oroanal as well as orogenital contact; there were no seroconversions.16
Figure 2
Figure 2
Summary of studies estimating HIV transmission probabilities for orogenital sex. Estimates are grouped as (a) transmission probability per-partner; (b) incidence per 100 person-years of exposure; (c) transmission probability per-study-participant and (more ...)
Table 1
Table 1
Transmission probabilities for orogenital intercourse—all types
There were five non-zero estimates (two per-partner,8,18 two per-study participant15,22 and one per-act9). The two non-zero per-partner estimates were 1% (range 0.85–2.3%) for receptive OI (ROI)8 and 20% (95% CI: 5.7–51.0%) for fellatio.18 The very high estimate by Giesecke et al. was based on only 10 heterosexual and homosexual discordant couples where the seronegative partner reported no concurrent or subsequent seropositive partner, no intravenous drug use and only OI exposure over follow-up.18 The high estimate may be due to underreporting of higher risk activity, or simply due to chance. Vittinghoff et al. reported a 0.04% risk per-act from men-to-men for unprotected ROI (UROI).9 Two per-study participant studies among MSM reported non-zero transmission probabilities for all OI15 and ROI22 in the absence of practising AI in the previous 12 and 6 months, respectively, but the number of partners and their serostatus were not determined. Therefore, as the exposure and the risk of infection depend on HIV prevalence in the population, these results cannot be generalized to other settings. Similar limitations apply to Vittinghoff et al.'s estimate, which reflects a risk per-act with sexual partners of infected or unknown serostatus and, therefore, very likely underestimates transmission probability per-act per infected partner for UROI.9 No study among heterosexuals reported transmission by OI, except possibly Giesecke et al., where the characteristics of the 10 couples were not stated (59 homosexual and 71 heterosexual couples comprised all discordant couples identified by the study).18 Due to the differences across studies and uncertainty regarding the quality of the estimates due to small sample sizes and misclassification biases due to difficulties in isolating OI as the only source of exposure, it was deemed inappropriate to pool study estimates by transmission types.
Very few studies reporting HIV transmission probabilities through OI or reporting sufficient data to calculate it were found. This may be due to the difficulty in identifying individuals with OI as their sole exposure, the tendency to ascribe any transmission events that occur to any higher risk exposure that is identified, such as AI, and the assumption that the associated risk is very low. Although transmission risk per-act or per-partner through any type of OI activity remains poorly quantified and despite the high estimate from Giesecke et al.,18 our review suggests a low but non-zero transmission probability.
Where OI exposure with no other HIV risk factors is reported, there are the possibilities of both social desirability bias and recall bias leading to underreporting of higher risk behaviour, which may lead to overestimation of transmission probability estimates. Celum et al. stated that in their study most men reporting UROI also reported protected AI and that for such studies that rely on self-reported behavioural data, ‘some seroconverters may not have recognized condom failure and others may have over-reported condom use, which could result in over-attribution of HIV transmission to oral sexual exposure’.26 In a MSM cohort study, Keet et al. reported that of 20 men denying receptive AI (RAI) in the 6–9 months prior to seroconversion in written questionnaires, 11 later reported this practice in face-to-face interviews.2 Conversely, transmission probability estimates from discordant couple studies such as de Vincenzi12 may be low and underestimate infectiousness because index partners are likely to be in the incubation period, after the period of high infectiousness during primary infection.
Different types of OI are likely to have different risks for HIV transmission. The report of a working group of the UK Chief Medical Officers' Expert Advisory Group on AIDS suggested that, ‘it would seem reasonable to assume that ejaculation increases the extent of exposure to HIV and that avoiding it may help reduce the risk of HIV transmission’.27 Again, there are insufficient data to investigate this assumption. Del Romero et al. provide per-partner estimates by type of act and direction of transmission, but there were no seroconversions in this study.19
Studies reporting risk per-study participant, where number of partners and the serostatus of partners for each participant were often not available, were included in this review because of the limited number of studies reporting any type of OI risk estimate. However, such studies may suffer additional reporting bias, as seroconversions from study participants with no risk factor other than OI are notable because such events are rare and, therefore, their occurrence may increase the likelihood of reports from cohorts mentioning them. For per-act infectiousness, Vittinghoff et al. could only quantify the OI risk per partner infected or of unknown serostatus, which would be an underestimate of risk per infected partner.9
Given the small number of studies, a meta-analysis was not considered appropriate as many zero estimates might have occurred because of the small sample size, the low risk of transmission through OI and the increased influence of misclassification biases. The low risk of transmission means large and expensive studies would be required to provide useful evidence to supply more precise estimates. Such estimates are important for prevention and counselling of individual patients. The relative contribution of OI to HIV transmission, despite its inherent low infectiousness, may be substantial if the frequency of unprotected OI is increasing relative to higher risk sexual practices, which may be protected.1,28,29 Nevertheless, the fact that infected study participants with solely this exposure have remained difficult to identify may suggest that indeed the contribution of OI to HIV incidence remains low. The contribution of OI to HIV incidence needs close monitoring and opportunities for further transmission probability studies should be identified and utilized in order to give greater understanding of this neglected mode of transmission.
Acknowledgements
This work was supported by the Wellcome Trust (R.F.B. [GR082623MA] and R.G.W. [GR078499MA]), GlaxoSmithKline (R.F.B.) and the UK Medical Research Council (R.G.W.). We thank Michel Alary, Eric Demers and Elaine Lavoie for providing additional data from their study22 and Veronique Baggaley for French translation. Those acknowledged have confirmed their agreement to be included. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust.
Conflict of interest: None declared.
KEY MESSAGES
  • It is important to assess risk of HIV transmission from OI (between men, between men and women and between women) but very few studies have been published which look at this.
  • Given the lack of information, summary estimates for risk, be it risk per act of OI or risk per partner where OI is practised, cannot be made.
  • More and larger (therefore expensive) studies would be required to derive more precise estimates.
  • However, despite the few data, it appears that risk of HIV transmission through orogenital sex is very low but not zero—individuals should protect themselves using condoms or dental dams to minimize this small risk.
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