dyn151 1..11

Systematic review of orogenital HIV-1

transmission probabilities

Rebecca F Baggaley,

* Richard G White

and Marie-Claude Boily

Accepted 23 June 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 obser-

vational studies. The PubMed database and bibliographies of rele-

vant 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 ¼ 5), incidence per-partner

(n ¼ 3), per-study participant (n ¼ 3, following initially seronegative

individuals whose partners are of unknown serostatus) and per-act

(n ¼ 3). Only four of 10 studies reported non-zero estimates: two

per-partner estimates (20%, 95% CI: 6–51, n ¼ 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 partici-

pant 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 iden-

tified 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

Introduction

The risk of HIV transmission through orogenital

intercourse (OI) has yet to be precisely quantified.

Various case reports suggest that the risk of OI trans-

mission is not nil but much lower than from vaginal

and anal intercourse (AI).

While some of these

reports may have been misattributed to OI transmis-

sion through underreporting of higher risk behaviours

such as AI,

this is unlikely to be true for all cases of

* Corresponding author. Department of Infectious Disease

Epidemiology, Imperial College London, St Mary’s Campus,

Norfolk Place, Paddington, London W2 1PG, UK.

E-mail: [email protected]

Department of Infectious Disease Epidemiology, Faculty of

Medicine, Imperial College London, London, UK.

Infectious Disease Epidemiology Unit, Department of

Epidemiology and Population Health, London School of

Hygiene and Tropical Medicine, London, UK.

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Published by Oxford University Press on behalf of the International Epidemiological Association

International Journal of Epidemiology

doi:10.1093/ije/dyn151

Int. J. Epidemiol. Advance Access published July 29, 2008

by on July 23, 2010 http://ije.oxfordjournals.orgDownloaded from

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.

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 indi-

viduals 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,

ours is the first study systematically

to review the evidence on transmission probability

estimates for receptive and insertive unprotected OI.

Methods

The systematic review was undertaken following

MOOSE guidelines for reviews of observational

studies.

Search strategy

The PubMed database was searched to July 2007

using the following search terms and Boolean opera-

tors, for matches under any field: (HIV OR LAV OR

HTLV III OR HTLV-III OR AIDS OR human immuno-

deficiency virus OR human T-lymphotropic virus

III OR acquired immunodeficiency) AND {infectious-

ness 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, iden-

tifying papers requiring further consideration. Biblio-

graphies 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 transmis-

sion probability estimates, the review included empir-

ical 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 dura-

tion of a sexual partnership with an infected indi-

vidual); (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 expo-

sure as their sole risk factor, with one or more part-

ners 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 correction

10,11

except for Samuel et al.

and

Vittinghoff et al.,

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,

where the number

of person-years exposure was not stated and, there-

fore, the published CI are shown.

Results

Of the titles 56 214 were searched from which 10

potentially appropriate studies were identified; two

additional studies were identified through bibliogra-

phies 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.

and

Raiteri et al.

were superseded by Detels et al.

and

Raiteri et al.,

respectively, which reported results with

longer durations of follow-up in each case. Winkelstein

et al.

was excluded because there was no previous HIV

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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).

Forest plots summarizing estimates for each transmis-

sion 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.

and Samuel et al.

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.

None of the MSM who

exclusively reported OI as a risk factor seroconverted in

Vittinghoff et al.’s study.

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.

There were five non-zero estimates (two per-

partner,

8,18

two per-study participant

15,22

and one

per-act

). The two non-zero per-partner estimates

were 1% (range 0.85–2.3%) for receptive OI (ROI)

56 214 abstracts identified

from PubMED and title

examined

733 abstracts examined

205 studies retrieved for

more detailed evaluation

13 potentially appropriate

studies identified

14 estimates

included

528 abstracts excluded due

to non-relevance

30 studies excluded due to

failure to meet inclusion

criteria (reviews, case

studies etc.)

3 excluded/superseded

studies

1 study identified through

discussion with experts,

supplemented with additional

data (Lavoie 2008, Alary 2008

personal communication)

55 481 titles excluded due to

non-relevance

40 studies retrieved for

more detailed evaluation

165 abstracts excluded for

relating to vaginal or anal

transmission only

5 per partner estimates

(from 5 studies)

3 per partner sero-

incidence estimates

(from 3 studies)

3 per study participant

estimates

(from 5 studies)

3 per act estimates

(from 3 studies)

10 studies included

2 studies identified through

bibliographies

(1 abstract: Balls 2004,

1 book chapter: Samuel 1994)

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.

Counting principal estimate by del

Romero et al. 2002 only (and not subdivisions by direction of transmission and type of act).

Counting only the estimate

by Balls et al. 2004 and Page-Shafer et al. 2002 restricted to participants reporting exposure to a seropositive partner or

partner of unknown serostatus

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and 20% (95% CI: 5.7–51.0%) for fellatio.

The very

high estimate by Giesecke et al. was based on only 10

heterosexual and homosexual discordant couples

where the seronegative partner reported no concur-

rent or subsequent seropositive partner, no intrave-

nous drug use and only OI exposure over follow-up.

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).

Two per-

study participant studies among MSM reported non-

zero transmission probabilities for all OI

and ROI

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

(a)

(b)

(c)

(d)

Study participants Description of exposure

Heterosexual/MSM couples Fellatio

Heterosexual couples Unprotected fellatio (with protected

vaginal or AI)

MSM All OI

Lesbian couples All OI (and other sexual practices

such as OAI for some couples)

Heterosexual couples All OI

Lesbian couples All OI (and other sexual practices

such as OAI for some couples)

Heterosexual couples All OI

MSM All OI (plus no AI in previous

12 months)

MSM Exposure to ejaculate of an HIV

positive or unknown serostatus partner

MSM ROI with ≥1 HIV positive and/or

casual partners but no AI in previous

6 months

Lesbian couples All OI (and other sexual practices

such as OAI for some couples)

MSM UROI with ejaculation from an infected

partner or partner of unknown serostatus

Heterosexual couples All OI

0% 10% 20% 30% 40% 50% 60%

Giesecke et al. 1992

de Vincenzi 1994

Samuel et al.1994

Raiteri et al. 1998

del Romero et al. 2002

Transmission probability per partner

024681012

de Vincenzi 1994

Raiteri et al. 1998

del Romero et al. 2002

Incidence per 100 person years

0.0% 0.1% 0.2% 0.3% 0.4% 0.5%

Raiteri et al. 1998

Vittinghoff et al. 1999

del Romero et al. 2002

Transmission probability per act

0.0% 0.2% 0.4% 0.6% 0.8% 1.0% 1.2% 1.4%

Detels

et al.

1989

Page-Shafer et al. 2002,

Balls et al. 2004

Lavoie et al. 2007, Alary

2008

Transmission probability per study participant

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 (d) transmission probability per-act. Bars represent 95% CIs except for Samuel et al.,

and

Vittinghoff et al.,

which represent highest and lowest estimates using various models and assumptions. Sizes

of boxes are proportional to sample sizes, except for Samuel et al.,

and Vittinghoff et al.,

which are denoted by

circles because no sample size is available. OAI, oro-anal intercourse.

Estimate used is 0.00 (0/83, 0.00–4.42)—sample

restricted to 19% of men reporting an HIV positive or unknown serostatus partner

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Table 1 Transmission probabilities for orogenital intercourse—all types

Study

Setting/study design/population/

date/gender

Description of

exposure

Direction of

transmission

Transmission

probability (%)

(x/n, 95% CI)

Duration of exposure (DE),

duration of partnership (DP)

or duration of follow-up (DF);

stage of HIV infection, other

risk factors, uncontrolled

cofactors

Per-partner

Giesecke et al. 1992

Sweden prospective 1989–1990

Index patients diagnosed in

Sweden and their partners identi-

fied through partner notification—

discordant couples identified

from a pool of heterosexual and

homosexual couples.

Fellatio NS 20.0 (2/10, 5.7–51.0) DF: <2 years

DE: <2 years

100% monogamy; HIV disease stage

not stated; other risk factors for

infection not stated.

de Vincenzi 1994

European Study Group prospective

1987–1991

Stable heterosexual discordant

couples percentage of partners

female not stated

Unprotected

fellatio with

protected vaginal

or AI

M-to-F and

F-to-M

0.0 (0/39, 0.0–9.0)

DF: median 24 months for the

entire cohort (n ¼ 256)

1994

Samuel et al. 1994

US prospective 1984 onwards

MSM from SFMHS

Series of mathematical Bernoulli

models assuming independent

risks for transmission for RAI,

IAI and ROI

ROI M-to-M 1.0 (range: 0.85–2.3,

n ¼ 410)

Dataset included 410 men with

multiple types of exposure (AI, OI),

with 46 seroconversions during

follow-up. Number of exposures to

HIV estimated from prevalence

data

. Range of estimates shown

here is produced from different

models and varying assumptions.

Raiteri et al. 1998

Italy prospective 1992–1997

Stable HIV discordant lesbian

couples (10 index cases and

28 partners)

All OI (and other

sexual practices

such as OAI for

some couples)

F-to-F 0.0 (0/28, 0.0–12.1) DF: median 10 months (range:

6–43; total 434 months, 849 OI

exposures)

DP: 56 months

100% monogamy, no IDU, no

heterosexual sex, no condom use

del Romero et al.

2002

Spain prospective 1990–2000

Heterosexual serodiscordant steady

couples

All OI M-to-F and

F-to-M

M-to-F

F-to-M

0.0 (0/135, 0.0–2.8)

0.0 (0/110, 0.0–3.4)

0.0 (0/25, 0.0–13.3)

DF: 210 person-years (19 316

contacts) 8% index cases with

AIDS; 16% with CD4 <200 cells/ml;

39% received ART during follow-up.

81% of partners female

Fellatio M-to-F and

F-to-M

0.0 (0/120, 0.0–3.1)

Partners had no other risk factor

for infection; no UAI or UVI.

M-to-F 0.0 (0/96, 0.0–3.8)

F-to-M 0.0 (0/24, 0–13.8)

(continued)

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Table 1 Continued

Study

Setting/study design/

population/date/gender

Description of

exposure

Direction of

transmission

Transmission

probability (%)

(x/n, 95% CI)

Duration of exposure (DE),

duration of partnership (DP)

or duration of follow-up (DF);

stage of HIV infection, other

risk factors, uncontrolled

cofactors

Fellatio without ejacu-

lation in oral cavity

M-to-F and

F-to-M

M-to-F

0.0 (0/83, 0.0–4.4)

0.0 (0/70, 0.0–5.2)

F-to-M 0.0 (0/13, 0–22.8)

Fellatio with

ejaculation in

oral cavity

M-to-F and

F-to-M

M-to-F

0.0 (0/37, 0.0–9.4)

0.0 (0/26, 0.0–12.9)

F-to-M 0.0 (0/11, 0–25.9)

Cunnilingus M-to-F and

F-to-M

0.0 (0/110, 0.0–3.4)

M-to-F 0.0 (0/98, 0.0–3.8)

F-to-M 0.0 (0/12, 0–24.3)

Per-partner sero-incidence

de Vincenzi 1994

European Study Group

prospective, 1987–1991

Stable heterosexual discor-

dant couples percentage of

partners female not stated

Unprotected

fellatio with protected

vaginal or anal sex

M-to-F and

F-to-M

0.0 Per 100 person-

years (95% CI 0.0–4.7,

n ¼ 39)

DF: median 24 months for the

entire cohort (n ¼ 256)

Raiteri et al. 1998

Italy prospective 1992–1997

Stable HIV discordant lesbian

couples (10 index cases and

28 partners)

All OI (and other sexual

practices such as OAI

for some couples)

F-to-F 0.0 Per 100 person-

years (95% CI 0.0–9.6,

n ¼ 28)

DF: median 10 months

(range: 6–43; total 434 months,

6742 exposures)

DP: 56 months

100% monogamy, no IDU, no

heterosexual sex, no condom use

del Romero et al.

2002

Spain prospective, 1990–2000 All OI M-to-F and

F-to-M

0.0 Per 100 person-

years (95% CI 0.0–1.8,

n ¼ 135)

DF: 210 person-years

(19 316 contacts)

Heterosexual serodiscordant

steady couples

M-to-F 0.0 Per 100 person-

years (95% CI 0.0–2.1,

n ¼ 110)

DF: 179 person-years

(17 621 contacts)

81% of partners female F-to-M 0.0 per 100 person-

years (95% CI 0.0–11.4,

n ¼ 25)

DF: 30 person-years (1695 contacts)

8% index cases with AIDS; 16%

with CD4 <200 cells/ml; 39%

received ART during follow-up.

Partners had no other risk factor for

infection; no UAI or UVI.

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Per seronegative study participant with partners of unknown serostatus

Detels et al. 1989

US prospective 1984–1987

(MACS Multicenter AIDS

cohort study)

MSM practising OI only,

seronegative at enrolment

No AI in previous 12

months (median 8

partners in previous 12

months)

M-to-M 0.37 (2/542, 0.10–1.34)

DF: range 6–24 months

No AI in previous 12 months

Page-Shafer et al.

2002

and Balls

et al. 2004

(abstract)

US cross-sectional (person-

years of exposure inferred

from participants’ reported

previous negative HIV tests

and patterns of risk behav-

iour) 1999-finish date not

stated

MSM HIV testers, tested for

recent HIV infection

All participants

(median 3 fellatio part-

ners in previous 6

months [IQR (1–10)]

Restricted to 19% of

men reporting an HIV

positive or unknown

serostatus partner

Restricted to men

reporting being exposed

to the ejaculate of an

HIV positive or

unknown serostatus

partner

M-to-M 0.00 0/439, 0–0.87)

0.00 (0/83, 0.00–4.42)

0.00 (0/23, 0.00–14.31)

DE: 1519 person-years (n ¼ 439)

No IDU, exclusively practised fell-

atio in past 6 months; 6% condom

use during fellatio (n ¼ 439)

Lavoie et al. 2008

and Alary (personal

communication

2008)

Canada cohort (Omega

Cohort Study) MSM practis-

ing OI only (at 51 of their

follow-up visits), seronegative

at enrolment

ROI with 51 infected

and/or casual partners

but no AI in previous

6 months

M-to-M 0.45 (3/660, 0.15–1.33) DF: 828.5 person-years

Per-act

Raiteri et al. 1998

Italy prospective 1992–1997

Stable HIV discordant lesbian

couples (10 index cases and

28 partners)

All OI (and other sexual

practices such as OAI

for some couples)

F-to-F 0.00 (0/849, 0.00–0.45,

n ¼ 28)

DF: median 10 months (range:

6–43; total 434 months)

DP: 56 months

100% monogamy, no IDU, no het-

erosexual sex, no condom use.

Other F-to-F exposures, notably

oroanal contact, were practised by

some couples.

Vittinghoff et al.

1999

US prospective 1992–1994

High risk MSM. Modified

Bernoulli regression model

using data from men with

complex patterns of exposure

[multiple types of exposure

(URAI, PIAI, etc.)].

Regression of participants

with multiple exposures with

multiple partners, often of

unknown serostatus. No

seroconversions among men

reporting only UROI.

UROI M-to-M with

ejaculation (defined as

per-act ‘risk’ rather

than per-act ‘infectivity’

i.e. risk per UROI

exposure from a partner

who is infected or of

unknown serostatus)

M-to-M 0.04 (0.01–0.17,

n ¼ 2189)

DF: 2633 person-years (from 2189

men with multiple sources of

exposure) CI shown here calculated

based on results from 100 simulated

datasets created to reflect the

uncertainty in the model para-

meters. No IDU.

(continued)

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Table 1 Continued

Study

Setting/study design/

population/date/gender

Description of

exposure

Direction of

transmission

Transmission

probability (%)

(x/n, 95% CI)

Duration of exposure (DE),

duration of partnership (DP)

or duration of follow-up (DF);

stage of HIV infection, other

risk factors, uncontrolled

cofactors

del Romero et al.

2002

Spain prospective, 1990–2000

Heterosexual serodiscordant

steady couples

All OI M-to-F and

F-to-M

M-to-F

F-to-M

0.00 (0/19 316,

0.00–0.02, n ¼ 135)

0.00 (0/17 621,

0.00–0.02, n ¼ 110)

0.00 (0/1695, 0.00–0.23,

n ¼ 25)

DF: 210 person-years

DF: 179 person-years

DF: 30 person-years

81% of partners female

Fellatio M-to-F and

F-to-M

M-to-F

F-to-M

0.00 (0/10 046, 0–0.04,

n ¼ 120)

0.00 (0/8965, 0–0.04,

n ¼ 96)

0.00 (0/1081, 0–0.35,

n ¼ 24)

8% index cases with AIDS; 16%

with CD4 <200 cells/ml; 39%

received ART during follow-up.

Partners had no other risk factor

for infection; no UAI or UVI.

Fellatio without ejacu-

lation in oral cavity

M-to-F and

F-to-M

0.00 (0/6545, 0–0.06,

n ¼ 83)

M-to-F 0.00 (0/5905, 0–0.07,

n ¼ 70)

F-to-M 0.00 (0/640, 0–0.60,

n ¼ 13)

Fellatio with ejaculation

in oral cavity

M-to-F and

F-to-M

0.00 (0/3501, 0–0.11,

n ¼ 37)

M-to-F 0.00 (0/3060, 0–0.13,

n ¼ 26)

F-to-M 0.00 (0/441, 0–0.86,

n ¼ 11)

Cunnilingus M-to-F and

F-to-M

0.00 (0/9270, 0–0.04,

n ¼ 110)

M-to-F 0.00 (0/8656, 0–0.04,

n ¼ 98)

F-to-M 0.00 (0/614, 0–0.62,

n ¼ 12)

F-to-F—female-to-female transmission; F-to-M—female-to-male transmission; IQR—interquartile range; IOI—insertive orogenital intercourse; M-to-F—male-to-female

transmission; M-to-M—male-to-male transmission; IAI—insertive anal intercourse; NS—not stated; OAI—oroanal intercourse; PIAI—protected insertive anal intercourse;

SFMHS—San Francisco Men’s Health Study; UAI—unprotected anal intercourse; UVI—unprotected vaginal intercourse.

Unless specified, exposure refers to all types of OI.

While Rothenberg et al.’s review

states that 50 couples practised unprotected OI but protected vaginal intercourse and AI in The European Study Group, we have been unable

to confirm this with study authors and so have used 39 as the sample size, as quoted in the paper.

Using a sensitive/less sensitive enzyme immunoassay strategy.

Authors suspected that one of the seroconversions may have occurred after RAI exposure directly preceding the period of follow-up: ‘if one assumes that the interval between

infection and appearance of antibody may extend beyond 6 months in some individuals, as has been reported.

23,24

Upper 95% CI given as 0.8% in Balls et al.

but recalculated as 0.009 using the Wilson ‘score’ method without continuity correction

as recommended by Newcombe.

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unknown serostatus and, therefore, very likely under-

estimates transmission probability per-act per infected

partner for UROI.

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).

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.

Discussion

Very few studies reporting HIV transmission prob-

abilities 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 transmis-

sion 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.,

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 under-

reporting 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’.

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.

Conversely, transmission probability estimates from

discordant couple studies such as de Vincenzi

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’.

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.

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 men-

tioning 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.

Given the small number of studies, a meta-analysis

was not considered appropriate as many zero esti-

mates 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 esti-

mates are important for prevention and counselling

of individual patients. The relative contribution of OI

to HIV transmission, despite its inherent low infec-

tiousness, may be substantial if the frequency of

unprotected OI is increasing relative to higher risk

sexual practices, which may be protected.

1,28,29

Never-

theless, the fact that infected study participants with

solely this exposure have remained difficult to iden-

tify may suggest that indeed the contribution of OI to

HIV incidence remains low. The contribution of OI

to HIV incidence needs close monitoring and oppor-

tunities 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 addi-

tional data from their study

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.

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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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