Sexual
Transmission of HIV May Remain a Risk despite Antiretroviral Therapy By
Liz Highleyman Early
this year, the Swiss
Federal Commission for HIV/AIDS sparked controversy when they issued a statement
indicating that HIV positive individuals
on antiretroviral therapy who
are fully adherent, maintain an undetectable viral load for at least 6 months,
and have no concurrent sexually transmitted infections (STIs) for all intents
and purposes cannot transmit HIV via sexual contact (or at least via heterosexual
vaginal intercourse). The
issue was a focus of continued debate at the XVII International
AIDS Conference this month in Mexico City, including a satellite session in
which the Swiss experts explained their deliberations at a closed hearing in Geneva
this past June, and international prevention experts discussed the implications
of the statement. Pietro
Vernazza, president of the commission and lead author of the original article,
emphasized that the statement was only intended to aid Swiss physicians in discussing
sexual risk with their patients, and was not intended as a more universal recommendation.
In addition, he acknowledged that the article's title -- indicating (in French)
that HIV positive people who have no other STIs and who are on effective antiretroviral
treatment do not transmit HIV through the sexual route -- was misleading. But
he added that under the specific circumstances described in the statement, unprotected
intercourse with a person with undetectable HIV was similar in safety to sex with
condoms -- not 100% safe, but within a "comfortable range" most people
could live with. Also
at the session, Julio Montaner of the British Columbia Centre for Excellence in
HIV/AIDS and incoming president of the International AIDS Society, reiterated
his view that expanded
antiretroviral therapy can be an effective prevention strategy, and advocates
for people with HIV/AIDS expressed their appreciation for the statement. Swiss
Meta-analysis In
a late-breakers session toward the end of the conference, researchers with the
University of Bern's Institute of Social and Preventive Medicine presented results
of a systematic review and meta-analysis of studies looking at risk of transmission
via sexual contact. The
investigators reviewed evidence in an attempt to verify the Swiss statement's
assumption that the risk per sex act of HIV transmission from an individual on
antiretroviral therapy with completely suppressed viremia and without another
STI is less than 1 per 100,000. To
that end, they searched for prospective cohort studies of HIV transmission within
serodiscordant couples, using a medical literature database search (Medline and
Embase), citations from resulting articles, and abstracts from all International
AIDS Society conferences and Conferences on Retroviruses and Opportunistic Infections
(CROI) from 1996 onwards. They also asked authors for missing information about
viral load, use of HAART, and the presence of other STIs. Results
•
After looking
at more than 200 published articles and 100 abstracts, the researchers found none
that precisely duplicated the conditions set forth in the Swiss statement.
•
Most studies
looked at serodiscordant heterosexual couples in Africa rather than industrialized
countries.
•
Only 1 study
included men who have sex with men.
•
In general
the studies did not include specific information about types of sex acts practiced.
•
Several studies
did not include precise information about type of antiviral therapy or treatment
outcomes.
•
In 1 study
that included treated patients with undetectable viral load (STI status unclear),
no cases of HIV transmission were reported.
•
In 4 studies
of untreated individuals with low viral load (< 400 copies/mL) (again, STI
status unclear), only 1 transmission occurred (at 362 copies/mL).
•
No transmissions
were identified from individuals with undetectable viral load below 40 copies/mL
(the threshold specified in the Swiss statement).
•
The suggested
risk of < 1 transmission per 100,000 sex acts by treated individuals with suppressed
viremia "could neither be confirmed nor excluded" from the limited data.
Although
the investigators are conducting further analysis of data, they suggested that
"At present, the negative impact of a public message that has been interpreted
as promoting unprotected sex might outweigh the potential benefit to the intended
recipients."
University
of North Carolina Meta-analysis
In
a related study presented at the conference and published in the August 4, 2008
advance online issue of The Lancet Infectious Diseases, researchers at
the University of North Carolina at Chapel Hill sought to estimate the effect
of cofactors on HIV infectivity via heterosexual sex, and to determine the accuracy
of the commonly cited rate of 1 transmission per 1000 sexual contacts.
They
conducted a systematic search through the end of April 2008 of PubMed, Web of
Science, and relevant bibliographies to identify articles estimating the heterosexual
infectivity of HIV, and used meta-regression and stratified random-effects meta-analysis
to assess differences in infectivity associated with cofactors and study methods.
Results
•
Infectivity
estimates were highly heterogeneous, ranging from 0 transmissions after more than
100 instances of penile-vaginal contact to 1 transmission per 3.1 episodes of
heterosexual anal intercourse.
•
Infectivity
differences, expressed as number of transmissions per 1000 contacts, were:
•
8.1 (95 % CI
0.4-15.8) -- that is, 8 times more likely -- when comparing uncircumcised to circumcised
susceptible men.
•
6.0 (95 % CI
3.3-8.8) -- or 6 times more likely -- when comparing susceptible individuals with
and without genital ulcer disease.
•
1.9 (95 % CI
0.9-2.8) -- about twice as likely -- when comparing index cases with late-stage
vs mid-stage HIV/AIDS.
•
2.5 (95 % CI
0.2-4.9) when comparing index cases with early-stage vs mid-stage disease.
"The
use of a single, 'one-size-fits-all' value for the heterosexual infectivity of
HIV-1 obscures important differences associated with transmission cofactors."
the investigators concluded.
"The commonly cited value of 0.001 [1
transmission per 1000 contacts] was estimated among stable couples with low prevalences
of high-risk cofactors, and represents a lower bound," they added. "Cofactor
effects are important to include in epidemic models, policy considerations, and
prevention messages."
8/19/08 References S
Attia, M Egger, N Low. Can unsafe sex be safe? Review of sexual transmissibility
of HIV-1 according to viral load, HAART, and sexually transmitted infections.
XVII International AIDS Conference (AIDS 2008). August 3-8, 2008. Mexico City.
(Abstract
THAC0505).
K
Powers, C Poole, A Pettifor, and others. Rethinking the heterosexual infectivity
of HIV-1: a systematic review and meta-analysis of observational studies. XVII
International AIDS Conference (AIDS 2008). August 3-8, 2008. Mexico City. Abstract
MOPE0317. K Powers,
C Poole, A Pettifor, and others. Rethinking the heterosexual infectivity of HIV-1:
a systematic review and meta-analysis. Lancet Infectious Diseases. August 4, 2008
[Epub ahead of print]. (Abstract).
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