Background:
The Centers for Disease Control and Prevention (CDC) sponsored a meeting in
Atlanta on October 23-24, 2008, entitled, “CDC Expert Consultation on the Effect
of Antiretroviral Therapy (ART) on Risk of Sexual Transmission of HIV Infection
and Superinfection.”
Approximately 50 HIV experts attended including laboratory scientists,
clinicians, social and behavioral scientists, and public health personnel from
CDC and other federal agencies, state and local health departments,
universities, advocacy groups, and international organizations.
Participants reviewed available data and discussed implications for treatment
and prevention programs and for future research.
Initial presentations reviewed the biology of sexual HIV transmission, with
an emphasis on the correlations between viral load and antiretroviral drug
concentrations in the blood, genital and rectal compartments. There were
presentations of mathematical models to estimate the population-level impact of
ART on infectivity, and data were reviewed on transmission between HIV-infected
partners (superinfection). Research on individuals’ perceptions of HIV
transmission risk in the setting of effective ART and the influence of these
perceptions on risk behavior and related ethical and public health communication
challenges were discussed. In breakout sessions, participants discussed what is
known about ART and prevention, programmatic implications, and additional
research that is needed on biomedical, ethical, behavioral and communications
issues and mathematical modeling.
Outcome:
The presentations and discussions indicated that there is evidence that the
infectiousness of HIV-infected persons is related to their blood viral load,
which is correlated with genital viral shedding. ART can be expected to reduce
HIV concentrations in the blood and seminal plasma, female genital tract
secretions, and rectal secretions. While some studies have shown
successful long-term suppression of genital HIV shedding with ART, in other
studies episodes of genital HIV shedding have been observed despite ongoing ART.
There is also significant variation in the penetration of antiretroviral drugs
from the blood into the genital tract. Observational studies to date have
shown that ART is associated with a decreased risk of transmission to sex
partners. A clinical trial to directly address this question is ongoing.1
Experts emphasized methodological challenges, especially in quantifying
vaginal and rectal viral shedding, the lack of data on rectal transmission and
the effect of ART on transmission among men who have sex with men, and the
unknown durability of the effect of ART on transmission. There were also
concerns related to the effects on anogenital viral shedding of blood viral load
“blips,” intermittent and potentially asymptomatic sexually transmitted
infections, and drug-resistant viral strains.
At the population level, some studies have found that ART has reduced HIV
transmission, while others have not shown such a reduction. Some modeling
studies suggested that widespread ARV treatment would substantially reduce HIV
transmission, although behavioral risk compensation could possibly undermine
that effect. Other modeling research that was presented indicated that as the
proportion of HIV-infected individuals on ART with complete viral suppression
increases, as might be achieved with more potent and tolerable regimens, the
relative contribution to transmission increases for those who are aware of their
infection but are not yet on ART.
Discussions on the public health impact of ART as prevention considered the
related issues of beginning ART earlier in the course of infection at higher CD4
counts for clinical reasons. While current U.S. guidelines recommend
starting ART at a CD4 count of <350/mm3, the guidelines state that other
potential benefits to starting treatment earlier may be taken into consideration
including the “decreased risk of HIV transmission to others, which will have
positive public health implications.” Participants raised concerns about ART
adherence, behavioral risk compensation, clinical capacity and financing for ART
for individuals with higher CD4 counts.
Ethical discussions emphasized that safeguards should be in place to enhance
the positive contributions of ART to HIV prevention while reducing unintended
negative consequences. Participants stressed that clear, accurate
information about what is known to date must be made available to the public.
The complexities of communicating about risk were acknowledged; it was also
noted that communications should emphasize the importance of adhering to
treatment and to other prevention modalities, including condom use.
Conclusion:
The consultation highlighted the contribution of ART to prevention of HIV
transmission, and the potential to increase the prevention benefit by expanding
HIV testing, ensuring linkage to and availability of treatment services, and,
possibly, making treatment available to infected individuals with CD4 counts
>350/mm3. However, additional laboratory, clinical, epidemiologic,
mathematical modeling, and behavioral research, along with health care financing
and policy discussions, are needed to inform specific guidance on these issues.
CDC is planning to issue a fact sheet on what is currently known about ART
and sexual transmission on the CDC website in the first quarter of 2009.
CDC will also submit a scientific statement for publication in a peer-reviewed
scientific journal. CDC reiterated its recommendation that people living
with HIV who are sexually active use condoms consistently and correctly with all
sex partners.2
1 HIV Prevention Trials Network.
HPTN 052 - A Randomized Trial to Evaluate the Effectiveness of Antiretroviral
Therapy Plus HIV Primary Care versus HIV Primary Care Alone to Prevent the
Sexual Transmission of HIV-1 in Serodiscordant Couples.
2 Centers for Disease Control and Prevention.
CDC Underscores Current Recommendation for Preventing HIV Transmission.
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