Treatment Dramatically Reduces Sexual Transmission
Early antiretroviral therapy (ART) decreased the likelihood
of HIV transmission between heterosexual partners by 96%
in the large international HPTN 052 trial.
combination antiretroviral treatment usually reduces HIV RNA
to a low or undetectable level, and people with a low viral
load are much less likely to transmit the virus. This has
been conclusively demonstrated for mother-to-child HIV transmission,
and new findings confirm that it applies to sexual transmission
HIV Prevention Trials Network (HPTN) Study 052 is a large
Phase 3 clinical study, sponsored by the National Institute
of Allergy and Infectious Diseases (NIAID), looking at the
effects of early ART on HIV transmission risk.
Myron Cohen from the University of North Carolina at Chapel
Hill and colleagues enrolled 1763 serodiscordant couples --
almost all of them heterosexual -- in 9 countries (Botswana,
Brazil, India, Kenya, Malawi, South Africa, Thailand, U.S.,
and Zimbabwe) starting in 2005. Couples were about evenly
divided between those with an HIV positive woman and those
with an HIV positive man; past research has shown that HIV
is more easily transmitted sexually from male to female than
At the time of enrollment the HIV positive partners had CD4
T-cells counts between 350 and 550 cells/mm3 -- above the
recommended threshold for treatment initiation at the start
of the trial. (U.S. treatment guidelines now
recommend starting when the CD4 count falls to 500 cells/mm3.)
HIV positive participants were randomly assigned to either
start a 3-drug antiretroviral regimen immediately or defer
treatment until their CD4 count fell below 250 cells/mm3 or
they developed an AIDS-related illness. Participants used
various combinations made up of 11 different drugs. In addition,
people in both groups received safer sex counseling, free
condoms, regular HIV testing, and screening and treatment
for other sexually transmitted infections.
positive men and women who started ART early were significantly
less likely to transmit the virus to their sexual partner.
interim analysis found 39 cases of HIV infection among
previously negative participants, 28 of which were genetically
linked to their regular HIV positive partner.
these 28 linked infections, only 1 occurred among couples
in the immediate ART arm, compared with 27 in the deferred
on these numbers, immediate ART reduced the risk of HIV
transmission by 96.3%.
17 cases of extrapulmonary tuberculosis occurred among
HIV positive partners in the deferred treatment arm compared
with just 3 cases in the immediate ART arm, a statistically
number of deaths was similar, however, with 10 in the
immediate ART arm and 13 in the deferred treatment group.
052 was originally designed to end in 2015, but an independent
Data and Safety Monitoring Board recommended that the study
should be halted and results released ahead of schedule after
an interim review showed that immediate ART substantially
reduced HIV transmission risk. HIV positive partners in the
deferred treatment arm will now be offered ART and participants
will be followed for at least a year.
"The results are the first from a major randomized clinical
trial to indicate that treating an HIV-infected individual
can reduce the risk of sexual transmission of HIV to an uninfected
partner," according to a NIAID press release.
Previous observational studies and mathematical models have
indicated that early ART could reduce transmission, but these
new findings from a "gold standard" randomized trial
provide stronger evidence.
"This new finding convincingly demonstrates that treating
the infected individual -- and doing so sooner rather than
later -- can have a major impact on reducing HIV transmission,
said NIAID Director Anthony Fauci. He added in a media briefing
that HPTN 052 "nails the concept down."
In 2008 the Swiss Federal Commission for HIV/AIDS sparked
controversy when it issued a statement saying, "An HIV-infected
person on antiretroviral therapy with completely suppressed
viremia...is not sexually infectious." The commission
emphasized that the statement only applied to vaginal intercourse
between heterosexual partners in which neither had other sexually
transmitted infections and the HIV positive person had a stable
undetectable viral load on ART for at least 6 months.
A number of researchers have reported rare cases of HIV transmission
from individuals on ART with undetectable viral load, however,
and many clinicians and advocates have argued that it is irresponsible
to suggest that people on treatment can safely engage in unprotected
Since HPTN 052 almost exclusively enrolled heterosexual couples,
its results cannot be applied to men who have sex with men.
There is good reason to expect that lowering viral load will
reduce transmission in this population as well, but similar
controlled studies are needed to show the magnitude of risk
The latest findings will further inform the ongoing debate
about treatment as prevention. These data lend support to
"test and treat" proponents who believe everyone
who tests HIV positive should begin treatment right away,
both for their own health and for the public health benefit
of reducing transmission. In early 2010 the San Francisco
Department of Public Health and San Francisco General Hospital
were the first to adopt
a policy of offering immediate ART to everyone diagnosed
Others, however, feel that the long-term effects of antiretroviral
agents are not yet fully understood, and argue that concerns
about drug resistance, lifelong adherence, and cost weigh
in favor of a more cautious approach.
"With these results we should redouble our efforts to
diagnose individuals with HIV earlier," said HIV Medicine
Association Chair Kathleen Squires in a press release issued
by HIVMA and the Center for Global Health Policy. "We
now have further evidence that effective treatment not only
benefits the individual but also will help reduce the spread
of this disease."
"This rigorously conducted clinical trial demonstrates
that ART dramatically reduces HIV transmission from an infected
partner to an uninfected spouse or partner," concurred
HPTN investigator Sten Vermund from Vanderbilt University
in a Family Health International press release. "Earlier
therapy is a superior option that benefits both an infected
individual and his or her uninfected partner and we support
global efforts to offer ART to everyone who needs it."
A NIAID press release describing HPTN 052 is available online
Questions and Answers about the study are available at www.niaid.nih.gov/news/QA/Pages/HPTN052qa.aspx.
NIAID. Treating HIV-infected People with Antiretrovirals Protects
Partners from Infection. Press release. May 12, 2011.
Family Health International. Initiation of Antiretroviral
Treatment Protects Uninfected Sexual Partners from HIV Infection
(HPTN Study 052). Press release. May 12, 2011.
HIV Medicine Association and Center for Global Health Policy.
Study Shows Early HIV Treatment Prevents New Infections and
Preserves Health. Press release. May 12, 2011.