Advances in HIV treatment since 1996, when potent
antiretroviral drug combinations became available, are well known. HIV
infection can now be considered a chronic disease for those with access to
care. However, success in HIV prevention has seemed a harder battle.
Clinical trials to prevent HIV spread through education
and behavioral efforts have seldom had dramatic results, and political barriers
have blunted the effect of proven methods such as condom use and clean needle
access for drug injectors. This bleak picture is, fortunately, changing
radically in a series of developments that rival the excitement of
antiretroviral therapy itself.
Paul A. Volberding, MD
Treatment is prevention
The first ray of hope and still a key tool was the
recognition that male circumcision is effective in reducing the transmission
and acquisition of HIV and other sexually transmitted infections. During the
past 2 years, even more excitement centers on the interface between treatment
and prevention. In fact, many prevention strategies now utilize the same
antiretroviral drugs in new ways to limit transmission or acquisition of HIV
with striking effects, especially for those most medication-adherent.
Many people, particularly women, cannot safely negotiate
sexual relationships to prevent HIV exposure but could protect themselves with
a self-administered device or microbicide. Cervical diaphragms have not been
found effective, and female condoms are obvious to a male partner not willing
himself to use barrier protection. Vaginal microbicides, typically gels
inserted before or after intercourse, are attractive targets of prevention
research. Vaginal gels of several products repeatedly failed to show any real
benefit, until the truly dramatic presentation of the CAPRISA 004 trial at the
AIDS meeting in Vienna in 2010.
This study used for the first time an antiretroviral
drug, tenofovir, as a 1% vaginal gel applied 12 hours before and 12 hours after
sexual intercourse. HIV transmission was reduced by approximately 40% or more
in women who reported the highest rates of appropriate use. For the first time,
a woman had at least one self-administered tool to prevent HIV infection, and
the scientific presentation was greeted by a prolonged standing ovation —
almost unheard of at an otherwise staid research conference. This promises to
be a very inexpensive product and is also being considered for rectal
PREP and iPrEx trials
Pre-exposure prophylaxis, or PREP, is another prevention
approach designed to reduce infection risk for those who can’t or
won’t demand condom protection or potentially for injection drug users
without clean needle access. Here, oral antiretroviral drugs are prescribed for
the uninfected person and used either continuously or at the time of exposure.
This long-debated concept was shown to be effective in another landmark study,
iPrEx, published in late 2010.
Here, very high-risk but HIV uninfected men who have sex
with men were prescribed a fixed-dose combination of tenofovir and
emtricitabine and assigned the combination daily during the entire trial.
Again, the results were striking and successful.
Overall, PREP was more than 40% effective, with even higher success (68%) in
those who reported more than 90% medication adherence. In fact, plasma and
cellular drug levels suggest almost complete protection in adherent
This trial, named one of the scientific breakthroughs of
2010 by Time magazine, was followed by three similar research efforts in
heterosexuals. The first, still unpublished, was not successful. However,
recently, two additional PREP trials have also shown PREP effects similar to
Together, the vaginal microbicide and PREP applications
of antiretroviral drugs to prevent HIV-infection have changed the face of
prevention, allowing an individual at least some control over the risk of
We have long known that starting antiretroviral drugs
during pregnancy can effectively block transmission of HIV from infected women
to newborns and that sexual transmission is minimal in those with naturally low
plasma viral titers. Although many have expected that ART would similarly
reduce sexual spread, this was recently proved in a prospective clinical trial,
known as HPTN 052.
In this African trial, serodiscordant heterosexual
couples agreed that the infected partner would either begin ART earlier than
local guidelines suggested or wait until that point in the disease stage.
The results, first announced at the IAS conference in
Rome this summer, indicated a striking reduction in HIV transmission (96%) and
also a lower rate for tuberculosis, the most common infection associated with
HIV in that part of the world.
These results are accelerating efforts to identify and
treat all HIV-infected people and to start treatment regardless of the CD4 cell
count, with the goal that community-wide antiretroviral coverage will decrease
HIV incidence in the general population. Already, several cities, including
Vancouver and San Francisco, have promoted this as a public health policy, and
testing of this as a strategy is being conducted in several cities, including
Washington D.C. — the city with the highest rates of new HIV-infection in
Where does all of this lead us as we seek to bring the
HIV pandemic under control? We clearly have potent new prevention methods, but
individually, each has limitations.
Microbicides and PREP only work in those able to achieve
and sustain excellent adherence. Treating HIV to reduce the viral load and,
thus, transmission, requires finding and treating all or most of the 200,000 or
so cases of HIV-infected people not already in care — a daunting task
— and maintaining full viremia suppression in all of those in care —
also not an easy goal, given adherence problems and other barriers. The cost of
universal treatment in resource-limited settings is obviously a real challenge
in times of global economic distress.
Finally, troubling evidence suggests that although HIV
transmission may be coming under control, especially in the gay community, the
incidence of other STIs, particularly syphilis, are again accelerating.
We are excited by the new potential control of HIV, but
must not expect that antiretroviral drugs will alone be sufficient or that we
can ignore the crucial alliance between the infectious diseases and public
health communities that will be needed to arrive at our ultimate goal of an
Paul A. Volberding, MD, is chief of medical service
at San Francisco Veterans Affairs Medical Center; professor and vice-chair of
the department of medicine and co-director of the Center for AIDS Research at
the University of California San Francisco and is the Chief Medical Editor of
Infectious Disease News. Disclosure: Dr. Volberding is an adviser to BMS
and on data and safety monitoring boards for Gilead, TaiMed and the NIH.