Review
www.thelancet.com Vol 378 July 16, 2011
269
Lancet 2011; 378: 269–78
Division of Epidemiology
(Prof N S Padian PhD) and
Institute
of Business and
Economic Research
(Prof N S Padian, S I McCoy PhD),
University of California,
Berkeley, CA, USA; Offi ce of the
US Global AIDS Coordinator, US
Department of State,
Washington, DC, USA
(Prof N S Padian, N Hasen PhD);
Bill & Melinda Gates
Foundation, Seattle, WA, USA
(S M Bertozzi MD); The
University of Washington,
Seattle, WA, USA (S M Bertozzi);
Instituto Nacional de Salud
Publica (INSP), Cuernavaca,
Mexico (S M Bertozzi); Centre
for the AIDS Programme of
Research in South Africa,
University of KwaZulu-Natal,
Durban, South Africa
(S S Abdool Karim MBChB);
Department of Epidemiology,
Mailman School of Public
Health, Columbia University,
NY, USA (S S Abdool Karim);
UN Development Programme,
HIV/AIDS Group, BDP, New
York, NY, USA (J Kim MD);
UNAIDS, Geneva, Switzerland
(M Bartos MEd,
B Schwartländer MD); College
of Health Sciences, Makerere
University, Kampala, Uganda
(E Katabira MD); and Institute
HIV prevention transformed: the new prevention
research agenda
Nancy S Padian, Sandra I McCoy, Salim S Abdool Karim, Nina Hasen, Julia Kim, Michael Bartos, Elly Katabira, Stefano M Bertozzi,
Bernhard Schwartländer, Myron S Cohen
We have entered a new era in HIV prevention whereby priorities have expanded from biomedical discovery to include
implementation, eff ectiveness, and the eff ect of combination prevention at the population level. However, gaps in
knowledge and implementation challenges remain. In this Review we analyse trends in the rapidly changing landscape
of HIV prevention, and chart a new path for HIV prevention research that focuses on the implementation of eff ective
and effi cient combination prevention strategies to turn the tide on the HIV pandemic.
Introduction
Until recently, HIV prevention lacked credibility with
data from prevention trials showing little or no decrease
in incident HIV.
5
Furthermore, when successes were
made public,
6–8
explanations were often confl icting and
lessons for application to other settings unclear. However,
the past year marked the end of this steady stream of
disappointing results, and a concomitant change is
evident in public perception and the opinions of policy
makers. The discourse on HIV prevention now includes
the possibility that the epidemic can be stopped.
9
Increasingly scarce fi nancial resources also drive this
renewed focus on prevention. The global economic crisis
has substantially aff ected funding for HIV, with resources
for prevention levelling off in the past decade and future
funding commitments unclear.
10
These reductions put
many programmes at risk and warrant a sharpened focus
on prevention. Fiscal constraints have created pressure
on prevention program mes to be more accountable by
providing clearer evidence of impact and delivering better
value for money.
We review developments in HIV prevention from the
past 3 years (since The Lancet Series on HIV prevention
in 2008
2–4
), with particular emphasis on gaps in knowledge
and a focus on what are now the most salient prevention
issues: discovery in the continued search for vaccines
and a cure; new challenges related to antiretroviral-based
prevention; implementation challenges that preclude
scale-up of prevention strategies known to be eff ective —
specifi cally, HIV testing, voluntary medical male
circumcision (VMMC), and prevention of mother-to-
child transmission (PMTCT); and progress on and
challenges for structural and behavioural interventions.
Vaccines and the search for a cure
Strategies for vaccine development include innate, cell-
mediated, or antibody-mediated resistance to infection, or
all three.
11
Successful modifi cation of HIV in Rhesus
macaque monkeys led to increased focus on cell-mediated
immunity;
12
however, the STEP trial
13
(using immunogens
that worked in macaques) showed neither protection from
HIV nor alteration in viral replication in vaccine recipients,
but did stimulate an immune response that exerted
pressure on the virus acquired.
14
In a trial in Thailand
15
a
canarypox vector vaccine (ALVAC-HIV) boosted with a
recombinant glycoprotein vaccine (AIDSVAX B/E) led to a
31% reduction of HIV incidence in vaccine recipients. The
immune responses that enabled protection are a focus of
intensive post-trial studies, including consideration of
non-neutralising antibodies that function via antibody-
dependent cellular cytotoxic eff ects (ADCC).
16,17
Renewed interest
18
in curing HIV was partly stimulated
by a report of a bone-marrow transplant of CCR5-deleted
stem cells to an HIV-positive patient, who seemed to
eliminate detectable HIV after engraftment of this tissue.
19
This result confi rmed the importance of the CCR5
receptor for HIV replication, and galvanised experiments
focused on gene therapy to modify this receptor, to date
conducted ex vivo and in a mouse model.
20
Investigators
committed to curing AIDS have further divided this work
into immunomodifi cation
21
and the use of antiretroviral
drugs to eliminate all HIV-infected cells.
22
For both
approaches, the latent reservoir of HIV-infected T cells is
the greatest challenge. At the start of HIV infection, the
virus is integrated into host DNA, and cells become
quiescent and allow HIV replication at a very low rate,
even with antiretroviral therapy (ART).
23
However, when
ART is discontinued, viral load returns to a level recorded
before therapy. A novel class of cancer drugs designed to
Search strategy and selection criteria
We covered several topics in HIV prevention (biomedical, behavioural, structural) that
together comprise combination prevention.
1
We focused on randomised trials, rigorous
observational studies, and systematic and meta-reviews completed since The Lancet Series
on HIV prevention in 2008.
2–4
The most recent reviews
5
were used as a starting point. We
searched PubMed and Medline for papers published in peer-reviewed journals since 2008,
and electronic conference proceedings of recent HIV/AIDS-related conferences up to the
end of April, 2011. We also reviewed relevant publications and websites from international
organisations, including UNAIDS and WHO, and non-governmental organisations and
advocacy groups involved in HIV prevention research. Search terms included “HIV”,
“prevention”, “antiretroviral therapy (ART)”, “vaccines”, “behavior”, “HIV testing”, “male
circumcision”, “microbicides”, “mother-to-child transmission (MTCT)”, “implementation
science”, and “operations research”. Because the eff ectiveness of a single intervention was
not the objective of the review, systematic review methods were not used. The goal was
instead to broadly review existing prevention interventions and identify salient issues,
research needs, and gaps in knowledge.