Within a couple of years’ time, we may know
if two crucial new HIV prevention approaches will work. If they do, what then?
A microbicide is a substance that can be
incorporated into a lubricant, gel or barrier such as a diaphragm that will
stop HIV transmission during sex. And PrEP is the concept of HIV-negative
people taking anti-HIV drugs in advance of sex (or needle-sharing) to prevent
Crucial trials of these new prevention methods
will start announcing their results soon. In 2010, we’ll have results from the
biggest microbicide trial to date, the Microbicides Development Partnership
trial of PRO2000 gel.
By 2011 we’ll know about tenofovir PrEP in
Thai drug users, tenofovir/FTC PrEP in South American gay men, and tenofovir
gel as a microbicide in South
Africa. 2012 will offer PrEP results from
men and women in Africa, and from a comparison
trial of tenofovir as a microbicide and PrEP.
New prevention methods in HIV have had
setbacks in the last few years, but following a promising result for the
microbicide PRO2000 announced earlier
this year, prevention advocates are daring to believe that positive results
could be on their way.
Carl Dieffenbach, director of the AIDS
Division of the US National Institute of Allergies and Infectious Diseases
(NIAID) laid out an apparently straightforward development strategy. “The first
thing we have to do is to prove that these concepts work. Then, with the
current agents, we have to develop alternative dosing schedules to maximise
adherence. We need to engage our
partners in social marketing programmes that are also pieces of operational
research. How are we going to market these products?”
“We also need to keep working on new
agents,” he said, echoed by Yasmin Halima,
the new director of the Global Campaign for Microbicides: I am really worried
about the lack of a drug pipeline for PrEP. If tenofovir doesn’t work, we’re
Others responded that the original question
of ‘proof of concept’ was not a simple one. What level of efficacy would be
regarded as a success? The PRO2000 trial was powered to demonstrate a
protective effect of only 30%: Most panel members said that if the second trial
demonstrated this, it would not be enough efficacy to take the product forward.
be enough? Most audience members said they would be happy with efficacy of 40
to 60% (roughly comparable to male circumcision), but some would want the product
to stop at least four out of five infections (80% efficacy, comparable with
real-world condom use).
Sharon Hillier, Director of the
Microbicides Trials Network, defined this as the problem of the ‘partial yes’.
She foresaw that people would need to use a variety of different prevention
methods, rather than putting all their faith in one.
“We need to identify approaches that are
going to be used by a wide variety of people,” she said, “which they are going
to want to use and have available. We need funders willing to buy them and
regulators willing to register them. We need to make sure our successes are not
Stephen Becker of the Bill and Melinda
Gates Foundation, a prime private-sector sponsor of new prevention technologies
said: “We can’t wait until clinical proof of concept has occurred,” he said. We
need to investigate delivery channels, how we engage with policy makers, and
how we will market these approaches now.”
Catherine Hankins contrasted PrEP with
microbicides. Although complementary, they may have to be prescribed and
marketed in very different ways.
Prophylaxis pills would always have to be
prescribed and countries would need to consider strategies for PrEP
“We will need to strengthen the knowledge
of countries as to where their next thousand HIV cases are going to come from. Which
groups do I give it to and in what way?
HIV drug side-effects might make PrEP
unpopular: “If you are going to introduce it in a country with widespread
experience of lipodystrophy due to d4T, you will find widespread resistance to
In contrast, some delegates said that if
PrEP trials came up with a positive result a black-market culture might follow.
Morenike Ukpong of Nigeria’s
New HIV Vaccine and Microbicide Advocacy Society said: “I tell you, if a result
is announced at a conference, PrEP will be on the market in 24 hours.”
Professor Helen Rees, Executive Director of
Reproductive Health and HIV Research Unit (RHRU), agreed: “If PrEP works, we can’t
waste a lot of time debating registration, because people will vote with their
feet and start to use it. There are several studies in Africa
to show that people are secretly taking it already.”
She emphasised the need to find out if PrEP
was safe for groups excluded from the trials such as pregnant women and
adolescents, and, like many delegates, stressed the urgent need to do trials of
With microbicides, unlike PrEP, the
potential still exists that they could eventually be sold over the counter.
Acceptability studies showed that people
liked microbicides. Sharon Hillier commented: “If they’re going to make sex
fun, people who don’t consider themselves at risk and who wouldn’t take a
medicine might use a microbicide.”
In one trial in Uganda, she said, the microbicide
had an unexpected double effect: firstly, women said it made sex fun and then, because of that, their male partners
were more faithful. But Dr Francois Venter, Director of the RHRU, described
himself as a microbicide sceptic. It was going to be an extremely hard job
persuading funders to pay for approaches with only partial efficacy, he said. “It’s not just about whether these
interventions will work and can be promoted ethically,” he said. “Can health
systems afford them?
Dr Yogan Pillay, Director of Strategic
Health at South Africa’s
Health Ministry, agreed, commenting that it was challenging enough “pay[ing]
for the cost of HIV treatment today and paying for TB and opportunistic
Pillay and others drew parallels between
the new technologies and circumcision. Three conclusive randomised, controlled
trials showing that circumcision prevented about 60% of infections in men had
not translated into national programmes.
Patrick Ndase, regional physician for the
Ugandan PrEP trial, said “We need to do convincing modelling studies of
efficacy and cost-effectiveness so that these options become really attractive
to people who are already trying to fund HIV or TB treatment. And we need to
decide what language we use with the ministries and the funders that is going
to make them decide to support an approach with 50% efficacy.“
Zeda Rosenberg, Director of the
International Partnership for Microbicides, summed up the feeling of the
meeting. “We’re used to scepticism,” she said. “The sceptics used to say ‘it
won’t work and women won’t use it’. Now they say ‘You won’t be able to fund and
deliver it to the people who need it’. That’s progress!”