In the UK, the majority of the HIV-positive gay and
bisexual men who are likely to transmit HIV remain undiagnosed,
Valerie Delpech of the Health Protection Agency said on Monday. Moreover,
modelling work suggests that 48% of all new infections in gay and bisexual men
are acquired from men with undiagnosed primary HIV infection, and 34% from men
with undiagnosed long-term infection.
Speaking to the IAPAC meeting Controlling the HIV
epidemic with antiretrovirals, she warned that good access to antiretrovirals
in the UK has not led to a reduction in new infections. “This is due to
the undiagnosed fraction and particularly men in primary infection,” she said.
Dr Delpech suggested that the situation in the UK
provides useful insights into what is possible when other countries expand
their access to antiretroviral treatment, perhaps motivated by considerations
of ‘treatment as prevention’ (TasP).
In the context of the UK's free, open-access
healthcare system, over 95% of people newly diagnosed with HIV are connected
with specialist care within three months, and over 95% of people who attend during
one year are retained in care the following year. Moreover, 87% of people with a
CD4 cell count below 350 cells/mm3 are taking antiretroviral
treatment. Few other countries have comparable results.
The area in which the UK performs poorly is testing
The area in which the UK performs more poorly is testing
and diagnosis. One quarter of people who have HIV are undiagnosed and one half
of people with HIV are diagnosed late: in other words, when they already need
HIV treatment (CD4 cell count below 350 cells/mm3). These figures
have not changed much over the past decade.
It is thought that only 15 to 25% of gay and bisexual men
take an HIV test in any given year.
Modelling work by Paul Birrell of the Medical Research
Council (unpublished at present) suggests that the annual number of new HIV
infections in gay and bisexual men (incidence) changed very little between 2001
and 2010, with between 2000 and 3000 new infections each year.
Dr Delpech commented: “Despite substantial progress of
‘test and treat’ prevention policies over the past decade in the UK, there is
no evidence of a reduction in the incidence of HIV infection in men who have
sex with men.”
In order to begin to explain this, she showed analyses
prepared by her Health Protection Agency colleague Alison Brown, who wished to
estimate the number of men who are ‘infective’; in other words, who have a viral load
above 1500 copies/ml, and so would be more likely to transmit the virus.
Dr Brown found that, of approximately 40,000 HIV-positive
gay and bisexual men living in the UK in 2010, one third (35%) were infective.
But, importantly, 62% of those who were infective remained undiagnosed.
Of those remaining, just 5% had a CD4 cell count below
350 cells/mm3 but weren’t taking treatment. A further 12% had CD4
cell counts between 350 and 500 cells/mm3 and 16% had a CD4 cell
count above 500 cells/mm3. Finally, 5% were taking treatment but were not yet virally suppressed.
So, although the number of people taking treatment could
be increased, this wouldn’t make a substantial difference to the epidemic. Dr Brown
found that changing guidelines so that treatment was recommended for
all with a CD4 cell count below 500 cells/mm3 would only reduce the
proportion of infective men from 35 to 29%.
Dr Delpech then presented further unpublished modelling
work, this time prepared by Andrew Phillips of University College London. This
individual-based stochastic computer simulation model incorporates an extensive
range of behavioural and public health surveillance data collected over three
The model aims to estimate new infections, disease
progression and the effect of antiretroviral therapy in gay and bisexual men in
Professor Phillips found that the high incidence of the
early 1980s declined following widespread condom use. Incidence then rose by
26% after the introduction of antiretroviral treatment, due to a modest
reduction in condom use, to reach approximately 0.5 per 100 person-years.
However, the finding of the modelling exercise that most surprised
delegates was that, in 2010, an estimated 48% of new infections were acquired
from undiagnosed men who themselves were in the phase of primary infection
(i.e. they were infected in the last six months and so would have had an
exceptionally high viral load).
A further 34% of new infections were acquired from other
undiagnosed men, those with long-term infection.
“How are we going to make TasP work if people are
infecting one another very early on when they are unaware of their status?”
asked Dr Delpech.
“The relative contribution of infections from those who
are either diagnosed or on treatment is actually very small in comparison,” she said. Just 10% of new infections were thought to have
originated in men who were diagnosed but not on
treatment, while 7% came from men on treatment.
Professor Phillips’ model also examined a series of 'what
if' situations, to see what might have happened to the UK epidemic in a range
of alternative scenarios. Incidence would have steadily and further increased
had HIV treatment never been introduced. Much more dramatically, it would have
quadrupled if all gay and bisexual men had stopped using condoms from the year
Dr Delpech underlined the continued importance of condom
use in limiting the spread of the epidemic, even when antiretroviral treatment
is widely used.
Another 'what if' scenario was to ask what would have happened if, from the year 2000,
treatment had been recommended to all as soon as they were diagnosed. This only
brought incidence down by about 20%.
A much more positive response would have been a combination of much
higher testing rates (two-thirds of men testing annually) and treatment for
everyone diagnosed. This would have brought incidence down by 62%.
Reducing the number of men with undiagnosed primary HIV
infection will be extremely challenging.
Looking at all these data together, Valerie Delpech
concluded that the problem of undiagnosed infection – especially undiagnosed
primary infection – poses a substantial challenge to the concept of ‘test and
treat’. She stressed that recommending treatment at a higher CD4 cell count
would not in itself make a significant difference.
“We have excellent care but unless we do something about
that undiagnosed fraction, as well as not disinvesting in primary prevention, I
don’t think we’re going to completely eliminate HIV from the UK,” she said.
Reducing the number of men with undiagnosed primary HIV
infection will be extremely challenging without far more frequent HIV testing,
further improvements in testing technologies, widespread behaviour change, targeted partner-notification services and better
awareness by healthcare staff of seroconversion symptoms.
Commenting on the presentation, Kevin Fenton of the
Centers for Disease Control and Prevention said that there were very different
patterns in the United States and the United Kingdom. Testing rates are
somewhat higher in the US, whereas retention in care and access to
antiretroviral treatment are considerably poorer. He said he believed that in
the US, they would have a “much bigger bang for the buck” by focusing on
"prevention with positives" – in other words, improving linkage to and retention in care, access to HIV treatment, risk reduction interventions and treatment of
sexually transmitted infections in people with diagnosed HIV.