News from the 2017 IAS HIV Cure and Cancer Forum
Monsef Benkirane at IAS 2017. Photo by Marcus Rose/IAS
The 2017 IAS HIV Cure and Cancer Forum, preceding the 9th International AIDS Society Conference on HIV Science (IAS 2017), brought together
researchers in the fields of HIV cure research and oncology to discuss the
emerging overlaps between the cutting edges of HIV and cancer research.
heard about the experimental use of new cancer drugs, called immune checkpoint
inhibitors, which might improve the ability of the immune system to clear
HIV-infected cells by blocking the cellular receptors which switch off some
Studies so far have been confined to people with HIV who
also have cancers, and show modest effects. Professor Sharon Lewin said that
more studies will be needed, in people with HIV who do not have cancer, to
establish whether these drugs can play a role in reducing the HIV reservoir.
One thing that would help efforts to cure HIV and to use new
types of drugs to eradicate HIV-infected cells would be if reservoir cells
could be identified more easily. The Forum heard that researchers at the
University of Oxford have found that in people with HIV, reservoir cells had
from 100 to 1000 times as much of the cellular receptor molecule CD32a on their
surface. Detection of CD32a has the potential to be an important tool in cure
Controlling HIV off treatment was also a focus of the Forum.
One of the most widely reported stories of the
conference was the discovery of a South African child who had
started treatment early but who had now been off antiretroviral therapy for 8.5 years without a
viral load rebound. Research is still ongoing to understand why viral rebound
has not occurred in this case, but other new findings from human and
animal studies presented at the Forum suggest that a very low level of the
anti-HIV antibodies of the type called IgG or very high levels of natural
killer cells may characterise the best 'controller' responses. These findings
may offer clues for the development of therapeutic vaccines that can help to
control HIV off treatment.
Curing HIV infection completely, by eradicating the virus
from the body, appears to have happened only in one case, after a bone marrow
transplant replaced Timothy Ray Brown’s stem cells. Researchers think that the
critical element in his case that led to eradication was the development of
graft versus host disease – a condition in which the grafted bone marrow cells
‘reject’ the body’s own cells as foreign. Spanish
researchers reported on a small international cohort of people living with HIV
who have undergone bone marrow transplants and who have no trace of HIV – like Timothy Ray
Brown. At the moment, all are taking antiretroviral therapy; experimental
treatment interruptions are planned next year to see whether viral rebound
Experimental treatment interruptions will be a critical
component of future cure studies, but the Forum heard from Michael Louella of
the University of Washington AIDS Clinical Trials Unit that the single biggest
barrier to recruitment to future cure studies may be a fear of becoming
infectious again after stopping antiretroviral treatment.
“People are loath to lose their hard-won viral
undetectability,” Louella commented.
US HIV funding decisions on PEPFAR in 2017 will have critical effect on ability to reach 90-90-90 goals
A withdrawal of United States funding for HIV
treatment and prevention in sub-Saharan Africa could lead to 7.9
million additional HIV infections and almost 300,000 AIDS deaths
between now and 2030,
according to modelling of the impact of US funding carried out by Imperial
College, London, and presented last week at IAS 2017 in Paris.
As the largest
global donor to the Global Fund to Fight AIDS, Tuberculosis and Malaria, and as
the largest bilateral funder through its President’s Emergency Plan for AIDS
Relief (PEPFAR), the funding provided by the United States government underpins
the global AIDS response.
To date, the
United States has given $70 billion through bilateral and multilateral
programmes to fight HIV. But, in budget proposals put forward earlier this
year, the new Trump administration proposed to cut the US foreign aid budget by
one-third, and PEPFAR funding from over $6 billion to $5 billion in the 2018
the potential impact of budget changes, and to show how US funding has affected
the trajectory of the HIV epidemic in 18 countries in sub-Saharan Africa
accounting for 80% of the HIV burden, researchers from Imperial College,
London, developed a model of the relationship between programme funding of
treatment and prevention, and new HIV infections and deaths.
2000, the model showed that the absence of US funding – and the absence of the
Global Fund, which the researchers assumed would not have come into being
without US support – would have led to approximately 4 million more HIV
infections by 2016 and 5 million additional AIDS deaths.
worst-case scenario, where US funding is withdrawn from the Global Fund and
PEPFAR programmes, up to 7.9 million additional HIV infections and around
300,000 AIDS deaths could occur by 2030.
The modelling also
showed that maintaining funding only at existing levels will lead to a
flatlining of the proportion of people living with HIV who are on treatment and
virally suppressed. On the other hand, if expansion of US funding is
accompanied by increases in domestic funding and more efficient allocation of
funding within each country, there could be rapid progress towards the 90-90-90
target by 2022.
Major PrEP demonstration study launched in France
The team at ANRS Prévenir. http://prevenir.anrs.fr
France is launching a new study which
will enrol 3000 new pre-exposure prophylaxis (PrEP) users over the next three
years, Jean-Michel Molina told IAS 2017 last week. Whereas previous studies, including
Molina’s own IPERGAY study, proved the benefit of PrEP to the individual taking
it, the new study has set an ambitious target in relation to the public health
benefit of PrEP. The aim is to show that having an extra 3000 people take PrEP
will result in a marked fall in HIV diagnoses among men who have sex with men
in the Paris region.
demonstration study will also gather data on the best ways to deliver PrEP and
on how to engage migrants and other social groups who currently have relatively
low awareness of PrEP.
France was the
first European country to approve PrEP, in January 2016. It is available
through hospitals, HIV testing centres and general practitioners and its cost
is fully reimbursed by the country’s health system.
The new study, called ‘Prévenir’ (prevent) focuses on
Île-de-France, which is the region of Paris and its suburbs. HIV is
concentrated in the capital region – of around 6000 new HIV diagnoses made in
France in 2015, 2500 occurred in Île-de-France. Gay men are particularly
are hoping to demonstrate that the scale-up of PrEP, with 3000 additional
people taking PrEP, will reduce the rate of new infections in men who have sex
with men in Île-de-France by 15%.
work out which dosing schedule works best for them and how they can put it into
practice will be peer counsellors from AIDES.
Daily or on-demand PrEP?
Hanne Zimmermann presenting at IAS 2017. Image credit: Ejay de Wit (@ejaydewit)
A study in the Netherlands has looked at
why gay men prefer daily or on-demand pre-exposure prophylaxis (PrEP), and why
they switch from one to the other.
beginning of the AmPREP demonstration study, almost three-quarters (72%) of men
chose daily PrEP and almost half (43%) of those who chose on-demand PrEP
subsequently switched to daily PrEP. Only 14% of those who chose daily PrEP
subsequently switched to on-demand PrEP.
In all, 83 out
of 376 men enrolled in the study have switched from one mode to the other.
users chose it because they wanted daily structure, or because they anticipated
adherence problems with on-demand dosing, or because they expected to have
frequent or unplanned sex.
users chose it because they usually planned when to have sex, or had risky sex
rarely, or had concerns about the toxicity of daily PrEP or their ability to
adhere to it.
switched from on-demand PrEP to daily PrEP did so because they were having
risky sex more frequently or found it difficult to plan sex. A small proportion
said that side-effects had made them switch from on-demand to daily PrEP.
from daily to on-demand PrEP because they were having less sex than expected,
or didn’t like taking it every day, or had experienced side-effects. Adherence
was rarely cited as a reason for switching by anyone in the study.
Although it was
rare for men to stop PrEP, those who stopped did so mainly due to side-effects
(8 out of 376 men who started PrEP), due to reduced sexual risk or lack of
say that their findings underline the importance of offering a choice of ways
to take PrEP; programmes will need to recognise that needs are likely to change
over time and that stopping, re-starting and changing PrEP dosing patterns will
First single-tablet protease inhibitor-based combination
Jean-Michel Molina at IAS 2017. Photo by Liz Highleyman, hivandhepatitis.com
antiretroviral therapy for first-line HIV treatment often involves single-tablet
regimens that are taken as one pill, once daily. Taking fewer pills can improve
adherence, but there are fewer single-pill options for second-line therapy.
Many treatment-experienced people who have developed drug resistance may
require a protease inhibitor, a drug class with potent and durable antiviral
activity and a high barrier to resistance.
The first once-daily single-tablet regimen
containing a protease inhibitor maintained viral suppression in almost everyone
who switched after achieving undetectable HIV RNA on a multi-pill regimen,
according to a report at the conference.
study evaluated the efficacy of switching to a single-tablet regimen – dubbed
D/C/F/TAF – containing the protease inhibitor darunavir (Prezista),
cobicistat as a booster, and emtricitabine and tenofovir alafenamide (TAF) as a nucleoside reverse transcriptase inhibitor
(NRTI) backbone. This regimen was compared to maintenance treatment with a
boosted protease inhibitor, emtricitabine and the older formulation of
tenofovir, TDF (tenofovir disoproxil fumarate).
showed that 96% of people who switched treatment maintained an undetectable
viral load 24 weeks later, and there was no difference in viral rebound between
those who switched and those who remained on a multi-pill regimen.
regimen has been recommended for approval by the scientific committee of the
European Medicines Agency and will be marketed as Symtuza in the
European Union after formal marketing approval by the European Commission later
Antibody delays but does not prevent viral rebound after interruption of treatment
Trevor Crowell at IAS 2017. Photo by Liz Highleyman, hivandhepatitis.com
The first test
of a broadly neutralising antibody to control HIV in people who stopped
treatment showed only a modest effect, but researchers say they still hope that
monoclonal antibodies, selected for their ability to neutralise many different
variants of HIV, will have some role in the future treatment of HIV.
Researchers have explored a wide range of approaches for curing HIV, or
more accurately, bringing about periods of long-term remission while off
antiretroviral drugs. Most of these avenues have been disappointing so far, but
researchers hold out some hope for broadly neutralising monoclonal antibodies,
or bNAbs, that can disable multiple strains of HIV.
Trevor Crowell of the US Military HIV Research Program presented results
of a small study of the antibody VRC01
in 19 people who had started HIV treatment very soon after infection.
Study participants had undetectable viral load for two years before joining the
study. Participants stopped treatment and received infusions of VRC01, or a
placebo, every three weeks for 24 weeks.
The researchers monitored viral rebound. In the placebo arm, all but one
participant had a rebound within three weeks. In the VRC01 arm, rebound was
slightly delayed. In two participants rebound was delayed by 7 and 9 weeks, and
in another by 42 weeks. Study investigators are now looking for factors
associated with delayed rebound before developing further studies of broadly neutralising
Stillbirth more common in women with HIV, UK and Ireland study finds
Graziella Favarato at IAS 2017. Image credit: Dr Heather Bailey (@DrHeatherBailey)
Women living with
HIV are significantly more likely to experience pre-term delivery, to deliver
babies with low birth weight and to have a stillborn baby. Much of the data on
the risk of adverse birth outcomes come from sub-Saharan Africa and less is
known about adverse birth outcomes in higher-income settings.
The stillbirth rate among women living with HIV
in the UK and Ireland from 2007 to 2015 was more than twice that of the general
Graziella Favarato, presenting on behalf of the National Study of HIV in
Pregnancy and Childhood (NSHPC), told participants at the conference last week.
Adolescents with HIV do better in more prosperous African countries
Presenter Amy Slogrove with IAS President Linda-Gail Bekker at IAS 2017. Photo by Steve Forrest/Workers' Photos/IAS
access to antiretrovirals is expanding, the emerging population of adolescents
with perinatally acquired HIV (passed on from mother to child during pregnancy,
birth or breastfeeding) continues to grow. Eighty per cent of adolescents living
with HIV live in sub-Saharan Africa.
Research presented at IAS 2017 showed that adolescents
who acquired HIV perinatally were less likely to die, grew faster and had
better immune restoration on treatment if they lived in upper-middle income countries
in sub-Saharan Africa
(Botswana, South Africa) when compared to the countries with the lowest income
in Africa (e.g. Ethiopia, Malawi, Mozambique, Rwanda, Tanzania, Uganda,
looked at outcomes of 30,296 adolescents living with HIV in sub-Saharan Africa
who entered care before the age of 10 years. In lower-income countries, 85%
received antiretroviral therapy (ART) at some point, compared to 87% in
lower-middle income and 95% in upper-middle income countries.
who had ever received ART, those in low- and lower-middle income countries had
a two and a half- to three-fold greater risk of death than adolescents in upper-middle income countries.
upper-middle income countries also had the greatest improvement in height.
suggest that factors beyond the ART programme still play an important role in
the health and wellbeing of adolescents with perinatally acquired HIV, said Dr
Amy Slogrove, presenting on behalf of the Collaborative Initiative for
Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration
Adolescent Project Team.
quality of health care and the burden of other infectious diseases are each
affected by the income level of a country and each will have an impact on the
survival, growth and immune status of adolescents.