Influencing global policy on antiretroviral treatment priorities
Submitting InstitutionUniversity College London
Unit of AssessmentPublic Health, Health Services and Primary Care
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Medical Microbiology, Public Health and Health Services
Summary of the impact
Our work with the World Health Organisation (WHO) had a major impact on
global HIV treatment priorities at a critical time in the roll-out of
anti-retroviral treatment (ART) worldwide. Concern had been expressed that
if ART was provided without simultaneous monitoring of HIV viral load to
determine switch in treatment, this would lead to an epidemic of drug
resistant HIV. It was argued that viral load monitoring should be
introduced as a priority, despite the fact that this was expensive and
would inevitably divert resources from ART provision. We used a simulation
model to predict the impact of lack of viral load monitoring and showed
that while development of viral load assays was important, ART should be
prioritised. As a result, the roll out of ART continued despite continued
lack of viral load monitoring, and there are now over 9 million people on
The underpinning research described below was carried out by the HIV
Epidemiology and Biostatistics Group at UCL led by Professor Andrew
Phillips, and was a collaboration with the WHO HIV/AIDS Department.
In the early-2000s, global plans were being put in place to expand access
to ART as rapidly as possible to low resource settings (particularly
sub-Saharan Africa) where most people with HIV live. In order to make this
feasible, the WHO developed a public health approach, which involved use
of standard regimens with little requirement for the monitoring that was
being used at that time in developed country settings. Use of CD4 counts,
particularly to select who should start ART, was encouraged but measures
of viral load were very expensive in the context of low resource settings
(the current fully loaded cost of a viral load test is the cost of around
8 months of ART for one person) and could not be used in most settings. At
that time, however, increasing concerns were being expressed that
widespread delivery of ART without use of viral load monitoring to
identify people failing ART could lead to widespread development of drug
resistance, with consequences for both the treated individuals and for the
population, due to transmission of drug resistant HIV. There was no
research available to evaluate the likely consequences of the ongoing
In previous work done by our group between 2003 and 2007, we had
developed a stochastic computer simulation model of HIV progression and
the effect of ART, based on our extensive work on studying HIV in cohort
studies. The first paper from this model, published in 2007, made
projections about the HIV population in the UK . As a result of
concerns about the roll out of ART in low-resource settings, we adapted
our model to investigate the impact of lack of viral load monitoring on
outcomes of ART in low resource settings  and included a
transmission component to consider transmitted drug resistance .
This work helped us understand what the consequences of provision of ART
without viral load monitoring were likely to be, in terms of patient
survival and transmission of drug resistance. We showed that eventual use
of viral load monitoring is important, particularly to avoid future
widespread transmission of drug resistance, and that development of new
tests which are not dependent on substantial laboratory infrastructure or
highly trained staff should be a key research and development priority.
However, we also showed that the impact on mortality of lack of viral load
monitoring was likely to be modest in the short to medium term, relative
to the mortality impact of failing to provide more widespread ART. Thus
the message was to continue the roll-out without re-directing resources to
viral load measurement but to encourage the development of cheaper tests.
Continuing our research in this areas, we are currently working with WHO
on assessing the impact on transmission of HIV drug resistance of starting
more people on ART earlier, and defining threshold levels of transmitted
drug resistance beyond which a change in public health policy is required.
In further work using the model, we are collaborating with GSK Biologicals
to model potential effects of their vaccines. We collaborate on this
research with health economist colleagues at the London School of Hygiene
and Tropical Medicine (Alec Miners) and, more recently, the University of
York (Paul Revill).
References to the research
 Phillips AN, Pillay D, Miners A, Bennett D, Gilks CF, Lundgren JD.
Outcomes from monitoring of patients on antiretroviral therapy in
resource-limited settings with viral load, CD4 cell count, or clinical
observation alone: a computer simulation model. Lancet. 2008 Apr
 Phillips AN, Pillay D, Garnett G, Bennett D, Vitoria M, Cambiano V,
Lundgren JD. Effect on transmission of HIV-1 resistance of timing of
implementation of viral load monitoring to determine switches from first
to second line antiretroviral regimens in resource-limited settings. AIDS.
2011 Mar 27;25(6):843-50. http://dx.doi.org/10.1097/QAD.0b013e328344037a
The research at this stage was directly funded by HEFCE (funding to
Details of the impact
The research described above provided an evidence base to continue the
rollout of ART in sub-Saharan Africa without diverting resources for ART
to measures of viral load — a policy which had come under question in
previous years. It was seen as critical to understand whether the
consequences of roll out of ART without viral load monitoring were so
severe (due to concerns over transmission of HIV drug resistance) as to
mean that introduction of such testing should be prioritised over
continued ART expansion by ART programmes. Our findings provided support
for continued roll out in settings where viral load monitoring was not
available. A comment paper written by colleagues from the Global Fund for
HIV, TB and Malaria (the body which, along with U.S. President's Emergency
Plan for AIDS Relief (PEPFAR), provided most funds for the ART roll-out)
concluded that "Phillips and colleagues' findings strengthen the policy
consensus and WHO recommendation — so far based on individual patient
outcomes and cost-effectiveness in the shorter term — that resource-poor
countries need not delay ART roll-out because of limitations in
laboratory capacity" [a].
The Director/Coordinator of Treatment and Prevention Scale-up at the WHO
HIV Department at that time reports that "the work... adapting the HIV
synthesis to model the outcome of ART in low-income settings under
different monitoring practices helped shape global ART roll-out policy
and practice. Furthermore, because of its unique utility and approach,
the modelling work and synthesis adaptations continue to be used to
inform global policy development" [b].
Since 2008, the trajectory of the number of people on ART has increased,
with 9.7 million people now on ART [c]. Almost all countries in
sub-Saharan Africa (with the exceptions of South Africa and Botswana) have
been providing ART without regular viral load monitoring. Point of care
tests for viral load are now close to coming to market and WHO has started
to encourage use of viral load testing in patient monitoring as resources
allow, so long as this does not inhibit roll-out.
Our publications in 2008 and 2011 were written jointly with colleagues at
WHO responsible for the public health approach [d], and influenced
their policy as described — i.e. to prioritise the continued expansion of
roll-out of ART over introduction of viral load monitoring, but to
encourage research and development of implementable viral load measurement
technology. The two publications are officially approved WHO publications
and our work has been cited in WHO guidelines. The 2008 WHO progress
report "Towards Universal access: Scaling up priority HIV/AIDS
interventions in the health sector" cites our publication from the
previous year as providing support for WHO's recommendations on scaling up
ART provision [e]. Furthermore, there were 11 references in total
to the wider work of the HIV Epidemiology & Biostatistics Group of the
Research Department of Infection & Population Health in the key WHO
guideline "Antiretroviral therapy for HIV infection in adults and
adolescents. Recommendations for a public health approach" [f].
Our model has also been used by the Bill and Melinda Gates Foundation in
their assessment of CD4 investment options, and was influential in them
deciding to support development of a new point of care test. A program
officer at the Foundation writes that: "I have used your modeling
analysis several times when we have been evaluating our options for CD4
investment. The impact of the Zyomyx test is a critical component of our
decision making and we are constantly re-evaluating our decisions as we
move forward, so your results have been considered again and again"
Sources to corroborate the impact
[a] Korenromp EL, Fakoya A, Viisainen K. Scaling-up antiretroviral
treatment in resource-poor countries: prioritization and choices. AIDS.
2011 Mar 27;25(6):857-9.
[b] Statement from Director of Treatment and Prevention Scale-up at the
WHO HIV Department. Copy available on request.
[c] WHO Global update on HIV treatment 2013: results, impact and
opportunities, June 2013.
[d] Gilks CF, Crowley S, Ekpini R, Gove S, Perriens J, Souteyrand Y,
Sutherland D, Vitoria M, Guerma T, De Cock K. The WHO public-health
approach to antiretroviral treatment against HIV in resource-limited
settings. Lancet. 2006 Aug 5;368(9534):505-10.
[e] World Health Organisation. Towards Universal access: Scaling up
priority HIV/AIDS interventions in the health sector. 2008 Progress
(See page 35)
[f] World Health Organisation. Antiretroviral therapy for HIV infection
in adults and adolescents. Recommendations for a public health approach.
[g] Statement from Senior Program Officer at the Bill and Melinda Gates
Foundation. Copy available on request.