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Africa: Ending AIDS?
Dec 1, 2008 (081201)
(Reposted from sources cited below)
"The [WHO] findings suggest that HIV transmission could be
virtually eliminated by 2020 in countries with high levels of HIV
prevalence, such as South Africa, if it were possible to persuade
everyone in the community to test for HIV infection once a year and
then provide antiretroviral therapy to all who test HIV-positive.
... [But there are many questions that require answers before such
a strategy could be implemented.]" - HIV & AIDS Treatment in
A new study from the World Health Organization, based on
mathematical modeling of much more proactive AIDS testing and early
treatment, has raised the prospect of turning the tide against
the pandemic in countries with very high HIV prevalence, reducing
new infections per year from from 20 per thousand to 1 per thousand
within ten years.
The study provides new hope that providing massive new resources
for testing, treatment, and prevention could have dramatic effects.
Three million people are now receiving AIDS treatment worldwide.
With an estimated 6.7 million still in need of treatment and a
further 2.7 million becoming infected during 2007, the scope for
additional action and the need for continuing and expanding AIDS
funding is clear.
Even if funding and other resources such as trained personnel were
available immediately, however, news headlines predicting the "end
of AIDS" are highly misleading, however, say experts and activists.
This AfricaFocus Bulletin contains a review of the new WHO student
and of practical questions remaining to be answered, by the on-line
publication HIV & AIDS Treatment in Practice
For previous AfricaFocus Bulletins on health issues, visit
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++++++++++++++++++++++end editor's note+++++++++++++++++++++++
Universal testing and immediate treatment could cut HIV infections
by 95% in 10 years
By Keith Alcorn
WHO publishes modelling study
HIV & AIDS Treatment in Practice. #123
27 November 2008
A regular electronic newsletter for health care workers and
community-based organisations on HIV treatment in resource-limited
The newsletter is edited by Theo Smart (Cape Town) and Keith
Alcorn, NAM's Senior Editor (London).
Universal HIV testing and immediate antiretroviral therapy for
everyone diagnosed with HIV in a country with very high HIV
prevalence could reduce new infections from 20 per thousand to 1
per thousand within ten years, according to findings from a
mathematical modelling exercise carried out by the World Health
Organization, published on November 26th by The Lancet.
The findings suggest that HIV transmission could be virtually
eliminated by 2020 in countries with high levels of HIV prevalence,
such as South Africa, if it were possible to persuade everyone in
the community to test for HIV infection once a year and then
provide antiretroviral therapy to all who test HIV-positive.
Transmission is expected to decline if more people are treated
because antiretroviral treatment reduces the amount of HIV in semen
and vaginal fluids, reducing the risk of transmission.
Currently only around 20% of people with HIV in sub-Saharan Africa
know their HIV status, and antiretroviral therapy in most countries
is available only to those with symptoms of HIV disease or severe
immunosuppression (a CD4 count below 200 cells/mm3).
Expanding treatment to all those who need it under current
guidelines will be a substantial undertaking. Three million people
are currently receiving antiretroviral therapy worldwide, but an
estimated 6.7 million are still in need of treatment and a further
2.7 million became infected during 2007, according to WHO's 2008
report on progress towards universal HIV treatment access.
Expanding treatment and testing to reach everyone with HIV,
particularly in southern Africa, would be a massive undertaking
that would require vastly greater human resources than currently
available for health care.
Dr Kevin de Cock, WHO's HIV department director says that universal
testing and treatment regardless of immune system status could not
become an official WHO recommendation without further research into
the feasibility, safety, acceptability, impact and
cost-effectiveness of the approach, as well as extensive
Nevertheless the findings are likely to stoke interest in expanding
access to antiretroviral therapy in order to limit the long-term
impact of the HIV epidemic in the most severely affected countries,
those in the southern African region where HIV prevalence in the
adult population ranges from 15 to 35%.
Treating everyone with HIV infection in order to reduce the number
of new HIV infections has been advocated previously by Professor
Julio Montaner of the University of British Columbia in Canada.
Prof. Montaner and colleagues published the results of their own
mathematical modelling in 2006, which projected that new HIV cases
would decline from 7 per thousand to 0.1 per thousand over 50
years if universal testing and treatment were implemented.
The introduction of door-to-door HIV testing and counselling and
antiretroviral therapy for all who qualified under Ugandan
treatment guidelines reduced new cases of HIV infection by around
90% over a three-year follow-up period, according to findings from
a US Centers for Disease Control study carried out in rural Uganda
over the past five years.
So far no country or region in the world has adopted a strategy of
universal testing and treatment. Current treatment guidelines in
the United States and Europe recommend treatment for everyone with
a CD4 cell count below 350 cells/mm3, although there is some
evidence that starting treatment at a CD4 count below 500 cells/mm3
reduces the risk of serious non-AIDS-defining illnesses when
compared to starting treatment at a CD4 count below 350 cells/mm3.
Encouraging treatment uptake in order to reduce HIV transmission is
an explicit public health goal in only one region of the world at
present, the Canadian province of British Columbia, where Professor
Montaner's research group has persuaded the provincial government
to adopt a more aggressive approach towards identifying everyone
currently eligible for treatment at a CD4 count of 350 cells/mm3 or
below. The group's modelling suggests this policy could avert more
than two-thirds of projected infections in the province between
2008 and 2030.
The WHO model used South Africa as an example, taking data on
infection rates and disease progression to model the effects of
expanding knowledge of HIV status and a growing uptake of
antiretroviral treatment. The model assumed that with a baseline
HIV prevalence of 16%, a 99% decline in infectiousness when
individuals started treatment, and 90% coverage of treatment in the
HIV-infected population by 2016, 104,000 deaths would be averted in
2015 alone when compared to starting treatment at a CD4 cell count
of 350 cells/mm3 (in itself an optimistic threshold).
The model assumed an annual treatment cost (including drugs,
monitoring and patient management) of $727 a year for first-line
treatment and $3290 for second-line treatment, with antiretroviral
drugs accounting for 30% of the cost.
The model showed that HIV transmission would decline very steeply
as HIV treatment coverage expanded, falling from around 15 new
infections per thousand adult and adolescent inhabitants today to
1 per thousand by 2016.
Although the universal treatment strategy would cost three times
more than treating everyone with a CD4 cell count below 350
cells/mm3 in 2015 ($3.4 billion a year), the yearly cost would
begin to fall after this point, and by 2030 the approach would
become less expensive than treating only those with CD4 counts
below 350 cells/mm3 (approximately $1.8 billion).
Professor Geoffrey Garnett of London's Imperial College, an HIV
epidemiologist, said in an accompanying commentary: "[The]
suggested strategy would be extremely radical, with medical
intervention for public health benefits rather than individual
patient's benefits. Because screening and treatment would be for
the public good, resources would have to come from the public
purse. The suggested strategy would reflect public health at its
best and its worst"
"At its best the strategy would prevent morbidity and mortality for
the population, both through better treatment of the individual and
reduced spread of HIV. At its worst, the strategy will involve
over-testing, over-treatment, side-effects, resistance and
potentially reduced autonomy of the individual in their choices of
care ... It is easy to see how enforced testing and treatment for
the good of society would follow from such an argument. Partial
success would lead to infection becoming concentrated in those with
a high risk, with an increased danger of stigma and coercion. The
history of the control of sexually transmitted infections documents
several examples of compulsory screening and treatment of
stigmatised populations, and there is a danger of a well-meaning
paternalistic medical model following such a route."
There was strong advocacy for achieving universal treatment
coverage on prevention grounds at this year's International AIDS
Conference in Mexico City. Professor Julio Montaner, who is also
President of the International AIDS Society, said: "We believe
there is now enough evidence to say to policymakers that if you
roll out HIV treatment with 100% coverage, you will see a reduction
in HIV transmission."
The study was endorsed as an important step forward by several
advocacy groups. GNP+, the global network of people living with HIV
and AIDS, said that the study represented a breakthrough in
thinking by WHO, but urged the agency to work closely with PLWHIV
networks to increase access to testing and treatment while
protecting human rights.
The International Treatment Preparedness Coalition (ITPC), a global
network of community-based HIV treatment advocacy groups, also
welcomed the publication.
"This article can help put an end to false debates pitting HIV
treatment against HIV prevention," said Aditi Sharma,
Co-Coordinator of the Treatment Monitoring and Advocacy Project
(TMAP) of ITPC. "If additional research supports this model, it
could signal a paradigm shift in the public health response to
HIV," Sharma said.
"The WHO study confirms what those of us working on the frontlines
of the epidemic know from personal experience: HIV prevention and
treatment are mutually reinforcing," Sharma added.
"We need research to determine the feasibility and long-term
implications of this change in the way HIV treatment is managed,"
said Gregg Gonsalves, a member of ITPC. "Starting therapy at high
CD4 counts may not have clinical benefits for a person living with
HIV and since ART comes with long term toxicities, very early
initiation may be problematic."
WHO will convene a meeting early next year bringing together
ethicists, funders, human rights advocates, clinicians, prevention
experts and AIDS programme managers to discuss this and other
issues related to the wider use of antiretroviral therapy for HIV
However, there will be no early change in guidelines based on a
modelling exercise alone.
WHO says it needs to know more about the following questions in
order to determine whether its modelling is accurate:
- What is the acceptability of universal HIV testing and will it be
- How infectious are people receiving antiretroviral therapy,
especially in settings where the rate of sexually transmitted
infections is high?
- How well do people adhere to antiretroviral therapy in the
- What are the long-term failure rates for antiretroviral therapy
and what are the subsequent resistance patterns? To what extent
will these restrict the response to second-line therapy?
- What are the effects of universal testing and antiretroviral
availability on sexual behaviour? In particular, would the greater
availability of treatment, alongside the message that treatment
reduces the risk of transmitting HIV, lead to a generalised
increase in risk behaviour during the early phase of treatment
scale-up leading to a paradoxical increase in HIV incidence?
The feasibility of the approach also needs to be tested in a real
health system, in order to determine the level of health personnel
and health system strengthening required, as well as the effects of
the approach on other public health goals.
Better data are urgently needed from real-life settings, but there
are several problems in obtaining them:
- Researchers are not altogether satisfied with the accuracy of
assays designed to capture HIV incidence in biomedical prevention
trials, leaving us reliant on combined antibody/antigen tests that
have varying levels of accuracy. Better assays are urgently needed.
- Measuring incidence at the community level is expensive and
requires a national or regional surveillance programme; treatment
programmes are not set up to measure incidence at present
(surprising though that may seem). These data could eventually be
gathered quite comprehensively for meta-analysis if major donors
such as the Global Fund and PEPFAR mandated the measurement over
time of HIV incidence in communities where treatment becomes
available as a result of their funding.
The most convincing long-term data are likely to come from
long-term randomised studies however. A study of the effects of
earlier initiation of antiretroviral therapy in HIV-discordant
couples is currently taking place in Malawi, Brazil, India,
Thailand, and Zimbabwe and is due to report around 2013. That
study, HPTN 052, is recruiting HIV-positive people with CD4 counts
between 350 and 550 cells/mm3 and their HIV-negative partners. The
HIV-positive partner is randomised either to begin treatment
immediately or to start treatment according to national guidelines
(at a CD4 count of 250-200 cells/mm3). The study will measure the
effect on incidence of the two treatment strategies, and is powered
to detect a greater than 35% reduction in HIV incidence in the
early treatment arm.
However, many of the operational questions about this approach
might be addressed in a community-randomised trial, in which
geographically separate districts within the same country are
randomised either to carry out treatment and testing according to
current guidelines, or to adopt the universal testing and treatment
approach. Such a study might take five to seven years to provide a
robust answer by the time it was funded, set up and allowed to run
for long enough to assess the operational difficulties inherent in
the new approach.
Several research groups based in the United Kingdom, Canada and
France are already working on ideas for studies.
Ultimately, Reuben Granich of WHO's HIV department told HATIP, WHO
will need a variety of sources of information on this topic before
it could issue a recommendation.
"WHO has a fairly rigorous guidelines process in order to make
recommendations. In that context randomised controlled trials are
usually the gold standard, but other types of data can be brought
into that process, and all that evidence would be weighed."
Other types of data might include a meta-analysis of incidence data
from communities with various levels of treatment coverage, as well
as operational research. Countries with good antiretroviral
coverage and a relatively well developed infrastructure, such as
Botswana and Namibia, could yield useful data relatively soon.
But will it be possible to sustain almost universal annual HIV
testing in a population over many decades? Such a seismic shift
would undoubtedly require a shift to community-level testing
initiatives, which might in themselves have prevention benefits. As
noted above, the US Centers for Disease Control (CDC) has
demonstrated that almost universal uptake of HIV testing is
feasible in its Home Based AIDS Care study in rural Uganda, by
going door to door.
On the other hand a national campaign to promote knowledge of HIV
status in Lesotho fell far short of its targets, probably due to
the fact that lay counsellors were poorly trained and there was
insufficient linkage between testing and treatment (unlike in the
CDC model). By August 2007 just 25,000 people had been tested
through the Know Your Status campaign. The target was 1.3 million
by the end of 2007. A qualitative research study by Human Rights
Watch and the AIDS and Rights Alliance for Southern Africa (ARASA)
found "a clear disconnect between planning on paper and the
capacity to implement what was planned." Counsellors had inadequate
training, particularly in the importance of informed consent and
confidentiality, and there was no training in couples counselling,
which was key to the CDC approach in Uganda.
Another concern is that there is no evidence at present of what is
necessary in order to achieve and sustain high levels of HIV
testing, particularly in urban and periurban settings. This issue
is of particular relevance to South Africa, the most urbanised
country in southern Africa, but growing urbanisation will make it
equally pertinent in other countries in sub-Saharan Africa.
Health system capacity to deliver treatment on the scale envisaged
is the big, unanswered question. More information is needed about
the level of health system strengthening that would be required in
order to facilitate such a level of testing and treatment, together
with evaluation of any distortionary effects on other health system
priorities. Such an approach would inevitably require a huge
devolution of care to the primary care and community level,
together with the adoption of a chronic disease management model
within primary health care, which in turn will require substantial
investment and training. Although some models of task-shifting
within HIV care have shown positive outcomes, not all task-shifting
results in a consistent standard of care or comparable outcomes
(see issue 116 of HATIP, published in September 2008, for more on
More information is also needed about the trade-off between earlier
treatment and drug toxicity. In many developing countries
first-line treatment includes drugs with quite high rates of
toxicity, including d4T (stavudine) and AZT (zidovudine). Using
these drugs, which are much cheaper than the better tolerated
first-line regimens now used in Europe and North America, could
have significant long-term disadvantages if they cause a high rate
of serious side-effects in otherwise healthy people. Some data
suggest up to one in five people may need to switch as a result of
toxicity. On the other hand, there is also evidence that the
side-effects of these drugs appear less frequently in people who
start treatment earlier.
These drugs are used because they cost around $100-$150 a year,
compared with $270-$400 a year for less toxic drugs. When
considering the cost of first-line treatment it is important to be
aware of the fact that the cheapest combinations all contain
nevirapine. However nevirapine is not suitable for use in women
with CD4 counts above 250 cells/mm3 or men with CD4 counts above
400 cells/mm3, due to the increased risk of life-threatening liver
toxicity above these thresholds. So, a substantial proportion of
treated people would need to receive other less toxic, more
expensive drugs if universal treatment was the aim.
It is unlikely that less toxic drugs will ever be as cheap as the
current first-line options, because they require more raw materials
and more complex chemistry, in the view of the Clinton HIV/AIDS
Universal testing and treatment is only likely to be cost-effective
in settings where HIV is hyper-endemic and where AIDS seriously
threatens long-term stability and growth. Further
cost-effectiveness analysis will be needed. The WHO analysis looks
at the relative costs of pursuing the universal approach or
treating people when their CD4 count falls below 350 cells/mm3. The
universal approach demands substantially greater expenditure during
the first two decades, but begins to become cheaper than the
default treatment approach by 2030. This balance and time-scale may
differ in other countries in the southern Africa region.
However, such large expenditure is likely to raise concerns about
distortion of health system priorities. A universal approach to HIV
treatment in settings where prevalence exceeds 15% is only likely
to avoid health system distortion if it is situated within a wider
package of essential health care delivered through the primary care
system. Universal testing and treatment would provide a major
opportunity to promote and strengthen primary health care services
and the integration of maternal/child health, TB and HIV care.
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