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G L O B AL H E AL T H

Persuasive evidence on HIV policyAntiretroviral therapy has revolutionized the fight against the HIV/AIDS pandemic. Surveillance analyses of a largepopulation in rural South Africa make a compelling case that sustained support for this therapy is essential.

G R A C E J O H N - S T E W A R T

In the tragic story of the global HIV/AIDSepidemic, one glimmering light is anti-retroviral therapy. This treatment involves

a combination of at least three drugs that sup-press HIV, and it prevents progression of theinfection to AIDS and death. As emergency 

investment to fight HIV/AIDS evolves intoa long-term response, it remains crucial tomeasure the direct and indirect benefits of HIVtreatment to sustain investment. Two studiespublished in Science (Tanser et al.1 and Boret al.

2) show a large increase in the overall pop-ulation life expectancy and a decrease in new cases of HIV infection after expanded use of antiretroviral therapy in South Africa (Fig. 1).

That antiretroviral therapy greatly increasesthe survival of individuals with HIV has beenknown since the 1990s3. Global scale-up of thistherapy, however, started in 2004, followinglarge investments by the US President’s Emer-gency Plan for AIDS Relief (PEPFAR) and theGlobal AIDS Program (GAP)4. Since then,antiretrovirals have been given to more than8 million people worldwide (Fig. 2), leadingto millions of life-years saved — an unprec-edented public-health success story 5.

Studies of HIV-discordant couples (in whichone partner has HIV and the other doesn’t)have shown6,7 that if the HIV-infected partnerreceives antiretroviral therapy, transmissionrarely occurs. The most compelling confirma-tion of this observation was a multi-country phase III clinical trial8 (HIV Prevention Tri-als Network 052), in which antiretroviralsdecreased the risk of sexual transmission of 

HIV between couples by 96%. These studies,however, involved motivated patients withhigh levels of adherence to treatment.

The Science papers add a unique perspec-tive on the benefits of antiretroviral therapy on life expectancy and transmission at a gen-eral population level. The studies investigatea meticulously characterized population of more than 101,000 individuals from house-holds in a 434-square-kilometre surveillancearea in rural KwaZulu-Natal, South Africa.Between 2000 and 2011, the households weresurveyed twice a year for birth and death databy the Africa Centre for Health and Popula-

tion Studies in KwaZulu-Natal. A subset of 

these individuals was serially tested for HIVto estimate the rates of new HIV infections.Starting in 2004, Tanser and colleagues’ map-ping of individual household location, localHIV prevalence and the proportion of HIV-infected individuals in specified geographi-cal areas who were receiving antiretrovirals(antiretroviral-therapy coverage) allowedthem to discern whether living in an area withbetter coverage was associated with lower risk 

of acquiring HIV infection.Both studies demonstrate the profound

impact of antiretroviral-therapy coverage at apopulation level. Bor and colleagues show thatexpansion of therapy programmes increasedthe overall adult life expectancy by 11.3 yearsin KwaZulu-Natal. Tanser et al. estimate thatin communities in which 30–40% of thoseinfected with HIV were taking antiretrovirals,uninfected individuals were 38% less likely toacquire HIV than those in communities inwhich the therapy was less widespread.

Population studies such as these, whichinvolve individuals who may have much

lower drug adherence than those participating

in carefully controlled clinical trials, are apowerful complement to clinical trials. They give us a sense of impact in the ‘real world’.The reality is that the new studies focus on afairly specific real world — one in which HIVprevalence was staggeringly high, allowingdetection of the impact of therapy on overalladult life expectancy. Nonetheless, the stud-ies are persuasive in the larger landscape of global HIV. Several other countries in south-

ern and eastern Africa that also have a highprevalence of HIV could expect to see similarresults. In 2012, 25 countries saw a declineof more than 50% in new HIV infect ions5.This decrease was due to multiple factors, butundoubtedly antiretroviral therapy played apivotal part.

These data, therefore, should persuadepolicy-makers to sustain or increase invest-ment in this form of therapy. Global aid fundsare constricting or staying stable, whereashealth needs are persisting or expanding. Itis clear from the two studies that for regionsof high HIV prevalence, including South

Africa, greater investment in antiretroviral

Figure 1 | A woman with HIV infection in KwaZulu-Natal, South Africa.

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therapy is essential. To attain one of the goalsof the Joint United Nations Program on HIV/AIDS (UNAIDS) — 15 million individualson antiretroviral therapy by 2015 — contin-ued support from GAP and PEPFAR will benecessary 5.

Scale-up of antiretroviral therapy has led togains in programme efficiencies. Not only havedrug costs decreased, but also systems to pro-

 vide antiretroviral therapy have diversified andbecome less expensive through recruitmentof less-highly trained health-care providersand introduction of less-intensive laboratory monitoring5. Moreover, funding sources forprovision of antiretroviral therapy are branch-ing out, with increased domestic investment by the affected countries to complement externalsupport5. For instance, South Africa has sub-stantially increased its domestic investment inantiretroviral therapy, and the present studiesprovide clear justification for sustaining andexpanding this investment.

At a national or global policy level, anti-retroviral therapy has been the subject of scrutiny in many ways: for its dual treatmentand prevention benefits; for its impact on

other health needs such as childhood illnesses,reproductive health or other infectiousdiseases, including tuberculosis; for thepotential strain the therapy places on healthsystems, for example whether there is anuneven focus on HIV/AIDS at the expenseof other illnesses in settings with shortages of health workers and resources; and for its con-tribution to well-being or economic productiv-ity. Antiretroviral-therapy programmes haveled to broad improvements in health systems,innovations in clinical education and over-hauls of laboratory and clinical infrastructure— much more than the global community 

initially envisioned. Financial investments

North Africa and the Middle East

2002 2005 2008 2011

     M     i     l     l     i    o    n    s

0

2

4

6

8

Europe and Central Asia

East, South and Southeast Asia

Latin America and the Caribbean

Sub-Saharan Africa

Figure 2 | Use of antiretroviral therapy. Thenumber of people receiving antiretroviral therapy by the end of each year between 2002 and 2011in low- and middle-income countries by region.

(Adapted from ref. 5.) 

were linked to measurable and diversebeneficial outcomes.

For the future, it remains important towrestle with what outcomes are most relevantto health-resource investment decisions.Although increased overall life expectancy anda reduction in new HIV infections at a popu-lation level are compelling for policy-makers

in regions with high HIV prevalence, othermetrics, including comparisons with otherhealth investments and impact on morbidity,quality of life or productivity, may be moreuseful in lower-prevalence settings. ■

Grace John-Stewart is in the Department of Global Health, University of Washington,

M AT E R I AL S S C I E N C E

Nanoparticle structuresserved up on a trayA neat approach that involves laying an array of nanoparticles on a graphenesheet supported on an iridium substrate has allowed accurate measurement of the nanoparticles’ atomic structure.

S I M O N B I L L I N G E

W

hether we are aware of the fact ornot, modern life would be pro-foundly different without precious-

metal nanoparticle catalysts1. Every drop of petrol used has passed over a platinum cata-lyst during production, and the exhaust gasesof a car’s engine similarly pass over thesecatalysts in the catalytic converter on the way out of the car. The catalysts are also essentialto future sustainable energy technologies,such as cars and buses powered by hydrogenfuel cells. These processes rely on chemicalreactions that take place on the catalystsurface. But despite our dependence on suchreactions, we know little about them becausewe lack the tools that can ‘see’ the processesinvolved and measure the interactions between

reacting molecules and the catalyst. Writing inPhysical Review Letters, Franz et al.2 describean ingenious exploitation of a  gift fromnature that will allow us to make a huge dentin this problem.

A catalyst plays host to a chemical reaction,allowing it to proceed without itself being con-sumed in the process. Much like a skilled hostat a party, it brings together like-minded guestswho then depart, leaving the host to find andfacilitate other favourable matchings. Under-standing the secrets of the successful match-maker will help us to find better, cheaper andmore naturally abundant materials that do the

same job. But how do we unlock those secrets?

Catalysis by precious metals takes place onthe surface of minute nanoparticles, whichmaximize the surface area available for thechemical reactions and, equally importantly,minimize the amount of expensive preciousmetal needed.

To understand these catalytic chemicalprocesses, we must follow the interactionsbetween the reagents and the metal atoms onthe nanoparticle surface. The surface atomsbecome rearranged to minimize the surfaceenergy, a feature called surface reconstruction,and the reactivity and interactions between theatoms and the reagents vary widely depend-ing on this rearrangement. But not only dowe not know what the surface structure lookslike, we do not even have robust methods forworking out the ‘bulk’ nanoparticle structure,a dilemma sometimes referred to as the nano-

structure problem3.When atoms become arranged into a peri-

odic structure, as if they were on a chessboard,they form crystals and we have powerful toolsfor locating them. More recently, with theadvent of intense synchrotron X-ray sourcesbased on particle accelerators, these methodshave been extended to the study of surfaceatoms. But, crucially, this can be done only when the arrangement of the surface struc-ture is also periodic. When the arrangementexists only on the nanoscale it is invisible, as if we are blindfolded. There are two approachesto addressing this problem: either develop

tools for solving structure at the nanoscale4,

Seattle, Washington 98104, USA.e-mail: gjohn@uw.edu

1. Tanser, F., Bärnighausen, T., Grapsa, E., Zaidi, J. &

Newell, M. L. Science 339, 966–971 (2013).

2. Bor, J., Herbst, A. J., Newell, M. L. & Bärnighausen, T.

Science 339, 961–965 (2013).

3. Palella, F. J. Jr et al. N. Engl. J. Med. 338, 853–860

(1998).

4. PEPFAR Blueprint: Creating an AIDS-Free Generation 

(US State Dept, 2012); available at go.nature.com/h27zl8

5. Global Report: UNAIDS Report on the Global AIDS 

Epidemic 2012 (UNAIDS, 2012); available at

go.nature.com/c4lupm

6. Bunnell, R. et al. AIDS  20,85–92 (2006).

7. Donnell, D. et al. Lancet  375, 2092–2098 (2010).

8. Cohen, M. S. et al. N. Engl. J. Med. 365, 493–505

(2011). 

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