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Barriers That Could
Stop HIV Treatment
Becoming HIV


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One of the key strategies involved in trying to bring an end to the HIV epidemic is to increase the proportion of HIV-positive people on antiretroviral therapy (ART), to the point where suppressing their viral load starts to reduce onward infection.

What is usually called ‘treatment as prevention’ lies behind the ambitious target announced by UNAIDS recently to diagnose 90% of people with HIV worldwide, treat 90% of them, and supress HIV below detectability in 90% of those – in other words to have 72.9% of all the HIV-positive people in the world virally undetectable by 2020.

A symposium session at the recent HIV Research for Prevention conference explored whether this was feasible and how its success could be measured – and heard about the barriers that could impede progress towards the UNAIDS goal.

Evidence Of Success

One of the few places in the world where a direct correlation between more people on treatment and fewer infections has been seen is in a rural part of northern KwaZulu Natal in South Africa. ART roll-out in this area started in 2004 and, by 2012, 45% of the entire local HIV-positive population was on ART. This had a welcome effect on adult life expectancy, which increased from 50 to 60 years between 2004 and 2012.

But it also had a prevention effect. Looking back, it was clear there was a strong correlation between ART provision and falling HIV incidence: initially, putting 10 to 20% of people on ART made little difference, but a ‘tipping point’ was reached between 30 and 40% on ART, and in neighbourhoods where more than 40% of people with HIV were on ART, people without HIV were 38% less likely to become infected.

There seemed to be a levelling-off after this, though: putting still more people on ART did not further push down the infection rate. Why? Could it be because only certain people were eligible for ART? Is it feasible to offer ART to everyone who is diagnosed with HIV, and would that bring HIV incidence down still further? Studies are underway to find out.

Trials Of Treatment As Prevention

ANRS12249 is one of several randomised trials designed to answer this question. Frank Tanser, who conducted the original surveillance study that first noted the link between treatment and incidence in KwaZulu Natal, described it and the other huge treatment-as-prevention comparison studies that are underway in southern and eastern Africa.

ANRS12249 is taking place in an area of KwaZulu Natal near that covered by the previous surveillance study. The entire population will be offered home-based HIV testing and those testing positive in intervention communities will be offered referral to care and immediate ART (in control communities, they will be offered treatment according to South African treatment guidelines). There are 90,000 people in the original surveillance area and 22,000 in the new intervention area – which, as we will see, is small compared to some other treatment as prevention studies.

Data were presented at the International AIDS Conference at Melbourne by principal investigator François Dabis, who noted that while home testing appeared to be very acceptable, people were taking longer than anticipated to come forward for treatment if they did test positive.

Tanser said, however, that already some benefits were being seen to the treat-everyone approach. In the intervention areas, 77% of everyone with HIV was diagnosed, of whom 73% were in care, of whom 80% were on ART, meaning 45% of everyone with HIV was on ART. Tanser said that an estimated 31% more people were in care and 28% more were on treatment than would be the case if treatment was being offered according to South African national guidelines.

Between now and 2019, four other huge treatment-as-prevention trials, each slightly different, and involving up to two million people, will test whether intensified treatment really can bring down HIV infections on a population level. 

The POPArt trial is the biggest of these, involving no fewer than 1.2 million people. The POPArt intervention includes home-based HIV testing by community health providers, an offer of ART upon HIV diagnosis at any CD4 count, voluntary medical male circumcision, the prevention of mother-to-child transmission, condom provision and tuberculosis (TB) monitoring and treatment. Communities are randomised into three arms: one receiving the full POPArt intervention; one receiving the POPArt prevention package but ART according to country guidelines (currently at below 500 CD4 cells/mmin Zambia and below 350 cells/mm3 in South Africa, though this is soon to rise to 500); and one receiving the standard of care in their country. The estimated completion date is 2018. As estimating HIV incidence for a trial this size would be expensive, a subset of around 50,000 people will be tested frequently for incident HIV infections.

The Botswana Combination Prevention Programme (BCPP) is studying 180,000 people in 30 villages in Botswana. It will randomise 15 villages to standard of care and 15 to a package similar to the POPArt one plus ART for everyone with a viral load above 10,000 copies/ml. It should report by late 2017.

The SEARCH trial is taking place in Kenya and Uganda, and is in some ways the most ambitious as it will also measure the effect of intensified treatment on a number of socioeconomic indicators and health outcomes not directly related to HIV. It will randomise 320,000 people in 32 communities to receive either standard of care or ART at any CD4 count, intensified linkage to and retention in care for people with HIV and frequent testing for high-risk individuals. Interestingly, it will also provide a multi-disease prevention campaign, testing people for malaria, hypertension (high blood pressure) and diabetes. It was fully enrolled this July and 89% of participants have had an HIV test. 

SEARCH will evaluate the programme not just for HIV incidence but for additional gains: maternal and child health, TB, education level, earning power and costs. The reason for testing people for hypertension and diabetes is to see if such an intervention could be of benefit in low-income areas where these are the most urgent health problems. SEARCH will report in 2019.

The final study, MaxART, is a three-year implementation study led by the Swaziland Ministry of Health and supported by a number of partners including the Clinton Foundation. It will not measure incidence directly; its aim is to study the feasibility, acceptability, scalability, and clinical outcomes, including AIDS, of a national roll-out of ART for all in this small but high-prevalence country.

Fourteen clinics in one region are included in the study implementation. Health facilities transit, two at a time, from the control (standard of care) to the intervention (ART for all HIV-positive clients) stage. The order in which the facility groups transition is randomized, with the health workers and study participants blinded to the timing so as to minimize bias. Community participation and a robust communications strategy are also an integral part of the study implementation to ensure that the community’s interests are heard and protected.

The Problem Of Recent Infection

Will such programmes achieve their aim of bringing down HIV incidence? One problem is that people who are recently infected and therefore undiagnosed (or, if very recently infected, untestable) may contribute disproportionately to infection due to the very high viral loads in the first month of HIV infection. Kimberly Powers of the University of North Carolina said that the peak of infectiousness was at about ten days after infection, but that even fourth-generation HIV tests that include testing for the viral protein p24 could not detect infection that was more recent than two weeks. This could be improved by heightening patient and physician awareness of the symptoms of acute HIV infection, but at present models estimate than anything between 20% and 50% of HIV infections, or even more, are transmitted by people in early infection.

Not all models show that testing more people, and more frequently, would reduce HIV incidence because it depends on the ‘incidence density’ or frequency of infection in a population. However, one model shows that as the proportion of transmissions due to recent HIV infection rises, the proportion of people who have to be on ART with an undetectable viral load in order to ensure that the epidemic is not self-sustaining rises from 35% – as may be the case in the ANRS12249 study – to over 70%. The latter may be the case with the more concentrated epidemics such as among men who have sex with men, and people who inject drugs. In addition, people diagnosed soon after acquiring HIV would not become instantly non-infectious if they took treatment – it takes time for viral loads to fall. However post-diagnosis behaviour change should contribute to reducing onward infections too.

Will Drug Resistance Jeopardise Treatment As Prevention?

Deenan Pillay of University College London and the Africa Centre for Health and Population Studies raised the question of whether drug resistance could jeopardise the success of treatment as prevention (and of treatment itself). Recent studies show that drug resistance rates have been climbing in this decade, after falling in the previous one. The proportion of virus that is drug resistant depends on patient adherence and the efficacy of treatments in suppressing viral load, but Pillay said that mathematical models show that as the number of HIV infections fall due to successful viral load suppression, so the proportion due to drug-resistant viruses would inevitably rise – and that it would rise somewhat more quickly if every diagnosed person was on treatment rather than just some people.

At present the proportion of people who are infected with resistant virus, as opposed to developing it on treatment, is at its highest in North America, with about 14% of gay men infected with HIV with some drug resistance, but this would rise (in the general population) to about 28% in the next 20 years if universal ART was offered but diagnosis rates did not rise, to as much as 48% if they did rise.

However, resistance does not necessarily mean treatment failure. The proportion of patients with resistance to any ‘third agent’ drugs – i.e. any class apart from the nucleosides (NRTIs) – was about 6% in the global south and 3% in high-income countries (due to better monitoring). Although some resistance to NRTIs was common, the prevalence in transmitted virus of the K65R class-limiting mutation, which stops tenofovir and abacavir working, was only 0.3% in the south and 0.1% in the high-income world.

Pillay reminded delegates that having ‘too many’ people on treatment was not a problem we currently had to face. Even in the population surveyed by the Africa Centre, only 30% of people were diagnosed within a year of infection and less than 5% started ART: within five years of infection, though 70% had tested, only 40% were linked to care and 20% were on ART.

Testing, Stigma And Disclosure

Finally, Valerie Delpech of Public Health England outlined how even high rates of treatment might not bring down HIV incidence, simply because the number of people with HIV in some populations – including gay men in the UK – continues to grow. In the UK, 87% of people diagnosed with HIV are on treatment – just short of the UNAIDS target. And encouragingly, even though BHIVA guidelines recommend treatment below a CD4 count of 350 cells/mm3, doctors seem to be taking to heart these guidelines’ recommendation that treatment as prevention is discussed as an option with patients. In 2008-9, the proportion of people starting ART at a CD4 count of over 500 cells/mm3 was only 10%, but by 2012 this had risen to 25%, and the proportion starting above 350 cells/mm3 is now 50%.

Although the proportion undiagnosed may have fallen slightly, from 27% in 2008 to 22% in 2012, HIV incidence in gay men has stayed virtually flat at about 2500 cases a year. This is partly because the message that gay men should test frequently has not been taken on board in the UK: only 40% test more than once a year. If this proportion was increased to 90% (as in the case in some parts of the US), it is estimated that the number of infections in gay men could fall to as low as 1000 a year.

However, Delpech emphasised that it was not necessarily a simple matter to achieve such frequent testing. There needed to be better community engagement and the support of non-HIV NGOs; the ‘syndemic’ of depression, substance use, stigma, violence and low disclosure rates in gay men also needed to be addressed. She ended by quoting statistics from the Positive Voices survey, which showed that 45% of patients said “It is very hard to tell people about my HIV status” and that 24% said “I worry very much about transmitting HIV”. The success of treatment as prevention may be imperilled as much by the social fear of HIV as much as by rates of testing, early diagnosis, retention, viral suppression and resistance, she emphasised.



Symposium no 3: Treatment as Prevention: The Promise and the Perils. HIV Research for Prevention (HIV R4P) Conference, Cape Town. 2014.




Setting A Course
For A Sustainable
Future in 2015


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In this article, Secretary-General of the United Nations, Ban Ki-Moon, talks about the ideas and trends that he believes will shape 2015, the importance of sustainability and the role of the private sector in achieving a sustainable future.


2015 will be an historic year for the United Nations. The Organization will celebrate its 70th anniversary, offering a chance to look back on its contributions to peace, human rights and development since its creation in 1945. The year will also be an opportunity to look forward -- and in particular how to ensure that people everywhere can thrive on our one and only planet. 2015 is when we will set our course for a sustainable future.

At its essence, sustainability means ensuring prosperity and environmental protection without compromising the ability of future generations to meet their needs. A sustainable world is one where people can escape poverty and enjoy decent work without harming the earth’s essential ecosystems and resources; where people can stay healthy and get the food and water they need; where everyone can access clean energy that doesn’t contribute to climate change; where women and girls are afforded equal rights and equal opportunities.

There is no country or society where sustainability is not important or necessary. We all share the responsibility to work for a sustainable future and we will all reap the benefits.

Three high-level international meetings in the year ahead give us the opportunity to chart a new era of sustainability. The first will be the International Conference on Financing for Development in Addis Ababa in July. The second will be the special Summit at UN Headquarters in New York in September, where world leaders will adopt a new development agenda, including a set of Sustainable Development Goals, expected to provide a blueprint for action until 2030. Then, in December, the groundswell of momentum for action on climate change will culminate at the UN Climate Conference in Paris to adopt a universal and meaningful climate agreement.

Many sustainability issues were addressed fifteen years ago when world leaders adopted the Millennium Development Goals -- or MDGs -- global targets to address extreme poverty and hunger, reduce child and maternal mortality, prevent disease and promote education. The Goals brought together diverse groups from across the world to join forces for what has become the most successful anti-poverty push in history. The lives of millions of people have been improved through MDG action. Global poverty continues to decline, more people have access to safe drinking water, more children than ever are attending primary school, and targeted investments in fighting malaria, AIDS and tuberculosis have saved millions.

We have made huge progress, yet much more is needed, especially to reach the most marginalized and vulnerable— the women, men and children living on a knife-edge of poverty, injustice and insecurity.

While the issues addressed by the MDGs persist, the world is facing a challenge that was not sufficiently high on the international agenda when the MDGs were articulated. We must now keep fighting poverty while addressing the growing impacts of a warming world.

Climate action is integral to a sustainable future. Just as more than 7 million people have participated in the MyWorld survey to share their vision of a sustainable future, this year saw hundreds of thousands of citizens showing their support for climate action— on the streets, online and through the consumer power of their spending choices. In New York City, just ahead of September's Climate Summit, I joined throngs of people marching for a cleaner, greener future. They sent a powerful message to the leaders— that they want action now. The Summit was a landmark event at which multi-stakeholder coalitions announced important steps to reduce emissions, build resilience and finance the transformation of our economies and societies.

The private sector has an essential role in achieving a sustainable future. Many of the recent successes in development and climate change have been achieved through public-private partnerships with the power to mobilize finance, expertise and knowledge. A sustainable approach to business can also help create decent jobs, improve public health, empower women and protect the environment. It is heartening to see many companies already reaping the benefits of climate action, for instance by reducing greenhouse gas emissions and by using energy cleanly and efficiently. More and more businesses are seeing that sustainability is not just in the common good but that sustainability is common sense.

In December I presented to all UN Member States my latest report, “The Road to Dignity by 2030”, which is meant to assist them as they shape an inspirational vision – including a set of Sustainable Development Goals -- for achieving shared prosperity and leaving no one behind. The United Nations is strongly committed to leading and supporting a transformative effort that will end poverty, tackle inequalities, protect our planet and promote just, safe and peaceful societies for all.

As we look back at 2014, we see a year marred by multiple security and humanitarian crises, many challenging the principles enshrined in the UN Charter. The UN is working hard to find solutions to complex crises which, aside from the terrible toll on people, have a devastating impact on development. When a society is affected by conflict, schools have to close, vaccination campaigns have to stop, infectious diseases spread unchecked and mothers have no safe place to deliver their babies. Problems arising from under-development can also be a driver of conflicts in the first place. Without peace and stability, there can be no sustainability; and a sustainable world is a safer one.

Seventy years ago the crafters of the UN Charter, living in a world torn apart by war and atrocities on a scale never before seen, laid down their vision for a better way of life. In 2015, we have the opportunity to move humankind towards the future we want. We must meet this test and usher in a new era of sustainability for all.