Clinical trials and scientific discoveries give renewed hope for an HIV vaccine

By – Professor Lynn Morris, Professor Carolyn Williamson & Dr Kathy Mngadi

We are at a pivotal point in the pursuit of a vaccine against HIV. Two large efficacy trials will begin in 2016, both aimed at testing whether antibodies can protect against HIV infection.

The first is a classical vaccine approach based on active immunization while the second will test a passively administered broadly neutralizing antibody. Results from these trials are expected in 3-4 years’ time at the earliest.

There have also been significant advances in the laboratory that are delivering new vaccine concepts which are being fast-tracked for testing. On the eve of AIDS 2016 we reflect on the progress we have made, since we last met in Durban in 2000, towards the development of the ultimate game-changer for the HIV epidemic: an HIV vaccine.

New vaccine trials in populations at risk of HIV infection

A major global effort has focused on building on the success of the first partially effective vaccine that was tested in Thailand in 2009, which protected 31% of people from HIV infection. Although protection has been linked to the presence of antibodies that bind to a part of the viral envelope (known as variable loop 2 or V2), the reason why this vaccine worked is still under investigation. HIV is a highly diverse virus and so the Thai vaccine was redesigned to target clade C viruses that are dominant in southern Africa.

The trial will recruit 5 400 people in South Africa at risk of HIV infection, who will receive a total of five vaccinations over a year. The vaccine is comprised of two parts, a canarypox vector prime (ALVAC) and a protein boost, both of which contain fragments of HIV that stimulate the body to mount an immune response to HIV.

If, after 3 years, at least 50% of people are protected, the vaccine will be considered successful and rolled out for general use. Even at this level of protection, this vaccine could have a significant impact on the epidemic. The decision to move forward with this vaccine was dependent on results from a smaller trial showing that it is safe and able to stimulate the right kinds of immune responses. As all criteria were met, the large vaccine trial known as HVTN 702 was given the green light in April 2016 and will start in November of this year.

It has taken seven years of planning and the formation of the Pox-Protein Public-Private Partnership (P5) to get to this point. P5 comprises the South African Medical Research Council, the National Institute of Allergy and Infectious Diseases (NIAID), the HIV Vaccines Trial Network (HVTN), the Bill and Melinda Gates Foundation, the US Military HIV Research Program and vaccine manufacturers (Sanofi Pasteur and GSK). A similar plan to test this vaccine in large efficacy trials is also planned for Thailand using the original vaccine that is based on circulating strains in that country.

Another vaccine, developed by Janssen Pharmaceuticals and which showed encouraging results in animal studies, is also on track for large scale testing in humans (possibly in 2017). This vaccine will also use a prime boost approach, however, in this case, it will comprise an Adenovirus 26 (Ad26) vector and a protein boost. The vaccine contains mosaic HIV genes that are designed to target viruses from around the world and will be evaluated in southern and east Africa, as well as in Asia.

Other promising vaccines that are still in the animal phase of testing include a cytomegalovirus-based vector, which persists for a long time following vaccination and induces an extraordinarily large number of cellular immune responses. An HIV vaccine based on VSV that was used to make the successful Ebola vaccine is also under development.

Ramping up to AMP

Probably the most remarkable development in the vaccine space has been the advent of passive immunization for HIV prevention.

This new approach was made possible as a result of the discovery of broadly neutralizing antibodies that have the ability to kill a large number of HIV viruses from different clades. A vaccine with high efficacy is likely to require antibodies with this kind of activity, but to date no vaccine has managed to do this. However, the isolation of these antibodies from infected people, and the ability to make them in large quantities in the laboratory, has allowed us to directly test this.

This is the concept behind the ‘AMP’ (antibody mediated protection) study, which started in the Americas and Africa in 2016 and will enrol a total of 4 200 people at risk of HIV infection. This trial is being done as a collaboration between the HVTN and the HIV Prevention Trials Network (HPTN). A monoclonal antibody, called VRC01, will be directly infused into the bloodstream of human volunteers to determine whether it can protect against HIV infection and what levels of antibody are needed. The antibodies will decay over time, and repeated infusions will be needed to keep the levels high enough to provide protection.

The use of antibodies as passive immunisation is a well-established approach to provide protection from other infectious diseases such Rabies and Respiratory Syncytial Virus. This monoclonal antibody, while providing invaluable information for vaccines, is not planned as an end-product as there is a pipeline of better, more potent antibodies which can be used alone, or in combination to increase the chances of killing more viruses.

Other modes of antibody delivery, including subcutaneous injections and gene therapy, are also being explored. It is important to remember that passive immunization provides temporary protection, unlike a vaccine which generally gives life-long protection.

How basic research is helping us make better vaccines

Until now, a major hurdle in the development of an HIV vaccine has been the inability to make proteins that look like those on the virus particle and are suitable for manufacture. The trimeric viral envelope spike which is the target of neutralizing antibodies is a highly complex protein that has eluded structural biologists for decades. With new technologies this puzzle has finally been solved and initial studies in animals have shown that these laboratory-generated envelope proteins do induce better neutralizing antibodies. There is a major push to test these proteins in small experimental trials to see if they can stimulate neutralizing antibodies in human volunteers.

How to elicit broad and potent neutralizing antibodies remains the biggest challenge in vaccine research. This is because HIV has devised cunning ways to avoid detection by the immune system. It has an extraordinary ability to mutate and in addition the HIV envelope cloaks itself with sugars (glycans) making it difficult for antibodies to reach vulnerable sites. This plasticity allows HIV to continually evade the neutralizing antibody response, like a perpetual game of cat and mouse.

Furthermore, only some HIV-infected people make broadly neutralizing antibodies after many years into the infection. This, together with the unusual features of HIV antibodies, highlights how difficult it is for the human immune system to make these types of protective antibodies.

Several landmark studies in the last few years by a number of research groups around the world have provided clues as to why and how some HIV infected people make broadly neutralizing antibodies. These studies were only possible because of HIV infected people enrolling into studies and continuing to participate in them for long periods of time.

Perhaps one of the most important clues is the need for the immune system to see and adapt to variation in the viral epitope that is the target of broadly neutralizing antibodies. What that means for vaccination strategies is that we may need to make and test a whole series of vaccines that vary slightly from each other and that drive the antibody response along the pathway towards neutralization breadth. In other words we need to mimic viral evolution by vaccination. This is unprecedented in the history of vaccination and would obviously make the manufacture and delivery of such a vaccination approach more complex.

The journey of vaccine discovery

Even though an HIV vaccine remains elusive, we have come a long way since Durban 2000. Unlike vaccines for Ebola (and possibly Zika), HIV presents a far bigger scientific challenge. That we still do not have an effective HIV vaccine despite tremendous efforts is testimony to the inherent difficulties in doing this. The next decade is likely to bring more significant advances and we await the outcome of the two large efficacy trials with anticipation. Successful products would, without doubt, bring about a major paradigm shift in the fight against the global AIDS epidemic.

* Professor Lynn Morris is the Head of HIV Research at the National Institute for Communicable Diseases.

*Professor Carolyn Williamson is the Head of the Division of Medical Virology at the Institute of Infectious Disease and Molecular Medicine, Professor at University of Cape Town.

*Dr Kathy Mngadi is Honorary Lecturer in the School of Laboratory Medicine and Medical Science at the University of KwaZulu-Natal

A cure for HIV: Are we getting any closer?

By – Dr Thomas A. Rasmussen & Professor Sharon R. Lewin

Antiretroviral therapy (ART) has revolutionised the lives of people living with HIV and in many countries, life expectancy for someone living with HIV is now almost the same as someone not living with HIV. But ART is not a cure.

When ART is stopped, the virus rebounds within a few weeks in almost all infected individuals, even after many years of suppressive therapy. Understanding where and how HIV persists on ART and using these insights to develop therapies, which will ultimately enable us to cure HIV infection, or allow people living with HIV to safely stop ART with the virus staying under control, remain key goals in HIV research.

Over the past decade, there has been a substantial increase in our understanding of where and how HIV persists when someone is on ART. It is now clear that integration of the HIV genome into long-lived resting cells is a major barrier to a cure. This state is called HIV latency. But virus can also persist on ART in other forms. In both monkey models of HIV and in HIV-infected individuals on ART, virus has been found in T follicular helper cells, which are found in a specialised compartment in the lymphoid tissue. These cells are found in a part of the lymph node where penetration of immune fighting cells, or cytotoxic T-cells is limited. In some tissues, penetration of ART may not be optimal, which could also contribute to persistence. Finally, there is also some evidence that, in at least some individuals and in some sites, the virus may still be replicating at very low levels.

To date, there has been just one case of a cure for HIV, which occurred in the context of haematopoietic stem cell transplantation (HSCT) for leukaemia with HIV-resistant donor cells. HSCT is clearly not a feasible curative strategy for HIV, but we have learnt here that complete eradication of HIV is theoretically possible. Similar approaches have been tried, but no others have yet been successful and all six individuals receiving a similar transplant died of infection or cancer relapse within 12 months of transplantation.

Scanning electron micrograph of HIV-1 budding (in green) from cultured lymphocyte. This image has been coloured to highlight important features.
Scanning electron micrograph of HIV-1 budding (in green) from cultured lymphocyte. This image has been coloured to highlight important features.

Other case reports have confirmed that HSCT, even from a regular stem cell donor, can drastically reduce the frequency of infected cells, but when ART was subsequently discontinued, virus still rebounded off ART, although it took months and not weeks to rebound. These cases demonstrate that although reducing the frequency of latently infected cells might delay time to viral rebound, there is a need for continued effective immune surveillance against HIV to keep whatever remains in check.

Using gene therapy to either make a cell resistant to HIV or to literally remove HIV from the cell is now being actively investigated. The initial target of gene therapy was CCR5 – the same gene that is missing in some rare individuals that are naturally resistant to HIV. Clinical trials of gene therapy to eliminate CCR5 and make cells resistant to HIV was safe, but there remains much work to be done to increase the numbers of gene-modified cells. Other work, which still is at the stage of test-tube experiments, uses gene scissors to target the virus itself. This approach might be trickier than targeting CCR5 as the virus can rapidly mutate and change its genetic code so that the gene scissors no longer work.

By starting ART very early – within days to weeks of infection – it is possible to substantially reduce the number of latently infected cells, and this also helps preserve immune function. Although not an option for the majority of HIV-infected individuals who are diagnosed too late, early diagnosis and treatment could be an effective strategy to maintain immune control for some patients. Several years ago, French investigators described that post-treatment control was possible in up to 15% of individuals treated within months of infection. These data remain a little controversial as in other cohorts, post-treatment control is far less common. We still don’t fully understand what factors are important for post treatment control, but it seems that the nature of the immune is critically important. Interestingly, post-treatment control may differ in different ethnic groups. A recent report from Africa suggested that post-treatment control could occur at far higher frequencies in African populations than in Caucasians.

Early treatment of HIV-infected children at birth may also present an opportunity to induce post- treatment control. In the highly publicised case of the Mississippi child, ART was started 30 hours after birth and following cessation of ART at age 18 months, this child had a period of 2 years of post-treatment control. Early treatment of infants may potentially shift virus from hiding in long-lived to short-lived T-cells. Therefore, understanding the differences in where virus persists in children and in adults could provide important insights into novel strategies to find a cure for HIV. We will hear a lot about these approaches in Durban.

The reality is that most people globally are diagnosed with HIV years and not days after infection. The main strategies being tested to achieve remission is to reduce the amount of persistent virus and also boost the immune response to allow for long term control.

Activating the expression of HIV proteins in latently infected cells by drugs called latency-reversing agents could drive elimination of virus-expressing cells through immune- or virus-mediated cell death. This approach is usually referred to as “shock and kill”. A substantial body of research has helped identify latency-reversing agents including histone deacetylase inhibitors and disulfiram, which have now been tested in experimental clinical trials. These studies demonstrated that although HIV expression can be induced in patients on suppressive ART, this did not reduce the frequency of infected cells. In other words, shock but no kill.

On-going studies are looking at ways to augment the killing of these cells by boosting the immune system, for example through vaccines or medications that trigger suicide of the infected cells. Cure research is likely to benefit from the very significant investment in vaccines that have been developed to protect people from getting infected, some of these vaccines could work in cure too – for example vaccines that potently stimulate cells that are programmed to kill infected cells or alternatively highly effective antibodies, called broadly neutralising antibodies, that can also trigger killing of an infected cell. These vaccines are now being investigated in the setting of clinical trials in infected individuals on ART.

There have been some spectacular recent advances in the treatment of some cancers using drugs that boost the immune response – called immune checkpoint blockers.

These drugs reinvigorate exhausted T-cells so they can move in to action – against cancer cells and in the same way, against HIV-infected cells. These drugs, one that blocks CTLA4 and another that blocks PD1 are now in clinical trial in HIV-infected patients being treated for different cancers. Another way to boost the immune system is to trigger a very primitive immune response designed to respond to infections. These drugs are called toll-like receptor (TLR) agonists. In monkeys, TLR-7 agonists, currently being developed by Gilead, stimulate latently infected cells and an effective immune response leading to a modest reduction in infected cells. Clinical trials are now underway in HIV-infected individuals on ART.

 

Now, four years after the launch of the 2012 International AIDS Society (IAS) Global Scientific Strategy Towards and HIV Cure, we have had some successes and failures. We now have a clearer idea of where virus persists on ART, but still much to learn about different T-cell subsets and what happens inside tissue. We need better ways to measure total virus, especially virus that can rebound. Some advances in X-Ray imaging might help here, which could give a total snap shot of where the virus is sitting in the body. We also now know that activating latent virus is not enough to kill the cells. Other interventions are needed. A successful strategy will likely need two components – reducing the amount of virus that persists on ART and improving long-term immune surveillance to target any residual virus. We need far more work to be done on HIV cure in low income settings to better understand the effects of different HIV strains, the effects of co-infection and the impact of host genetics. Lessons from other fields, particularly oncology, transplantation and fundamental immunology, are all relevant to inform the next advances we need in cure research. Finally, we have to ensure that any intervention leading to a cure must be cost effective and widely available.

The implementation of combination ART in the mid-1990s is still regarded one of the most remarkable achievements in modern medicine. Life-long ART remains the single best option for any person infected with HIV. Finding a cure for HIV remains a major scientific challenge but many believe it to be within the realms of possibility and it will hopefully play an important role in seeing an end to HIV.

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*DR Thomas A. Rasmussen is a Clinical Research Fellow at the Doherty Institute

*Professor Sharon R Lewin is the Director of the Doherty Institute for Infection and Immunity and Professor at the University of Melboune

Dear Nkosi

By – Anso Thom

It has been 15 years since you exhaled for the last time, you would have turned 27 this year. I would imagine it was a relief…a long breath that spoke of having carried a heavy burden and responsibility in your much too short life.

You were the Hector Peterson of the HIV generation in the 80s and 90s, a reluctant hero and activist who smiled bravely when you first hit the headlines after your primary school were grappling with how to deal with your disease.

The rest, as they say, is history.

Nkosi Johnson
Nkosi Johnson

You spoke out often, your words speaking of an old soul that has experienced way too much, seen way too much with your big, beautiful eyes.

I recall the iconic image of you standing on that huge stage at Kings Park Stadium, the dark suit hanging onto your fragile and tiny frame. But your big heart was there for all to see. You had been rehearsing your speech for weeks, understanding and knowing that what you said would be important…I remember how excited and nervous you were at the thought that then President Mbeki would be in the audience, but I also remember your profound disappointment when you realized he had walked out before you had completed your speech. But Nkosi, you did not need for him to be there, thousands heard you, millions continue to repeat and hold onto those words that continue to reverberate around the world. Your speech touched so many:

Hi, my name is Nkosi Johnson. I live in Melville, Johannesburg, South Africa.
I am 11 years old and I have full-blown AIDS. I was born HIV-positive.

When I was two years old, I was living in a care centre for HIV / AIDS-infected people. My mommy was obviously also infected and could not afford to keep me because she was very scared that the community she lived in would find out that we were both infected and chase us away.

I know she loved me very much and would visit me when she could. And then the care centre had to close down because they didn’t have any funds. So my foster mother, Gail Johnson, who was a director of the care centre and had taken me home for weekends, said at a board meeting she would take me home. She took me home with her and I have been living with her for eight years now.

I know that my blood is only dangerous to other people if they also have an open wound and my blood goes into it. That is the only time that people need to be careful when touching me.

In 1997 mommy Gail went to the school, Melpark Primary, and she had to fill in a form for my admission and it said does your child suffer from anything so she said yes: AIDS.

My mommy Gail and I have always been open about me having AIDS. And then my mommy Gail was waiting to hear if I was admitted to school. Then she phoned the school, who said we will call you and then they had a meeting about me.

Of the parents and the teachers at the meeting 50% said yes and 50% said no. And then on the day of my big brother’s wedding, the media found out that there was a problem about me going to school. No-one seemed to know what to do with me because I am infected. The AIDS workshops were done at the school for parents and teachers to teach them not to be scared of a child with AIDS. I am very proud to say that there is now a policy for all HIV-infected children to be allowed to go into schools and not be discriminated against.

And in the same year, just before I started school, my mommy Daphne died. She went on holiday to Newcastle- she died in her sleep. And mommy Gail got a phone call and I answered and my aunty said please can I speak to Gail? Mommy Gail told me almost immediately my mommy had died and I burst into tears. My mommy Gail took me to my Mommy’s funeral. I saw my mommy in the coffin and I saw her eyes were closed and then I saw them lowering it into the ground and then they covered her up. My granny was very sad that her daughter had died.

I hate having AIDS because I get very sick and I get very sad when I think of all the other children and babies that are sick with AIDS. I just wish that the government can start giving AZT to pregnant HIV mothers to help stop the virus being passed on to their babies. Babies are dying very quickly and I know one little abandoned baby who came to stay with us and his name was Micky. He couldn’t breathe, he couldn’t eat and he was so sick and Mommy Gail had to phone welfare to have him admitted to a hospital and he died. But he was such a cute little baby and I think the government must start doing it because I don’t want babies to die.

Because I was separated from my mother at an early age, because we were both HIV positive, my mommy Gail and I have always wanted to start a care centre for HIV / AIDS mothers and their children. I am very happy and proud to say that the first Nkosi’s Haven was opened last year. And we look after 10 mommies and 15 children. My mommy Gail and I want to open five Nkosi’s Havens by the end of next year because I want more infected mothers to stay together with their children- they mustn’t be separated from their children so they can be together and live longer with the love that they need.

When I grow up, I want to lecture to more and more people about AIDS- and if mommy Gail will let me, around the whole country. I want people to understand about AIDS- to be careful and respect AIDS- you can’t get AIDS if you touch, hug, kiss, hold hands with someone who is infected.

Care for us and accept us- we are all human beings. We are normal. We have hands. We have feet. We can walk, we can talk, we have needs just like everyone else- don’t be afraid of us- we are all the same!”

(An extract from his speech delivered in July 2000).

I remember how excited you were at traveling to the United States to meet Robin Williams who you said made you laugh. You always loved jokes…you would tell the worst jokes and laugh the loudest. I think that is where my son got his crazy sense of humour from!

Do you remember when you once visited us in Cape Town. You were so sick already and I remember waiting for you at Cape Town International Airport and having to hide my shock at seeing how much you had deteriorated…the crust of thrush sitting thick around your lips, the windbreaker completely dwarfing your frame. You were so excited to be in Cape Town and immediately wanted to go and eat ribs – you ordered the biggest rack of ribs only to stare at it and asking if we could take it home. The thrush was so bad that it was impossible for you to eat most food. The diarrhoea became to severe that we rushed you to our doctor where she put you on a drip to tide you over even though you should have probably been in hospital.

You loved music so much, one of your favourites the soundtrack from The Commitments…You would listen to it over and over again and of course my CD went home with you!

Do you remember us going to the Carols by Candlelight at Kirstenbosch? You managed to get us a ride on the golf cart, all the way to the lawns where you lay in our laps, covered in thick blankets and singing each carol at the top of [your voice. Your look of amazement when you looked back and saw the sea of candles will always stay with me.

Nkosi, on 18 July we will all return to Durban. Some of us are returnees, others are newbies who joined the HIV activist bus along the way. I want to promise you that we will not go to Durban and accept empty rhetoric, lofty promises and articulate but empty political speeches. No, we will go to Durban expecting to live up to your dream where no child is born HIV-positive, no child needs to be separated from their mothers because of disease and poverty and stigma is just an ugly swear word.

This will be a conference where the South African government will hear your message, this we owe to you and to the many other children who faced the same fate.

Lala Kakuhle gentle, beautiful warrior, we will feel your presence in Durban we will carry you in our hearts and songs.

All our love, admiration and respect.

ANSO THOM is the Head of Communications at SECTION 27 and an editor of Spotlight.

Is HIV elimination a pipe dream?

 by Dr Leigh Johnson –

 

A number of UNAIDS publications have promoted the idea that it is possible to “end the AIDS epidemic by 2030”. There are several encouraging signs to suggest that this may be true. It is now well-established that patients who are on antiretroviral treatment (ART) and with suppressed viral loads are virtually non-infectious.With the recent revisions to WHO treatment guidelines, which now recommend ART for all HIV-positive individuals regardless of CD4 count or clinical stage, it is theoretically possible that a high proportion of HIV-positive individuals will be treated. This could drive down HIV transmission rates to very low levels. UNAIDS has stated that critical to HIV elimination will be the achievement of the ‘90-90-90’ targets: by 2020, 90% of the HIV-positive population needs to be diagnosed, 90% of diagnosed individuals need to be on ART, and 90% of patients on ART need to be virologically suppressed.

But how likely is HIV elimination? Central to answering this question are mathematical models, which attempt to predict the future based on observed historical trends in HIV prevalence, and based on assumptions about the effect of different HIV prevention and treatment strategies on HIV transmission. This article briefly reviews some of the recent modelling studies that have attempted to answer this question, and discusses some of the limitations and uncertainties associated with modelling.

The first point to note is that the term ‘HIV elimination’ is a misnomer. Most frequently, modelling studies refer to ‘virtual elimination’, which is conventionally defined as an adult HIV incidence rate of less than 0.1% per annum. But even if HIV incidence among 15-49 year olds were constant at 0.1% per annum, the long-term HIV prevalence in 15-49 year olds would not drop below 1.7% (assuming a relatively high ART coverage and a near-normal life expectancy on ART). This is still an appreciable HIV prevalence, even by the standards of many countries in West Africa.

Even if we accept this definition of HIV elimination, mathematical models are not conclusive about whether universal ART eligibility and high rates of HIV testing and ART uptake (so-called ‘test and treat’ strategies) would lead to elimination. In a systematic comparison of several different models that were applied to South Africa, Eaton et al found that out of nine models, six suggested that ‘test and treat’ strategies would not be sufficient to achieve virtual elimination by 2050. Notably, the models were generally quite optimistic about the extent to which ART would reduce HIV infectiousness (in all cases by 90% or more), though a subsequent systematic review of observational data estimated an average reduction of only 64%. It was also subsequently found that almost all the models had under-estimated the HIV prevalence that was measured in a South African household survey, conducted after the initial model projections were published. Although this points to the fallibility of mathematical modelling, it is perhaps more important to note that the models generally did not show that HIV elimination was a likely outcome, despite erring on the side of optimism.

A question that naturally follows is whether a ‘test and treat’ strategy might achieve HIV elimination when combined with other HIV prevention strategies. In a recent study, we attempted to address this question for South Africa by projecting future HIV incidence trends using a wide range of different intervention scenarios. This study predicted that – given the current uncertainty around HIV prevention and treatment programmes in South Africa – the virtual elimination target of 0.1% would be reached by 2035 in only 2% of scenarios (Figure 1). The model also predicted that although South Africa would probably reach the first 90% target by 2020, the second and third 90% targets were quite unlikely: in only 0.4% of scenarios were all three targets met.

Figure 1: HIV incidence trends in South African adults aged 15-49
Figure 1: HIV incidence trends in South African adults aged 15-49

Solid lines represent mean of model estimates. Dashed lines represent 95% confidence intervals (taking into account uncertainty regarding future epidemiological parameters). Shaded grey area represents virtual elimination threshold. Source: Johnson et al

This study also assessed which epidemiological parameters it would be most important to focus on in order to reduce HIV incidence. The most important parameter was the rate of virological suppression in ART patients: for every 10% increase in the fraction of ART patients who are virologically suppressed, it was predicted that there would be a 14% reduction in the average annual number of new HIV infections. This implies that increasing rates of virological suppression in South African ART patients from the current level of around 77% to the 90% target would achieve an 18% reduction in HIV incidence. Other parameters that were significant included the rate of condom use in non-cohabiting relationships, the introduction of intensified risk-reduction counselling for HIV-positive adults, and the uptake of medical male circumcision. Interestingly, the timing of the change to universal ART eligibility was only the 5th-most important parameter. This suggests that the recent change to universal ART eligibility is not by itself likely to have as dramatic an impact on HIV incidence as many other interventions.

The case of South Africa stands in stark contrast to the case of Denmark, the subject of another recent modelling study. In this study, it was estimated that in 2009 the HIV incidence among Danish men who have sex with men (MSM) was 0.14% per annum, very close to the virtual elimination threshold of 0.1%. Although the fraction of HIV-positive adults in Denmark who were diagnosed was very similar to that estimated in South Africa (around 80% in 2013), the fraction of diagnosed individuals on ART was 92%, and the fraction of ART patients who were virologically suppressed was 98% – both well ahead of South Africa (Figure 2).

Figure 2: Treatment cascades in Denmark and South Africa in 2013
Figure 2: Treatment cascades in Denmark and South Africa in 2013

As the authors of this study note, Denmark is exceptional. In many other high income countries, there has been a resurgence in HIV incidence among MSM, despite increasing levels of ART coverage. This resurgence is often attributed to risk compensation and ‘disinhibition’, i.e. increased levels of sexual risk behaviour due to reduced fear of HIV in the era of highly effective therapy – and perhaps also reduced public messaging around safe sex as the HIV response has become increasingly medicalised.

Taken together, these results suggest that treatment alone is not going to end the HIV epidemic, although it might be possible in concentrated epidemic settings with exceptionally high levels of virological suppression. It will be important not to neglect the ‘traditional’ HIV prevention strategies in the pursuit of the 90-90-90 targets, and the allure of new prevention approaches should not detract from the need to sustain and improve existing programmes. But even with co-ordinated strengthening of existing programmes and introduction of new prevention approaches (such as universal ART eligibility and pre-exposure prophylaxis), it is unlikely that virtual elimination will be achieved in hyper-endemic settings such as South Africa within the next 20 years. Even if ‘elimination’ is achieved, there would need to be continued high levels of HIV testing and HIV prevention messaging over the longer term if a resurgence in HIV were to be avoided. Achieving true elimination will require fundamentally new technologies such as HIV vaccines. Until we have these in place, HIV elimination needs to be seen as an aspirational ideal rather than a practical target.

DR Leigh Johnson is a Researcher at the Department of Public Health & Family Medicine for the University of Cape Town.