The HIV epidemic predates the Internet and today’s youth have never known a world without it, says Dr Linda-Gail Bekker, president of the International AIDS Society and deputy director of the Desmond Tutu HIV Centre. ‘But the medical advances that have transformed HIV treatment have yet to alter the stark reality for young people, particularly in low- to middle-income countries.’
Bekker writes in a CNN report: “It arrived before the Internet, before the Berlin Wall came down, and at a time when you could still smoke on airplanes. It can be difficult to fathom but, unlike those of us from earlier generations, today’s young people have never known a world without Aids.
“Since those frightening early days of the epidemic, when few survived an HIV diagnosis, the introduction of antiretroviral therapy in the mid-1990s dramatically altered our ability to manage HIV infection. After Aids-related mortality peaked in 2004, Aids-related deaths have fallen by 42%.
“But the medical advances that have transformed HIV treatment have yet to alter the stark reality for young people, particularly in low- to middle-income countries, such as those in sub-Saharan Africa, and young people within key populations. Even as Aids-related mortality overall decreased in recent years, Aids-related deaths among adolescents increased by 50%. Aids, in other words, is far from over, especially for young people. Infection is still a real and continuing threat for them. The world needs to know about the socio-cultural factors that influence the spread of HIV and that there are new tools available, such as pre-exposure prophylaxis, or PrEP, to fight the disease.
“Simultaneously, the world also needs to respond and scale up investment in infrastructure to increase access to the tools we know work.
‘HIV is the second leading cause of death among adolescents globally and the No 1 cause of death among adolescents in Africa. Adolescent girls and young women are particularly vulnerable, accounting for a startling 91% of new HIV infections among people aged 15-19 in sub-Saharan Africa, whereas young men in the same age group represent roughly 11%.
“The tragic reality is at the threshold of adulthood when they are poised to realise their full human potential, millions of young people worldwide acquire a life-threatening disease.
“How is this happening? In high-prevalence settings, many HIV-negative young women – who face limited educational or economic opportunities, exacerbated by gender-based violence – have their earliest sexual relationships with older men. These older men are far more likely than younger men to be living with HIV, as men’s HIV risk steadily increases with age. This pattern is only one of many that increase young people’s risk of acquiring HIV.
“Young people at risk of HIV are as diverse as the world itself. No ‘one size fits all’ option exists to protect them from infection. To truly reach adolescents, we do not need one single thick blanket approach pulled over everyone. Rather, we need multiple layers of different interventions that cover different areas and that can be layered thickest where the force of infection is high. This means that prevention programs need to focus their efforts where they will have the greatest impact. Nigeria alone, for example, accounts for more than a quarter of the 150,000 new infections in children last year.
“The good news is that the toolkit for HIV prevention has dramatically expanded in recent years. The new kid on the block, PrEP, is set to change the game again. Through PrEP, the same drugs used to treat HIV infection can also sharply reduce the risk of HIV acquisition if taken regularly by HIV-negative individuals. Although PrEP is a potential game-changer for HIV prevention – including for young women, who often lack the means to get their male partners to use a condom – we are only at the very beginning of efforts to make this new tool widely available to the young people who need it. Given the scarcity of youth-friendly clinical services in many parts of the world, innovation, commitment and focused funding will be needed to establish health delivery options that meet young people’s specific needs.
“Moreover, biomedical tools such as PrEP, although essential, are unlikely on their own to reverse the epidemic among young people. This is because this population often experiences social and structural factors that increase their risk of acquiring HIV and diminish their ability to access essential services. Addressing these structural factors – for instance, by keeping young people in school – helps ensure that young people are informed and safe.
“Keeping young people in school increases HIV prevention, as a young girl’s risk of contracting HIV is halved for every additional year of secondary school that she obtains. The DREAMS project of the United States Emergency Plan for AIDS Relief, as well as youth-oriented national initiatives, such as those in South Africa and Kenya, are working to strengthen HIV prevention by investing in efforts to mitigate the social and structural factors that increase young women’s HIV risks.”
Professor Bekker writes in The Conversation that the rate at which people are being infected by HIV remains greater than that at which people are initiating treatment. She says this imbalance will stop the eradication of HIV/Aids, adding that the mismatch begs for increased investment in primary prevention. Primary prevention caters for people who are HIV-negative. It aims to reduce their chance of becoming infected, Bekker says.
She writes: “In certain populations, known as key populations, the burden of infection is disproportionately high. These include men who have sex with men, sex workers, people who inject drugs, transgender people, and, in sub-Saharan Africa, adolescent girls and young women. Primary prevention should be tailored, and scaled up, for these groups.
Bekker writes that numerous clinical trials and demonstration projects in diverse settings and populations have been conducted with PrEP all showing that it works, that it is easy to take and also that it is largely side-effect free and safe. However, she notes, the one hitch is that it has to be taken consistency at the time of HIV exposure and adherence has been oral PrEP’s biggest stumbling block.
Bekker writes: ‘That is why a huge effort is being made to find alternative ways to take PrEP. New formulations in the pipeline include long-acting injections, monthly vaginal rings, implants and topical gels, films and dissolving topical pills. The hope is that new formulations will make PrEP more accessible and convenient, particularly for adolescents and young people who may find a daily intervention cumbersome.”
Bekker emphasises that adherence is key. To block HIV transmission PrEP must be “in the system” at the time of HIV exposure. Its effectiveness decreases rapidly when this “effective coverage” is inconsistent. Good adherence gives almost 100% HIV transmission prevention. Poor adherence results in little to no protection.
Bekker says that in PrEP trials the following reasons were given for poor adherence: fear/experience of side effects; fear of interactions with alcohol and other drugs; forgetfulness; dislike of pill-taking, and fear of the discrimination associated with taking an anti-HIV pill. She says alternative dosing strategies using longer-acting formulations and PrEP delivery methods may well be another way to increase PrEP effectiveness.
Topical gels, which can be applied before and after sex to rectal and vaginal tissue, were the first alternative formulations to be tested. But the results in women have been inconsistent. She says this formulation still holds promise in men who have sex with men although efficacy trials have not yet been conducted.
An alternative strategy is a monthly vaginal ring, which in its current form contains slow-release dapivirine (an antiretroviral). Two large phase III clinical trials have demonstrated that the ring is effective and can reduce the chance of HIV infection by 27%-31%. In a sub-analysis of different ages, older women once again fared better than young women.
Bekker points out that the benefit of the vaginal ring is that there are fewer side effects because the drug is released locally and only a small amount enters the blood stream. The other huge advantage is that women are encouraged to insert and forget it, only changing the ring monthly. The limitation is that it is only suitable for women and vaginal intercourse. The vaginal ring is undergoing further investigation.
Bekker writes that another tool that is being investigated and could overcome the need for a daily pill is a long-acting monthly injection. “An injection of the antiretroviral cabotegravir (cabotegravir LA) has been shown to be very effective at lowering viral loads in people being treated for HIV when administered every two months. Also being investigated are dissolving vaginal films – a bit like breath fresheners – as well as quick-dissolving pills.”
Bekker writes that perhaps most exciting of all is the prospect of an implant, a small rod that can be surgically placed just under the skin and will slowly release antiviral protection over months. She says new formulations are being investigated that will combine treatment for contraception and preventing sexually transmitted infections. It is hoped that these multifunctional preventions may further encourage people to use these products consistently.
Bekker writes that in sub-Saharan Africa, teenage girls and young women are most at risk of HIV infection. There are 2,000 new infections in this group every week. She says these women are vulnerable because of the high prevalence of gender-based violence and the commonality of age-disparate relationships and transactional sex. These conditions can make it difficult for women to negotiate safer sex practices and, she says, PrEP would enable these women to protect themselves in advance, without their partner’s knowledge or consent.
Kenya and South Africa are the only African countries that have granted regulatory approval for PrEP. Neither have started to roll it out.
Bekker writes that new interventions can only be useful if deployed and scaled up to the populations most in need. This raises questions of cost versus impact. “It is hoped new formulations and delivery systems will enhance choice, encourage use, and provide a platform from which PrEP distribution can be advocated,” she is quoted as saying.
In their statement marking World Aids Day 2016, Dr Anthony S Fauci, director, US National Institute of Allergy and Infectious Diseases and Dr Carl W Dieffenbach, director, division of Aids, NIAID say:
“This year, the world marked the 35th anniversary of the first published reports of what would come to be known as HIV/Aids. This disease has wrought enormous suffering and devastation and caused more than 35m deaths. Yet today, thanks to remarkable achievements in biomedical science and public health, we have the tools to build a better future for individuals living with HIV and for those at risk of infection. We are hopeful that new approaches currently under exploration could expedite the end of the HIV/Aids pandemic.
“The greatest scientific accomplishment in HIV research has been the development of effective treatments that suppress the virus and prolong the lives of those living with HIV. Over time, scientists have refined and optimised antiretroviral therapy, delivering safer, more effective drugs that are easier to take. Today, a person living with HIV on antiretroviral therapy can expect to live a nearly normal lifespan.
“Antiretroviral therapy has been transformational for both individuals and communities. Large studies conducted in diverse settings, from US cities to African villages, have demonstrated the power of treatment to preserve the health of those living with HIV. Additionally, studies have proven that when an individual living with HIV is on antiretroviral therapy and the virus is durably suppressed, the risk that he or she will sexually transmit the virus is negligible. Research also has repeatedly demonstrated that HIV incidence diminishes when HIV testing is aggressively implemented, individuals with HIV infection are linked to treatment, and support is provided to keep them in care. The power of treatment as prevention cannot be underestimated in helping to achieve global targets to dramatically reduce new infections and improve the health of those already living with HIV.
“The National Institutes of Health (NIH) is supporting the development of new, innovative methods to prevent the spread of HIV, building on proven HIV prevention tools such as antiretroviral treatment; condoms; voluntary medical male circumcision; and pre-exposure prophylaxis (PrEP), a daily pill that uninfected people can take to prevent infection.
“Earlier this week, NIH announced the start of HVTN 702, a large HIV vaccine efficacy trial in South Africa that builds on the modest success of the RV144 vaccine trial conducted in Thailand. The HVTN 702 vaccine candidate is designed to prevent infection by the HIV strain most commonly found in southern Africa. About 3,700 people become infected with HIV every day in sub-Saharan Africa.
“In April, NIH launched the Antibody-Mediated Prevention Trial (AMP) to test whether a broadly neutralising antibody delivered intravenously to uninfected individuals is safe, tolerable and effective at preventing HIV infection. Many scientists believe that if an HIV vaccine could elicit broadly neutralizing antibodies in people, it would protect them from infection. By giving participants this antibody directly, researchers expect to gain critical insights to inform HIV prevention and vaccine science.
“NIH is testing HIV prevention options that address the unique needs of women, such as a vaginal ring infused with the antiretroviral drug dapivirine, which reduced the risk of HIV infection by only a modest 27 percent in a large clinical trial reported this year. Additional analyses suggest that this product may be much more effective when used regularly. A study launched in July aims to clarify further the relationship between adherence to the ring and efficacy, as well as to understand better the complexities women face when adhering to a vaginal ring.
“Science has made remarkable strides in preventing the transmission of HIV from mother to infant during pregnancy, birth and breastfeeding. This summer, researchers reported the results of the PROMISE study, which demonstrated that for mothers living with HIV whose immune systems are in good health, taking a three-drug antiretroviral regimen during breastfeeding essentially eliminates HIV transmission to their infants.
“While preventing new infections is essential, it remains critical that the 36.7m people living with HIV globally benefit from cutting-edge science. Today’s treatments are lifesaving, yet people living with HIV still suffer from higher rates of chronic disease than their uninfected counterparts.
“Clinical trials are exploring interventions to help prevent these diseases. One example is the REPRIEVE study, a large, international trial exploring the use of a statin drug to prevent heart disease in women and men living with HIV.
“Researchers also are working toward the goal of inducing sustained viral remission or absence of viral rebound following discontinuation of antiretroviral therapy. They are testing a number of approaches to successfully withdraw antiretroviral therapy in individuals whose virus is well controlled.
“In October, a provocative and potentially important advance was achieved in an animal study: An antibody directed against a cell surface marker involved in the homing of lymphocytes to the gut given together with antiretroviral therapy for 5 weeks in monkeys infected with a monkey version of HIV led to a sustained suppression of viral rebound for up to 2 years following discontinuation of all therapy. A study is now underway to explore this strategy in people living with HIV.
“These global efforts bring hope on this World AIDS Day that an end to the HIV/Aids pandemic is achievable. We applaud the trial participants, researchers, health care professionals, advocates and others who are working to make this future a reality.”
“Today… we stand in solidarity with the 78m people who have become infected with HIV and remember the 35m who have died from Aids-related illnesses since the first cases of HIV were reported,” said Michel Sidibé, executive director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), under-secretary-general of the UN in his statement commemorating World Aids Day.
He said: “The world has committed to end the Aids epidemic by 2030 as part of the Sustainable Development Goals. We are seeing that countries are getting on the Fast-Track – more than 18m people are on life-saving HIV treatment and country after country is on track to virtually eliminate HIV transmission from mother to child.
“We are winning against the Aids epidemic, but we are not seeing progress everywhere. The number of new HIV infections is not declining among adults, with young women particularly at risk of becoming infected with HIV.
“We know that for girls in sub-Saharan Africa, the transition to adulthood is a particularly dangerous time. Young women are facing a triple threat: a high risk of HIV infection, low rates of HIV testing and poor adherence to HIV treatment.
“Co-infections of people living with HIV, such as tuberculosis (TB), cervical cancer and hepatitis C, are at risk of putting the 2020 target of fewer than 500 000 Aids-related deaths out of reach. TB caused about a third of Aids-related deaths in 2015, while women living with HIV are at four to five times greater risk of developing cervical cancer. Taking Aids out of isolation remains an imperative if the world is to reach the 2020 target.
“With access to treatment, people living with HIV are living longer. Investing in treatment is paying off, but people older than 50 who are living with HIV, including people who are on treatment, are at increased risk of developing age-associated noncommunicable diseases, affecting HIV disease progression.
“Aids is not over, but it can be if we tailor the response to individual needs at particular times in life. Whatever our individual situation may be, we all need access to the tools to protect us from HIV and to access antiretroviral medicines should we need them. A life-cycle approach to HIV that finds solutions for everyone at every stage of life can address the complexities of HIV. Risks and challenges change as people go through life, highlighting the need to adapt HIV prevention and treatment strategies from birth to old age.
“The success we have achieved so far gives us hope for the future, but as we look ahead we must remember not to be complacent. We cannot stop now. This is the time to move forward together to ensure that all children start their lives free from HIV, that young people and adults grow up and stay free from HIV and that treatment becomes more accessible so that everyone stays Aids-free.”
“There is no magic bullet to solve the Aids problem,” according to Professor Salim S Abdool Karim, chair of the UNAIDS Scientific Expert Panel, the director of the Centre for the Aids Programme of Research in South Africa (CAPRISA), based at the University of KwaZulu-Natal, and the CAPRISA professor of global health at New York’s Columbia University.
Stephen Coan reports that Abdool Karim was referring to the UNAIDS 90-90-90 initiative launched in 2014 which aims to end the Aids epidemic by 2030 with 2020 as the target year when 90% of those living with HIV will know their status, 90% with HIV will be on antiretroviral therapy and 90% of those will have viral suppression.
“Globally, we have set an ambitious target to end Aids as a ‘public health threat’,” said Abdool Karim. “People tend to overlook the last bit. They only see 90-90-90 as ending Aids. We cannot end Aids anytime soon since we have 37m people are living with Aids worldwide. So Aids is not going to go away, and there’s no cure.”
“We need to reduce the number of infections so that we have the epidemic under control. This is what is meant by ending Aids as a public health threat”
Africa has 70% of all HIV infections while southern and eastern Africa accounts for half of all global infections. In 2015, an estimated 7m South Africans were living with HIV while the same year saw 380,000 new infections and the deaths of 180,000 people from Aids-related illnesses.
There is no doubt 90-90-90 is a big ask for South Africa. “Here we have a generalised epidemic with large numbers of the population affected. We have to aim for high proportion of people living with HIV being virally suppressed in order to reduce the spread of the virus to others. In order for that to happen people have to know they have HIV and to take treatment diligently.”
“Once you have 90-90-90, which translates into 70% to 75% of those infected virally suppressed, the epidemic can’t sustain itself in most settings and goes into a downward spiral.”
Why is HIV/Aids still a huge problem in South Africa while no longer a headline issue in other countries? “The ‘trick’ with any new infectious disease is to do everything you can to prevent the virus gaining a foothold in the general population,” said Abdool Karim. “In the US, Europe and Australia, thanks to a quick response and effective interventions early on, it wasn’t able to get that foothold. It remained a disease found in gay men, drug users and the incarcerated populations.”
In South Africa, HIV did not spread into the general population through gay and bisexual men, “the virus in men who have sex with men is a separate virus known as Subtype B,” said Abdool Karim. “The virus found in the general population in southern Africa is Subtype C. These two separate epidemics are still ongoing.”
The pathway for the disease to South Africa was created by the long established economic and labour migration patterns of the region. HIV entered the general populations of Zimbabwe, Botswana, Zambia, Malawi and Mozambique. “People coming from those countries to work in South Africa, mostly on the mines, meant that it would only be a matter of time before we got it.”
Government-endorsed Aids denialism was another driver but since government policy was reversed and now that anti-retroviral (ARV) treatment is readily available have we rewound the clock? “You can never make up for lost time once it’s gone,” said Abdool Karim. “The Mbeki era denied several million people ARV treatment, many of those individuals died. But what we did do during that time enabled us to catch up quickly once things changed in 2009, when ARV roll-out went to scale post-Mbeki.”
During the denialist period, funding was not accessible to provide Aids treatment from either the South African government or the Global Fund due to the latter organisation’s undertaking to comply with prevailing government policies in countries to which they gave money. But such constraints did not apply to the US President’s Emergency Plan For AIDS Relief (PEPFAR). “So research centres such as CAPRISA and many other NGOs were already diagnosing and treating Aids during the Mbeki era with PEPFAR funding. Accordingly, when government reversed its stance we had a rolling start, not a standing start, and we could scale up treatment much faster.”
Stigma and denialism within communities was also decreasing. “Ending discrimination at ground level is critical and treatment made that possible,” said Abdool Karim. “In one of our study areas sick people were being brought to our clinic in wheelbarrows. After two weeks of antiretroviral treatment they would come back healthy and say ‘I’m going back to work’. Treatment made the denialists look silly.”
The post-2009 government intervention has been nothing short of miraculous, according to Abdool Karim. “Life expectancy has increased, people are living about 10 percent longer. Post HIV it was 50 years, now its 50 to 60 years. That is due to the decrease in Aids related deaths thanks to treatment.”
“The other big positive is that South Africa turned HIV transmission from mother to child around, it was 25% to 30% about 10 years ago while today, it’s 1% to 2%. Fifteen years ago most children born with HIV died before the end of their second year. Now they don’t. So we have a generation of HIV free children.”
All the more tragic that those saved from infection as infants should now be getting HIV as teenagers. “In young girls, from teenagers to young women in their early twenties, we are seeing high rates of infection and high vulnerability to infection. One of the main reasons for this risk in young women is sex with men in their thirties who are HIV-positive.”
The vulnerability in young women is probably both behavioural and biological. At the recent Aids conference, a bacteria, Prevotella bivia, currently the subject of a CAPRISA study, found in large amounts in the vaginas of younger women, increases the chances of HIV infection in women and is currently the subject of a CAPRISA study.
The age disparity in sexual activity was first identified in a 1990 study done by Abdool Karim’s wife, Professor Quarraisha Abdool Karim, associate scientific director of CAPRISA and a member of the UNAIDS Scientific Expert Panel and scientific advisor to the executive director of UNAIDS. Follow up studies show that it is now entrenched with even higher infection rates.
“When you ask teenage girls why they are having sex with older men and not with those within their own age group they say ‘what’s an 18 year-old boy got for me? What do I get? What presents do I and the family get?’ It’s a quid pro quo activity.”
“In the communities where we conduct our research, people do not take the view that the age disparity among partners is wrong. It is part of the problem: we are fighting something that has become accepted. It’s really a challenge.”
The Abdool Karims have now spent nearly three decades working towards slowing the rate of new infections in teenage girls. “It became our life’s calling to find solutions to that problem.”
The solution proved elusive until the appearance of an antiretroviral drug called Tenofovir. A CAPRISA study tested a microbicide gel containing Tenofovir and found that it was effective in preventing HIV transmission in women, cutting the infection rate by 39% overall and 54% in women who used the gel diligently.
That was the good news but compliance to the necessary medication regime proved a stumbling block in subsequent studies of both gels and pills. “If you are a healthy woman why should you protect yourself against an infection you might not get? It was a tall order. Some women don’t see themselves at risk while others are not able to take control of their lives and do it for themselves.”
Now the Abdool Karim’s are hoping for better success using broadly neutralising antibodies, so-called because they are able to kill multiple strains of HIV. Rare individuals make such antibodies. One such person is known only by the codename CAPRISA 256. “For over a decade she has developed very unusual antibodies.”
“The HI-virus hides its proteins under a layer of sugar, rather like a smartie sweet,” said Abdool Karim. “We found that this woman’s antibodies have ‘long arms’ that can reach through the sugar shield to reach the viral protein and neutralise the virus. CAPRISA 256 has one of the most potent antibodies in the world.”
However, this antibody works better for the Subtype C virus found in southern Africa than for Subtype B virus found in US and Europe. Hence, the CAPRISA researchers have teamed up with the National Institutes of Health in the US to combine the CAPRISA antibody with others that are more effective Subtype B viruses.
“We hope to have both antibodies to put into humans by the middle of 2017,” said Abdool Karim. “The monkey studies with the CAPRISA 256 antibody are very promising but that doesn’t mean it will work in humans. It will be a five-year development programme just to see if it does work and that it is safe. Only then will we consider production. In scientific medicine, developing new treatments is not achieved quickly.”
The same applies for a cure to the disease. “This virus is ‘smarter’ than us at the moment; it presents a challenge by hiding deep in our cells that is currently beyond our ability to defeat it. But we will outsmart it, but we need the time; we are unlikely to have a cure anytime soon.”
Abdool Karim is optimistic that a vaccine will eventually be produced. “Research in this country is world-class, we are right up there in the front line with the support of the funders like the National Research Foundation, Medical Research Council and the Department of Science and Technology. While the existing laboratory technology is enabling scientists to understand the virus better, the new technologies coming along will open up further ways of understanding the virus. I am confident that the scientific progress we are making in Aids will place us in a good position to defeat this virus and save millions of lives.”