Health

Antiretroviral drugs have been successful in holding HIV at bay. But the quest for an AIDS-free generation has a long way to go. By Wendy Zukerman.

The long road to freeing the world of HIV/AIDS

Internationally renowned HIV/AIDS researcher Professor Sharon Lewin, of Monash University, co-chairman of the AIDS 2014 Conference.
Credit: KATRINA FERGUSON, MONASH UNIVERSITY

Jason was a teenager when his friends started dying. “It was really intense,” he says. It was the 1980s and the worst epidemic of the late 20th century was emerging. Over the next three decades, AIDS would kill 36 million people, and HIV would infect almost 75 million. Now, for the first time, people are talking about an AIDS-free generation. News reports splash that some have been “cured”. 

While there are promising advances, both a cure and an AIDS-free world remain elusive. About 35 million people are living with HIV. Australia’s diagnosis rates are at a 20-year high, and “cured” individuals have since relapsed. “We’ve got a long way to go,” says Diana Gibb, a paediatrician at the University College London, who has been studying HIV for 25 years.

Powerful new antiretroviral drugs have transformed HIV from a death sentence to a chronic yet manageable condition. Without a vaccine or cure these drugs are our most promising arsenal against the disease. And in the fight to achieve an AIDS-free generation, the World Health Organisation (WHO) has been recommending their use with growing vigour. 

Once prescribed only for those with a low immune cell count or symptoms of the disease, the WHO now suggests that asymptomatic HIV-positive individuals (that is, those not yet exhibiting any symptoms) start lifelong treatment, before there are signs of damage to their immune system. The latest recommendation in July went further, proposing that certain uninfected gay men take them, too, as a preventive measure.

Some are uncertain about this gung-ho approach. They cite the unknowns of long-term treatment, possible resistance emerging and the impracticalities of getting a constant supply of drugs to many parts of the world. “We haven’t got an answer,” says Gibb. “You’ll find those who believe that ‘We can treat ourselves out of it’ and those who are more cautious.”

HIV emerged from a virus found in chimpanzees in central Africa about a century ago. It’s thought to have jumped species when locals butchered chimps for food. Through colonisation and emerging globalisation, the virus probably reached New York and San Francisco in the 1960s. It silently swept through promiscuous gay circles, aided by anal sex, which is more likely to cause small tears and transmit the virus than vaginal sex. 

In June 1981, the US Centres for Disease Control and Prevention published the first official report of what would become the AIDS epidemic. It described rare infections in five young gay men in Los Angeles and suggested there might be a problem with their immune system. A month later, The New York Times wrote its first article about the disease. “Indirect evidence actually points away from contagion,” it read. “None of the patients knew each other.”

Seven years later panic was rife. In 1988, a US Federal Court ruled that a mentally disabled girl with AIDS could only attend school if she sat in a glass enclosure.

It was around this time that Jason discovered he was HIV positive. He was about 16 and thought he had three years to live. He went to a nightclub and started crying. A tranny approached him. “She was like an angel,” he says. “She joked that being HIV positive was the best thing that ever happened to her – she lost three inches off her hips!”  

HIV targets immune cells known as CD4 T cells. It kills some T cells and inserts itself into the DNA of others. These cells usually protect us against viruses and bacteria, so each time the body encounters a new infection, say pneumonia, the T cells become activated. “HIV uses that activation machinery to replicate itself,” says Edwina Wright at Monash University in Melbourne. Eventually, the virus overwhelms the immune cells, allowing viruses, bacteria and cancer cells, which our immune systems usually manage, to instead become life-threatening. Years can pass before symptoms are felt, which helps the virus spread undetected. In Australia, the average person has been infected for about three years before diagnosis, says Wright. 

In the 1990s, antiretrovirals first became available. They stopped HIV replicating, causing the amount of virus in someone’s blood – the “viral load” – to drop. But the drugs were nasty. Patients took up to 20 pills a day and had severe side effects, such as diarrhoea, nerve damage and a stigmatising facial deformation: “the AIDS look”. “My friends were the guinea pigs – the medication was stripping everything away,” says Jason, who refused treatment for almost a decade. By then, his immune cell count plunged, but better drugs had arrived. His survival underscores the success of the later generations of antiretrovirals. 

Wright describes today’s much-improved pills as “magicians”. People start with one or two tablets a day, which tackle HIV at various stages of its replication, and there are few immediate side effects. But these drugs cannot cure HIV. Once the virus integrates into the patient’s DNA, it lies dormant inside cells where the drugs can’t see it. If antiretrovirals are stopped, eventually the virus re-emerges.

Recently, large trials have found other benefits of antiretrovirals. Lowering the viral load, for example, drops the risk of transmitting HIV. In 2011, a study called HPTN 052 found the risk of infecting a sexual partner dropped by about 96 per cent if infected individuals vigilantly took antiretroviral drugs. While it was heralded as the “2011 Breakthrough of the Year” by the prestigious journal Science, two years later a study published in The Lancet found only a 26 per cent reduction in HIV transmission when couples were tracked in “real world” conditions rather than a clinical trial. 

Similarly, if a pregnant, HIV-positive woman takes antiretrovirals throughout her pregnancy and during breastfeeding, her infant has only about a 1 per cent chance of becoming infected. Consequently, the WHO recently recommended that countries with high rates of HIV-positive pregnant women should start treatment for life. But there are practical challenges. In some areas, women still need to travel considerable distances by foot. Sometimes there is no stock of the drugs. Research conducted by Gibb and colleagues in Malawi estimated that about 10 per cent of pregnant women starting lifelong treatment stopped returning to the clinics for drugs within a year. 

In July, the WHO announced its new recommendation that uninfected at-risk people should take antiretrovirals. Widely reported as “WHO Wants All Gay Men to Take HIV Prevention Medication”, in truth, the recommendation is aimed at sexually active gay men engaged in risky behaviour, such as not using condoms. The approach is called pre-exposure prophylaxis, or PrEP. “Taking drugs to prevent infection is appropriate for some, but probably not all, gay men,” says Sharon Lewin, co-chairman of the AIDS 2014 Conference held in Melbourne last month.  

A clinical trial found that healthy men in a relationship with an infected person can reduce their risk of HIV infection by 92 per cent if antiretrovirals are taken consistently. But sometimes they aren’t. When people don’t take their pills properly the protection drops to less than 50 per cent. It’s a frighteningly low figure if people are taking the drugs off and on, having unsafe sex and expecting to be protected from HIV.

It also raises the problem of drug resistance. Generally, when people don’t take antibiotics or antivirals appropriately, it can lead to the development of so-called “superbugs”. A 2012 WHO report found some evidence of emerging HIV resistance for infected patients receiving treatment. But Lewin says concerns of superbug HIV have not been borne out. Modern treatment regimens attack HIV replication at three sites, and “that seems to be enough to stop it,” she says. The situation might be different for PrEP, so Lewin warns that we need to keep monitoring this. 

There are additional uncertainties about the long-term side effects of antiretrovirals. “Drugs have different side effects, some short term and some long term,” says Gibb. “Osteoporosis and depression can occur with the most commonly used drugs.” A paper published in The Lancet in July also found long-term antiretroviral users had higher than expected rates of cancers, but overall, there was no increased risk of death. Of course, for those with HIV, the prospect of drug side effects is most likely less daunting than the risks of HIV itself. But for the uninfected? Diligent safe sex practices might be preferable. 

Meanwhile, scientists continue the hunt for the Holy Grail: a cure that finds HIV’s genetic hiding place and rids the body of it completely. In Petri dishes, researchers have succeeded in developing genetic tools to “snip out” HIV from DNA. Other scientists, including Lewin, are trialling cancer drugs to wake up the dormant virus in order to flush it out. “We are really in the early days of finding a cure,” Lewin says.

Despite the hopeful whispers coming from HIV research, there is a long road before we reach an AIDS-free generation. Turning 42 next week, Jason is aware the world will likely not be rid of this disease for decades, and he devotes little time to thinking about it. Instead, he takes his pills every day, grateful for the life they have given him, and he’s doing well.

This article was first published in the print edition of The Saturday Paper on Aug 2, 2014 as "The long road". Subscribe here.

Wendy Zukerman
is a science journalist and host of the Science Vs. podcast.