ARVs effective as an HIV prevention tool
Treatment as prevention has arguably been the most significant shift in ideas around attempts to turn the tide against the HIV/Aids epidemic – and history will judge the world harshly if it fails to implement scientific findings as speedily as possible.
That was the message from speaker after speaker at the 19th International Aids Conference in Washington, DC that ended on Friday. At the global gathering, the use of antiretroviral drugs (ARVs) to prevent HIV-infected people from transmitting the virus to their sexual partners and thereby drive down the rate of new infections featured high on the agenda.
But, as usual in the Aids sphere, this was not without controversy and conflict.
Last year, a trial known as HPTN 052 produced findings that radically changed the way scientists think about ARVs. Prior to the study, which was named scientific "breakthrough of the year" by the prestigious journal Science, adults' ARV use was generally confined to treating HIV-infected people whose immune systems were no longer strong enough to protect them from Aids-related infections. Doctors measure the strength of patients' immune systems with a test called a CD4 count. World Health Organisation guidelines recommend that an HIV-positive person with a CD4 count of 350 and below receive ARV treatment.
The HPTN 052 study revealed that heterosexual HIV-infected individuals who received ARVs much earlier – as soon as they had been diagnosed – were 96% less likely to transmit the virus to their HIV-negative sexual partners. For two years the study followed almost 2000 couples who were "discordant", that is, one was HIV positive and the other negative.
Test and treat
Dr Kevin Rebe of South Africa's Anova Health Institute's Health4Men project said: "If a discordant man and woman visit my clinic and tell me they use condoms for only about half their sexual encounters, the HIV-negative partner is going to get infected with the virus at some point. But if I put the positive partner on treatment, regardless of his or her CD4 count, the uninfected person is likely to stay negative for life.
"If the drugs are given at an early stage of infection, the main goal is therefore not to treat the HIV patient, because the person is still relatively healthy, but rather to prevent that individual from spreading the virus."
Prior to the HPTN 052 study, doctors knew ARVs made HIV-infected people less infectious. But they had no idea how much.
ARVs stop HIV from replicating in someone's body and, if used correctly, reduce the amount of "live" virus in a person's body to low levels.
Based on these findings, "test and treat" has become a central part of the United States's HIV-prevention strategy. Last month, healthcare providers in the District of Columbia – the state in which the conference's host city is based – were instructed to put all patients who tested HIV positive on ARVs immediately. People placed on such early treatment are far less likely to transmit HIV to uninfected sexual partners.
A series of mathematical modelling studies published in the research journal PLOS Medicine in the run-up to the conference estimate that the rate of new HIV infections, or HIV incidence, would be reduced by more than 90% if ARV programmes started HIV patients on treatment soon after infection and retained them in care.
"It will cause the epidemic to go into remission in the long run as the number of new cases that the average HIV-infected person produces will be less than one," said the co-author of the studies, Dr Alex Welte from Stellenbosch University's Centre for Epidemiology and Analysis.
South Africa's HIV incidence is about 2%. This means every year an additional 2% of the population becomes infected. But this figure is much higher in areas of the country where HIV infection rates continue to soar. "The lifetime HIV acquisition risk of a woman in some parts of KwaZulu-Natal is, for instance, about 70%," said Welte.
Modelling studies estimate that South Africa's HIV incidence would have been even higher had the country not introduced ARVs in the public sector in 2004. New infections, the studies say, would have been 17% to 32% higher without ARV programmes. HIV-infected individuals with CD4 counts of 350 and below qualify for free treatment in the public health system.
At the conference it emerged that, even in the case of children, treatment as prevention had already had a significant impact. By using ARVs to prevent HIV-positive pregnant women from infecting their babies with the virus, mother-to-child-transmission has almost been eliminated in the developed world.
Mother-to-child transmission rates have also declined dramatically in South Africa over the past four years: whereas 8% of babies were born with HIV in 2008, new data shows that only 2.7% of infants born to HIV-infected mothers now test positive at six weeks.
Many scientists and policymakers are now adamant that giving ARVs to everyone with HIV will change the face of Aids as we know it and could result in an "Aids-free generation" during which no one is born with the virus. And, as people become older, they will be at a far lower risk of becoming infected than they are today. If they do get infected, they will receive treatment that keeps them healthy and prevents them from transmitting the virus to others.
But some medical experts warn that implementing such a strategy is daunting and comes with many challenges, costs and risks. It also comes at a time that international funding for HIV programmes in the developing world is dwindling – and a treatment-as-prevention strategy would entail ARV budgets four to five times their current size. For one, the strategy would require a massive scaling up in HIV testing efforts. "People can't access treatment if they don't know they've got HIV. Even though HIV-infected South Africans can access treatment with a CD4 count of 350, significant numbers don't because they have no idea they've got the virus. They only get to us once they fall ill and have CD4 counts as low as 100," said Professor Francois Venter, chief of the South African HIV Clinicians Society.
Although HIV testing figures have increased in South Africa, they are still relatively low. According to the third National HIV Communication Survey released at the conference this week, 10.6-million people were tested for HIV in the past year – about a quarter of the population. Venter said: "You're going to have to get the other 75% to come forward and do the same, if you'd like to put them on early treatment. It will be hard and require an enormous adaptation from the health department as well as the introduction of home testing."
And getting HIV-infected people who still feel healthy to take ARVs for the benefit of others, rather than for themselves, could be an even greater obstacle, according to medical experts. A Kenyan study published in the Journal of AIDS has found that 42% of HIV-infected men and 31% of women in discordant couples in a city in the East African country were unwilling to take ARVs solely to lessen the risk of them infecting their partners. They cited fear of side effects, stigma, the burden of taking yet more pills and the potential for developing drug resistance as concerns.
According to Professor Nelly Muga, who is based at Nairobi's Kenyatta National Hospital, refusal rates are likely to be even higher among HIV-infected people who are not in stable relationships, because the people who will be protected from infection will be "faceless" and the incentive for taking the drugs therefore less.
Getting healthy HIV-infected individuals to take their pills correctly – at the same time every day, for the rest of their lives – was also likely to be much more difficult than in the case of ill people who feel compelled to take ARVs, said Muga. "ARVs work only when taken correctly. If not, they're ineffective and patients run the risk of building up resistance to the drugs and spreading a drug-resistant virus."
According to Venter, the South African health system's ability to handle larger numbers of people on treatment also has to be considered. "Treatment as prevention would require us to triple or quadruple the numbers of people on ARVs immediately. There are four to five million people wandering around that would need to be put on treatment in the next year. But we need to be realistic. It has taken us eight years to get just less than two million people on treatment. We need to ask ourselves: Is our health system able to handle more?"
Medical experts such as Muga argue that a more realistic treatment-as-prevention option for Africa would be to target high-risk populations at once, rather than everyone with HIV. Young women in sub-Saharan Africa, for instance, have twice the HIV infection rate as young men.
But Stellenbosch University's Alex Welte warned that this could create serious ethical dilemmas.
"Teenage females in South Africa are at high risk of HIV infection because they are having sex with older men. The question here is: Who should be treated? To protect those women, the HIV-positive men who are exposing them should be treated. But that seems absurd. Effectively, you would be rewarding men who are exploitative of younger women by giving them good clinical care before anyone else," he said.
Targeting other high-risk populations, such as sex workers, can be equally complex because they are hard to reach. "Being a commercial sex worker in South Africa is illegal. How do you get them to come for testing and treatment if they run the risk of being arrested by cops waiting for them at the clinic?" Venter said.
Mia Malan works for the Discovery Health Journalism Centre at Rhodes University