Reactions to the test-and-treat models

The global test-and treat models were controversial from the start. In a commentary on the WHO model published in the same issue of The Lancet,¹ Professor Geoffrey Garnett and Rebecca Baggaley of London’s Imperial College, both HIV epidemiologists, said: “[The] suggested strategy would be extremely radical, with medical intervention for public health benefits rather than individual patient’s benefits. Because screening and treatment would be for the public good, resources would have to come from the public purse.

“The suggested strategy would reflect public health at its best and its worst,” they continued. “At its best the strategy would prevent morbidity and mortality for the population, both through better treatment of the individual and reduced spread of HIV. At its worst, the strategy will involve over-testing, over-treatment, side-effects, resistance and potentially reduced autonomy of the individual in their choices of care.

“It is easy to see how enforced testing and treatment for the good of society would follow from such an argument. Partial success would lead to infection becoming concentrated in those with a high risk, with an increased danger of stigma and coercion. The history of the control of sexually transmitted infections documents several examples of compulsory screening and treatment of stigmatised populations, and there is a danger of a well-meaning paternalistic medical model following such a route.”

Some HIV experts were a good deal more optimistic about treatment as prevention models. At the 17th International AIDS Conference in Mexico City in 2008, shortly after the publication of the second British Columbia model,² there was a striking degree of unanimity among a range of experts that expanding the number of people on antiretroviral treatment would reduce the number of new infections at a population level.

Professor Myron Cohen of the University of North Carolina at Chapel Hill commented that “a lot of science” went into the mathematical model.

Preceding the study, substantial evidence had already emerged that antiretroviral therapy not only reduces virus levels in semen and vaginal fluid, but also substantially reduces onward transmission. In Taiwan, for example, investigators estimated that HIV transmission fell by 53% after antiretroviral therapy was introduced in 1997.³ Evidence was also cited from the Tororo and Rakai studies in Uganda that HIV incidence could be reduced by up to 90%.^{4 5}

But Julio Montaner, who was by now incoming president of the International AIDS Society and chair of the Conference, cautioned that: “no one here is talking about treating our way out of the epidemic – treatment is not enough.” Audience members pointed out that wider availability of treatment had led to an increased rate of new HIV infections among men who have sex with men in European countries such as Germany, but Cohen said that this was due to lack of early enough diagnosis and treatment coverage, and the lack of treatment of sexually transmitted infections.

“If we were doing a good job with prevention in the US, the average CD4 count at diagnosis would be rising,” he said. “It’s not. We’re doing a bad job at finding these people.”

A month after the publication of the WHO model, one of the pioneers of AIDS research, former Harvard retrovirology professor William Haseltine, said that universal testing and treatment now offered the best hope of controlling the HIV pandemic.⁶

“History has shown that epidemics can be controlled, even in the absence of a vaccine,” he said. “Both syphilis and tuberculosis were pandemic at the end of the 19th century, and both epidemics were controlled by effective diagnosis and treatment.” He recommended that WHO, PEPFAR and the Global Fund begin studies to assess the effectiveness of universal testing and early treatment.

At the same time, at a seminar at Oxford University in February 2009,⁷ Professor Jonathan Weber of London’s Imperial College said that after 27 years in HIV research, he no longer believed a vaccine to be achievable. Instead, he believed that population-based antiretroviral therapy (PopART) was the only strategy currently available that holds out the prospect of HIV eradication.

However, epidemiologist Christophe Fraser of Imperial College, London, speaking at CROI 2009,⁸ noted that his own modelling, using the other assumptions contained in the WHO model, suggests that if the preventive efficacy of ART is even a little less than 99%, there is a much less substantial decline in HIV incidence. An efficacy of 80% would result in a paradoxical increase in HIV incidence in the short term. He called for multiple groups of epidemiologists to explore the issue of 'treatment as prevention' very carefully before policy is made, with a particular focus on determining whether all the assumptions in models are based on robust evidence.

Other sceptical voices were raised in criticism of the universal test-and-treat paradigm at the Fifth International Aids Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town in 2009.

Dr Francois Venter, President of the South African HIV Clinicians Society, said that debates about starting treatment earlier in developing countries ignored the fact that programmes were doing very badly at retaining patients in care after diagnosis, or starting people on treatment before they become seriously ill.⁹ He pointed out that the current average CD4 count at which patients start treatment in South Africa is 87 cells/mm³.

Despite treatment being available in Johannesburg, for instance, he still found that patients tended to not want to start treatment until their counts were below 200 – and the average time that people started was at 80-100 T-cells, a factor that hadn’t changed much since 2004. The use of stavudine (d4T) and the toxicities associated with this drug had deterred some from initiating treatment, he said.

The cost of treatment may deter policymakers, both in richer and poorer countries, from supporting earlier treatment. However, the conference also heard Dr José Gatell, of the University of Barcelona, cite modelling by his own team which calculated that, while delaying treatment until a CD4 count of 350 is reached might save 30% over five years when compared with treating before the CD4 count falls below 500, when considered over a 30-year time frame the saving in medical costs attributable to delayed treatment fell to 13%.¹⁰

Speaking at CROI 2010, Brian Williams, one of the architects of the WHO mathematical model, suggested¹¹ that a universal test-and-treat (UTT) approach could bring incidence down even faster if it was combined with pre-exposure prophylaxis (PrEP). He suggested that PrEP should be given to the most HIV-vulnerable young people in a country. In the example of South Africa, vulnerability is so high in young people that Williams believes PrEP should be given to all adolescents for five years, starting at 14 in girls and 18 in boys). UTT approaches would then be used with those adults who are already infected or become so despite PrEP. Assuming that PrEP works, Williams argued that this would reduce HIV infections much faster, as it would eliminate the steep rise in incidence seen in young people who start to become sexually active and then have to be diagnosed and treated.