No to treating our way out of the epidemic, say South African experts

No, we cannot treat our way out of the HIV epidemic, was the resounding sentiment of a panel of expert clinicians and the audience, at a debate held at the 2014 Southern African HIV Clinicians Conference in Cape Town, South Africa, last month.

Professor Richard Chaisson of the Johns Hopkins University School of Medicine argued that antiretroviral therpay (ART) is essential to decrease the size of the HIV epidemic. He argued that the UNAIDS’ 90-90-90 treatment paradigm of 90% of HIV-positive people being tested for HIV, 90% of eligible people being on treatment and 90% of people on treatment being virally suppressed is possible, and has already been shown to be achievable in some lower- and middle-income countries.

Avoiding HIV deaths is one of the ways of treating our way out of the epidemic, due to the rapid movement towards normal lifespans for people living with HIV on treatment.

“Treatment as treatment is important, and treatment as prevention is key for achieving an AIDS-free generation,” according to Prof. Chaisson. He examined the main ways in which ART is used to prevent the transmission or acquisition of HIV, including prevention of mother-to-child transmission (PMTCT), post- and pre-exposure prophylaxis (PEP and PrEP) and the treatment of chronic infections, arguing that ART is key to PMTCT, PrEP can work and that treatment as prevention (TasP) has population-level impacts and is feasible.

Regarding treatment of chronic infection or treatment as prevention, Prof. Chaisson cited the HPTN 052 trial, which showed a 96.3% reduction in the risk of transmission when comparing immediate versus delayed treatment in serodiscordant heterosexual couples. He pointed to the effect of ART coverage on incidence in a rural South African population which also showed that for every 10% increase in coverage, there was a 17% reduction in the individual risk of HIV acquisition. Prof. Chaisson also presented UNAIDS data, which showed that in countries with an adult ART coverage of less than 40%, the decrease in incidence was 20% between 2001 and 2011, compared to a 50 to 70% decrease in incidence in countries with an adult ART coverage of more than 60%.

Professor Ian Sanne of Right to Care was the only panellist who agreed that we should treat our way out of the epidemic and that the long-term cost savings and the potential long-term effects of untreated HIV should be taken into consideration.

Professor Gary Maartens, of the Division of Pharmacology at the University of Cape Town, argued that we are by no means ready to treat our way out of the HIV epidemic and that there was not enough clinical evidence to indicate that we should do so. He noted that the reduction in clinical events in the HPTN 052 studies was largely driven by a reduction in cases of tuberculosis (TB), and that only 52 of 1763 participants received isoniazid to prevent the development of active TB. In the pre-ART era, TB was the predominant clinical event in people with CD4 cell counts above 350, occurring with twice the frequency seen in people without HIV infection.

He added that a massive scale-up would be needed to roll-out the test-and-treat approach and that in a climate where donor funding has reached a plateau, this would not be possible.

Prof. Maartens warned that ART side-effects can both impair quality of life and that treating asymptomatic patients with high CD4 counts could worsen quality of life. Although severe ART adverse drug reactions are rare with newer regimens, it is unclear whether the very small clinical benefits of early ART outweigh the risks.

Prof. Maartens also presented data from observational studies of serodiscordant couples where ART decreased the risk of transmission by 64% compared to the HPTN 052 trial, which showed a 96% reduction in transmission after a median follow up period of 1.7 years. This shows that in real settings the reduction in HIV transmission may be much less than is evidenced in randomised controlled trials (RCTs).

Prof. Maartens also explained that in all of the models that show the benefits of the test-and-treat approach, they are sensitive to loss to follow-up (LTFU), which will likely worsen with implementation – undermining the benefits of treatment as prevention, and argued that we need good evidence that this approach works in real-world settings. There are results of RCTs pending, but Prof. Maartens cautioned that long-term follow-up is needed to assess the intervention.

He argued that considering the low ART coverage and retention, “[only] when we are treating those who need it and retaining them in care, test and treat could be considered.”

Other panellists at the debate including Dr Eric Goemaere of Médecins Sans Frontières, Dr Graeme Meintjes from the University of Cape Town and Mark Heywood of Section 27, as well as the majority of the audience, agreed that we could not treat our way out of the HIV epidemic.

Dr Meintjes stated that “we do not have hard data on why we should treat everyone” as there is no individual or public health benefit of starting ART at a CD4 threshold of greater than 350 cells/mm³.

Mark Heywood stated that the debate question was dangerous and wrong and “indicative of a level of complacency” and that the question that should be asked is “how do we enrol and keep people on treatment?”

Dr Eric Goemaere stressed that if the main aim of the test-and-treat approach is for prevention purposes, there are other ways of ensuring that HIV incidence decreases, by targeting key populations at higher risk of HIV acquisition, such as young women, through very specific interventions, such as outreach efforts, to attract them to care.

Marcus Louw of the Treatment Action Campaign commented that we are losing control of the global AIDS response and that organisations such as UNAIDS are moving towards test and treat without thinking about individual patients’ needs and the crumbling health systems where this would need to be implemented.