Universal HIV testing and immediate antiretroviral therapy for everyone diagnosed with HIV in a country with very high HIV prevalence could reduce new infections from 20 per thousand to 1 per thousand within ten years (a 95% reduction), according to findings from a mathematical modelling exercise carried out by the World Health Organization, published on November 26th by The Lancet.
The findings suggest that HIV transmission could be virtually eliminated by 2020 in countries with high levels of HIV prevalence, such as South Africa, if it were possible to persuade everyone in the community to test for HIV infection once a year and then provide antiretroviral therapy to all who test HIV-positive.
Currently only around 20% of people with HIV in sub-Saharan Africa know their HIV status, and antiretroviral therapy in most countries is available only to those with symptoms of HIV disease or severe immunosuppression (a CD4 count below 200 cells/mm3).
Expanding treatment to all those who need it under current guidelines will be a substantial undertaking. Three million people are currently receiving antiretroviral therapy worldwide, but an estimated 6.7 million are still in need of treatment and a further 2.7 million became infected during 2007, according to WHO’s 2008 report on progress towards universal HIV treatment access.
Expanding treatment and testing to reach everyone with HIV, particularly in southern Africa, would be a massive undertaking that would require vastly greater human resources than currently available for health care.
Dr Kevin de Cock, WHO’s HIV department director says that universal testing and treatment regardless of immune system status could not become an official WHO recommendation without further research into the feasibility, safety, acceptability, impact and cost-effectiveness of the approach, as well as extensive consultation.
Nevertheless the findings are likely to stoke interest in expanding access to antiretroviral therapy in order to limit the long-term impact of the HIV epidemic in the most severely affected countries, those in the southern African region where HIV prevalence in the adult population ranges from 15 to 35%.
Treating everyone with HIV infection in order to reduce the number of new HIV infections has been advocated previously by Professor Julio Montaner of the University of British Columbia in Canada. Prof. Montaner and colleagues published the results of their own mathematical modelling in 2006, which projected that new HIV cases would decline from 7 per thousand to 0.1 per thousand over 50 years if universal testing and treatment were implemented.
The introduction of door-to-door HIV testing and counselling and antiretroviral therapy for all who qualified under Ugandan treatment guidelines reduced new cases of HIV infection by around 90% over a three-year follow-up period, according to findings from a US Centers for Disease Control study carried out in rural Uganda over the past five years.
So far no country or region in the world has adopted a strategy of universal testing and treatment. Current treatment guidelines in the United States and Europe recommend treatment for everyone with a CD4 cell count below 350 cells/mm3, although there is some evidence that starting treatment at a CD4 count below 500 reduces the risk of serious non-AIDS-defining illnesses when compared to starting treatment at a CD4 count below 350 cells/mm3.
Encouraging treatment uptake in order to reduce HIV transmission is an explicit public health goal in only one region of the world at present, the Canadian province of British Columbia, where Professor Montaner’s research group has persuaded the provincial government to adopt a more aggressive approach towards identifying everyone currently eligible for treatment at a CD4 count of 350 cells/mm3 or below. The group’s modelling suggests this policy could avert more than two-thirds of projected infections in the province between 2008 and 2030.
The WHO model used South Africa as an example, taking data on infection rates and disease progression to model the effects of expanding knowledge of HIV status and a growing uptake of antiretroviral treatment. The model assumed that with a baseline HIV prevalence of 16%, a 99% decline in infectiousness when individuals started treatment, and 90% coverage of treatment in the HIV-infected population by 2016, 104,000 deaths would be averted in 2015 alone when compared to starting treatment at a CD4 cell count of 350 cells/mm3 (in itself an optimistic threshold).
The model assumed an annual treatment cost (including drugs, monitoring and patient management) of $727 a year for first-line treatment and $3290 for second-line treatment, with antiretroviral drugs accounting for 30% of the cost.
The model showed that HIV transmission would decline very steeply as HIV treatment coverage expanded, falling from around 15 new infections per thousand adult and adolescent inhabitants today to 1 per thousand by 2016.
Although the universal treatment strategy would cost three times more than treating everyone with a CD4 cell count below 350 cells/mm3 in 2015 ($3.4 billion a year), the yearly cost would begin to fall after this point, and by 2030 the approach would become less expensive than treating only those with CD4 counts below 350 cells/mm3 (approximately $1.8 billion).
Professor Geoffrey Garnett and Rebecca Baggaley of London’s Imperial College, both HIV epidemiologist, said in an accompanying commentary: “[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”
“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," they continues. 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.”
There was strong advocacy for achieving universal treatment coverage on prevention grounds at this year’s International AIDS Conference in Mexico City. Professor Julio Montaner, who is also President of the International AIDS Society, said: “We believe there is now enough evidence to say to policymakers that if you roll out HIV treatment with 100% coverage, you will see a reduction in HIV transmission.”
WHO says it needs to know more about the following questions in order to determine whether its modelling is accurate:
- What is the acceptability of universal HIV testing and will it be genuinely universal?
- How infectious are people receiving antiretroviral therapy, especially in settings where the rate of sexually transmitted infections is high?
- How well do people adhere to antiretroviral therapy in the long-term?
- What are the long-term failure rates for antiretroviral therapy and what are the subsequent resistance patterns? To what extent will these restrict the response to second-line therapy?
- What are the effects of universal testing and antiretroviral availability on sexual behaviour?
The feasibility of the approach also needs to be tested in a real health system, in order to determine the level of health personnel and health system strengthening required, as well as the effects of the approach on other public health goals.
More information is also needed about the trade-off between earlier treatment and drug toxicity. In many developing countries first-line treatment includes drugs with quite high rates of toxicity, including d4T (stavudine) and AZT (zidovudine). Using these drugs, which are much cheaper than the better tolerated first-line regimens now used in Europe and North America, could have significant long-term disadvantages if they cause a high rate of serious side-effects in otherwise healthy people.
Granich R et al. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. The Lancet (online publication, November 26 2008): doi:10.1016/S0140-6736(08)61697-9
De Cock K et al. Can antiretroviral therapy eliminate HIV transmission? The Lancet (online publication, November 26 2008): doi: 10.1016/S0140-6736(08)61732-8.
Garnett G, Baggeley RF. Treating our way out of the HIV pandemic: could we, would we, should we? The Lancet (online publication, November 26 2008): doi: 10.1016/S0140-6736(08)61698-0.