Model Suggests Universal HIV Testing and Treatment Could Halt Epidemic within 50 Years

By Liz Highleyman

HIV transmission could potentially be eliminated if universal testing were implemented and all people who test positive received prompt antiretroviral therapy (ART), according to a mathematical model described in the November 25, 2008 advance online issue of The Lancet.

Roughly 3 million people worldwide were receiving antiretroviral therapy at the end of 2007, but an estimated 6.7 million are still in need of treatment, the World Health Organization (WHO) study authors wrote as background. Furthermore, the epidemic continues to spread, with an estimated 2.7 million new infections last year.

It is well-known that effective ART suppresses HIV viral load, and that people with undetectable HIV RNA are much less likely to transmit the virus -- though this is not impossible, since some people experience transient viral load increases, or "blips," and HIV may be present in semen and female genital fluid even when it is undetectable in the blood.

Earlier this year, Julio Montaner from the British Columbia Centre for Excellence in HIV/AIDS and colleagues reported results from a model showing that treating all people with HIV according to current antiretroviral treatment guidelines could dramatically reduce the rate of new infections.

But HIV positive people can transmit the virus for a long time before they require therapy themselves when they develop symptoms of immune suppression or their CD4 count falls below 350 cells/mm3 (the current threshold in the U.S. and European guidelines) or 200 cells/mm3 (the practical threshold in many resource-limited areas).

In particular, people often have a very high viral load immediately after infection, when most do not yet know their serostatus; some studies suggest that as many as half of all new HIV cases may be transmitted by someone with early infection. Furthermore, many people with advanced HIV/AIDS remain unaware that they are infected.

In the present study, the WHO researchers used mathematical models to investigate a theoretical strategy of universal voluntary HIV testing and immediate treatment with ART, and examined the conditions under which the HIV epidemic could be driven towards elimination.

They used a stochastic model to explore the effect of testing and early ART on the case reproduction number, and a deterministic transmission model to estimate long-term dynamics of the epidemic. The models assumed that all people age 15 or older would be voluntarily tested for HIV each year, and that those found to be infected would voluntarily start ART regardless of CD4 count.

Data from South Africa were used as a test case. The model assumed a high overall HIV prevalence (16%), that all transmission was via heterosexual sex, and that infectiousness is reduced by 99% when a person starts effective ART.

According to the authors, the model indicated that, "The studied strategy could greatly accelerate the transition from the present endemic phase, in which most adults living with HIV are not receiving ART, to an elimination phase, in which most are on ART, within 5 years."

They estimated that the universal testing and treatment strategy could reduce HIV incidence by about 95%, from 15-20 cases per 1000 persons per year to 1 case per 1000 persons per year by 2016, or within 10 years of full implementation. Within 50 years, total HIV prevalence would be reduced to less than 1% and the number of deaths due to HIV/AIDS would fall by more than 50%, from 8.7 million to 3.9 million.

Performing similar modeling but looking at a low-prevalence area where most transmission occurs via male-to-male sex (British Columbia, Canada), Montaner's group previously estimated that treating all HIV positive individuals regardless of medical need could reduce the rate of new infections to less than 0.1 cases per 1000 persons within 45 years.

The WHO researchers estimated that the peak cost of their theoretical universal testing and treatment strategy could reach U.S. $3.4 billion, which is higher than the present approach of less widespread testing and treatment only when medically indicated. However, they calculated that by 2032, the cost of the theoretical strategy and the present approach would be about the same, at U.S. $1.7 billion. After this time, the cost of the present approach would continue to increase, while that of the theoretical strategy would decrease as fewer and fewer people needed treatment.

"Universal voluntary HIV testing and immediate ART, combined with present prevention approaches, could have a major effect on severe generalized HIV/AIDS epidemics," the authors concluded. "This approach merits further mathematical modeling, research, and broad consultation."

"Although other prevention strategies, alone or in combination, could substantially reduce HIV incidence," they continued, "our model suggests that only universal voluntary testing and immediate initiation of antiretroviral drugs could reduce transmission to the point at which elimination might be feasible by 2020 for a generalized epidemic, such as that in South Africa."

At this time, the universal approach remains theoretical, and WHO is not changing its current testing and treatment recommendations, although WHO HIV/AIDS director Kevin De Cock (one of the study authors) indicated that he plans to convene a meeting next year to discuss the findings. The study comes at a time when many experts in wealthy countries are starting to suggest that treatment should be initiated earlier than the current guidelines indicate.

The universal strategy faces several barriers, including the cost and logistics of implementing widespread testing and treatment in resource-poor countries with limited health infrastructure and personnel, the risk of long-term antiretroviral drug toxicities in people who do not yet need treatment for their own health, the potential for increased emergence of drug resistance, and the possibility of coercive testing and treatment.

"At best, the strategy would prevent morbidity and mortality for the population, both through better treatment of the individual and reduced spread of HIV," Geoffrey Garnett and Rebecca Baggaley of Imperial College London wrote in an accompanying editorial. "At its worse, the strategy will involve over-testing, over-treatment, side effects, resistance, and potentially reduced autonomy of the individual in their choices of care."

12/2/08

References

R Granich, C Gilks, C Dye, and others. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. The Lancet. November 25, 2008 [Epub ahead of print]. (Abstract).

K De Cock, C Gilks, Y-R Lo,and others. Can antiretroviral therapy eliminate HIV transmission? The Lancet. November 25, 2008 [Epub ahead of print].

G Garnett and R Baggeley. Treating our way out of the HIV pandemic: could we, would we, should we? (Editorial). The Lancet. November 25, 2008 [Epub ahead of print].