Using nine structurally different models, Jan Hontelez and colleagues investigate timeframes for HIV elimination in South Africa using a universal test and treat strategy.
Please see later in the article for the Editors' Summary
Expanded access to antiretroviral therapy (ART) using universal test and treat (UTT) has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study's finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV.
Methods and Findings
We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ≤350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study's major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled.
Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic models show that elimination is likely to occur at a much later point in time than the initial model suggested. Also, UTT is a cost-effective intervention, but less cost-effective than previously predicted because the current South African ART treatment policy alone could already drive HIV into elimination.
Please see later in the article for the Editors' Summary
About 34 million people (mostly in low- and middle-income countries) are currently infected with HIV, the virus that causes AIDS, and every year another 2.5 million people become infected. HIV, which is usually transmitted through unprotected sex with an infected partner, gradually destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, people infected with HIV often died within ten years of infection. Then, in 1996, antiretroviral therapy (ART) became available, and, for people living in affluent countries, HIV/AIDS became a chronic condition. However, ART was expensive, so HIV/AIDS remained a fatal condition for people living in resource-limited countries. In 2006, the international community set a target of achieving universal ART coverage by 2010, and ART programs were initiated in many resource-limited countries. Although universal ART coverage has still not been achieved in South Africa, where nearly 6 million people are HIV-positive, 80% of people in need of ART were receiving a World Health Organization–recommended ART regimen by October 2012.
Why Was This Study Done?
ART is usually started when a person's CD4 count falls below 350 cells/µl blood, but it is thought that treatment of all HIV-positive individuals, regardless of their CD4 count, could reduce HIV transmission by reducing the infectiousness of HIV-positive individuals (“treatment as prevention”). Might it be possible, therefore, to eliminate HIV by screening everyone annually for infection and treating all HIV-positive individuals immediately? In 2009, a mathematical modeling study suggested that seven years of universal test and treat (UTT) could eliminate HIV in South Africa. The deterministic (nonrandom) model used in that study has been widely criticized, however, and some subsequent modeling studies have reached different conclusions, probably because of differences in the models' structures and in the assumptions built into them. A better understanding of the reasons for the discrepancies between models would help policy-makers decide whether to introduce UTT, so, here, the researchers developed several increasingly complex and realistic models of the South African HIV epidemic and used these models to predict the long-term impact of UTT in South Africa.
What Did the Researchers Do and Find?
The researchers developed nine structurally different mathematical models of the South African HIV epidemic based on the STDSIM framework, a stochastic microsimulation model that simulates the life course of individuals in a dynamic network of sexual contacts and in which events such as HIV infection are random processes. The simplest model, which resembled the original deterministic model, was extended by sequentially adding in factors such as different HIV transmission rates at different stages of HIV infection and up-to-date assumptions regarding the ability of ART to reduce HIV infectiousness. All the models replicated the prevalence of HIV in South Africa (the proportion of the population that was HIV-positive) between 1990 and 2010, and all predicted that UTT (defined as annual screening of individuals age 15+ years and immediate ART for all HIV-infected adults starting in 2012 and scaled up to 90% coverage by 2019) would result in HIV elimination (less than one new infection per 1,000 person-years). However, whereas the simplest model predicted that UTT would eliminate HIV after seven years, the more complex, realistic models predicted elimination at much later time points. Importantly, the most comprehensive model predicted that, although elimination would be reached after about 17 years of UTT, the current strategy of ART initiation for HIV-positive individuals at a CD4 cell count at or below 350 cells/µl would also lead to HIV elimination, albeit ten years later than UTT.
What Do These Findings Mean?
These findings confirm previous predictions that UTT could eliminate HIV in South Africa, but the development of more realistic models than those used in the past suggests that HIV elimination would occur substantially later than originally predicted. Importantly, the most comprehensive model suggests that HIV could be eliminated in South Africa using the current strategy for ART treatment alone. As with all modeling studies, the accuracy of these findings depends on the assumptions built into the models and on the structure of the models. Thus, although these findings support the use of UTT as an intervention to eliminate HIV, more research with comprehensive models that incorporate factors such as data from ongoing trials of treatment as prevention is needed to determine the population-level impact and overall cost-effectiveness of UTT.
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001534.
This study is further discussed in a PLOS Medicine
Perspective by Ford and Hirnschall
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in South Africa, on HIV treatment as prevention and the possibility of HIV elimination (in English and Spanish)
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
The World Health Organization provides information about universal access to AIDS treatment (in several languages); its 2010 ART guidelines can be downloaded
The PLOS Medicine Collection Investigating the Impact of Treatment on New HIV Infections provides more information about HIV treatment as prevention
Personal stories about living with HIV/AIDS are available through Avert, through NAM/aidsmap, and through the charity website Healthtalkonline