Two weeks ago, the United Nations Joint Programme on HIV/AIDS (UNAIDS) released Treatment 2.0, the latest global strategy for making HIV treatment more efficient, accessible, and effective. Although refreshing in its emphasis on alternative or newer methods to approach HIV treatment and prevention, the strategy document stops short of offering practical guidance on how to act or fund its five key recommendations for invigorating the global HIV/AIDS response:

i) Recognize and use HIV treatment as a tool for preventing new infections

ii) Develop better combination antiretroviral medications and cheaper diagnostics tools

iii) Find ways to lower other HIV-related costs

iv) Expand the availability of HIV testing and build stronger links between HIV testing and care

v) Encourage and support community leadership in expanding and improving local HIV responses.   

UNAIDS suggests if countries can provide antiretroviral therapy (ART) to all people living with HIV who need treatment, the Treatment 2.0 strategy could prevent up to one million new HIV infections each year and as many as 10 million AIDS-related deaths by 2025.

Treatment is prevention
Treatment 2.0 is one of the first formal documents to recognize and recommend ART as a prevention tool.  In part, the guidelines reflect the now substantial data, which show that the risk of HIV transmission is greater when a person’s viral load is higher. This data provides a compelling argument for putting a person living with HIV on ART both to improve the individual’s health and to lower the risk of transmitting HIV to sexual partners. [1] More compelling data on whether ART can prevent heterosexual transmission from an infected individual to their discordant partner will come from the ongoing HPTN052 randomized clinic trial.  In this study, people living with HIV are randomly assigned to a group that receives either immediate or delayed ART based on their clinical histories and CD4 count. The frequency of HIV transmission between partners will then be compared between the groups. Of course, the broadest ART coverage would require putting all people living with HIV on treatment regardless of CD4 count as proposed in a recent “Test and Treat strategy” reviewed by the World Health Organization . [2] This strategy is particularly contentious given the current economic outlook. Instead, the Treatment 2.0 strategy proposes a less ambitious plan of starting treatment when CD4 counts drop below 350 cells/mm³, which means people would still be started on treatment earlier than in the past when a CD4 threshold of 250 cells/mm³ was standard. This ‘new’ strategy to start treatment earlier is based on considerable data, also reflected in the recently revised DHHS guidelines in the United States. [3] The ongoing HPTN052 trial will also offer additional evidence of the individual clinical benefits of starting ART at CD4 counts between 350-550 cells/mm³. The trial’s initial results are expected in 2012.

 A call for new, less toxic, more convenient treatment regimens
Treatment 2.0 calls for the innovation of ART regimens, specifically combination ART regimens with fewer side effects/toxicities when taken for long periods of time and that are more impervious to resistance.  Some of the newer ART medications have been shown to cause less toxicity, but are largely unavailable in developing countries due to higher cost. Similarly, a fixed-dose combination ART pill taken once daily is currently available and has been shown to improve adherence, but is not widely available in resource-constrained settings. In the Treatment 2.0 report, UNAIDS calls for the development of a one pill, once-a-day ART regimen that has fewer toxic side effects and is less likely to lead to drug resistance.  However, the document does not address how such therapy will be developed or made affordable in resource-poor settings.  Practical concerns aside, this type of treatment regimen has tremendous potential to bolster the success of treatment for HIV-infected individuals and allay the costs associated with second- and third-line ART regimens for those failing first-line regimens, which are often still unavailable in many countries with national ART programs. 

Cheaper diagnostics are crucial to lowering the cost of HIV treatment
In addition to newer, better drugs, Treatment 2.0 emphasizes the need for cheaper, more low-tech diagnostic tools such as those used to determine CD4 cell count and viral load. Currently, these tools can account for a large proportion of the costs of ART programs because the assays, transportation of samples, and laboratory infrastructure are expensive. Several options for cheaper, point-of-care CD4 cell count assays are under development, but have not been validated in large scale trials yet. [4] Initial efforts to develop low-tech tests that can detect HIV RNA are promising, but none of these tests are clearly designed to measure viral load in the blood, which is how a person’s response to ART is assessed [5-9]. It is not clear when these tests will be validated and available for implementation.

Starting treatment when people are well can cost less
In addition to the preventative benefits of ART, Treatment 2.0 suggests that treating HIV-infected individuals earlier will decrease AIDS-related disability and costs.  Studies in developed countries suggest that earlier therapy reduces HIV-related morbidity [10] and mortality [11]; however, studies have not yet been done to show whether this will hold true in developing countries [10]. Recently my colleague Chris Penders blogged about models presented at AIDS 2010 suggesting that it would be more cost-effective to offer ARVs to all HIV-infected individuals in South Africa, but even the less ambitious approach of offering ARVs to  people with a CD4 count less than 350 cells would pay for itself by 2013.

We have to also lower other costs associated with treatment
The Treatment 2.0 report points that the cost of ART drugs represent only one-third of HIV treatment associated costs; another third of the costs come from laboratories. There are also the costs of visiting a health center regularly, which includes things as simple as the cost of getting to the health center. In rural areas in the developing world, transportation costs can be significant and may limit individual’s ability to refill their medications or adequately monitor treatment progress. UNAIDS appropriately emphasizes a need for more creative solutions than currently used for lowering the indirect costs associated with HIV treatment, and addressing the ongoing epidemic.

Encourage testing and build stronger relationships with communities
Finally, in the Treatment 2.0 report UNAIDS recognizes the pressing need for more people to know their HIV status so they can be put on treatment early to preserve their health and prevent ongoing transmission. Making this happen will require substantial community support and initiative as recommended in Treatment 2.0. Importantly, UNAIDS points out how stigma and discrimination can prevent people from seeking testing and health services and the role of community-based initiatives in reaching and encouraging widespread testing among high-risk populations. However, Treatment 2.0 provides little guidance to countries or communities on how to dramatically or systematically increase uptake of HIV testing. A starting place would be the widespread implementation of UNAIDS and WHO’s joint recommendations for ‘provider-initiated HIV testing’ which have not been widely implemented in most HIV prevalent settings. Communities and community health workers must be involved in creating and leading widespread testing efforts that address real fears of stigma and discrimination and directly link HIV-infected individuals with treatment.

References

1. Cohen M.S., C.L. Gay. 2010. "Treatment to prevent transmission of HIV-1: Clin Infect Dis 50 Suppl 3:S85-95.
2. World Health Organization. 2009. Antiretroviral therapy for HIV prevention. Geneva, Switzerland: World Health Organziation.
3. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. December 1, 2009.  Department of Health and Human Services 1-161.
4. Holmes D., H. Morgan. 2010. "Single cell impedance cytometry for identification
5. and counting of CD4 T-cells in human blood using impedance labels." Analytical Chemistry 82(4):1422-1461.
6. Nargessi D., C.Y. Ou. 2010. "MagaZorb: a simple tool for rapid isolation of viral nucleic acids." J Infect Dis 201 Suppl 1:S37-41.
7. Zhang N., D.H. Appella. 2010. "Advantages of peptide nucleic acids as diagnostic platforms for detection of nucleic acids in resource-limited settings." J Infect Dis 201 Suppl 1:S42-45.
8. Tang W., W.H. Chow, Y. Li, H. Kong, Y.W. Tang, B. Lemieux. 2010. "Nucleic acid assay system for tier II laboratories and moderately complex clinics to detect HIV in low-resource settings." J Infect Dis 201 Suppl 1:S46-51.
9. Tang S., I. Hewlett I. 2010. "Nanoparticle-based immunoassays for sensitive and early detection of HIV-1 capsid (p24) antigen." J Infect Dis 201 Suppl 1:S59-64.
10. Lee H.H., M.A. Dineva, Y.L. Chua, A.V. Ritchie, I. Ushiro-Lumb, C.A.Wisniewski. 2010. "Simple amplification-based assay: a nucleic acid-based point-of-care platform for HIV-1 testing." J Infect Dis 201 Suppl 1:S65-72.
11. El-Sadr W.M., J.D. Lundgren, J.D. Neaton, F. Gordin, D. Abrams, R.C. Arduino, et al. 2006. "CD4+ count-guided interruption of antiretroviral treatment." N Engl J Med 355:2283-2296.
12. May M., J.A. Sterne, C. Sabin, D. Costagliola, A.C. Justice, R. Thiebaut, et al. 2007. "Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies." AIDS 21:1185-1197.