With no end to the global funding retreat in sight, new strategies are required to change the way we provide treatment to the world’s 33 million people infected with HIV.
On June 7-10, the Clinton Health Access Initiative (CHAI) hosted a conference, Opportunities to reduce the cost of anti-retroviral (ARV) treatment, to explore opportunities to significantly lower the costs of antiretroviral therapy (ART). Dose finding during drug development often maximizes tolerability but sometimes fails to explore minimally effective dosing. The earliest example of dose adjustment was AZT (zidovudine), which was initially tested at much higher doses (1500 mg daily compared with today’s dose of 600 mg daily).1 Back in 1990, activists applied pressure to speed up the FDA’s approval of AZT’s use at the lower, safer, equally effective dose.2,3
With clinicians, pharmacologists, chemists, researchers, regulatory experts, and community advocates in attendance, discussions included reformulation, dosage optimization and manufacturing along with attendant issues of regulatory pathways and ethical considerations for optimized ARV regimens. If dose optimization and reformulations are proven to be safe, efficacious and significantly cheaper, many more people could be enrolled on first-line ART using existing funding flows — in effect, more people on treatment for the same drug costs.
A significant step toward dose optimization is in motion with the Evaluation of Novel Concepts in Optimization of antiRetroviral Efficacy (ENCORE) study to evaluate reduced doses of efavirenz which is being conducted at the University of New South Wales, Australia. The study will be conducted through an international research network with sites in high-, middle- and low-income settings. Data are expected by mid-2013. If successful, this could set the stage for cheaper regimens, new fixed dose combinations and most importantly, more people on ART.
References
- Fischl MA, Parker CB, Pettinelli C, Wulfsohn M, Hirsch MS, Collier AC, Antoniskis D, Ho M, Richman DD, Fuchs E, et al. A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group. N Engl J Med. 1990 Oct 11;323(15):1009-14.
- Treatment + Data Committee, ACT UP/New York, memorandum to Anthony S. Fauci, NIAID, NIH; U.S. Food & Drug Administration and Burroughs-Wellcome; Applying Results of ACTG 002 and 019 to ACTG Trials and Clinical Practice: Lowering AZT Dosage Regimens, 12 December 1989.
- Gina Kolata, Lag in Approving Low AZT Doses Is Assailed, The New York Times, 27 December 1989.