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Four million people have been initiated on antiretroviral treatment in low and middle income countries. However, an additional 5 million people eligible for treatment are not receiving it. Of the 27-29 million people infected with HIV but not currently receiving treatment, most will need to start antiretrovirals as their disease progresses. Funding for access programmes is restricted, partly because of the Global Financial Crisis. Antiretroviral treatment programmes have to lower overall costs, so that the maximum number of people with HIV can be treated for limited budgets. Antiretroviral treatment can account for the majority of the total cost of access programmes. During the development of antiretrovirals, several doses are normally evaluated in Phase 2 dose-ranging trials. In the case of efavirenz, lopinavir/ritonavir and raltegravir, there was no difference in efficacy between doses evaluated at Phase 2, but the higher doses were then taken into Phase 3 registration trials, leading to regulatory approval. Re-analysis of the dose-ranging trials of raltegravir showed equal efficacy for doses in the range of 100 to 600mg twice daily. The main Phase 2 trial of efavirenz, DMP-005, suggests that a 400mg once daily dose should show equal efficacy to the standard 600mg once daily dose. The dose-ranging trials of lopinavir/ritonavir showed the highest efficacy at the 200/100mg mg twice daily dose, compared with the standard 400/100 mg twice daily dose. Re-optimisation of doses could dramatically lower costs of first and second-line treatment for low and middle income countries. For example, it may be possible to manufacture raltegravir 100 mg twice daily for US $75-100, allowing first- line use in low income countries. Costs of efavirenz could be lowered by 30%, and lopinavir/ritonavir by 35%, using re- optimised doses. There may also be safety benefits to these new doses.

Dose Optimisation: A Strategy to Improve Tolerability and Lower Antiretroviral Drug Prices in Low and Middle Income Countries