Registration problems for antiretrovirals in Africa
Last December, Médecins Sans Frontiéres (MSF) faced critical shortages of tenofovir in programmes it supports in South Africa and Zimbabwe. The drug is not registered in these countries, but can be used via special authorisation from the drug-regulatory authorities. Procurement of the drug, however, requires an extraordinary supply line between the USA and Africa, which is costly, complex, and all too fragile, leading to a heightened risk of treatment interruption.
Tenofovir disoproxil fumarate has been registered since October, 2001, in the USA and since February, 2002, in Europe and is commonly prescribed as part of a first-line antiretroviral therapy in developed countries. The drug will also be included in the latest WHO guidelines for first-line and second-line antiretroviral therapy in resource-limited settings.1
In South Africa, MSF uses tenofovir to replace stavudine in first-line therapy for patients who develop symptomatic hyperlactataemia, the main cause of toxicity-driven first-line regimen change in the country.2 The incidence of stavudine-related side-effects will increase as the cohort of patients receiving first-line antiretroviral therapy expands and matures.
Recognising this, physicians have requested that the department of health include tenofovir in the first-line treatment regimen in South Africa. The need for tenofovir will certainly increase over time, and possibly dramatically so. Some clinicians have also expressed a strong desire to use tenofovir as a first-line drug. The present reality, however, is that few, if any, clinicians in the public sector have the ability to ship drugs from California; for them, tenofovir is a non-existent drug.
In December, 2002, Gilead announced a programme offering a preferential price for tenofovir in 68 developing countries.3 This list was expanded to 97 countries by March last year.4 However, as of October, 2005, almost 3 years after the first preferential prices were announced, tenofovir was registered in only 10 of 97 eligible countries.
Lack of registration is a major barrier to accessing tenofovir in the developing world. In South Africa, the registration filing for tenofovir was not completed until last December. In most other African countries, the dossier has not even been submitted: as of last month, registration of tenofovir had only been applied for in 11 of 53 African countries.
Delays in registration can be caused by national drug-regulatory authorities, which have the power to expedite the registration of essential medicines that can often take years. But the regulatory authorities cannot be blamed if a company has not even submitted the file. The registration of other antiretrovirals launched around the same time as tenofovir have been much quicker: efavirenz is registered in 49 developing countries, the old formulation of lopinavir and ritonavir (Kaletra) in 54 developing countries.
This problem is by no means limited to tenofovir. In China, many antiretroviral dosages and formulations were, as of late last year, not registered (eg, stavudine and efavirenz syrups) or marketed (such as Kaletra, nevirapine suspension, and nelfinavir). Registration of the new formulation of Kaletra - which does not require refrigeration and is therefore a critical medicine for resource-poor settings - will not be attempted in Africa before it has been granted in Europe.
Companies gain good publicity for announcing discounts for the developing world, but their intentions have to be backed up by a proper commitment to actually make the drugs available. Without this commitment, attempts to reach global treatment targets for HIV/AIDS in the developing world will be seriously hampered. For now, doctors in south Africa faced with patients at risk of developing life-threatening lactic acidosis will have to inform them that, because the drug they need isn't registered, there is nothing they can offer them.
We declare that we have no conflict of interest.