At the end of 2005 we were again faced with a worrying delay in accessing the antiretroviral drug tenofovir. Completing all the steps to access tenofovir in South Africa took over two months. About half that time was due to unexpected delivery delays. This left us with only two bottles of tenofovir in our programme, whereas 13 patients were at the time receiving the drug. After considerable time spent chasing up the order, it finally arrived at the beginning of December.
Tenofovir is an important drug for patients who suffer from lactic-acidosis, a side-effect of the first-line antiretroviral d4T. It is also needed as a salvage regimen for patients in South Africa who have been on first-line for a very long time and have developed resistance to one or more of the first line drugs.
However, the drug is virtually impossible to access because it is not registered in South Africa and so must be accessed through Section 21 – special authorization from the Medicines Control Council for use on a 6-month, named-patient basis – and shipped directly from California.
The number of patients in Khayelitsha relying on tenofovir has today risen to 21, and increasing at 2-3 a month. These patients are extremely privileged: as an international organisation MSF is able to manage considerable bureaucratic and logistic challenges of shipping medicines directly from California, as well as high freight costs. Nevertheless, we are increasingly concerned that after two years of experience importing tenofovir we have not been able to establish a reliable importation system. This seriously prevents us to start new patients on the drug who need it as a matter of life and death, since we can't assure continuity of the supply.
For MSF the picture becomes further fragmented as patients are transferred out of Khayelitsha to other clinics where there is no possibility of accessing tenofovir, and clinicians there rely on MSF to continue to supply to those patients. The reality is that for most clinicians in South Africa tenofovir might as well not exist. This is also the case in many other African countries (see panel).
Tenofovir situation in other African countries where MSF works
- In Ethiopia tenofovir is the chosen second-line but is currently not registered and unavailable
- In Zambia tenofovir is registered but teams have to purchase through a local supplier and have to pay double the access price ($27 per vial vs $17)
- In Zimbabwe, like South Africa, tenofovir it is not registered and has to be accessed on a named patient basis and shipped from California; for local doctors it is out of the question. Registration has not been submitted by Gilead, and will likely take a long time.
- In Malawi, the drug isn't registered and so not available in country. MSF is able to use the drug but has to import it from Europe, which can incur significant delays: the team is currently waiting on an order that was submitted over 2 months ago
- In Mozambique tenofovir is not registered and the drug is unlikely to become available any time soon
Nevertheless, we are also forced to ration tenofovir much more than we would like, switching patients much later than is ideal. Drug registration, which would overcome this issue very quickly, appears very far away.
The history of tenofovir registration in South Africa and elsewhere highlights the lack of priority placed in making drugs truly available to developing countries. Almost three years have passed between Gilead announcing preferential prices for the developing world (December 2002) and the dossier being properly submitted for registration (late November 2005). A dossier was apparently submitted to the MCC earlier but had to be revised. This does not however go any way near to explaining this three year delay. Moreover, no interim measure has been forthcoming from either Gilead or its distributor Aspen Pharmacare. The situation regarding registration is dire across Africa: data from Gilead in late October 2005 shows that tenofovir registration had only been applied for in 11 of 53 Africa countries.
The need for tenofovir is much greater than simply for patients with lactic acidosis or who need salvage therapy. Clinicians in South Africa have expressed a strong desire to be able to use tenofovir. They argue that if d4T were replaced by tenofovir, it would make the first line regimen much safer and allow the first regimen to be dosed daily. In addition, because cross-over resistance with the current second-line regimen would happen in a minority of individuals and not significantly compromise second-line efficacy. This in turn could reduce the need for ongoing viral load monitoring in patients who have responded well to therapy.
Two major issues working against the broad availability of tenofovir are lack of registration and cost. In South Africa yhe time from dossier submission to registration of a drug can be expected to take up to 18 months. It is uncertain whether fast-track registration has been applied for, although even an approved fast track registration process needs the commitment of the company to promptly respond to the MCC's queries during the review process. While cost through the private sector is high, the best price available through the Gilead Access programme is $17 per vial, and we should be able to expect that the price would fall further as the drug is more widely used. Generic sources are in the pipeline and will hopefully be available soon.
Meanwhile, with no interim measure being proposed, clinicians will have to continue to rely on a system which at best rations tenofovir use and results in fragile stocks, but for the majority of physicians in the public sector makes tenofovir as good as non-existent.