Second-line ARV treatment: Unaffordable luxury?

This price difference is largely due to the lack of generic competition in the second-line market.
ALT Espen Rasmussen

What is needed:

  • Cheaper second-line drugs (both originator and generic).
  • Fixed-dose combinations of second-line drugs, which would make adherence easier for patients.
  • Adapted formulations that do not need refrigeration and that allow a reduction of the pill burden.

Xolani has been on antiretroviral treatment at MSF's clinic in Khayelitsha, South Africa, for three years - but now tests indicate that his treatment is failing. Xolani will have to be shifted from the first-line drugs he has been receiving up until now to more powerful second-line drugs.

After 24 months on ARVs, data from Khayelitsha suggest that between 10% and 30% of patients will need to switch from first- to second-line therapy.

As first-line, Xolani was taking zidovudine (AZT), lamivudine (3TC) and nevirapine. Because AZT and 3TC come in a fixed-dose combination, this means he was taking two pills twice daily.

Xolani's second-line treatment will consist of didanosine (ddI), ritonavir-boosted lopinavir (LPV/r), and tenofovir (TFV). This brings his daily pill count up to 11 pills, taken at three different times of the day. The surge is due to the fact that there are presently no fixed-dose combinations of second-line drugs and little effort is being made to develop them.

There are other problems too. The drug ddI comes in two formulations: "buffered" and "enterocoated". But the easier-to-take enterocoated version is not yet commercially available in South Africa. Xolani will therefore have to take the buffered form, which has to be taken on an empty stomach, an hour before a meal. Further, he will have to ensure that the LPV/r remains properly refrigerated.

These complicating factors will make it more difficult for Xolani, and others in the same situation, to adhere to treatment.

Furthermore, the price of second-line therapy is far higher than first-line. The first-line used in Khayelitsha costs US$363 per year - but the second-line used there costs US$1285 per year, three and a half times more than the first line. Xolani himself won't need to pay this, as treatment at the clinic is free. But the higher costs will limit the numbers of people the country's health providers can treat.

This price difference is largely due to the lack of generic competition in the second-line market: there are presently no generic versions of TFV and only one generic version of LPV/r. There are generic versions of enterocoated ddI, but they are not available in South Africa and many other countries. The manufacturer Bristol-Myers Squibb has refused to include enterocoated ddI in its differential pricing policy, making the drug much more expensive.

[This example is a composite of several patients' stories.]