On average this opportunistic infection affects 9% of people living with AIDS. In some countries the prevalence is much higher (19% in Zaire, 20-25% in Thailand).

The treatment recommended by the World Health Organization (WHO) includes an induction phase comprising amphotericin b i.v. for at least 6 weeks, plus fluconazole for 12 weeks (see table 2). But patients should remain on maintenance therapy (secondary prophylaxis) for life, either with amphotericin B i.v. alone, or with fluconazole orally.

Amphotericin B is a very complicated drug to manage, among other reasons because of its route of administration (intravenous) which implies that the patient should remain in the hospital. It also has severe secondary effects.

In contrast, Fluconazole can be taken orally and is, generally, well tolerated. Therefore, even if in the treatment phase both drugs should be combined, a life-long maintenance treatment based on oral fluconazole presents huge advantages, with less clinical risks, better compliance, less risk of professional (needle stick) accidents and less burden on the health care system.

Fluconazole is also recommended as second choice drug for the treatment of systemic candidiasis, and coccidiomycosis, both common fungal infections of HIV-infected people.

In countries where the patent is not recognized, alternative sources of fluconazole exist; in these countries patent law was not in force when Pfizer was granted the patent in 1983. In India fluconazole is produced locally by various generic drug manufacturers as Cipla, who sells fluconazole at $US 0.64 per 200 mg capsule. Similarly, In Thailand fluconazole is not patented. However, under pressure from the US, the Thai Food and Drug Administration implemented a process called the Safety Monitoring Programme, which effectively conferred a period of market exclusivity as a patent would. Thus, the generic local industry was not allowed to produce this molecule until last year 1998. Before that time, Pfizer price per capsule 200 mg was around $US 7, after fluconazole was released from the Safety Monitoring Programme, three Thai companies began to produce it. Against this competition, Pfizerís decreased their price to $US 3.60. Nevertheless, the current price of the generic product is significantly cheaper. For example, Biolabís price is six times cheaper (August 1999: $US 0.60 per capsule of 200 mg). This obviously makes an enormous difference in compliance to a patient who must take a capsule everyday of his/her life.

It also underlines the effect of competition on drug pricing, particularly in a country like Thailand where there is no governmental control on pharmaceutical prices. This is even true in Europe: for example, in Spain, benefiting from its previous Patent Act (which did not recognize product patent but process patent), there is local production of fluconazole; the cost being 20% less than Pfizerís price. (see table 1).

At the level of the national health expenditure, the price is of course crucial: in 1995, fluconazole was the 5^th Thai drug expenditure, with 151 millions bahts (around $US 4 million). Pfizerís fluconazole world sales were $US 881 million in 1997.

Comparing the most expensive source of fluconazole with the price in a country like Thailand, where there is available generic fluconazole up to 20 times of the budget could be saved for the monthly cost of maintenance treatment (Table 2; protocol 2).

Assumptions: Exchange rate:, $US 1 = 37 baht; average weight of patient:, 50 Kg; cost of amphotericin B, (1 vial 50 mg), $US 10

Protocol 1: induction phase: amphotericin B i.v. 0.5-1.0 mg/kg daily for at least 6 weeks; maintenance phase : amphotericin B i.v. 0.5-1.0 mg/kg weekly, lifelong.

Protocol 2: induction phase: amphotericin B i.v. 0.5-1.0 mg/kg daily for 2 weeks, plus fluconazole capsules, 400 mg/day, orally, for 6 weeks; maintenance phase: fluconazole 200 mg/day orally, lifelong.

Using the above prices, if South Africa imported generic fluconazole from Thailand the national cost of treating 10.000 patients of cryptococcal meningitis in South Africa will decrease from $US 34.80 million to $US 2.16 million per year of maintenance treatment (see table 3).

In other words, each year, with a given budget of $US 2.16 million, South Africa would be able to treat 620 patients with Pfizerís fluconazole but 10, 000 patients with generic fluconazole imported from Thailand. This means 9,380 lives saved each year for the same budget.

World-wide, there is a problem of access to life-saving drugs for the majority of AIDS patients. Most of these drugs are still patent protected marketed at prohibitive price for developing countries.

This limited study of fluconazole pricing in different countries presented here illustrates the critical influence a patent can play in access to medicines, from which a number of recommendations can be made.

Countries still not compliant with TRIPS agreements ñ and therefore still not recognizing product patents ñ could register fluconazole from foreign generic manufacturers (after evaluating the quality), allowing them to market the product in their territory.

Countries that already comply with TRIPS should lobby Pfizer to decrease substantially the price where the GNP per capita of the population demonstrates that the treatment is not affordable. Alternatively, a voluntary license should be sought from Pfizer in order that a national company can produce fluconazole at an affordable price. If all negotiation with the drug company should fail, a compulsory license should be sought for the local production or import of fluconazole.

This must be implemented as soon as possible. Patients suffering from crytococcal meningitis cannot be expected to wait until the Pfizer patent expires.