Responding to the evidence for improved treatment for cryptococcal meningitis in resource-limited settings

To the Editor: The World Health Organization (WHO) issued the first evidence-based treatment guidelines for cryptococcal meningitis in December 2011.1 Although its incidence has decreased with increased access to antiretroviral therapy, cryptococcal meningitis remains a major cause of death in people with HIV/AIDS, with over 500 000 deaths every year in sub-Saharan Africa. It is a leading cause of death in the Médecins sans Frontières (MSF) HIV/AIDS programmes in Africa.2 , 3

The preferred treatment in the WHO guidelines combines amphotericin B injectable with oral solid formulations of either flucytosine or fluconazole. The liposomal injectable form of amphotericin B is also indicated as an alternative to conventional amphotericin B because it is associated with fewer side-effects. However, it is acknowledged that this option is currently too expensive for routine use in most countries.1

Access to fluconazole was a major concern a decade ago, with 100-fold price differences reported in developing countries with the similar gross domestic product.4 In South Africa, the drug became an early symbol of the struggle to improve access to affordable treatment for people living with HIV/AIDS. In early 2000 the Treatment Action Campaign imported generic versions of fluconazole from Thailand, in defiance of patent laws at the time. Fluconazole is generally available today, with quality-assured generics costing as little as US$0.07 per 200 mg capsule.5 However, access to the preferred drugs, amphotericin B and flucytosine, is a challenge, as highlighted by a rapid survey of MSF HIV/AIDS programmes in 9 countries. Amphotericin B was available in only 4 countries, and cost between US$70 and $170 per patient for a 2-week induction treatment. Data on the registration status, availability and price of flucytosine and amphotericine B in 7 African countries is available at http://tinyurl.com/857zxdf.

MSF uses amphotericin B in its HIV/AIDS projects, but national availability is poor. For instance, although the drug is registered in Ethiopia and the Democratic Republic of the Congo, it is not available. Access to flucytosine is even more problematic; it was not registered in the 9 countries surveyed and was only available in South Africa under legislation for special prescription at US$252 per patient for a 2-week induction treatment.

The development of guidelines for the treatment of cryptococcal meningitis and other opportunistic infections is an important advance. The WHO should be congratulated for commissioning a thorough review of the evidence and recommending treatment options based on the patients’ best interests, not simply on what is available. The urgent challenge ahe­­­ad for all involved in translating these guidelines into practice is to accelerate access to affordable treatment by supporting the registration and procurement of flucytosine and amphotericin B at affordable prices in all the countries where these drugs are needed.

We thank all MSF staff who co-operated in providing registration, availability and price data.

Barbara Milani

Médecins sans Frontières

78 rue de Lausanne

1211 Geneva

Switzerland

Nathan Ford

Médecins sans Frontières

and

Centre for Infectious Disease Epidemiology and Research

University of Cape Town

nathan.ford@msf.org

1. Park BJ, Wannemuehler KA, Marston BJ, et al. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009;23:525-530. [http://dx.doi.org/10.1097/QAD.0b013e328322ffac]

2. Marshall C, Spelman T, Curtis A, et al. Impact of WHO Stage 3 and 4 conditions on mortality in people commencing antiretroviral therapy in Médecins Sans Frontières supported projects in resource-limited settings. 16th ICASA, Addis, 4-8 December 2011.

3. World Health Organization (WHO). Rapid Advice: Diagnosis, Prevention and Management of Cryptococcal Disease in HIV–infected Adults, Adolescents and Children. Geneva: WHO, 2011.

4. Perez-Casas C, Chirac P, Berman D, Ford F. Access to fluconazole in less-developed countries. Lancet 2000;356:2102. [http://dx.doi.org/10.1016/S0140-6736(05)74314-2]

5. World Health Organization (WHO). Global Price Reporting Mechanism. Geneva: WHO, 2011. http://apps.who.int/hiv/amds/price/hdd/ (accessed 14 December 2011).