The World Health Organization (WHO), drug companies, drug regulators, NGOs and national governments have been working together to minimise the disruption of antiretroviral therapy to individuals affected by the near-global recall of nelfinavir (Viracept).

Although it was initially thought that the recall only affected Europe following the alerts issued by Roche, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMEA) on June 6 ^th, it has, in fact, affected every country in the world with the exception of the United States and its territories, Canada and Japan.

"A very difficult situation"
On June 14^th, WHO issued a statement on the recall, saying that "Roche informed WHO on 8 June 2007 of its global recall of its nelfinavir products (Viracept)." Roche estimates that around 45,000 individuals are affected by the recall globally.

Roche’s International Communications Manager for HIV and Hepatitis, Janet Kettels told aidsmap.com: "This is obviously a very difficult situation, as many people living with HIV/AIDS in the least developed countries do not have easy access to a wide range of alternative treatments."

The WHO statement highlights that "adults or children currently taking Viracept should not interrupt their antiretroviral therapy. However, they should see their antiretroviral therapy provider as soon as possible, to change from Viracept to a suitable alternative."

"In the meantime," adds Ms Kettels, "Roche is working as quickly as possible to get new batches of Viracept to patients in these and other countries affected by the recall. In addition, we are working with the NGOs and have provided a list of alternative treatments that could be considered."

WHO recommends nelfinavir alternatives

WHO-recommended options include:

• a boosted protease inhibitor;

• nevirapine – with close observation for toxicity if CD4 is above 250 cells/mm³;

• efavirenz – unless in the first trimester of pregnancy;

• triple nucleoside therapy.

WHO notes that “nelfinavir belongs to the protease inhibitor (PI) class of antiretroviral medicines. Wherever possible, the PI class should be reserved for second-line therapy, particularly in settings, where availability of ARV formularies is limited. In choosing the PI for second-line therapy for adults and children, a PI boosted by ritonavir (/r) is recommended for antiviral potency.”

It adds that although ritonavir-boosted indinavir, saquinavir, atazanavir or fosamprenavir are alternatives for adults, lopinavir/r (Kaletra) “is the preferred boosted PI, as it has the advantage of being available as a fixed-dose combination and has recently been approved in a new heat-stable formulation, which eliminates the need for refrigeration.

“In children,” WHO notes, “saquinavir is only licensed for use in children over 25kg” and atazanavir and fosamprenavir are not yet approved for use in children.”

WHO also provides specific recommendations for pregnant women who “sometimes exceptionally” take nelfinavir as first-line therapy. “If this is the case and no other PI is available, then substitution of Viracept by another active ARV from another class of drugs will need to be considered.” It adds that the non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine “need to be used with caution in pregnant women.”

Nelfinavir is also often used for post exposure prophylaxis (PEP) and the WHO states that “countries that have included Viracept in post-exposure prophylaxis packs, should remove and replace it with a suitable boosted protease inhibitor. If no boosted PI are available, dual nucleoside therapy without a PI will remain effective.”

Snapshots from around the globe
According to the Latin American News Agency Prensa Latina, Brazil’s Health Ministry – which supplies nelfinavir at no cost to 9,000 adults and 250 children – told clinics to immediately replace Viracept with Kaletra.

In Botswana, the Ministry of Health is to negotiate with Roche for a refund according to Dr Loeto Mazhani, Director of Health Services in an interview with the Botswana Press Agency. He said that although more than 85,000 individuals are on first-line antiretroviral therapy, fewer than 1,000 patients were taking nelfinavir. He added that patients treated in government or government assisted facilities have also been switched to Kaletra.

In Zambia, where Pelekelo Mwangisha, pharmaceutical evaluator of the Zambian Pharmaceutical Regulatory Authority (PRA) told the Zambian Daily Mail that nelfinavir was being taken by 100 patients, and that each patient’s doctor would have to decide which drug to switch to. He also said that the PRA is undertaking spot checks in private health centres to ensure that Viracept has been taken off the market.

Virawan Taengkaew, deputy secretary general of the Thai Food and Drug Administration (FDA), told The Nation newspaper that the recall would affect very few people in Thailand. In 2006, 22 hospitals had prescribed nelfinavir to 190 individuals, but this year just 144 people were taking the drug. She added that individuals taking nelfinavir could ask for compensation if it is proven that they have been harmed by the contamination.

Roche collaborating with Pfizer, EMEA, NGOs
Roche’s Janet Kettels confirms that Roche is taking steps to import non-contaminated supplies of the drug, with a focus on least-developed nations. “Unfortunately, I can’t tell you how much, when or where as we are still working on these critical details,” she tells aidsmap.com “I can tell you that Roche are investigating every possible avenue to get new supplies of Viracept to patients as quickly as we can.

“We are currently working with the EMEA to establish when we will be able to recommence supply of Viracept. Once we have the go-ahead from the EMEA, we will be able to quickly co-ordinate re-supply including to the NGOs that supply Viracept to many of the least developed countries,” she says.

“In addition,” she continues, “Roche International are talking with the central Pfizer group about supply. However, there are regulatory requirements that we need to abide by, meaning that as the Pfizer formulations of Viracept are not registered outside of the United States, Canada and Japan we cannot simply buy the stock for other countries and distribute it.”

Risk to patients under assessment
The day following the recall, Roche UK’s Associate Head of Medical Affairs, Dr Dilruwan Chaminda Herath, told aidsmap.com that Roche had attempted to ascertain the risk to patients who may have ingested the contaminant, ethyl mesylate, based on test tube and animal studies. “In a worse case scenario,” he said, “the amount ingested by someone on Viracept would be 100 fold less than was found to cause tumours in rats.”

Ms Kettels adds that Roche is “working with the EMEA and the CHMP [the European Union’s Committee for Medicinal Products for Human Use] to assess fully any potential risk to patients who have been exposed to Viracept and will provide this information to the NGOs as we receive it.”

The complete WHO statement on the nelfinavir recall is available on WHO's HIV and AIDS website in English, French and Spanish.

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