Summary of evidence and Expert Committee recommendations
In 2005, the Expert Committee considered an application from the manufacturer for tenofovir (TDF) and emtricitabine as an FDC. At that meeting, the Committee noted “the fixed-dose combination had only recently been approved by the US Food and Drug Administration, but that it is increasingly being used in national programmes. However, it would be illogical to consider the combination so long as the individual medicines had not been added to the Model List. The Committee concluded that listing of the combination at this stage would be premature, and decided to defer its decision because of the lack of information, for example, in comparison with lamivudine.”
Tenofovir and emtricitabine are listed in current WHO treatment guidelines for adults (1) as one option for first-line combination treatment as part of the NRTI backbone, and as an alternative to abacavir (ABC).
The evidence for comparative effectiveness and safety in this application consists of trials that were the basis of the USA’s regulatory approval of the FDC and two studies of bioequivalence and pharmacokinetics. It is not
clear that any of the large trials used the proposed FDC. Safety data based on the use of the components individually and in combination, not as an FDC, is as presented in the applications for the single components. There is no evidence of use of this combination in resource-poor settings. The Committee noted that differential pricing of the FDC is proposed through an access programme: 30 days supply for US$ 26.25. No formal cost-effectiveness evaluation was provided.
The Committee noted that this combination is one of several proposed in the WHO treatment guidelines, and is one combination for first-line treatment. The combination can be used in adult HIV patients but not children; there
is limited information about its use in pregnant women. It is specifically recommended for use in patients co-infected with hepatitis B virus (HBV). One product of adequate quality exists, containing appropriate doses of the components, and there have been clinical studies using the components of the FDC at the same doses, but no clinical studies of the use of the FDC; there are also bioequivalence and pharmacokinetic studies. There is limited experience of use of this product in resource-poor settings.
The Committee therefore decided to add the combination of tenofovir and emtricitabine to the core list, noting particularly its utility in patients with HBV co-infection and with an accompanying note that 3TC is an acceptable alternative to FTC, based on knowledge of the pharmacology, the resistance patterns and clinical trials of ARVs.
1. Antiretroviral therapy for HIV infection in adults and adolescents in resource limited settings: toward universal access. Recommendations for a public health approach – 2006 revision. Geneva, Switzerland, World Health Organization, 2006 (http://www.who.int/hiv/pub/guidelines/adult/en/index.html).