To the Editors:
Access to antiretroviral (ARV) drugs in resource-limited countries has dramatically expanded in recent years. This was made possible by a decrease in drug prices because of the availability of generic ARV drugs on the international market. Various global health organizations [World Health Organization (WHO), United Nations Programme on HIV/AIDS (UNAIDS)] support the use of generic ARV drugs. Two specific measures have been implemented to promote procurement of generic ARVs: (1) the establishment of prequalification lists of drugs sponsored by WHO1 aimed at guaranteeing quality medicines and (2) the availability of drug price guides2,3 enabling purchasers to compare prices offered by the various suppliers.
In 2012, global production of ARV drugs was provided by 8 proprietary and 7 generic pharmaceutical companies. They supplied the 22 molecules that make up the various therapeutic regimens that usually combine 3 drugs from different classes, based on periodically revised international recommendations.
A MARKET APPROACH LEADS TO PROLIFERATION
Currently in developing countries, the majority of distributed ARVs are generic drugs. Each country purchases its drug supply independently. Procurement occurs through tendering procedures and competition between international suppliers, with selection based on the best prices. The attribution rule for the lowest bidder and dividing purchases among several suppliers (to guard against nondelivery) has meant that a drug could be supplied by 2, even 3, different suppliers during the period covered by the tender (1–2 years). Because each supplier independently defines the brand name and characteristics of its drugs, a single drug will undergo a veritable proliferation of names, sizes, shapes, and colors.
In Senegal from 1998 to 2010, there were 5 different forms of Zidovudine and as many for Lamivudine, 5 different forms each for Nevirapine and the combination Lamivudine–Zidovudine, and 6 for Lamivudine. The brand name—commonly used by health care professionals and sometimes by patients since it appears on the packaging—varied for Lamivudine among Epivir, Avolam, Larvir, Lamivir, Heptavir, and Lamivudine; the names for Nevirapine were Viramune, Nevipan, Nevirex, Nevirapine, Nevimune, Nevir, etc.
Given that a treatment regimen usually combines 3 different drugs and that each one can vary several times in the same year, a treatment's appearance can change frequently. For example, for the years 2008 and 2009, 4 forms of Tenofovir, 2 forms of Abacavir, and 2 forms of Lopinavir/Ritonavir meant that some patients received from 2 to 5 different forms of the same treatment combination (Fig. 1). This range of names and appearances, along with their frequent variations, has multiple and serious consequences for both patients and health professionals.
NEGATIVE IMPACTS ON PATIENTS AND HEALTH CARE PROFESSIONALS
For patients, each change raises questions and can be disruptive, even when health care professionals have provided patients with information and support about the change. Changes in name or appearance confuse identification markers for drugs and disrupt intake routines. To date, no systematic study that can establish the health impact has been published, but empirical observations have reported many patients' stories that demonstrate their anxiety about changes in presentation and accounts about errors when taking drugs (eg, confusion between the 2 forms of Abacavir and Lopinavir/Ritonavir, taking a double dose of Tenofovir for several months, etc.). Moreover, changes in appearance are often perceived as changes in treatment. Patients question the reasons for the change, fearing an aggravation of the disease concealed by the doctor or an error in the doctor's prescription or in the pharmacist's dispensation. These changes rekindle perceived adverse effects related to “adapting” to treatment and fears about new adverse reactions. They threaten proper compliance and treatment adherence, particularly for populations with low education levels (or who lack full command of the dominant language). In Dakar, some patients have refused to take what they perceive as a “new treatment.”
Changes in drug name and appearance also have an impact on the job performance of health care professionals who deliver the drugs by complicating dispensation and drug supply management. When drugs are dispensed, health care professionals must inform patients of each change, explain the reasons, reassure them that the treatments are similar, and prevent and manage possible new side effects; they must also point out and describe how each drug has changed in appearance and ensure that patients understand. The range of names is a key factor causing confusion in drug supply management and errors in drug delivery. For example, discrepancies were noted in a pharmacy where inventory shelves were labeled with a drug's brand name and the International Nonproprietary Name; yet, the boxes on the shelf corresponded to a different brand name. Another example occurred in a peripheral health facility where the person in charge of delivering drugs was sending patients home after informing them of a break in stock because she was unaware that boxes received over the past few weeks contained a drug whose name and appearance had changed.
These risks for errors are all the more deserving of attention because drug dispensation in resource-constrained countries often occurs in the context of task shifting involving staff who are not pharmacists and who have often only received minimal training that is not updated.
STANDARDIZATION: A PUBLIC HEALTH APPROACH
These problems can be avoided by standardizing the appearance and names of ARV drugs. This is not a new idea. The history of pharmacy has shown that diversification of forms and names stems from the desire among proprietary pharmaceutical companies to single out their products to promote brand identification. A drug's physical appearance and name are sometimes protected by an intellectual property right covering trademark and trade dress that prohibits generic pharmaceutical companies from imitating features of the brand name drug.
Nevertheless, health officials from several countries required specific identifiable attributes—particularly for color—for some drug categories (eg, bronchodilators in Great Britain) to make it easier for patients to identify them. In Canada, most generic drugs resemble the original in terms of size, shape, and color; officials in some provinces recommend that the original and generic drugs resemble each other.4 This decision highlights the inherent value of the drug's appearance in terms of public health. This value has been increasingly recognized by the law, which deems that a drug's form is a major factor in its ease of use and is therefore a component of health safety.5
For the specific case of anti-HIV drugs for developing countries, the principle of standardization should be applied to the appearance of ARV drugs to streamline drug management and promote patient treatment adherence. It is necessary and urgent to establish criteria for perfect similarity in appearance between drugs that are bioequivalent with the same active ingredient and dosage and marketed by the different pharmaceutical companies, whether brand name or generic. The issue of names should also be considered because different names for the same treatment confuse both patients and primary health care providers. The next step should be to standardize the name of each medicine, based on the INN.6 To ensure this measure is applied quickly, these factors must be included in the WHO-defined criteria for prequalification of ARV drugs.
The authors acknowledge Sharon Calandra who translated the article and edited the final version.
1. World Health Organization. Prequalification programme. A United Nations programme managed by WHO. Available at: http://apps.who.int/prequal/
. Accessed March 20, 2013.
2. Médecins sans Frontières. Untangling the Web of antiretroviral price reductions. Available at: http://utw.msfaccess.org/
. Accessed March 20, 2013.
4. Canadian Generic Pharmaceutical Association. The Size, Shape & Colour of Generic Medicines. 2013. Available at: www.generiquescanadiens.ca/
. Accessed March 20, 2013.
5. Greene J, Kesselheim A. Why do the same drugs look different? Pills, trade dress, and public health. N Engl J Med. 2011;365:83–89.