WHO statement: generic antiretroviral therapy is safe and effective

1 February 2013. Related: Treatment alerts, Antiretrovirals.

A recent BBC report that inaccurately commented on safety issues in relation to generic HIV treatment was sufficiently erroneous and widely distributed to prompt the unusual response of this public statement from the WHO.

WHO Department of HIV/AIDS and Department of Essential Medicines and Health Products

On 16 January 2013, an article entitled “Study questions generic HIV drug use” appeared on BBC News Health (note this article has since been modified) [1]. The article was based on original research by Rochelle Walensky et al that was published in the Annals of Internal Medicine on 15 January 2013, and describes a mathematical simulation of HIV disease. [2]

Unfortunately, the BBC News Health article presented the findings of the modelling study as indicative of the need to make an ethical trade-off between cost savings and efficacy. The response below from WHO’s Department of HIV/AIDS and Department of Essential Medicines and Health Products points out that such an interpretation is misleading and not supported by the extensive global evidence of the efficacy of quality-assured generic antiretroviral therapy. [3]

Generic antiretroviral therapy is safe and effective

Rochelle Walensky and colleagues provide important estimates of the potential cost savings associated with the introduction of generic-based antiretroviral therapy (ART) in the United States. Using conservative assumptions, they estimate first-year savings of up to US$ 920 million and lifetime average savings of US$ 42,500 per eligible patient. However, the authors of the study caution that this may require a tradeoff between drug efficacy and cost savings, as the regimens proposed in the model are not available fixed-dose combinations and may have inferior efficacy and could lead to poor adherence.

We would like to highlight three points related to this analysis.

First, the assumption of inferior efficacy is based on the suggesting that lamivudine (3TC) has poorer efficacy than emtricitabine (FTC). This assumption is in contrast to a recent systematic review that found no evidence of any difference between the two drugs in terms of efficacy and safety [4].

Second, the assumption of poorer adherence is based on the fact that generic formulations are not available as fixed-dose combinations. This may be the case in the United States, but quality-assured generic fixed-dose combinations of tenofovir, emtricitabine and efavirenz (TDF+FTC+EFV) do exist and are used in other parts of the world. [5].

Third, each of the scenarios includes the originator TDF product because TDF is patented in the US, and the estimated cost of this regimen is US$ 9,200 per patient/year. However, a fixed-dose combination of TDF+FTC+EFV including generic TDF is currently available internationally and costs less than US$ 200 per patient/year [6]. Taken together, these points suggest that potential cost savings in the United States of using generic regimens could be even greater than concluded by this analysis, with no negative consequences in terms of efficacy or adherence. It is important to also highlight that in this analysis, presumed differences between generic and originator regimens are associated with the use of different drugs (3TC versus FTC), and formulations (separate tablets rather than fixed-dose combinations), and not the use of generic drugs per se:

Walensky et al rightly consider quality-assured generic and originator drugs to be equivalent in terms of safety and efficacy. Despite ongoing doubts and controversies about the use of generic antiretrovirals over the last decade [7], comparative studies have found no differences in safety or efficacy between originator and quality-assured generic antiretrovirals [5]. Ensuring access to affordable antiretroviral therapy has been an essential precondition of the global scale up of antiretroviral therapy, and both generic and originator companies have an important role to play in ensuring that current and future antiretroviral regimens are accessible and affordable for all who need them.

The study by Walensky et al opens an important discussion about the extent to which patients in the United States are able to access more affordable, fixed-dose antiretroviral regimens that are already available in many other countries. Unfortunately, the findings of the modeling study are being portrayed as indicative of the need to make an ethical trade-off between cost savings and efficacy. Such an interpretation is misleading and is not supported by the extensive global evidence of the efficacy of quality-assured generic ART.

comment

Generic, off-patent medicines account for 65-85% of all NHS prescriptions.

Maintaining clarity on these issues will become increasingly important for confidence in HIV care in the UK, as patents are due to end for several of the most widely prescribed ARVs.

References:

1. BBC News: Study questions generic HIV drug use.
   http://bbc.co.uk/news/health-21012160
2. Walensky RP et al. Economic savings versus health losses: the cost-effectiveness of generic antiretroviral therapy in the United States. Annals of Internal Medicine, 15 January 2013, 158(2):84-92.
   http://annals.org/article.aspx?articleid=1556848
   http://www.natap.org/2013/HIV/000060520130115000002.pdf (full PDF)
3. Hirnschall G and de Joncheere C. Prequalification update. Generic antiretroviral therapy is safe and effective. World Health Organisation, Geneva, Switzerland. 24 January 2013.
   http://apps.who.int/prequal/info_press/pq_news_24January2013_BBCarticle.htm
4. Pharmacological equivalence and clinical interchangeability of lamivudine and emtricitabine: a review of current literature:
 technical update on treatment optimization. World Health Organization, Geneva, July 2012.
5. Untangling the web of antiretroviral price reductions. Medecins Sans Frontieres, Geneva, July 2012.
   http://utw.msfaccess.org
6. Ford N, ‘t Hoen E. Generic medicines are not substandard medicines. Lancet. 2002 Apr 13;359(9314):1351;
7. Stringer J et al. Effectiveness of generic and proprietary first-line antiretroviral regimens in a primary
health care setting in Lusaka, Zambia: a cohort study
   http://bbc.co.uk/news/health-21012160. Int J Epidemiol 2012;41:448-59.