A high rate of early virologic non-response has been observed in a clinical study of therapy-naïve adults receiving once-daily three-drug combination therapy with lamivudine (Epivir®), abacavir (Ziagen®) and tenofovir (Viread™) (1).

Based on these results:

• Abacavir and lamivudine in combination with tenofovir should not be used as a triple antiretroviral therapy when considering a new treatment regimen for naive or pre-treated patients;

• Any patient currently controlled on therapy with this combination should be closely monitored and considered for modification of therapy; and

• Any usage of this triple combination with other antiretroviral agents should be closely monitored for signs of treatment failure.

ESS30009 is a randomized, open-label, multicentre study on the safety and efficacy of efavirenz (EFV) versus tenofovir (TDF) when administered in combination with an investigational abacavir(ABC)/lamivudine (3TC) fixed-dose combination tablet as a once-daily regimen in antiretroviral-naïve HIV-1 infected adults.

Shortly after initiation of this study the sponsor, GlaxoSmithKline, received reports from investigators of poor efficacy in patients receiving TDF+3TC+ABC. An urgent, unplanned interim analysis was conducted to assess virologic non-response. Results are shown in the table below. The precise nature of any interaction leading to non-response in this study is not known. Preliminary genotypes of viral isolates from 14 patients with non-response taking the TDF+3TC+ABC regimen have shown all 14 isolates had the M184V mutation in HIV reverse transcriptase. In addition, 8 of the 14 (57%) isolates also had the K65R mutation.

On review of these results, GSK promptly informed all participating clinical investigators and terminated the TDF+3TC+ABC arm in this study. Clinical investigators are working with patients to change therapy based on genotype and clinical judgement. The once daily EFV+3TC+ABC arm performed well and continues unchanged in this clinical study.

In addition to study ESS30009, a pilot study (2) has provided data in 20 patients receiving TDF+3TC+ ABC once daily for initial therapy. A high rate of virologic non-response was also documented.

References

1. GlaxoSmithKline letter to health care providers published on www.FDA.gov/medwatch.

2. Farthing, et al. 2nd annual meeting of the International AIDS Society, July 2003, Paris, France.

3. Informative Note 2003/09. Spanish medicines Agency, 31 July 2003 http://www.agemed.es.