COLATE study shows no clinical benefit from continuing 3TC to maintain M184V mutation

For many years there have been few data on whether maintaining the 3TC-associated M184V mutation can have an impact on viral fitness that translates into any clinical benefit. The theoretical basis for this was first suggested in early 3TC studies and several small studies have supported this.

The COLATE study planned to randomise 160 patients to either drop or continue 3TC when switching a failing combination following at least two consecutive viral load counts >1000 copies/mL. This study first enrolled patients in June 1999 and despite being an international European study with 18 sites it took almost three years to enroll 76 patients failing their first combination and 55 patients failing their second or higher combination. The study was terminated early by the trial’s data and safety monitoring board on the basis of futility. Nevertheless, the results presented from the 133 patients followed for at least 48 weeks still had sufficient power to detect any significant difference between the two arms.

No differences were seen in the proportion of patients with renewed viral suppression to <50 or <400 copies/mL and HIV RNA reduced by 1.4 log copies/mL in both arms. Primary efficacy calculated by average under the curve changes in viral load from baseline also found comparable results in each arm when adjusting for baseline CD4 count. Most patients adhered to their study arm. Discontinuation rates and numbers of drugs used in the subsequent regimen were both similar in each arm. There was no difference in the time to protocol-defined failure of less than 0.5 log drop compared to baseline or an increase of >1 log compared to nadir response. There were also no differences in change of CD4 count or time to increase of >100 cell/mm3.

The M184V mutation was present in most patients at baseline and was maintained in those who continued to take 3TC, but generally became difficult to detect after six months in patients who discontinued 3TC.

Dragsted U, Fox Z, Mathiesen L et al for the COLATE trial group. Final week 48 analysis of a Phase IV, randomised, open-label, multi-centre trial to evaluate safety and efficacy of continued 3TC twice-daily versus discontinuation of 3TC in HIV-1-infected adults with virological failure on ongoing combination treatments containing 3TC: the COLATE trial. 11th CROI 2004, Abstract 549.