Systematic review and meta-analysis shows equivalence of 3TC and FTC

The nucleoside reverse transcriptase inhibitors (NRTIs) 3TC and FTC are equally effective, results of a meta-analysis and systematic review published in PLOS ONE show. Pooled results from twelve randomised studies showed that the drugs were equivalent, with near-identical rates of viral suppression for the drugs. The risk of treatment failure was also the same for both antiretrovirals.

“This systematic review of published and unpublished data from randomized trials found no significant differences in the efficacy of lamivudine [3TC] and emtricitabine [FTC]”, comment the authors. They suggest their findings are “consistent with the very similar chemical structure of these two nucleoside analogues”.

National and international HIV treatment guidelines consider 3TC (lamivudine, Epivir, also in the combination pill Kivexa) and FTC (emtricitabine, Emtriva, also in Truvada, Eviplera and Atripla) to have similar clinical efficacy. The drugs form a core component of the NRTI 'backbone' of antiretroviral combinations for people starting treatment for the first time (treatment naive) and people changing treatment (treatment experienced). However, some research has suggested that regimens including 3TC lack the virological potency of combinations containing FTC. This means that there is ongoing uncertainty about the clinical equivalence of the two drugs.

An international team of investigators therefore conducted a systematic review and meta-analysis of randomised studies to assess and compare the effectiveness of the drugs.

The authors identified randomised and quasi-randomised studies in which 3TC and FTC were used for the treatment of either treatment-naive or treatment-experienced patients. They only included studies if they allowed direct comparison between 3TC and FTC. Therefore, the other drugs in the regimens taken by people treated with 3TC or FTC had to be identical or comparable. Studies where patients took abacavir (Ziagen, also in Kivexa) and tenofovir (Viread, also in Truvada, Eviplera and Atripla) were included but only if the study population did not start therapy with a viral load above 100,000 copies/ml. This is because of evidence suggesting inferior virological outcomes among people taking abacavir who have a viral load above this level at the start of therapy.

A total of twelve randomised studies with 15 different randomised comparisons met the inclusion criteria and were included in the authors’ analyses. These studies provided data on 2251 people taking 3TC and 2662 people taking FTC. The studies were published between 2002 and 2013. Three studies directly compared 3TC with FTC.

Treatment success rates were comparable in all twelve studies. The three studies that provided a direct comparison between 3TC and FTC showed a non-significant difference in the chances of treatment success (RR = 1.03; 95% CI, 0.96-1.10; p = 0.3).

Overall, the odds of treatment success were identical (RR = 1.00; 95% CI, 0.97-10.2). Outcomes did not differ by sub-group.

The risk of treatment failure was also comparable for the two drugs (RR = 1.08; 95% CI, 0.94-1.22). Once again, the risk of failure did not differ in sub-group analysis. 

Two of the three studies with identical backbone regimens provided data on the rate of side-effects. One of the studies showed there was no difference between 3TC and FTC in the frequency of moderate and serious adverse events. In the other, 4% of people taking FTC discontinued treatment but there were no discontinuations among people taking 3TC.

“The overall findings provide supportive evidence for recommendations of current international and national treatment guidelines to treat emtricitabine and lamivudine as interchangeable,” the authors conclude. They believe their results will provide “reassurance to countries that, for reasons of affordability or availability have opted for lamivudine as part of first-line antiretroviral therapy.”