Continuing 3TC therapy after viral rebound shows no benefit

HIV-positive individuals who have resistance to the antiretroviral drug 3TC (lamivudine, Epivir) do not derive any virological or immunological benefit from continuing treatment with the drug, according to the results of a randomised trial published in the October edition of Antiviral Therapy.

It is generally recommended that HIV-positive individuals who have developed resistance to one or more drugs in their anti-HIV treatment combination should change to a completely new set of drugs (if they have options available to them). However there is some evidence that remaining on 3TC therapy, even when HIV has developed the M184I or M184V resistance mutation against it, may have some virological benefits as HIV with these mutations are thought to be less able to replicate and evolve.

There are, however, no data from comparative studies about the benefits or otherwise of continuing 3TC therapy in the presence of M184I/V resistance. Investigators from the COLATE (Continuation of Lamivudine Treatment in Europe) study therefore designed a randomised trial involving 131 individuals. All were taking 3TC as part of their antiretroviral therapy and had experienced a rebound in their viral load to above 1,000 copies/ml.

They were randomly assigned on an equal basis to either change to an antiretroviral combination of drugs that did not include 3TC, or to continue to take 3TC as part of their HIV therapy. The study lasted for 48 weeks and the investigators compared changes in viral load, CD4 cell count and the genetic evolution of HIV between the two arms of the study.

Overall at the end of the study, viral load fell by a mean of 1.4 log₁₀ in the patients who stopped 3TC therapy and 1.5 log₁₀ amongst those who continued to tale 3TC. This difference was no statistically significant.

Similarly there was no difference in the magnitude of CD4 cell change between the two arms of the study. Median CD4 cell count increased by 87 cells/mm³ amongst patients continuing 3TC and by a median of 76 cells/mm³ amongst patients stopping 3TC. These differences were not statistically significant.

But the researchers did find that patients who discontinued 3TC were more likely to lose the M184I/V resistance mutations after 48 weeks – of the patients who continued 3TC, only one patient lost this mutation compared to 78% of patients who stopped taking 3TC. Furthermore, the investigators found that there were significantly fewer changes in the nucleotide genetic structure of virus that contained M184I/V compared to HIV that reverted to wild-type, or sensitive to all drugs (p

Although the investigators conclude that patients in their study derived no virological or immunological benefit from continuing with failing 3TC therapy and the M184I/V mutation, they do not completely rule out this approach to treatment. They note that patients in their study were still relatively inexperienced, having taken a median of only four anti-HIV drugs, and their findings “do not exclude a minor benefit in subpopulations of more treatment experienced patients harbouring this mutation.”