Reduced replicative capacity of M184V explains benefit of 3TC monotherapy compared to stopping all drugs

Last year at the Bangkok IAS conference an Italian E-184V study, of 60 patients with CD4 counts >500 cells/mm3 who had the M184V mutation on HAART, and who wanted to stop treatment, reported lower CD4 reductions and additional clinical benefits in patients who maintained 3TC monotherapy, compared to patients who interrupted all their drugs.

At the Resistance Workshop, Nicola Gianotti and colleagues an analysis of viral replicative capacity from this study. Replicative capacity (RC) from the first 31 consecutive patients in the study was measured as p24Ag productivity from recombinant clones after four days in culture. Median replicative capacity ratio was calculated as RC at week 24 divided by RC at study baseline; this was 11.42 (IQR 2.4-57.1) in the treatment interruption group and 1.14 (IQR 1.00-1.28) in the 3TC monotherapy group (p=0.0006).

Protocol defined failure in the study was a CD4 drop to below 350 cells/mm3. In this analysis patients with protocol failure prior to 24 weeks had greater RC recovery compared to those without early failure. RC ratio also correlated with CD4 and CD4% decreases at week 24 (r=-0.46, p=0.01 and r=-0.55, p=0.001, respectively); but not with baseline CD4, CD4%, viral load, 24-week increase in viral load, or 48-week changes in CD4 and viral load.

RC recovery was consistent with reduction in resistance in protease and RT mutation and with the outgrowth of wild-type virus at position 184, although statistically analysis for this is still ongoing.

Gianotti E, Menzo S, Danise A et al. E-184V study: immunological and virological correlates of HIV-1 replicative capacity. 14th HIV Drug Resistance Workshop, 7-11 June 2005, Quebec City, Canada. Abstract 160.