Important note: Information in this article was accurate in September 2005. The state of the art may have changed since the publication date.
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Benefit of maintaining the M184V mutation with 3TC monotherapy: final 48-week results
HIV Treatment Bulletin - Vol. 6, No. 9, September 2005
Simon Collins, HIV i-Base
Final results were presented from the E-184V study [1] whose interim results were presented at the Bangkok conference last year and at this year Resistance Workshop in Quebec. [2, 3]
Castagna and colleagues from Vita-Salute San Raffaele University in Milan randomised 58 patients with viral rebound on 3TC-containing regimens and confirmed M184V resistance and who wanted to take a treatment interruption, to either discontinue all treatment or to maintain 3TC monotherapy. All patients had CD4 counts >500 cells/mm3.
After 48 weeks, the group that continued taking 3TC had a reduced viral load rebound (+0.57 versus +1.11 log10 copies/mL) and a smaller drop in CD4 count (-141 versus -215 cells/mm3) compared to the group that stopped all treatment. 12/29 (41%) in the 3TC group vs 20/29 (69%) in the treatment interruption group experienced protocol defined failure (development of HIV-related symptoms or CD4 count <350 cells/mm3.
Maintaining M184V mutation was associated with reduced viral replicative capacity in patients taking 3TC monotherapy. There were no difference in the virological and CD4 responses between patients in each group who needed to restart treatment.
Comment
These 48-week results confirm previous analyses from this important study. [2, 3]
Although this will be a very useful option though for people are considering stopping treatment who already have the M184V mutation, the importance of this study is probably less to do with the benefits of 3TC monotherapy.
The virological benefit from maintaining M184V potentially suggests use of 3TC as an additional active drug in salvage therapy, and has provided evidence (through a different trial design) that the Colate study (which was closed after three years by the DSMB due to poor enrolment) was never able to achieve. [4]
FTC has cross-resistance with 3TC because of a similar relationship to the M184V mutation, and would be expected to produce similar results to 3TC in this study. The impact of using abacavir for this strategy has not been studied.
References:
| 1. | Castagna A, Danise A, Menzo S et al. E-184V study. Lamivudine monotherapy vs treatment interruption in failing HIV-1 infected subjects, harbouring the M184V mutation: 48-week final results. IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (abstract no. WeFo0204). |
| 2. | Gianotti E, Menzo S, Danise A et al. E-184V study: immunological and virological correlates of HIV-1 replicative capacity. Antivir Ther. 10, Suppl 1:S175 (abstract no. 160); Simon Collins, "Reduced replicative capacity of M184V explains benefit of 3TC monotherapy compared to stopping all drugs", HIV Treat Bull 2005 Jul;6(7). |
| 3. | Castagna et al. "E-184V. Pilot study to evaluate immunological response to lamivudine monotherapy vs treatment interruption in failing HIV-1 infected subjects, harbouring the M184V mutation" - Int Conf AIDS. 2004 Jul 11-16;15:(Abstract No. WeOrB1286); Simon Collins, "Another chance for 3TC in patients with M184V mutation?", HIV Treat Bull. 2004 Sep;5(7). |
| 4. | COLATE study shows no clinical benefit from continuing 3TC to maintain M184V mutation. HIV Treat Bull 2004 Apr;15(3). |
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