 |
|
|
| |
No Residual Raltegravir Activity After Resistance Emerges
|
| |
| |
16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal
Mark Mascolini
A study of 4 people who stopped only raltegravir in a salvage regimen after emergence of integrase mutations found no evidence that the drug exerts residual activity after mutations evolve.
"Even if further observations will be useful to be certain" of this finding, Marc Wirden and Paris colleagues concluded, "it seems unnecessary to keep this drug in such a context. Moreover, the withdrawal of raltegravir avoids the risk of accumulating mutations for future compounds within this class."
The four patients were taking a raltegravir-containing regimen with a stable, detectable viral load for at least 2 months. Wirden and coworkers measured viral load and CD4 count at day 0 (the day patients stopped only raltegravir), then for up to 90 days as the patients continued the same regimen. A substantial viral load gain during this time would indicate that raltegravir had been exerting some antiviral activity after resistance mutations emerged.
In the last month of raltegravir therapy, the hallmark integrase mutation N155H emerged in patients A, C, and D, while the classic Q148H mutation arose in patient B. Virus from all 4 patients also had evidence of other mutations with these signature mutations. Trough raltegravir concentrations were in the therapeutic range (from 118 to 268 ng/mL) when these people stopped raltegravir, then quickly became undetectable.
Follow-up continued for 28 days in patients A and C, for 90 days in patient B, and for 42 days in patient D. Variations in viral load during follow-up were minimal:
· Patient A: -0.04 log, +51 CD4s
· Patient B: -0.17 log, +25 CD4s
· Patient C: +0.19 log, -56 CD4s
· Patient D: -0.20 log, +252 CD4s
Wirden and colleagues noted that all viral load variations were well below a meaningful cutoff of 0.5 log.
Regardless of what other antiretrovirals people were taking with raltegravir, integrase mutations did not disappear during follow-up. Because of this finding, the investigators suggested, "the discussion remains open about impact [of these mutations] on replication capacity."
Reference
1. Wirden M, Simon A, Schneider L, et al. Raltegravir interruption has no effect on HIV-1 RNA plasmatic level in patients harboring viruses with resistance-associated mutations to this drug. 16th Conference on Retroviruses and Opportunistic Infections. February 8-11, 2009. Montreal. Abstract 622.
(This poster is online at http://www.retroconference.org/2009/PDFs/622.pdf.)
Background: Raltegravir (RAL) is today the first drug available in the new antiretroviral class of integrase inhibitors. This compound is powerful and its use is increasing in HIV treatment especially in a context of drug resistances to the earliest classes. However, the emergence of resistance mutations has been already associated to RAL-regimen failure, with high resistance levels in vitro. It is important to know whether a residual antiretroviral activity of RAL is still present in such a context in vivo, and so whether it could be useful to keep the drug in the subsequent salvage therapy.
|
| |
|
|
|
|
|
