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  51th ICAAC
Chicago, IL
September 17-20, 2011
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Dropping Inactive NRTI Does Not Compromise 4- or 5-Drug Salvage Combos
  51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17-20, 2011, Chicago

Mark Mascolini

Eliminating an inactive nucleos(t)ide reverse transcriptase inhibitor (NRTI) from a salvage combination including 4 or 5 antiretrovirals did not threaten virologic response through 24 weeks of follow-up and had no apparent clinical consequences in a small, single-arm study in Montreal [1].

People with multidrug-resistant HIV may take combinations of four or five antiretrovirals typically including two or more NRTIs. Clinicians at Montreal's Clinique Medicale l'Actuel questioned whether it makes sense to keep NRTIs in such regimens if genotypic evidence indicates that those NRTIs are no longer active against a patient's virus.

Some evidence suggests NRTIs may exert partial activity against HIV even after mutations conferring resistance to those NRTIs develop. In particular, principal investigator Benoit Trottier told NATAP, clinicians often lean toward maintaining lamivudine in a rescue regimen after the M184V mutation arises because some work shows that M184V virus has reduced replications capacity. And reduced replication capacity may be beneficial when constructing a salvage regimen, especially since lamivudine is relatively cheap and has few side effects.

But Trottier suggested that retaining lamivudine in the presence of M184V after a salvage regimen controls HIV may make less sense. The Montreal investigators observed that continuing largely inactive NRTIs may add toxicity, unwanted drug interactions, and cost. Furthermore, antiretroviral guidelines offer no advice on keeping inactive NRTIs in a rescue regimen. Therefore, they planned this single-arm, open-label trial to test the hypothesis that dropping such drugs from a salvage regimen would not compromise virologic response or cause clinical problems.

The study involved 31 adults with multidrug-resistant HIV and an undetectable viral load while taking a stable regimen that included one or more inactive NRTIs, as determined by most recent genotype or cumulative mutations interpreted by the French ANRS algorithm.

All study participants had a CD4 count at or above 250, all were men, and 29 (94%) were gay men. The group averaged 50 years in age (interquartile range [IQR] 46 to 56) and had taken antiretrovirals for an average 14 years (IQR 12 to 16). Median CD4 count at the time of the study stood at 525 (IQR 360 to 680), and the group had a median lowest-ever (nadir) CD4 count of 158 (IQR 69 to 210).

Twenty-two men (71%) were taking four antiretrovirals and the remaining 9 were taking five. Twenty-nine men (94%) dropped lamivudine or emtricitabine from their regimen, and 1 each cut zidovudine and tenofovir.

Twenty-four weeks after the men stopped these NRTIs, all still had a viral load below 50 copies. CD4 counts remained essentially unchanged, with an average gain of 10 cells (P = 0.62). No one's CD4 count slipped below 200. No grade 2 or worse lab abnormality occurred, no serious adverse events developed, and no one died.

Trottier and colleagues noted that the small sample size "may limit the ability to detect meaningful differences between baseline and follow-up," so they called for further studies to validate the safety of this approach and to calculate how much money this strategy may save.


1. Trottier B, Machouf N, Longpre D, et al. Removing an inactive NRTI from an effective salvage regimen is safe and maintains virologic suppression: week 24 results from the VERITAS trial. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17-20, 2011. Chicago. Abstract H2-787.