ICAAC 2011: Omitting Inactive NRTIs from Salvage Regimen Can Maintain Viral Suppression

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Simplifying therapy by discontinuing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) that no longer demonstrate activity against HIV due to resistance appears to be a safe strategy that does not compromise virological control, according to a study presented at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011) this month in Chicago.

People with highly resistant HIV may use so-called "salvage" regimens containing multiple drugs with varying degrees of efficacy. Current treatment guidelines do not take a position on keeping inactive agents in a regimen that is working well, and many clinicians and patients hesitate to fix something that's not broken.

But continuing inactive drugs can add toxicities, contribute to drug interactions, and increase cost. There may also be benefits; some research suggests that the M184V mutation conferring resistance to lamivudine (3TC, Epivir) and emtricitabine (Emtriva) makes the virus less fit.

Benoit Trottier and colleagues from Clinique Medicale l'Actuel in Montreal conducted an open-label prospective study of people with multidrug-resistant HIV who had undetectable viral load on a stable antiretroviral regimen containing at least 1 non-active NRTI.

The trial enrolled 31 participants, all men, with a mean age of 50 years. They had been on treatment for an average of 14 years. The median nadir (lowest-ever) CD4 T-cell count, 158 cells/mm3, reflected serious past immune deficiency, but the group had achieved good immune recovery, with a current median of 525 cells/mm3.

Results

 

o      lamivudine or emtricitabine: 29 people (94%);

o      zidovudine (AZT; Retrovir): 1 person;

o      tenofovir (Viread): 1 person.

Based on these findings, the researchers concluded, "Removing non-active NRTI from a regimen with > 4 [antiretroviral agents] in patients with suppressed viral load appears to be safe and did not affect the ability of the regimen to maintain the viral load under the limit of detection through 24 weeks."

If confirmed, these results suggest that omitting inactive drugs is a safe strategy that could save money and reduce side effects.

However, most people in this study stopped lamivudine or emtricitabine, which are inexpensive and generally well-tolerated. More research is needed to see if this strategy will remain safe when removing stronger but potentially more toxic NRTIs such as tenofovir or abacavir (Ziagen).

Investigator affiliation: Clinique Medicale l'Actuel, Montreal, Canada.

9/30/11

Reference

B Trottier, N Machouf, D Longpre, 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 2011). Chicago, September 17-20, 2011. Abstract H2-787.