Resuming nucleoside analogue treatment with new drugs appears to be safe in the majority of patients who are forced to interrupt treatment due to lactate elevations caused predominantly by d4T treatment.
San Diego researchers reported on the results of starting a new nucleoside analogue combination in individuals who had stopped treatment due to symptomatic hyperlactatemia or lactic acidosis. US treatment guidelines have suggested that it may be best to resume treatment using a nucleoside-sparing regimen, but Dr Tyler Lonergan pointed out that it may be difficult to sustain viral suppression in patients with pre-existing non-nucleoside reverse transcriptase inhibitor or protease inhibitor resistance.
Symptomatic hyperlactatemia (defined as nausea/vomiting, abdominal pain, anorexia/weight loss, fatigue associated with two or more consecutive venous lactates > 2 times the upper limit of normal (4.2mmol/l) was identified in 12 individuals receiving treatment at the University of California San Diego Owen clinic between July 1998 and August 2002. Individuals had been receiving d4T/3TC (6), d4T/ddI (4) and abacavir/d4T (2). Ten out of 12 had been on their first HAART regimen, and thus did not have extensive exposure to NRTIs, permitting a switch. Patients had been off treatment for a median of 123 days before starting the new regimen, and median lactate levels had fallen to 2.1 mmol/l by this time. The researchers reviewed the response to the following new nucleoside analogues in the patients:
- Abacavir/3TC (5 patients)
- Abacavir/3TC/AZT (5 patients)
- AZT/3TC (2 patients)
One relapse of symptomatic hyperlactatemia occurred amongst the patients who resumed therapy, and two had stopped treatment. The median lactate in the remaining nine patients was 1.3mmol/l after a median of 283 days on the new regimen.
Lonergan T et al. Long term safety and efficacy of rechallenging patients who have recovered from serious symptomatic hyperlactatemia with new NRTI-containing regimen. 42nd ICAAC, San Diego, abstract H-1080, 2002.