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At 1 year, regimen failure was not more likely among those omitting NRTIs versus adding NRTIs to an optimized new regimen (30% vs.
5% of patients, which is similar to other NRTIs [43-45], while other studies have found a small but significant reduction in renal function over time in comparison with other NRTIs [46,47].
Late detection of treatment failure resulted in extensive cross-resistance to NRTIs, limiting treatment options and impairing the effectiveness of (standard) second-line regimens.
Stavudine and didanosine are the most frequent NRTIs implicated in mitochondrial toxicity.
Certain NRTI combinations are contraindicated for toxicity reasons (e.
Severely symptomatic individuals with acidosis should avoid NRTI therapy entirely and opt for an NRTI-sparing regimen.
A recent analysis from CHIPS indicated that among treated children undergoing resistance testing between 1998 and 2004 [6], NRTI resistance (at least one mutation) peaked in 1999 at around 85% and declined thereafter to around 65% in 2004.
A paper published by Daniel Kuritzkes and colleagues in the Journal of Acquired Immune Deficiency Syndromes contributes to the body of evidence showing that dual NRTI therapy, although able to suppress virus for some patients for a limited duration, is not as strong as triple combination therapy in terms of keeping resistance at bay for the longest duration.
Early preclinical studies suggest that festinavir could have an improved safety profile over previous generations of NRTIs.
The prevalence was lower, at 12%, among patients whose exposure included an NNRTI plus an NRTI or all three classes of drugs.
The problem with the approach used in the Abbott study became clear within a few months, however--simply adding a PI into a background of what later would be considered a failing NRTI background.
ATC is Avexa's lead program and has successfully completed the 96 week dosing of its Phase IIb clinical trial and commenced its Phase III trials worldwide in January 2008 in HIV patients with NRTI resistance.