( protease inhibitors and ritonavir-boost...)Is There Any Clinical Benefit to Staying on a Failing Regimen?,Health

protease inhibitors and ritonavir-boosted protease inhibitors. 43% of patients were receiving two nucleoside analogues and a single protease inhibitor, while 39% were receiving a regimen containing drugs from all three classes.

One genotypic resistance test was used to define the baseline resistance pattern in 75 patients; two genotypic tests defined resistance in 23, and three tests defined resistance in the remaining 12 patients. Thymidine analogue mutations (TAMS) accounted for 75% of all DRGs and the mutation was primarily at the 184V codon. The evolution of resistance was then evaluated between the baseline test (t0) and a subsequent test a median of six months later (t1) (range 2-28 months).

From the time of the first genotypic test to the second, 77% of patients acquired one or more extra International AIDS Society (IAS)-defined drug resistance mutations, with an overall six month increase of 1.96 mutations. Using the Rega interpretation system, this meant an overall average loss of 1.25 active antiretroviral drugs per each six-month period that a patient remained on a failing regimen (this includes all ARVs available in January 2006). The authors note though that depending on the drug regimen followed and the extent of resistance, it cannot be assumed that the accumulation of mutations is limitless.

In this same time period, the mean CD4 cell count remained relatively stable at ~280 cells/mm3 with an estimated loss of 9.79 cells/mm3 while viral load rose by approximately 0.14 log10 copies/mL, resulting in a mean viral load of 3.87 log10 copies/mL.

The prevalence of resistance to the failing regimen at the time of the first resistance test was not predictive of the accumulation of drug resistance mutations when an adjusted analysis was performed. The main predictor of change in the number of IAS-defined mutations over time was an inverse association with CD4 cell count nadir. Those patients in the cohort with re
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