• TMC125 Monotherapy for 1 Week Results in a Similar Initial Rate of Decline of HIV-1 RNA as Therapy With a Five-Drug Regimen
  Abstract 5
  Authored by S. Sankatsing¹, G. Weverling¹, G. van't Klooster², J. Prins¹, and J. Lange¹ (¹Univ. of Amsterdam, The Netherlands, and ²Tibotec-Virco NV, Mechelen, Belgium)
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Increasing the potency of antiretroviral therapy remains an important goal of drug development, as there is still evidence of residual viral replication even in patients with "suppressed" viral loads. To that end, there has been considerable excitement about TMC125, an investigational NNRTI being developed by the Belgian company Tibotec. Following up on the seven-day monotherapy study presented at ICAAC -- where a mean 1.99 log viral load reduction was demonstrated -- J. Lange today compared this impressive viral load response with that obtained from a five-drug regimen.

The comparator regimen was chosen from the previously-conducted ERA study, and consisted of AZT/3TC/abacavir/indinavir/nevirapine; results were published in the journal AIDS in 1998. In this study, early viral load measurements were done at days 0, 1, 3, 4, and 7, versus daily in the TMC125 study. Compared with the TMC125 study group, at baseline those in the ERA study were older and had slightly higher baseline viral loads and lower CD4 cell counts.

Based on the seven-day measurements, the following results were obtained:

None of the above differences between the five-drug ERA regimen and TMC125 were statistically significant.

Although cross-study comparisons should be made cautiously, these data underscore the robust antiviral activity of TMC125 in drug-naive patients, achieving at seven days results comparable to a five-drug regimen. As noted in Abstract 4, TMC125 also has activity (albeit somewhat lower in magnitude) in most patients who have experienced virologic failure to NNRTIs. The excitement about TMC125's ongoing development must be tempered somewhat by the drug's currently unpalatable formulation, which requires ingestion of 18 tablets twice daily! On an encouraging note, Tibotec is actively pursuing a more user-friendly formulation, one that will significantly reduce this pill burden.