New NNRTI Is Effective Against NNRTI-resistant HIV

NEW YORK (Reuters Health) - TMC 125, a new nonnucleoside reverse transcriptase inhibitor (NNRTI), reduces viral load in HIV-infected patients with high-level phenotypic NNRTI resistance, European investigators report in a Fast-Track article in the December 5th issue of AIDS.

And in a concise communication in the same issue, physicians show that monotherapy with TMC 125 in previously untreated patients leads to a rate of decline of plasma HIV-1 RNA no less than that associated with a 5-drug regimen during 1 week of therapy.

TMC 125 is a diarylpyrimidine derivative with molecular flexibility to accommodate mutational changes in the binding pocket of the reverse transcriptase, Dr. Brian G. Gazzard, at The Chelsea and Westminster Hospital, London, and colleagues explain. In vitro studies showed activity against more than 1000 NNRTI-resistant HIV mutants.

In a proof-of-concept study, Dr. Gazzard's group administered TMC 125, 900 mg b.i.d. for 7 days to 15 patients previously treated with regimens containing the NNRTIs efavirenz or nevirapine. The median number of NNRTI mutations was two; three patients had three mutations and one had four. They also had NRTI mutations and all but had protease mutations.

When TMC 125 was substituted for the previous NNRTI, viral load decay rate was 0.13 log10 RNA copies/mL per day. Median decrease at day 8 was 0.89 log10 copies/mL, and seven patients had a decrease of > 1 log10.

There were no severe adverse events. Most commonly reported mild or moderate events were diarrhea and headache.

If further studies confirm these findings, the authors suggest that TMC 125 may be of benefit following failure with a current NNRTI, and may even be used in NNRTI-naïve patients.

In the second report, Dr. Joep M. A. Lange, at the University of Amsterdam, The Netherlands, and colleagues compared treatment efficacy during 1 week of therapy with TMC 125 or with a five-drug regimen (lamivudine, abacavir, indinavir, nevirapine and zidovudine or stavudine) in HIV-infected patients naive to antiretroviral therapy.

In the 12 patients on TMC 125, the median plasma HIV RNA decline was 1.92 log10 copies/mL, compared with 1.76 log10 copies/mL in 11 patients on the 5-drug regimen. Median increases in CD4 cells were 119 and 60 cells/µL in the two groups, respectively.

Dr. Lange and colleagues suggest that "starting treatment with a TMC 125-containing regimen could give a better suppression of HIV replication in the long run."

Source: AIDS 2004;17:F49-F54,2623-2627. [ Google search on this article ]

MeSH Headings: Retroviridae Proteins : Viral Core Proteins : Viral Proteins : Drugs, Investigational : Viral Structural Proteins : Gene Products, pol : HIV-1 Reverse Transcriptase : Nucleocapsid Proteins : Polyproteins