Cenicriviroc, an orally active CCR5 antagonist for the potential treatment of HIV infection.

The advent of highly active antiretroviral therapy (HAART) in the 1990s has led to a dramatic decline in rates of opportunistic infection, progression to AIDS and mortality in individuals infected with HIV [969323], [1007325]. The current armamentarium of antiretrovirals includes six different classes of drugs: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, fusion inhibitors, integrase inhibitors and CCR5 inhibitors [1064526]. Limitations to HAART, however, include the potential for treatment-naive patients to acquire a strain of HIV-1 virus with transmitted drug resistance and the potential for treatment-experienced patients to develop drug resistance as a result of long-term therapy. Both of these scenarios may limit treatment selections for HIV-1-infected patients [1007332], [1007341], [1106004], [1106006]. Researchers at the CDC analyzed transmitted drug-resistance-associated mutations (TDRMs), using the WHO mutation list, in treatment-naive individuals infected with HIV-1 who were newly diagnosed with HIV in 2007 [1106004]. Of 2480 genomic sequences analyzed, 388 (16%) contained one or more TDRMs. The most frequent TDRMs were NNRTI mutations (8%), followed by NRTI mutations (6%), followed by protease inhibitor mutations (4%). Single-drug-class TDRMs were noted in 13% of the sequences, whereas two-drug-class TDRMs were observed in 2% of the sequences and three-drug-class TDRMs in < 1% [1106004]. A recent study evaluated drug resistance in treatment-experienced patients infected with HIV-1 using novel modeling approaches to estimate