Novel compounds for the treatment of HIV type-1 infection.

Despite the recent licensure of several new antiretroviral compounds, there is still a need to develop additional agents. Problems with antiviral activity, tolerability, ease of administration, extent of cross-resistance and pharmacokinetic as well as pharmacodynamic interactions still represent important obstacles to life-long control of HIV type-1 replication by highly active antiretroviral therapy. Several compounds stem from the same classes as currently available drugs: apricitabine and elvucitabine (nucleoside reverse transcriptase inhibitors), rilpivirine (non-nucleoside reverse transcriptase inhibitor), vicriviroc and INCB009471 (CCR5 inhibitors) and elvitegravir (integrase inhibitor). The potential of other compounds with new modes of action is less clear. Currently, maturation inhibitors appear promising but for other drugs, obstacles to continued development, such as the need of parenteral application (that is, monoclonal antibodies) or toxicity (for example, immune modulating agents and pegylated interferon), are already apparent. For even more compounds in the preclinical development phase, an assessment of their possible clinical role is still premature. This review provides an overview and a summary of the current status of drug development in the field.