Manion DJ, Merrill DP, Hirsch MS; Infectious Disease Unit, Massachusetts General Hospital, Boston, MA.
Increasing clinical use of antiretroviral drugs in combination has allowed for the selection of isolates resistant to multiple drugs in monotherapy. We sought to determine the in vitro susceptibility of such HIV-1 clinical isolates to 2-drug combinations of the following compounds: zidovudine (AZT), didanosine (ddI), lamivudine (3TC), stavudine (d4T), nevirapine (NVP), indinavir (IDV) and saquinavir (SQV). Drug interactions were determined by median-dose effect analysis with the combination index (CI) calculated at several efficacy doses (ED(50), ED(75), ED(90), ED(95), ED(99)). For an RT-inhibitor multidrug resistant isolate (JID 1995;172:70-8), the combinations of ZDV/3TC, ZDV/NVP and ZDV/IDV demonstrated synergism at all efficacy doses. All other combinations demonstrated antagonism, most notably ZDV/d4T (CI:5.7-16.0). These studies are being extended to other isolates (ZDV/3TC dually-resistant and protease inhibitor multidrug resistant isolates). In vitro combination drug studies will allow for the rational choice of therapeutic regimens to be considered for future clinical trials as well as potential salvage therapy in individuals with HIV-1 strains demonstrating multidrug resistant phenotypes.
Keywords: AEGIS, HIV-1, Stavudine, Lamivudine, Indinavir, Zidovudine, Anti-HIV Agents, Didanosine, Nevirapine, Reverse Transcriptase Inhibitors, HIV Protease Inhibitors, Saquinavir, HIV-1 Reverse Transcriptase, Pharmaceutical Preparations, In Vitro, AIDS
