Application of HIV-1 genotypic-resistance testing prevents the evolution of further resistance mutations in heavily pretreated patients

Background: Resistance-associated mutations in HIV-1 evolve even under high ly active antiretroviral therapy. Objective: To evaluate the clinical effic acy of genotypic-resistance testing (GRT), to estimate the potential of a g iven antiretroviral therapy for prevention of further resistance mutations. Study design: Ten patients were treated prospectively with drugs, accordin g to the results of a CRT. Five patients were allocated to group I in which antiretroviral therapy could be switched to an effective regimen (consisti ng of at least three sensitive drugs, from at least two different classes o f antiretroviral substances). Five patients: (group II) had no option for e ffective therapy, and continued to be treated non-effectively (at least one applicated substance class only intermediately sensitive, or resistant). G RT and quantitative viral cultures were performed longitudinally for 8 mont hs. Also, plasma HIV-1 RNA, total CD4+ cells, and rates of productively inf ected CD4+ cells were determined. Results: All the patients in group I show ed a significant decrease of HIV-RNA of > 1 log/ml (mean, - 1.35 log/ml, P = 0.025). The mean increase of CD4+ cells was 46 (not significant). The rat e of productively infected CD4+ cells decreased significantly (mean, - 16 p roductively infected CD4+ cells per 10(6) total CD4+ cells, P=0.04). In thi s group no further resistance mutations were detected after 8 months. In gr oup II, none of the patients showed a significant decrease of HIV-1 RNA (me an, + 0.05 log/ml), total CD4+ cells decreased (mean, - 35, not significant ), the rate of productively infected CD4+ cells increased significantly (me an, + 124 productively infected CD4+ cells per 106 total CD4+ cells, P = 0. 04), and 4 of 5 patients had additional mutations in the RT gene conferring multi-drug resistance within 8 months (P = 0.048). Conclusions: GRT is pre dictive of the efficacy of a therapeutic regimen, in particular regarding e volution of further resistance mutations. (C) 2001 Elsevier Science B.V. Al l rights reserved.