Importance of additional active drugs for NNRTI-naive patients using NNRTI-based salvage regimens

Simon Collins, HIV i-Base

It is well accepted that high level resistance to NNRTIs can result from single mutation and that these drugs therefore should only be used within maximally suppressive regimens.

This is as true in second-line and salvage regimens as much as with first line therapy and the limited benefits, and subsequent loss of sensitivity to the non-nucleoside class was shown in a second analysis of results from the GART study.

Of 153 patients failing a PI-based regimen in the GART study, 101 received an NNRTI-based combination (nevirapine 78%, efavirenz 12%, delavirdine 10%). The study analysed the response to treatment in the 69 patients who were NNRTI-naïve and who had neither genotypic nor phenotypic NNRTI resistance.

40/69 (58%) experienced viral failure defined as VL >500 at week 12. Of these, 33/40 had >4-fold change in the IC50 and 33/40 had developed mutations associated with NNRTI resistance (K103N, Y181C, G190A).

The contributing role of active drugs and risk of virological failure shown for people receiving 0-1 active drug compared to those receiving >3 active drug was highly statistically significant for relative risk of failure (p=0.02), developing genotypic resistance (p=0.006) and developing phenotypic resistance (p=0.002). This confirmed the importance of using additional active drugs when NNRTIs are used in treatment experienced patients.

See Table 1 below for results.

Table 1

No. additional active drugs % failure wk 12 RR of failure* RR Geno resist* RR Pheno resist*
0-1 (n=15) 80% 7.2 (p=0.02) 11.5 (p=0.006) 18.6 (p=0.002)
2 (n=40) 56.7% 1.7 (p=0.34) 1.6 (p=0.44) 1.9 (p=0.29)
>3 (n=24) 45.8%

* compared to patients receiving >3 additional active drugs


Hoover M et al – Non-nucleoside reverse transcriptase inhibitor phenotypic and genotypic resistance in patients with virological failure during salvage therapy: 12-week outcome from the GART study (CPCRA 046). Abstract 105. Antiviral Therapy 2001; 6 (Supplement1):79

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