An open-label multicentre pilot study evaluating the pharmacokinetics (PK) of co-administered lopinavir (LPV) and nevirapine (NVP) in HIV+ adults

Purpose of the study

Co-administration of LPV/r SGC with NVP, an inducer of CYP3A, necessitates a LPV/r dose increase. The objectives of "The NRTI Sparing Study" were to evaluate the PK of co-administered LPV/r and NVP in HIV-infected subjects at week 4 and to assess any changes in these PK parameters at 48 weeks follow-up.

Methods

In this prospective, 48-week (wk), multicentre study, 40 patients (39 ART-naive) were recruited to receive LPV/r SGC (533/133 mg BID) plus NVP (200 mg BID) and undergo PK sampling (0–12 hr) at wk 4 and wk 48. In one of the two participating centres, switches to the LPV/r tablet formulation (400/100 mg BID) were allowed between wk 4 and 48, once HIV-RNA was <50 copies/ml. LPV concentrations were determined by HPLC-MS/MS and NVP concentrations via HPLC-UV. PK parameters were calculated via non-compartmental analysis and within-subject changes assessed by geometric mean ratios (GMR) with 95% confidence intervals (95% CI).

Summary of results

Wk 4 PK data were available on 35 patients. Geometric mean (95% CI) LPV AUC and C were 92012 ng.h/ml (81237–104215) and 3979 ng/ml (3159–5011), respectively. For NVP these values were 62749 ng.h/ml (55621–70790) and 4594 ng/ml (4023–5246), respectively. At wk 24, five individuals had HIV-RNA >50 copies/ml. Wk 4 PK data was available on 4/5 of these patients, all of whom had LPV and NVP concentrations greater than the proposed trough concentration desirable in patients with wild-type HIV-1 (1000 and 3000 ng/ml, respectively). Twenty-five patients also underwent wk 48 PK sampling; of these 10 remained on SGC, while 15 switched to the tablet formulation (400/100 mg BID). No significant intra-individual changes in PK were observed over 48 wks for patients remaining on SGC (p > 0.24). In those switching to the tablet, PK parameters were not significantly different (p > 0.68), although there was a trend towards lower LPV C at wk 48 (see Table 1).

Table 1

Conclusion

This study explored an NRTI sparing strategy. We recognise that one limitation is that some patients were switched to the LPV/r tablet formulation. The issue of whether, if starting with this strategy, a dose of 400/100 mg or 600/150 mg tablet would be used, has not been addressed here. PK parameters at wk 4 and 48 did not differ significantly in patients receiving co-administered LPV/r and NVP. However, there was a trend towards lower LPV C in patients who switched to LPV/r tablet. Therefore, there is a need for caution and a consideration for TDM-guided dose adjustment depending on the population.