TABLE 2.
Summary of findings from studies evaluating changes in artemether-lumefantrine exposure in the setting of nevirapine-based ART
| Study location and reference(s) | Study design | Effectsa |
|||
|---|---|---|---|---|---|
| Artemether | DHA | Lumefantrine | Nevirapine | ||
| Nigeria (present study) | Two groups, rich artemether-lumefantrine PK sampling (0–96 h after last dose); non-HIV-infected, non-malaria-infected patients (n = 16) vs HIV-infected, non-malaria-infected patients on nevirapine-based ART for ≥2 yr | Decreased 67% (P < 0.01) | Unchanged | Decreased 49% (P = 0.048) | Unchanged |
| Uganda (8, 22)b | Crossover, rich artemether-lumefantrine PK sampling (0–120 h after last dose); HIV-infected, non-malaria-infected patients (n = 21) before ART and 4 wk after initiation of nevirapine-based ART | Decreased 70% (P < 0.01) | Decreased 37% (P < 0.01) | Decreased 21% (P = 0.4) | Decreased 46% (P < 0.01) |
| South Africa (10) | Parallel groups, rich artemether-lumefantrine PK sampling (0–504 h after last dose); HIV-infected, non-malaria-infected, ART-naive patients (n = 18) vs HIV-infected patients (n = 18) on nevirapine-based ART for ≥6 wk | Decreased 55% (P = 0.12) | Decreased 25% (P = 0.01) | Increased 56% (P < 0.01) | NA |
| Nigeria (11) | Parallel groups, single lumefantrine PK sampling on day 7 (120 h after last dose); malaria-infected, non-HIV-infected patients (n = 99) vs malaria/HIV-coinfected patients on NVP-based ART (n = 68) (duration of NVP treatment not reported) | NA | NA | Increased 29%c (P < 0.01) | NA |
| Tanzania (13, 14) | Parallel groups, lumefantrine PK sampling on day 7 (120 h after last dose); malaria-infected, non-HIV-infected patients (n = 60) vs malaria/HIV-coinfected patients on NVP-based ART for ≥8 wk (n = 121) | NA | NA | Increased 16%c,d (P = 0.06) | NA |
Results represent noncompartmental AUC comparisons after the last dose of artemether-lumefantrine unless otherwise noted. The reported changes in drug exposure were observed for patients receiving nevirapine-containing ART, compared to the control group. NVP, nevirapine; PK, pharmacokinetic; NA, not available.
Noncompartmental results are presented; however, nonlinear mixed-effects modeling of the same data found a statistically significant decrease in exposure and an increase in the clearance of lumefantrine.
Day 7 concentration.
Noncompartmental results are presented. Nonlinear mixed-effects modeling of sparse sampling from the same study estimated a 24.6% increase in lumefantrine AUC0–∞; no P value was reported (14).