Does an increase in nevirapine plasma levels cause complete virologic suppression in patients experiencing early...

Patients on two nucleoside analogs plus nevirapine (NVP) who show low-level plasma HIV RNA might have insufficient NVP plasma levels and therefore might benefit from an increase in NVP dosing.

The dose of NVP was increased from 400 mg/day to 600 mg/day in 25 participants taking NVP-containing triple combinations for at least 3 months and experiencing a first virological failure (>50 HIV RNA copies/mL). The levels of NVP were measured in plasma samples taken prior to and 3 months after the intervention. HIV genotyping was performed at the time of dose increase. A control group of 25 participants who showed early virological failure with NVP continued with standard doses of the drug for 3 months.

The median HIV RNA and CD4 cell counts were 100 copies/mL and 635 cells/mm(3), respectively. Similar figures were recorded in the control arm. Mean NVP plasma levels that were reached with a dose of 600 mg/day were significantly higher than those with 400 mg/day (7.4 microg/mL [95% CI, 6.4-8.4] vs. 3.4 microg/mL [95% CI, 2.9-3.9]; p <.0001). Thirteen (52%) participants reached <50 HIV RNA copies/mL after the intervention. The greater levels of NVP were relatively well tolerated, with no development of rashes and only mild elevations in transaminase levels. NVP-associated mutations were recognized in 9 of 10 participants who did not respond but only in 3 of 9 responders (p =.019). More frequent mutations appeared at positions 181, 103, 106, and 190. The levels of NVP did not change significantly in participants who were included in the control arm, and only one reached complete virological suppression after continuing treatment for 3 additional months.

An increase of one pill of NVP per day led to a significant rise in NVP plasma levels. A greater virologic response was noticed among participants with higher NVP plasma levels. Major resistance mutations that conferred resistance to NVP were recognized in all participants who failed to regain virological suppression after increasing NVP dose.