Building clinical pharmacology laboratory capacity in low- and middle-income countries: Experience from Uganda.

Background: Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda.

Intervention: Existing laboratory infrastructure was repurposed, and new equipment was acquired.

Monocytes from neonates and adults have a similar capacity to adapt their cytokine production after previous exposure to BCG and β-glucan.

The Bacillus Calmette-Guérin (BCG) vaccine is administered at birth in tuberculosis (TB) endemic countries. BCG vaccination is also associated with protective non-specific effects against non-tuberculous infections. This seems at least in part mediated through induction of innate immune memory in myeloid cells, a process termed trained immunity.

Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults.

Objectives: Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions. We investigated drug-drug interactions between artemether/lumefantrine and efavirenz or nevirapine.

Methods: We performed a cross-over study in which HIV-infected adults received standard six-dose artemether/lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state.

Nevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin.

Background: rifampicin lowers nevirapine plasma concentrations by inducing cytochrome P450. However, few data are available on this interaction during the lead-in period of nevirapine treatment.

Methods: eighteen HIV-1/tuberculosis co-infected adults receiving rifampicin daily as part of anti-tuberculosis therapy were evenly randomized to nevirapine initiation by dose escalation (NVP200) or nevirapine initiation at 200 mg twice daily (NVP400).

Suboptimal nevirapine steady-state pharmacokinetics during intrapartum compared with postpartum in HIV-1-seropositive Ugandan women.

Background: Conflicting data exist regarding the effect of pregnancy on steady-state nevirapine pharmacokinetics (PK), although steady-state nevirapine concentrations during pregnancy have never been characterized in sub-Saharan Africa.

Methods: This was a longitudinal intensive PK study in Ugandan pregnant women receiving nevirapine-based antiretroviral therapy. Participants underwent intensive 12-hour PK sampling during the second trimester (T2; n = 4), third trimester (T3; n = 15) and 6 weeks postpartum (PP; n = 15).