Dihydroartemisinin-Piperaquine in the Context of Antiretroviral Therapy

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Open-label prospective intensive pharmacokinetic study of dihydroartemisinin-piperaquine (DP) in HIV-infected children on efavirenz (EFV)-, lopinavir/ritonavir (LPV/r)-, or dolutegravir (DTG)-based antiretroviral therapy (ART) and HIV-uninfected children not on ART. All children will be malaria-uninfected at the time of enrollment.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of California, San Francisco
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Makerere University; Yale University
• Treatments: Artenimol; Dihydroartemisinin; Piperaquine

Criteria

Inclusion Criteria:

All participants:

• Agreement to come to clinic for all follow-up PK and safety evaluations

• Provision of informed consent.

HIV-infected participants:

• Residency within 30km of Mulago Hospital.

• Confirmed HIV infection (confirmed positive rapid HIV test or HIV RNA as per

• Ugandan guidelines).

• On stable EFV-, LPV/r- or DTG-based ART for at least 10 days prior to enrollment.

• Age 3 - 10 years if on EFV-based ART or LPV/r-based ART.

• Age 11 - 17 years if on DTG-based ART.

HIV-uninfected participants:

• Residency within 30km of Masafu General Hospital

• Confirmed HIV negative test (confirmed positive rapid HIV test or HIV RNA as

• per Ugandan guidelines)

• Age 3 - 17 years.

Exclusion Criteria:

• History of significant comorbidities such as malignancy, active tuberculosis or

• other active WHO stage 4 disease

• Receipt of any medications known to affect CYP450 metabolism (except ART)

• within 14 days of study enrolment (see 4.2.1)

• Hemoglobin < 7.0 g/dL

• Current malaria infection or recent treatment with antimalarials within 28 days of

• enrolment.

• Asymptomatic parasitemia detected by microscopy or rapid diagnostic test (RDT)

• History of side effects with DP

• Prior history of cardiac disease (personal or family), baseline corrected QT intervals (QTc) >450msec, or

• receipt of any cardiotoxic drugs or those known to prolong QT intervals History of

• significant comorbidities such as malignancy, active tuberculosis or other WHO

• stage 4 disease

• Weight < 6kg

• HIV-infected females on DTG-based ART and age 13-17 years who are pregnant

• or of childbearing potential and do not agree to consistent and reliable

• contraception.

The following medications are disallowed within 3 weeks prior to receiving study drug:

• Carbamazepine

• Clarithromycin

• Erythromycin (oral)

• Ketoconazole

• Phenobarbital

• Phenytoin

• Rifabutin

• Rifampicin

• Halofantrine

• Any other medication known to significantly affect CYP450 metabolism.

• Grapefruit juice should be avoided during the study due to its potential effects on CYP3A4.