Optimizing Malaria Treatment for HIV-Malaria Co-infected Individuals

• Status: Not yet recruiting
• Trial end date: 2024-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Optimal is a Randomized clinical trial to optimize treatment of malaria in HIV -malaria co infected patients. It has been demonstrated that, when the antimalarial drug Artemether Lumefantrine is co administered with Efavirenz based ART in HIV-malaria co-infected individuals, sub therapeutic levels of the drug are achieved hence resulting in poor malaria treatment outcomes.

The study then hypothesizes that, : HIV-malaria co-infected individuals receiving efavirenz-based ART plus a double-dose or 5-day course of artemether-lumefantrine will achieve higher and adequate artemether-lumefantrine serum concentrations with adequate 42-day treatment outcomes compared to individuals with HIV-malaria co-infection receiving efavirenz-based ART plus a standard-dose of artemether-lumefantrine.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Makerere University
• Treatments: Artemether; Artemether, Lumefantrine Drug Combination; Dolutegravir; Efavirenz; Lumefantrine

Criteria

Inclusion Criteria:

1. Written informed consent

2. Willing and able to comply with study treatment and procedures

3. Age above 18 years

4. Confirmed HIV positive and receiving efavirenz or dolutegravir based ART for objectives 3 and 4

5. Confirmed Malaria blood film positive without evidence for severe malaria for objectives 3 and 4

6. Confirmed Malaria blood film negative for objectives 1 and 2

Exclusion Criteria:

1. Serum alanine transaminase levels above 3x upper limit of normal

2. Serum creatinine levels above 2x upper limit of normal

3. Use of known inducers/inhibitors of CYP or glucuronyl transferase UGT1A1 within past 2 months (e.g. anticonvulsants, TB medications, HIV agents for prophylaxis, azole antifungals)

4. Pregnant women or female subjects who are unwilling to use a suitable contraceptive method for the duration of the study (condom, diaphragm, IUD or contraceptive implant)

5. Likely to be poorly adherent based on clinician's medical judgement

6. Known to be current injection drug user

7. Administration of any additional antimalarial drugs that are not study drugs within 24 hours before study enrollment and during the course of the study.

8. Presence of any non-malarial febrile illness which may interfere with the classification of malaria treatment outcome

9. Movement away from the study area interfering with follow-up assessment

10. Patients with contraindications to taking the study drugs

11. Evidence of QT prolongation on ECG (rate adjusted QT interval>45ms (men (or >470ms for women