HIV Infections, Malaria
Conditions
Keywords
HIV, Malaria prophylaxis, Treatment Experienced
Brief summary
Malarone® (atovaquone/proguanil) is frequently used in malaria prophylaxis. Unfortunately, there are indications that certain anti-HIV agents may decrease atovaquone plasma levels by induction of atovaquone metabolism. For travelling HIV patients, the clinical consequences of these possible drug drug interactions are serious, since a diminished exposure to the anti-malarial drug will result in suboptimal prophylaxis of malaria and potential development of drug resistant strains of Plasmodium falciparum. The purpose of this study is to find out if HIV patients using HAART regimes with either lopinavir/ritonavir, atazanavir/ritonavir or efavirenz have lower atovaquone plasma levels than healthy volunteers after a single dose of atovaquone/proguanil.
Interventions
DRUGAtovaquone / Proguanil
Sponsors
Radboud University Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
For healthy volunteers * 18 - 65 years * smoking habits \< 10 cigarettes, 2 cigars or 2 pipes * BMI between 18 and 30 kg/m2 * able and willing to sign informed consent form * subject is in a good age-appropriate health condition * subject has a normal blood pressure and pulse rate For HIV patients * HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot. * CD4+ \> 200 \* 10E6 per Liter. * 18 - 65 years * BMI between 18 and 30 kg/m2 * able and willing to sign informed consent form * use of lopinavir/ritonavir, atazanavir/ritonavir or efavirenz for at least 1 month in a dose of 400/100mg bid, 300/100 mg QD, or 600 mg QD respectively
Exclusion criteria
healthy volunteers: * History of sensitivity/idiosyncrasy to atovaquone/proguanil or chemically related compounds or excipients. * Positive HIV test. * Positive HbsAg test (hepatitis B) or positive hepatitis C test. * Therapy with any drug (for two weeks preceding dosing), except for paracetamol. * Creatinine clearance \< 60 mL/min (calculated from serum creatinine) * Current diarrhoea. * Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion. * History of or current abuse of drugs, alcohol or solvents. * Inability to understand the nature and extent of the trial and the procedures required. * Participation in a drug trial within 60 days prior to the first dose. * Donation of blood within 60 days prior to the first dose. * Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female. * Abnormal serum transaminases, determined as levels being \> 3 times up-per limit of normal * Febrile illness within 3 days before the first dose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic blood samples will be taken just before dosing Malarone, and 12 samples in the time between 0,5 hour and 168 hours after dosing. | — |
Secondary
| Measure | Time frame |
|---|---|
| Blood will be taken for genotyping of CYP2C19 at study day 1. | — |
| HIV-1 RNA and CD4 determination will be done (HIV patients only) at inclusion screening | — |
Countries
Netherlands
Outcome results
None listed