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

Exclusion criteria HIV patients:

• History of sensitivity/idiosyncrasy to atovaquone/proguanil or chemically related compounds or excipients.
• Suspicion of non-adherence to the HIV medication.
• Current diarrhoea.
• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
• Inability to understand the nature and extent of the trial and the procedures required.
• 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 upper limit of normal
• Creatinine clearance < 60 mL/min (calculated from serum creatinine).
• Any change in antiretroviral medication within 1 month immediately pre- ceding the dose of atovaquone/proguanil.
• Concomitant use of medications that interfere with atovaquone or proguanil pharmacokinetics: anti-coagulants, aurothioglucose, chloroquine, cimetidine, fluoxetine, fluvoxamine, metoclopramide, omeprazole, magnesiumtrisilicate, rifabutin, rifampin, tetracycline, typhoid vaccine, topiramate.
• Use of a HAART regime containing both lopinavir/ritonavir and another protease inhibitor or a NNRTI.
• Use of a HAART regime containing both atazanavir/ritonavir and another protease inhibitor or a NNRTI.
• Use of a HAART regime containing both efavirenz and one or more protease inhibitors or nevirapine.
• Active hepatobiliary or hepatic disease
• Alcohol abuse