Combined Oral Contraceptive (COC) Antiretroviral (ARV) Pharmacokinetics (PK) and Pharmacodynamics (PD) in Malawi

A Pilot Study of Pharmacokinetic and Pharmacodynamic Activity of LoFemenal

The purpose of this research study is to learn about the birth control pill called LoFemenal in HIV+ and HIV negative women who live in Malawi. This is a pilot study to determine the effect of antiretroviral therapy on the pharmacokinetics of the most commonly used oral contraceptive in HIV+ women; and to measure ovulation suppression in women taking the oral contraceptive pill and antiretroviral therapy at the same time. Nine women will be enrolled and will be followed for a total of 4 months.

Inclusion Criteria:

• Can provide informed consent
• Women ages 21-35 with known HIV status
• If HIV negative must have had an HIV test within the last 3 months
• Intend to stay in Lilongwe region for the duration of the study
• Desire to prevent pregnancy for at least the next six months
• Desires to use LoFemenal for contraception
• Has no known history of infertility
• Has intact uterus and at least one ovary
• Has regular monthly menses defined by menses occurring every 21-35 days
• Has not used another form of systemic hormonal contraception within the last six months.
• Has no contraindications to the combined oral contraceptive LoFemenal which include; any thrombophlebitis or thromboembolic disorders; cerebral-vascular or coronary-artery disease (current or history); thrombogenic valvulopathies; thrombogenic rhythm disorders; major surgery with prolonged immobilization; diabetes with vascular involvement; headaches with focal neurological symptoms; uncontrolled hypertension; known or suspected carcinoma of the breast or personal history of breast cancer; carcinoma of the endometrium or other known or suspected estrogen dependent neoplasia; undiagnosed abnormal genital bleeding; cholestatic jaundice of pregnancy or jaundice with prior pill use; hepatic adenomas or carcinomas or active lever disease, as long as liver function has not returned to normal; known or suspected pregnancy.

Exclusion Criteria:

• Hemoglobin < 10 mg/dL.
• Body mass index < 18.6 kg/m^2.
• Using any drugs known to interfere with cytochrome P450 system (such as rifampicin, phenytoin, carbamezapine, among others)
• In the opinion of the PI or study staff the individual cannot complete the study
• Cannot be adherent to other medications.

Additional inclusion criteria for the 3 HIV+ women on antiretroviral therapy:

• Must be on antiretroviral therapy which includes nevirapine for at least three consecutive months immediately prior to enrollment into the study
• Must report adherence to medication and medical visits
• Must be willing to use a barrier or backup method of contraception.