The purpose of the study is to examine the interaction between a stable protease inhibitor (PI)- based regimen containing ritonavir- boosted lopinavir (LVP/r) and two forms of contraceptive medications, the transdermal contraceptive patch, Ortho Evra, and an oral contraceptive, Ortho Novum (ON 1/35), in HIV-1 infected women of reproductive age.

Study Hypothesis: There will be no difference in the ethinyl estradiol (EE) area under the concentration time curve (AUC) at transdermal contraception week 3 between women on stable LPV/r and those not on PIs, nonnucleoside reverse transcriptase inhibitors (NNRTIs), or any antiretroviral (ARV) therapy.

Condition	Intervention	Phase
HIV Infection Contraception	Drug: Lopinavir  Drug: Ritonavir  Drug: Ortho Evra  Drug: Ortho Novum 1/35	Phase II

Further Study Details: 

Primary Outcomes: Days 17, 18, 19, and 24 Ortho Evra transdermal contraceptive EE AUC
Secondary Outcomes: Intensive EE AUC PK after single dose ON 1/35 on Day 1 and after Ortho Evra administration on Days 17, 18, 19, and 24; intensive EE AUC PK after single dose ON 1/35; Day 17, 18, 19, and 24 norelgestromin (NGMN) AUC; changes in viral load, CD4 and CD8 counts and their respective percentages, sex hormone binding globulin levels, and liver enzymes from baseline and Days 17, 18, 19, and 24; occurrence of nausea and vomiting, breast tenderness, headache, skin irritation, vaginal bleeding, change in weight, change in blood pressure, change in appetite, mood changes, vaginal infection, and gallbladder disease; PK parameters of LPV in Arm A at baseline and Days 17, 18, 19, and 24
Expected Total Enrollment:  54

Both PIs and oral contraceptives are metabolized by the same pathway significantly decreasing the effectiveness of oral contraceptives and limiting the contraceptive choices available to HIV infected women. More effective hormonal contraceptive methods are necessary for preventing unintended pregnancy in women taking ARV medications. Because Ortho Evra is administered as a contraceptive patch worn on the skin, it may by-pass the metabolic pathway common in both PIs and oral contraceptives, making it a viable contraceptive option for HIV infected women on PI-based regimens.

This study will last 6 weeks. Participants will be assigned into one of two study arms depending on their ARV regimen at study entry. Arm A participants will take 400 mg LPV and 100 mg ritonavir twice daily along with two additional NRTIs. Arm B participants will either be on a regimen containing only NRTIs or on no ARV therapy. All participants will receive a single dose of ON 1/35 on Day 1 and will start the Ortho Evra contraceptive patch on Day 3. A physical exam, pap smear, pregnancy test, viral load test, CD4 and CD8 counts, and blood collection will occur at or before study entry and on Day 24. Pharmacokinetic analysis will occur on Days 1- 3, 17- 19, and Day 24.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• HIV infected
• For participants in Arm A, taking LPV/r for at least 60 consecutive days prior to study entry and taking the same dose twice daily for at least 14 days prior to study entry
• For participants in Arm B, not taking a PI- or NNRTI- based regimen for at least 30 days prior to study entry and not planning on starting PIs or NNRTIs during the 6-week study period. Women who have not been on any ARV therapy for at least 30 days prior to study entry are also eligible.
• CD4 count of 200 cells/mm3 or greater
• Viral load of less than 55,000 copies/mL
• Weight of 198 pounds (90 kilograms) or less
• Written informed consent from parent or legal guardian
• Negative pregnancy test within 45 days prior to study entry
• Willing to use acceptable forms of contraception

Exclusion Criteria:

• Use of systemic hormonal therapies that contain estrogens, progestins, or anabolic steroids or the use of anabolic therapies within 60 days prior to study
• Use of systemic glucocorticoids within 14 days prior to study entry
• History of thrombophlebitis, thromboembolism, deep vein thrombosis, coronary artery disease, cerebrovascular disease, valvular heart disease with complications, sever hypertension, diabetes with vascular involvement, headaches with focal neurological symptoms, need for prolonged bed-rest after major surgery, known or suspected breast or endometrial cancer, known or suspected estrogen dependant cancer, cholestatic jaundice of pregnancy, jaundice with prior hormonal contraceptive use, acute or chronic hepatocellular disease with abnormal liver enzymes, hepatic adenoma or carcinoma, less than four weeks following delivery or second trimester abortion
• Smokers greater than 35 years of age
• Use of NNRTIs within 30 days prior to study entry
• Use of tenofovir (TDF) within 30 days prior to study entry
• Nausea, vomiting, or abdominal pain of grade 3 or higher within 30 days prior to study entry
• Any known allergy or sensitivity to EE, NGMN, or components of the Ortho Evra contraceptive patch
• Any known allergy or sensitivity to norethindrone or components of the ON 1/35 oral contraceptive pill
• Serious illness requiring systemic treatment or hospitalization within 14 days prior to study entry
• Undiagnosed abnormal vaginal bleeding
• Use of Depo-Provera (DMPA) within 180 days prior to study entry
• Use of Lunelle within 90 days prior to study entry
• Use of certain medications within 30 days prior to study entry
• Active drug or alcohol use or dependence that, in the opinion of the investigator, may interfere with the study
• Unable to adhere to the ARV therapy, Ortho Evra contraceptive patch, and single dose ON 1/35 regimen

Please refer to this study by ClinicalTrials.gov identifier  NCT00125983

California
      Los Angeles County Medical Center/USC, Los Angeles,  California,  90033,  United States; Recruiting
Maryland
      University of Maryland, Institute of Human Virology, Baltimore,  Maryland,  21201,  United States; Recruiting

Study chairs or principal investigators

Lori Kamemoto, MD, MPH,  Study Chair,  Hawaii AIDS Clinical Research Program, University of Hawaii School of Medicine   
Mary Vogler, MD,  Study Chair,  New York University Medical Center, Adult AIDS Clinical Trials Group   

Study ID Numbers:  AACTG A5188
Last Updated:  August 1, 2005
Record first received:  August 1, 2005
ClinicalTrials.gov Identifier:  NCT00125983
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-02