Pregnant women infected with HIV who take anti-HIV medications during pregnancy lower the risk of passing HIV to their infants. This study will compare how well two different combinations of anti-HIV medications control HIV in pregnancy, and whether these combinations of drugs are effective in preventing HIV from being transmitted from a pregnant woman to her baby. The two combinations to be studied are: 1) abacavir sulfate/lamivudine/zidovudine (ABC/3TC/ZDV) and 2) zidovudine/lamivudine (ZDV/3TC) plus lopinavir/ritonavir (LPV/RTV).

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Abacavir sulfate, lamivudine, and zidovudine  Drug: Lamivudine/zidovudine  Drug: Lopinavir/ritonavir	Phase III

Antiretroviral therapy in pregnancy has dramatically reduced the rates of perinatal HIV transmission. Many pregnant women infected with HIV may not meet the criteria for treatment as set forth by the Department of Health and Human Services’ guidelines and would not be started on therapy if they were not pregnant. Pregnant women are prescribed a variety of treatment regimens; the optimum regimen for pregnant women who plan to discontinue therapy after delivery is unknown. An optimum regimen would account for the need for maximum viral suppression, minimized fetal toxicity, and preservation of future therapeutic options for the mother. This study will compare an all nucleoside reverse transcriptase inhibitor (NRTI) regimen of ABC/3TC/ZDV with a standard protease inhibitor (PI) regimen of LPV/RTV and 3TC/ZDV. This study is expressly designed for women who plan to take antiretrovirals only while pregnant and do not meet the criteria for treatment initiation if not pregnant.

Women in this study will be randomly assigned to one of two groups. Women in Group A will receive one pill ABC/3TC/ZDV twice a day. Women in Group B will receive one pill 3TC/ZDV and 4 pills LPV/RTV twice a day. Women will take their assigned medications until they go into labor. Once in labor, women will be give zidovudine through an intravenous (IV) infusion; they will stop taking oral zidovudine but will continue with their other medications. After delivery, all infants will be given zidovudine for six weeks.

Women will have study visits every 2 weeks for the first 8 weeks of treatment, and then every 4 weeks until Week 28. Depending on where a woman is in her pregnancy when she enrolls in the study, she will also have study visits at Weeks 20, 28, and 34 of her pregnancy. At each visit, women will have a medical interview, a physical exam, and an obstetrical exam. Blood and urine tests will also be performed. Some women in Group B may also have special drug level testing that will take 12 hours. After delivery, women will stop taking the study medications but will continue to have study visits at approximately 6, 8, 12, 24, 36, 48, and 52 weeks after delivery. Infants will have study visits at 2, 8, 16, and 24 weeks after birth. A medical history, physical exam, and laboratory tests will be conducted at the infant study visits. Women will also be asked to enroll their infants in PACTG 219C, a long-term study that follows infants who are born to HIV infected mothers.

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

Criteria

Inclusion Criteria for Mothers:

• HIV infected
• Between the 12th and 30th week of pregnancy
• Intend to continue pregnancy
• Viral load less than 55,000 copies/ml within 30 days of study entry
• CD4 count greater than 350 cells/ml within 30 days of study entry
• Have not previously taken anti-HIV medications. Women who have taken zidovudine for 8 weeks or fewer are eligible.
• Intend to stop taking anti-HIV medications after pregnancy
• Willing to have her infant tested for HIV
• Informed consent from parent or guardian, if applicable
• Have access to a participating site and are willing to be followed for the duration of the study

Exclusion Criteria for Mothers:

• Chemotherapy for active cancer
• Active opportunistic infection or severe medical condition within 14 days of study entry
• Chronic diarrhea within 1 month of study entry or unresolved acute diarrhea within 7 days of study entry
• Certain abnormal laboratory values
• Diabetes when not pregnant. Participants who have gestational diabetes are not excluded.
• Alcohol or other substance abuse
• Acute hepatitis within 90 days of study entry
• Intend to breastfeed
• Major birth defects
• Severe skin disorder (e.g., eczema or psoriasis) that requires systemic treatment
• Medical condition that may, in the opinion of study officials, interfere with the study

California
      UCSD Mother, Child & Adolescent HIV Program, San Diego,  California,  92103,  United States; Recruiting
Georgia
      The Medical Center, Columbus,  Georgia,  31901,  United States; Recruiting

Study chairs or principal investigators

Andrew D. Hull, MD,  Study Chair,  University of California, San Diego   

Study ID Numbers:  PACTG P1039
Record last reviewed:  September 2004
Record first received:  June 30, 2004
ClinicalTrials.gov Identifier:  NCT00086359
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-08