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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00017719
Other study ID # P1022
Secondary ID 10192ACTG P1022P
Status Completed
Phase Phase 3
First received
Last updated
Start date May 2002
Est. completion date March 2006

Study information

Verified date October 2021
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The best anti-HIV treatment regimen for pregnant women is not known. Protease inhibitors (PIs) are often used, but they have side effects that may be harmful for pregnant women. It is not known if treatment regimens that do not include PIs are as effective in pregnant women as those that include PIs. This trial will compare two anti-HIV treatment plans, one with and one without PIs, in women who start HIV treatment during pregnancy. The study will evaluate the effects of the anti-HIV drugs on the developing infant and prevention of mother-to-child HIV transmission during pregnancy.


Description:

The optimal treatment strategy for women who initiate antiretroviral therapy during pregnancy is not known. Although PI-based antiretroviral regimens are prescribed with increasing frequency among pregnant women, the efficacy and safety of this approach is unknown. Pregnant women are at increased risk for glucose intolerance and insulin resistance; PIs are associated with glucose intolerance. Physiologic differences between pregnant women and nonpregnant adults may alter the pharmacokinetics of antiretroviral regimens. Fetal safety considerations and effects on perinatal HIV transmission must also be considered when selecting an antiretroviral regimen for pregnant women. This trial will compare PI-based and PI-sparing antiretroviral regimens for women initiating antiretroviral therapy in pregnancy. Women will be stratified on the basis of viral load (50,000 or less copies/ml or greater than 50,000 copies/ml) and gestational age at entry (20 or less weeks or greater than 20 weeks) and then randomized to one of two treatment groups. Group A will receive the PI nelfinavir (NFV) with zidovudine (ZDV) and lamivudine (d4T); Group B will receive nevirapine (NVP) with ZDV and d4T. Women will have clinic visits for physical and obstetrical examinations at 2, 4, 6, and 8 weeks after entry and then every 4 weeks until delivery. After delivery, infants in both groups may receive ZDV until they are 6 weeks old. Infants are evaluated for safety and to test the infant's blood for HIV-1 at birth and at Weeks 2, 8, 16, and 24. Women will continue on assigned antiretroviral therapy postpartum and will have 11 postpartum clinic visits over a period of 2 years. Blood samples from women will be evaluated for safety and for virologic, pharmacokinetic, and metabolic studies. The first 12 women randomized to Group A will undergo a 4-hour pharmacokinetic profile at 32 to 36 weeks gestation and at 8 weeks postpartum to determine the timing of the nelfinavir trough. The first 20 women randomized to Group B will undergo an 8-hour pharmacokinetic profile at either 16 to 24 weeks or 32 to 36 weeks gestation and then again at 8 weeks postpartum to characterize pharmacokinetics of nevirapine at steady state in pregnancy and in the postpartum period.


Recruitment information / eligibility

Status Completed
Enrollment 440
Est. completion date March 2006
Est. primary completion date
Accepts healthy volunteers No
Gender Female
Age group 14 Years and older
Eligibility Inclusion Criteria: - HIV infected - 10 to 30 weeks pregnant - Plan to continue pregnancy - CD4 count less than 250 cells/mm3 within 30 days of study entry - HIV RNA load greater than 1,000 copies/ml within 30 days of study entry - Antiretroviral naive (except ZDV for 8 weeks or less, including prior pregnancy) - Willing to follow study requirements and plan to continue receiving anti-HIV treatment for at least 2 years after delivery - Understand that NFV will not be supplied by the study (except for the first 12 women in Group A) - Understand the study drug NVP will not be supplied after 1 year following delivery and is reasonably certain that she can obtain NVP by prescription for the second year of the study - Access to a participating site - Willing to have infant followed until 24 weeks old - Parent or guardian willing to provide informed consent, if applicable Exclusion Criteria: - Alcohol or drug abuse - Chemotherapy for an active cancer - Require certain medications - AIDS-related opportunistic infection and/or serious bacterial infection or unstable or serious medical condition within 14 days of study entry - Chronic malabsorption or diarrhea - Diabetes, unless it only occurs during pregnancy - Major fetal problem or abnormality - Abnormal amniotic fluid volume - Plan to breastfeed - Acute hepatitis within 90 days of study entry - Skin problems such as psoriasis or eczema that require systemic treatment - Any serious disease that, in the opinion of the study official, would compromise study participation

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Lamivudine

Lamivudine/Zidovudine

Nelfinavir mesylate

Nevirapine

Zidovudine


Locations

Country Name City State
Bahamas Princess Margaret Hosp. Bahamas NICHD CRS Nassau
Brazil SOM Federal University Minas Gerais Brazil NICHD CRS Belo Horizonte Minas Gerais
Brazil Hosp. dos Servidores do Estado CRS Rio de Janeiro
Brazil Hosp. dos Servidores Rio de Janeiro NICHD CRS Rio de Janeiro
Puerto Rico San Juan City Hosp. PR NICHD CRS San Juan
United States Med. College of Georgia School of Medicine, Dept. of Peds., Div. of Infectious Diseases Augusta Georgia
United States Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases Baltimore Maryland
United States Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology Baltimore Maryland
United States BMC, Div. of Ped Infectious Diseases Boston Massachusetts
United States Brigham and Women's Hosp., Div. of Infectious Disease Boston Massachusetts
United States HMS - Children's Hosp. Boston, Div. of Infectious Diseases Boston Massachusetts
United States Bronx-Lebanon Hosp. IMPAACT CRS Bronx New York
United States Montefiore Med. Ctr. - AECOM Bronx New York
United States Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program Chicago Illinois
United States Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease Chicago Illinois
United States Univ. of Cincinnati CRS Cincinnati Ohio
United States Case CRS Cleveland Ohio
United States MetroHealth CRS Cleveland Ohio
United States Columbus Regional HealthCare System, The Med. Ctr. Columbus Georgia
United States Children's Hospital of Michigan NICHD CRS Detroit Michigan
United States DUMC Ped. CRS Durham North Carolina
United States Texas Children's Hosp. CRS Houston Texas
United States Univ. of Mississippi Med. Ctr Children's Hosp. Jackson Michigan
United States Usc La Nichd Crs Los Angeles California
United States Regional Med. Ctr. at Memphis Memphis Tennessee
United States St. Jude/UTHSC CRS Memphis Tennessee
United States Univ. of Miami Miller School of Medicine - Jackson Memorial Hosp. Miami Florida
United States Univ. of Miami Ped. Perinatal HIV/AIDS CRS Miami Florida
United States Vanderbilt Univ. Med. Ctr., Div. of Ped. Infectious Diseases Nashville Tennessee
United States Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease New Haven Connecticut
United States Tulane Univ. Health Science Ctr., Tulane Univ. Hosp. & Clinic New Orleans Louisiana
United States Tulane/LSU Maternal/Child CRS New Orleans Louisiana
United States Columbia IMPAACT CRS New York New York
United States Nyu Ny Nichd Crs New York New York
United States Rutgers - New Jersey Medical School CRS Newark New Jersey
United States Oregon Health & Science Univ. - Dept. of Peds., Div. of Infectious Disease Portland Oregon
United States Strong Memorial Hospital Rochester NY NICHD CRS Rochester New York
United States UCSD Mother-Child-Adolescent Program CRS San Diego California
United States UCSF Pediatric AIDS CRS San Francisco California
United States Seattle Children's Hospital CRS Seattle Washington
United States Univ. of Washington NICHD CRS Seattle Washington
United States UW Medicine - Harborview Med. Ctr., Northwest Family Ctr. Seattle Washington
United States UW School of Medicine - CHRMC Seattle Washington
United States Baystate Health, Baystate Med. Ctr. Springfield Massachusetts
United States SUNY Stony Brook NICHD CRS Stony Brook New York
United States SUNY Upstate Med. Univ., Dept. of Peds. Syracuse New York
United States Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases Torrance California
United States Howard Univ. Washington DC NICHD CRS Washington District of Columbia
United States WNE Maternal Pediatric Adolescent AIDS CRS Worcester Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
National Institute of Allergy and Infectious Diseases (NIAID) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Bahamas,  Brazil,  Puerto Rico, 

References & Publications (4)

Capparelli EV, Aweeka F, Hitti J, Stek A, Hu C, Burchett SK, Best B, Smith E, Read JS, Watts H, Nachman S, Thorpe EM Jr, Spector SA, Jimenez E, Shearer WT, Foca M, Mirochnick M; PACTG 1026S Study Team; PACTG P1022 Study Team. Chronic administration of nev — View Citation

Hitti J, Frenkel LM, Stek AM, Nachman SA, Baker D, Gonzalez-Garcia A, Provisor A, Thorpe EM, Paul ME, Foca M, Gandia J, Huang S, Wei LJ, Stevens LM, Watts DH, McNamara J; PACTG 1022 Study Team. Maternal toxicity with continuous nevirapine in pregnancy: re — View Citation

Loutfy MR, Walmsley SL. Treatment of HIV infection in pregnant women: antiretroviral management options. Drugs. 2004;64(5):471-88. Review. — View Citation

Moodley J, Moodley D. Management of human immunodeficiency virus infection in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2005 Apr;19(2):169-83. Epub 2004 Dec 15. Review. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Proportion of women in each treatment group who continue on original therapy with virologic suppression to less than 500 copies/ml at 34 weeks gestation (or the last viral load determination prior to delivery)
Primary proportion of women in each treatment group who continue on original therapy with virologic suppression to less than 500 copies/ml at 48 weeks postpartum
Secondary Proportion of women in each treatment group who continue on original therapy with virologic suppression to less than 50 copies/ml at 34 weeks gestation (or the last viral load determination prior to delivery)
Secondary proportion of women in each treatment group who continue on original therapy with virologic suppression to less than 50 copies/ml at 48 weeks postpartum, and to less than 500 and 50 copies/ml at 104 weeks postpartum
Secondary study treatment adherence and health status by self-report, correlated with predose nelfinavir or nevirapine level at 34 weeks gestation and 8 weeks postpartum
Secondary difference between postpartum and pregnancy 12-hour area under the concentration curve (AUC) for nevirapine
Secondary time of trough levels in relation to the morning dose of nevirapine and nelfinavir at 34 weeks gestation and 8 weeks postpartum and correlation of trough levels with viral load
Secondary incidence of HIV viral resistance by genotype among women in each treatment group at the time of virologic failure
Secondary incidence of abnormal glucose tolerance, gestational diabetes, and abnormal lactate levels during pregnancy in each treatment group
Secondary incidence of impaired glucose tolerance, diabetes, hyperinsulinemia, and elevated cholesterol and triglycerides at 8 weeks postpartum in each treatment group
Secondary incidence of anemia, hypoglycemia, and abnormal liver function studies among infants born to women in each treatment group
Secondary incidence of prematurity (less than 37 weeks), extreme prematurity (less than 32 weeks), low birth weight (less than 2.5 kg), and very low birth weight (less than 1.5 kg) among infants born to women in each treatment group
Secondary perinatal HIV transmission among infants born to women in each treatment group
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