Expired Study
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Augusta, Georgia 30912


Purpose:

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.


Study summary:

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.


Criteria:

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 is Available At:


Original ID:

P1022


NCT ID:

NCT00017719


Secondary ID:

10192


Study Acronym:


Brief Title:

Combination Treatment With and Without Protease Inhibitors for Women Who Begin Therapy for HIV Infection During Pregnancy


Official Title:

Randomized Trial of Protease Inhibitor-Including vs. Protease Inhibitor-Sparing Regimens for Women Who Initiate Therapy of HIV Infection During Pregnancy


Overall Status:

Completed


Study Phase:

Phase 3


Genders:

Female


Minimum Age:

14 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institute of Allergy and Infectious Diseases (NIAID)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Randomized, Endpoint Classification: E


Number of Arms:

0


Number of Groups:

0


Total Enrollment:

440


Enrollment Type:


Overall Contact Information

Official Name:Jane Hitti, MD, MPH
Study Chair
Department of Obstetrics/Gynecology, University of Washington Medical Center

Study Dates

Start Date:May 2002
Completion Date:March 2006
Completion Type:Actual
Verification Date:November 2013
Last Changed Date:November 25, 2013
First Received Date:June 8, 2001

Study Outcomes

Outcome Type:Secondary Outcome
Measure:perinatal HIV transmission among infants born to women in each treatment group
Safety Issues:False
Outcome Type:Secondary Outcome
Measure: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
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:incidence of anemia, hypoglycemia, and abnormal liver function studies among infants born to women in each treatment group
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:incidence of impaired glucose tolerance, diabetes, hyperinsulinemia, and elevated cholesterol and triglycerides at 8 weeks postpartum in each treatment group
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:incidence of abnormal glucose tolerance, gestational diabetes, and abnormal lactate levels during pregnancy in each treatment group
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:incidence of HIV viral resistance by genotype among women in each treatment group at the time of virologic failure
Safety Issues:False
Outcome Type:Secondary Outcome
Measure: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
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:difference between postpartum and pregnancy 12-hour area under the concentration curve (AUC) for nevirapine
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:study treatment adherence and health status by self-report, correlated with predose nelfinavir or nevirapine level at 34 weeks gestation and 8 weeks postpartum
Safety Issues:False
Outcome Type:Secondary Outcome
Measure: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
Safety Issues:False
Outcome Type:Secondary Outcome
Measure: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)
Safety Issues:False
Outcome Type:Primary Outcome
Measure: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
Safety Issues:False
Outcome Type:Primary Outcome
Measure: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)
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:Lamivudine
Intervention Type:Drug
Name:Lamivudine/Zidovudine
Intervention Type:Drug
Name:Nelfinavir mesylate
Intervention Type:Drug
Name:Nevirapine
Intervention Type:Drug
Name:Zidovudine

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Institute of Allergy and Infectious Diseases (NIAID)
Agency Class:NIH
Agency Type:Collaborator
Agency Name:Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation: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 nevirapine during pregnancy: impact of pregnancy on pharmacokinetics. HIV Med. 2008 Apr;9(4):214-20.
PMID:18366444
Reference Type:Results Reference
Citation:For the PACTG 1022 Study Team. Maternal Toxicity With Continuous Nevirapine in Pregnancy: Results From PACTG 1022. J Acquir Immune Defic Syndr. 2004 Jul 1;36(3):772-776.
PMID:15213559
Reference Type:Reference
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.
PMID:15778108
Reference Type:Reference
Citation:Loutfy MR, Walmsley SL. Treatment of HIV infection in pregnant women: antiretroviral management options. Drugs. 2004;64(5):471-88.
PMID:14977385

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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