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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00017719
• Other study ID #: P1022
• Secondary ID: 10192ACTG P1022P
• Status: Completed
• Phase: Phase 3
• 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
• 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
• 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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Infections
• Pregnancy

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

External Links

•   Click here for more information on HIV and pregnancy
•   Click here for more information on medication regimens for HIV positive pregnant women
•   Click here for more information on medication safety during pregnancy
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