Clinical trial NCT00017797: Problems Associated With the Use of Anti-HIV Drugs in HIV-Infected Pregnant Women
Official title: Evaluation of Metabolic Complications Associated With Antiretroviral Medications in HIV-1-Infected Pregnant Women
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Pregnancy
Keywords: Pregnancy Complications, Infectious
HIV-1
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Glucose Intolerance
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2001-08-31
Enrollment: 160
Sex: FEMALE
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL

Brief summary: The purpose of this study is to find out if HIV-infected pregnant women who take protease inhibitors (PIs) are more likely to have blood sugar problems than those who do not take PIs.

HIV-infected people generally are treated with a combination of different types of anti-HIV drugs, 1 of which is usually a PI. The same holds true for pregnant women, but not much is known about the use of these drugs in pregnancy. Blood sugar and liver problems caused by anti-HIV drugs in nonpregnant patients are well known but their effects in pregnancy are not. Also, certain physical changes brought about by pregnancy may affect the way drugs are handled in the body. There remains a need for further study into the use of anti-HIV drugs during pregnancy and their effect on the safety of the mother and baby.

Detailed description: The dramatic impact of potent combination antiretroviral therapies on the course of HIV disease has made the use of PIs routine in the care of HIV-1-infected individuals. Combination therapy likewise has become the standard of care in pregnant individuals, even though information on use of these drugs during human pregnancy is limited. There are no published prospective evaluations of toxicities experienced by pregnant women on PI-containing antiretroviral regimens, despite findings of metabolic disturbances of glucose, fatty acids, and cholesterol, as well as lactic acidosis/hepatic steatosis in nonpregnant individuals treated with antiretrovirals. Gastrointestinal (GI) side effects also are well documented in nonpregnant individuals treated with PIs, but have not been systematically evaluated in pregnancy. In addition, the physiologic changes brought about by pregnancy may influence the pharmacokinetics, safety, and side effects of antiretroviral drugs. There remains a need for further evaluation of the use of antiretrovirals during pregnancy and their impact on maternal, fetal, and infant safety.

Patients are stratified according to whether or not they are on a PI-containing antiretroviral regimen and the number of weeks of gestation (26 weeks or less versus greater than 26 weeks). Patients are followed at 8-week intervals from the time of entry until delivery or pregnancy termination, with an additional visit at 12 weeks after delivery or pregnancy termination. All infants born to study participants are evaluated at the time of delivery (anthropometrics and HIV DNA PCR) and are seen again at the mothers' 12-week post-delivery visit. Glucose tolerance testing and other metabolic studies are performed serially during pregnancy and again postpartum. This is an observational study and drugs are not supplied. Patients receiving antiretroviral therapy must obtain their own medications.

Eligibility criteria: Inclusion Criteria

Patients may be eligible for this study if they:

* Are HIV-positive.
* Are female and 13 years of age or older.
* Are between 20 and 34 weeks pregnant at study entry.
* Had an ultrasound performed at 16 or more weeks of pregnancy.
* Have consent of a parent or guardian if under 18 years of age. The father of the baby, if available, also must give consent.
* Have taken the same anti-HIV drugs, including a PI, during the 8 weeks just before study entry. If not taking a PI or any anti-HIV drug, must not have taken a PI during the 8 weeks just before study entry. Patients must carry on this way for the entire study.

Exclusion Criteria

Patients will not be eligible for this study if they:

* Have diabetes. Patients who have had diabetes caused by pancreas problems or steroid use in the past, but now have normal blood sugar without having to take drugs or special diets, are allowed. Patients who have had blood sugar problems in a past pregnancy also are allowed.
* Had a serious infection or medical condition within 30 days before study entry.
* Are enrolled in another study which requires a lot of blood tests.
* Take, or have taken in the 6 weeks before study entry, any of the following drugs: hormones (growth hormone, testosterone, or steroids), thalidomide, interleukins or interferons, efavirenz, hydroxyurea, drugs to control blood sugar, and anti-cancer drugs.
* Take, or have taken in the year before study entry, steroids, e.g., prednisone, for more than 14 days in any 3-month period. Inhaled steroids and steroid creams/ointments are allowed.
* Take, or have taken in the 30 days before study entry, PIs with lovastatin or simvastatin (2 drugs that lower the amount of fat in the blood).
* Have an ultrasound showing a major abnormality in the baby.
* Have problems with their pregnancy and/or are expecting more than 1 baby.
* Abuse drugs or alcohol.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham - Pediatric
state: Alabama
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Howard Univ Hosp
state: District of Columbia
city: Jacksonville
country: United States
facility: Univ of Florida Health Science Ctr / Pediatrics
state: Florida
city: Miami
country: United States
facility: Univ of Miami (Pediatric)
state: Florida
city: Columbus
country: United States
facility: The Med Ctr Inc
state: Georgia
city: Honolulu
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Mt Sinai Hosp Med Ctr / Dept of Pediatrics
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Chicago
country: United States
facility: The CORE Ctr
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp of Indiana / Life Care Clinic
state: Indiana
city: Indianapolis
country: United States
facility: Wishard Hosp
state: Indiana
city: Baltimore
country: United States
facility: Univ of Marlyand (Pediatric)
state: Maryland
city: Boston
country: United States
facility: Brigham and Womens Hosp
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Med Ctr of Springfield
state: Massachusetts
city: Worcester
country: United States
facility: Univ of Massachusetts Med School
state: Massachusetts
city: Detroit
country: United States
facility: Hutzel Hospital
state: Michigan
city: Detroit
country: United States
facility: Children's Hosp of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Med Ctr
state: Minnesota
city: Minneapolis
country: United States
facility: Univ of Minnesota
state: Minnesota
city: St.Louis
country: United States
facility: Washington Univ (St.Louis)
state: Missouri
city: New Brunswick
country: United States
facility: St Peter's Med Ctr
state: New Jersey
city: Newark
country: United States
facility: Univ of Medicine & Dentistry of New Jersey / Univ Hosp
state: New Jersey
city: Bronx
country: United States
facility: Jacobi Med Ctr
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Metropolitan Hosp Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve Univ
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Med Ctr
state: Ohio
city: Pittsburgh
country: United States
facility: Univ of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: Saint Jude Children's Research Hosp of Memphis
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Univ Med Ctr
state: Tennessee
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
city: Seattle
country: United States
facility: Children's Hospital & Medical Center / Seattle ACTU
state: Washington
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp
Study officials:
name: Elizabeth Livingston
role: STUDY_CHAIR
References:
citation: Livingston EG, Cohn SE, Yang Y, Watts HD, Bardeguez AD, Jones TB, Smith LM, Umbleja T, McComsey GA. Lipids and lactate in human immunodeficiency virus-1 infected pregnancies with or without protease inhibitor-based therapy. Obstet Gynecol. 2007 Aug;110(2 Pt 1):391-7. doi: 10.1097/01.AOG.0000271210.79340.4c.