Clinical trial NCT00041964: A Study of HIV Levels During Pregnancy and After Childbirth
Official title: A Prospective Observational Study of Virologic and Immunologic Changes in HIV-Infected Women During the Postpartum Period
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Pregnancy
Keywords: Lopinavir
Pregnancy Trimester, Third
Pregnancy Complications, Infectious
HIV Protease Inhibitors
Ritonavir
Nelfinavir
Viral Load
puerperium
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2002-07-22
Enrollment: 129
Sex: FEMALE
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: The purpose of this study is to find out if HIV-infected pregnant women taking anti-HIV drugs have an increased amount of HIV in their blood (viral load) after having the baby.

The purpose of A5153s, a substudy of A5150, is to characterize two anti-HIV drugs (nelfinavir \[NFV\] and lopinavir/ritonavir \[LPV/r\]) in HIV-infected women during pregnancy and after childbirth.

Sometimes pregnant women have an increase in their HIV viral load after their baby is born. This study will try to find out how often this happens. It will also examine possible reasons why the increase in viral load occurs.

Detailed description: Limited data suggest that HIV-infected pregnant women develop postpartum viral rebound. However, viral load changes in the postpartum period have not been adequately characterized. Changes in adherence to antiretroviral therapy, pregnancy-related changes in pharmacokinetics of antiretroviral medications, and decline in immune competence are mechanisms by which postpartum viral load rebound may occur. This study is designed to characterize the incidence and magnitude of postpartum viral rebound during the initial 24 weeks postpartum and to explore the mechanisms and consequences of viral rebound.

Eligible patients are evaluated at gestational weeks 34 and 36, at delivery, and at regular visits for 96 weeks postpartum. Most evaluations include a medical history, physical exam, laboratory tests, and adherence and quality-of-life questionnaires. Viral load and CD4/CD8 cell counts are measured frequently.

Patients are expected to receive at least 8 weeks of stable HAART before delivery, and to continue HAART throughout the remainder of the study. The choice of HAART is left to the primary provider. No antiretroviral drugs are provided by this study.

Patients participating in the A5153s substudy receive either NFV or LPV/r as part of their HAART. Pharmacokinetic blood sampling takes place at 36 weeks gestation, 6 weeks postpartum, and 24 weeks postpartum. Patients record the administration times and doses of their NFV or LPV/r for 48 hours prior to each substudy visit, and hold their regularly scheduled doses of antiretroviral medications on substudy days. Patients arrive at the clinic fasting (no food or drink for the previous 8 hours) and are given a standardized breakfast prior to supervised administration of their NFV or LPV/r dose. An intravenous catheter is placed in an arm vein for blood collection at pre-dose and 1, 2, 4, and 6 hours post-dose.

Eligibility criteria: Inclusion Criteria

Patients may be eligible for this study if they:

* Are age 13 or older.
* Are between 22 and 30 weeks pregnant.
* Have had their pregnancy confirmed by ultrasound at 14 weeks gestation or later.
* Are infected with HIV.
* Are planning to receive at least 8 weeks of highly active antiretroviral therapy (HAART) by the time they have their baby.
* Are available for follow-up for the duration of the study.

Exclusion Criteria

Patients may not be eligible for this study if they:

* Intend to terminate their pregnancy.
* Intend to breast-feed their baby.
* Are carrying a baby with major abnormalities, including spina bifida, anencephaly, hydrops, or ascites.
* Have taken certain medications.
* Are enrolled in other studies that require large blood draws.
* Will be taking anti-HIV drugs only to prevent mother-to-child transmission of HIV, and not to treat the maternal infection itself.
* Actively abuse drugs or alcohol in a way that would interfere with participation in the study.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Los Angeles County Medical Center/USC
state: California
city: Los Angeles
country: United States
facility: UCLA School of Medicine
state: California
city: San Diego
country: United States
facility: UCSD Mother, Child & Adolescent HIV Program
state: California
city: San Francisco
country: United States
facility: San Francisco General Hosp
state: California
city: Jacksonville
country: United States
facility: Univ of Florida- Health Science Ctr
state: Florida
city: Atlanta
country: United States
facility: Emory Univ
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp Core Ctr
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Chicago
country: United States
facility: Chicago Childrens Memorial Hospital (Pediatric)
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Detroit
country: United States
facility: Hutzel Hospital
state: Michigan
city: Detroit
country: United States
facility: Childrens Hospital of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Med Clinic
state: Minnesota
city: Newark
country: United States
facility: Univ of Med & Dentistry of NJ/Univ Hosp
state: New Jersey
city: Bronx
country: United States
facility: Jacobi Med Ctr
state: New York
city: New York,
country: United States
facility: NYU/Bellevue
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Stony Brook
country: United States
facility: State Univ of New York at Stony Brook
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: 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: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Miriam Hosp / Brown Univ
state: Rhode Island
city: Memphis
country: United States
facility: The Regional Med Ctr, Memphis
state: Tennessee
city: Nashville
country: United States
facility: Comprehensive Care Clinic
state: Tennessee
city: Dallas
country: United States
facility: University of Texas, Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: Univ of Washington (Seattle)
state: Washington
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp
Study officials:
name: Beverly Sha
role: STUDY_CHAIR
name: Alice Stek
role: STUDY_CHAIR
References:
citation: Melvin AJ, Burchett SK, Watts DH, Hitti J, Hughes JP, McLellan CL, King PD, Johnson EJ, Williams BL, Frenkel LM, Coombs RW. Effect of pregnancy and zidovudine therapy on viral load in HIV-1-infected women. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Mar 1;14(3):232-6. doi: 10.1097/00042560-199703010-00006.
citation: Rich KC, Siegel JN, Jennings C, Rydman RJ, Landay AL. CD4+ lymphocytes in perinatal human immunodeficiency virus (HIV) infection: evidence for pregnancy-induced immune depression in uninfected and HIV-infected women. J Infect Dis. 1995 Nov;172(5):1221-7. doi: 10.1093/infdis/172.5.1221.
citation: Cao Y, Krogstad P, Korber BT, Koup RA, Muldoon M, Macken C, Song JL, Jin Z, Zhao JQ, Clapp S, Chen IS, Ho DD, Ammann AJ. Maternal HIV-1 viral load and vertical transmission of infection: the Ariel Project for the prevention of HIV transmission from mother to infant. Nat Med. 1997 May;3(5):549-52. doi: 10.1038/nm0597-549.
citation: Burns DN, Landesman S, Minkoff H, Wright DJ, Waters D, Mitchell RM, Rubinstein A, Willoughby A, Goedert JJ. The influence of pregnancy on human immunodeficiency virus type 1 infection: antepartum and postpartum changes in human immunodeficiency virus type 1 viral load. Am J Obstet Gynecol. 1998 Feb;178(2):355-9. doi: 10.1016/s0002-9378(98)80025-2.
citation: Sha BE, Tierney C, Cohn SE, Sun X, Coombs RW, Frenkel LM, Kalams SA, Aweeka FT, Bastow B, Bardeguez A, Kmack A, Stek A; Aids Clinical Trials Group ACTG A5150 Team. Postpartum viral load rebound in HIV-1-infected women treated with highly active antiretroviral therapy: AIDS Clinical Trials Group Protocol A5150. HIV Clin Trials. 2011 Jan-Feb;12(1):9-23. doi: 10.1310/hct1201-9.