Shortened Zidovudine Regimens to Prevent Mother-to-Child Transmission of HIV Type 1

Study Description

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Brief Summary:

The purpose of the study was to test the equivalence of a short zidovudine (ZDV) regimen as compared to a longer, ACTG-076-like, ZDV regimen in reducing the risk of mother-to-child transmission of HIV: and to assess and compare the safety and tolerance of the long and shortened ZDV regimens.

Condition or disease	Intervention/treatment	Phase
HIV Infections; Pregnancy	Drug: ZDV Short (mother)-Short (infant): Comparison of zidovudine durations; Drug: ZDV Short (mother)-Long (infant): Comparison of zidovudine durations; Drug: ZDV Long (mother)-Short (infant): Comparison of zidovudine durations; Drug: ZDV Long (mother)-Long (infant): Comparison of zidovudine durations	Phase 3

Detailed Description:

Multicenter, randomized, four arms, double-blind, controlled study. Consenting pregnant women were tested for HIV from the beginning of pregnancy until 26 of gestational age (GA). If HIV-positive and eligible, women completed a Pre-entry baseline check-up. Enrollment took place at 28 weeks' gestational age. Women meeting selection criteria were randomly assigned to one of four study arms (see below).

AMENDMENT (March 20, 1999)

Data Safety and Monitory Board interim review (March 17, 1999) The DSMB reported that the transmission rate in the longest arm (long treatment of both mother and baby), was significantly lower than that in the shortest arm (short treatment of both the mother and the baby) and this discrepancy was larger than the previously agreed on difference which, if found, would call for changing the study design. In addition, the transmission rates in the remaining two arms of the study were similar to that in the longest arm. The difference that was found could not be explained by any baseline characteristics of the participants, such as maternal age, gestational age at delivery, birth weight, cesarean section rate, or any others.

The DSMB recommended that enrollment into the shortest arm of the study be terminated, and the study be continued with a modification of design so that new enrollees would enter one of the three remaining arms.

All women enrolled before this amendment was effective and delivering after March 20th, 1999, and previously randomized to the Smother-Sinfant arm, were unblinded in order to give their infants open label zidovudine for 6 weeks.

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	1554 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double
Primary Purpose:	Prevention
Official Title:	Short ZDV Course to Prevent Perinatal HIV in Thailand
Study Start Date :	June 1997
Actual Study Completion Date :	August 2000

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 1; Maternal ZDV treatment starting at 35 weeks Gestational Age (GA) and continuing through labor and delivery, and three days of infant ZDV treatment starting at birth (Smother-Sinfant)	Drug: ZDV Short (mother)-Short (infant): Comparison of zidovudine durations; Maternal ZDV treatment (300 mg, twice daily) starting at 35 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Three days of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Smother-Sinfant)
Experimental: 2; Maternal ZDV treatment starting at 35 weeks Gestational Age (GA) and continuing through labor and delivery, and six weeks of infant ZDV treatment starting at birth (Smother-Linfant)	Drug: ZDV Short (mother)-Long (infant): Comparison of zidovudine durations; Maternal ZDV treatment (300 mg, twice daily) starting at 35 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Six weeks of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Smother-Linfant)
Experimental: 3; Maternal ZDV treatment starting at 28 weeks Gestational Age (GA) and continuing through labor and delivery, and three days of infant ZDV treatment starting at birth (Lmother-Sinfant)	Drug: ZDV Long (mother)-Short (infant): Comparison of zidovudine durations; Maternal ZDV treatment (300 mg, twice daily) starting at 28 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Three days of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Lmother-Sinfant)
Active Comparator: 4; Maternal ZDV treatment starting at 28 weeks Gestational Age (GA) and continuing through labor and delivery, and six weeks of infant ZDV treatment starting at birth (Lmother-Linfant). This study arm was the reference regimen.	Drug: ZDV Long (mother)-Long (infant): Comparison of zidovudine durations; Maternal ZDV treatment (300 mg, twice daily) starting at 28 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Six weeks of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Lmother-Linfant)

Outcome Measures

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Primary Outcome Measures :

1. Definitive HIV infection in children as assessed by positive PCR on two peripheral blood samples collected at two separate occasions.

Secondary Outcome Measures :

1. Safety: clinical and biological assessment.

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Pre-inclusion

Women are eligible for Pre-Entry if they:

• have evidence of HIV infection (confirmed on a second sample);
• present themselves for prenatal care before 26 weeks GA, based on last menstrual period and/or sonogram results;
• intend to stay in the province for at least 18 months after delivery;
• can provide informed consent;
• have given written informed consent to participate in the study;
• intend to carry the pregnancy to term.

Inclusion Criteria:

• all pre-entry criteria;
• date of enrollment: 28 weeks GA, based on last menstrual period and/or sonogram results;
• the following laboratory values within 21 days prior to randomization:
• hemoglobin > 8.0 g/dL;
• absolute neutrophil count > 750 cells/mm3;
• SGPT < 5 x upper limit of normal;
• serum creatinine < 1.5 mg/dL (women with a serum creatinine > 1.5 mg/dL must have a measured eight-hour urine creatinine clearance > 70 mL/min.);
• agreement not to breastfeed.

Exclusion Criteria:

• AIDS according to the Thai Communicable Diseases Control (CDC) classification;
• pre-existing maternal/fetal condition that contraindicates the use of ZDV
• oligohydramnios, unexplained polyhydramnios, fetal hydrops or ascites or other evidence of pre-existing in-utero anemia;
• clinically significant history of intolerance to ZDV treatment resulting in discontinuation of therapy for more than 4 weeks;
• receipt of ZDV during the current pregnancy for any indication, or women who need ZDV for their own health (women are then followed separately);
• receipt of other antiretroviral agents, passive immunotherapy, anti-HIV vaccines, cytolytic agents (usually referred as chemotherapy), radiation therapy, or corticosteroids during this pregnancy except steroids less than 7 (see Zidovudine Investigator's Brochure);
• simultaneous participation in another clinical trial.

Contacts and Locations

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Locations

Thailand
Phpt - Ird 174
Chiang Mai, Thailand, 50200

Sponsors and Collaborators

Institut de Recherche pour le Developpement

Harvard School of Public Health

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator:	Marc Lallemant, MD	Institut de Recherche pour le Developpement

More Information

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Publications of Results:

Lallemant M, Jourdain G, Le Coeur S, Kim S, Koetsawang S, Comeau AM, Phoolcharoen W, Essex M, McIntosh K, Vithayasai V. A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1. Perinatal HIV Prevention Trial (Thailand) Investigators. N Engl J Med. 2000 Oct 5;343(14):982-91.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sripan P, Le Coeur S, Amzal B, Ingsrisawang L, Traisathit P, Ngo-Giang-Huong N, McIntosh K, Cressey TR, Sangsawang S, Rawangban B, Kanjanavikai P, Tréluyer JM, Jourdain G, Lallemant M, Urien S. Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the Efficacy of Interventions for the Prevention of Perinatal HIV. PLoS One. 2015 May 19;10(5):e0126647. doi: 10.1371/journal.pone.0126647. eCollection 2015. Erratum in: PLoS One. 2015;10(8):e0137368. PLoS One. 2015;10(6):e0130917.

ClinicalTrials.gov Identifier:	NCT00386230 History of Changes
Other Study ID Numbers:	PHPT-1; NIH 5 R01 HD33326-05
First Posted:	October 11, 2006
Last Update Posted:	May 2, 2008
Last Verified:	May 2008

Keywords provided by Institut de Recherche pour le Developpement:

transmission; infant; HIV	pregnancy; HIV-1 infection; HIV Seronegativity

Additional relevant MeSH terms:

HIV Infections; Immunologic Deficiency Syndromes; Anti-HIV Agents; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immune System Diseases	Zidovudine; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents