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

French Public Scientific and Technological Institution (EPST)

Status and phase: Completed; Phase 3

Conditions: HIV Infections; Pregnancy

Treatments: Drug: ZDV Long (mother)-Long (infant): Comparison of zidovudine durations; Drug: ZDV Long (mother)-Short (infant): Comparison of zidovudine durations; Drug: ZDV Short (mother)-Long (infant): Comparison of zidovudine durations; Drug: ZDV Short (mother)-Short (infant): Comparison of zidovudine durations

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00386230

NIH 5 R01 HD33326-05

PHPT-1

Details and patient eligibility

About

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.

Full 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.

Sex: Female

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,554 participants in 4 patient groups

1

Experimental group

Description:

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)

Treatment:

Drug: ZDV Short (mother)-Short (infant): Comparison of zidovudine durations

2

Experimental group

Description:

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)

Treatment:

Drug: ZDV Short (mother)-Long (infant): Comparison of zidovudine durations

3

Experimental group

Description:

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)

Treatment:

Drug: ZDV Long (mother)-Short (infant): Comparison of zidovudine durations

4

Active Comparator group

Description:

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.

Treatment:

Drug: ZDV Long (mother)-Long (infant): Comparison of zidovudine durations