OUTLINE OF AVEG PROTOCOL 102/ACTG PROTOCOL 234

Subjects: Pregnant women who are HIV infected but without AIDS-defining illness and with CD4 lymphocyte counts of 400/mm³ or above. In addition, they must have no special obstetrical risks. Their infants, although not directly immunized, will participate in the study during follow-up after delivery. Maternal therapy with zidovudine (ZDV) will not be a contraindication to participation in the trial.

Schema: Control versus 640 µg recombinant HIV gp160 (VaxSyn) beginning from week 16 through week 24 of gestation with monthly booster injections concluding at end of pregnancy for a total of at most 5 immunizations. Placebo controls will receive an equal number of injections. Mothers and infants will be followed through 18 months after the end of pregnancy. Vaccinees were given the option of booster immunizations at 3, 6, 9 and 12 months after delivery.

Product Description: VaxSyn: baculovirus/insect cell-derived HIV-1 LAI gp160 in alum [MicroGeneSys]

Time Period: First volunteer enrolled on 05/26/93 and the last on 09/23/93; follow-up of approximately 24 months. Enrollment was terminated in 03/94.

Clinical Site: Yale University

AVEG Clinical Coordination: Vanderbilt University

Study Chairs: Peter Wright, Vanderbilt University and John Lambert, Johns Hopkins University

INCLUSION CRITERIA

• Without clinical criteria for a diagnosis of AIDS (Appendix B), but with proven HIV-1 infection documented by ELISA and one other confirmatory test such as Western Blot or culture. Generalized lymphadenopathy does not preclude entry into the trial.
• Proven pregnancy in a woman between the ages of 16 and 40 years of age inclusive, and between the 16th and 24th week of gestation inclusive at the time of the first immunization. Use of ZDV will be prescribed by the attending obstetrician, and women on ZDV may be included in the trial.
• History and physical examination compatible with a normal course of pregnancy. No obstetrical high risk factors other than HIV infection identified on screening. The woman must intend to continue the pregnancy to delivery and agree to being followed by the AVEU for the duration of the study.
• The mother must be able to provide informed consent. In accordance with Federal regulations the father of the fetus (if available after a reasonable attempt to contact him) must also provide informed consent.
• Acceptable entry laboratory parameters defined as:
  • Hematocrit >28%
  • Platelets >100,000/mm³
  • Total WBC >3000 cells/mm³
  • Creatinine <1.5 mg/dl
  • Baseline CD4 cells >400 cells/mm³
  • SGPT <3 times upper limit of normal

  NOTE: Baseline CD4 count will be the average of all determinations performed during the preceding month, or a minimum of two determinations one week apart.

EXCLUSION CRITERIA

• Known hypersensitivity to a component of the vaccine.
• Systemic manifestations related to HIV other than HIV-induced lymphadenopathy.
• HIV p24 >30 pg/ml
• Current use of illicit drugs or known chronic alcohol use. Subjects who have used illicit drugs, and are actively participating in a treatment program (such as methadone maintenance) may be included.
• Evidence of fetal abnormality at screening ultrasound (sonogram).
• Evidence of maternal risk factors including insulin dependent diabetes, moderate to severe hypertension, repeated fetal wastage (>3), Rh-sensitization or other blood group alloimmunization, severe renal disease, previous infants with malformations or other factors obstetrically judged to constitute a special risk of spontaneous abortion or premature birth.
• Intent to breast feed.
• Subjects may not have received antiretroviral or immunomodulating agent other than ZDV within 90 days of entry into the study or during pregnancy. [Treatment with Acyclovir will not be exclusionary.]
• Evidence of active syphilis in the mother.
• Positive circulating hepatitis B surface antigen.

STUDY GOALS

Primary Objective

• To evaluate the safety of the candidate vaccine in asymptomatic, HIV-1 infected pregnant women.

Secondary Objectives

• To evaluate the immunogenicity of the candidate vaccine in asymptomatic, HIV-1 infected pregnant women, and the passive acquisition of vaccine-specific antibody in the infant.
• To evaluate the effects of the candidate vaccine on course of pregnancy, and outcome in infant. The study is not designed as an efficacy trial. It should establish the feasibility of maternal immunization and allow assessment of the potential benefit of vaccination in a primary or additive role in subsequent efficacy trials.
• To evaluate the long term safety (18 months postpartum) of the candidate vaccine in women who received the vaccine during pregnancy.
• To evaluate the long term immunogenicity and safety of the candidate vaccine in women given postpartum immunizations.