Evaluating the Safety of Immediate Versus Deferred Isoniazid Preventive Therapy Among HIV-Infected Pregnant Women
Condition: HIV Infections; Tuberculosis
MeSH terms: Tuberculosis
Intervention: Isoniazid (INH); Placebo for isoniazid (INH)
Intervention description: 300-mg tablet once daily by mouth, either from entry through Week 28 antepartum (Arm A) or from Week 12 postpartum through Week 40 postpartum (Arm B); Placebo tablet once daily by mouth, either from Week 28 visit through Week 40 postpartum (Arm A) or from entry until Week 12 postpartum visit (Arm B)
Intervention MeSH terms: Isoniazid
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 956.0
Sex: Female
Minimum age: 13 Years
Healthy volunteers: No

Summary:

      Tuberculosis (TB) is a leading cause of death among HIV-infected persons in low-income
      settings and can be a serious complication for HIV-infected pregnant women and their infants.
      Isoniazid (INH) preventive therapy (IPT) is effective in preventing TB infection in
      HIV-infected adults, but the safety of IPT in pregnant women is unknown. This study evaluated
      the safety of IPT among HIV-infected pregnant women.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented HIV-1 infection, defined as positive results from two samples collected at
             different time points. All samples tested must be whole blood, serum, or plasma. More
             information on this criterion can be found in the protocol.

          -  Documented HIV treatment, according to World Health Organization (WHO) guidelines, for
             prevention of mother-to-child transmission (PMTCT) and standard of care for HIV
             infection

          -  Pregnant females age 18 years or older

          -  Pregnant females between greater than or equal to 13 and less than 18 who are able and
             willing to provide signed informed consent under local law or pregnant females unable
             to consent under local law whose parents/legal guardians provide consent or "minimum
             age of consent according to locally applicable laws or regulations"

          -  Pregnancy gestational age confirmed by best available method at site to be greater
             than or equal to 14 weeks through less than or equal to 34 weeks (34 weeks, 6 days)

          -  Weight greater than or equal to 35 kg at screening

          -  The following laboratory values obtained within 30 days prior to study entry:

               -  Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3

               -  Hemoglobin greater than or equal to 7.5 g/dL

               -  Platelet count greater than or equal to 50,000/mm^3

               -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT),
                  alkaline phosphatase (ALT)/serum glutamic pyruvic transaminase (SGPT), and total
                  bilirubin less than or equal to 1.25 times the upper limit of normal (ULN).
                  (Note: If participant is taking atazanavir, direct bilirubin may be used to
                  determine eligibility.)

          -  Intent to remain in current geographical area of residence for the duration of the
             study

        Exclusion Criteria:

          -  Any woman with a positive TB symptom screen per WHO guidelines, including any one or
             more of the following: any cough, fever, self-reported weight loss, or night sweats.
             Note: If a potential participant is found to be negative for TB upon further testing,
             the participant may be rescreened for the study.

          -  Any positive acid-fast bacillus (AFB) smear, Xpert, or any other rapid TB screening
             test or culture from any site within the past 12 weeks, or chest radiograph (x-ray)
             with findings suggestive of active TB, or clinician suspects active TB

          -  Known exposure to AFB smear-positive active TB case within past 12 weeks prior to
             study entry

          -  Reported INH exposure (more than 30 days) in the past year prior to study entry

          -  Receipt of any TB or atypical mycobacteria therapy for more than 30 days in the past
             year

          -  Evidence of acute hepatitis, such as jaundice, dark urine (not concentrated urine),
             and/or acholic stools sustained for more than 3 days within 90 days prior to entry.
             More information on this criterion can be found in the protocol.

          -  Grade 1 or higher peripheral neuropathy. More information on this criterion can be
             found in the protocol.

          -  History of acute systemic adverse reaction or allergy to INH

          -  Known current heavy alcohol use (more than 2 drinks per week) or alcohol exposure
             that, in the investigator's opinion, would compromise participation and the outcome of
             this study

          -  Presence of new AIDS-defining opportunistic infection that has been treated less than
             30 days prior to study entry

          -  Receipt of an investigational agent or chemotherapy for active malignancy within 30
             days prior to study entry

          -  Any clinically significant diseases (other than HIV infection) or clinically
             significant findings during the screening medical history or physical examination
             that, in the investigator's opinion, would compromise participation and the outcome of
             this study