Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double Blind, Placebo Controlled Trial to Determine the Efficacy of Isoniazid (INH) in Preventing Tuberculosis Disease and Latent Tuberculosis Infection Among Infants With Perinatal Exposure to HIV
Brief Summary: Tuberculosis (TB) is highly endemic in sub-Saharan Africa. The increased burden of TB in settings with high prevalence of the Human Immunodeficiency Virus (HIV) is associated with high rates of transmission of Mycobacterium tuberculosis (M.tb) to both adults and children. Children infected with TB have a higher risk of developing severe disease than adults with TB. The purpose of this study was to determine if the antibiotic isoniazid (INH) prevented TB infection in infants born to HIV-infected mothers.


Options:
A: Inclusion Criteria:

1. HIV-infected
2. Age \>=18 years
3. Tuberculin skin test positive or negative
4. Laboratory:

   * Hemoglobin (Hgb) \>6.5 gm/dl;
   * Neutrophil count \>1,000 cells/mm3;
   * Platelets \>75,000/mm3;
   * AST (SGOT) \<122 U/L;
   * Creatinine \<1.5 mg/dl;
   * Beta HCG = negative
5. Karnofsky performance status \>=60
6. Signed informed consent

Exclusion Criteria:

1. History of TB in the last 3 years or current active TB
2. History of noncompliance to chronic therapies
B: Inclusion Criteria:

* patients with positive TST and the suitable criteria for treatment, in accordance with the guidelines of the CDC:

Exclusion Criteria:

* HIV infection.
* Hepatopathy
* Previous treatment of of latent tuberculosis infection.
* Allergy to drugs.
C: INCLUSION criteria:

* Males or nonpregnant, non-nursing females \> 2 years old.
* Tuberculin (PPD) skin test reactors at high risk for developing TB but without evidence of active TB. High-risk reactors are defined as:

  1. Household and other close contacts of persons with culture-confirmed TB who are TST-positive as part of a contact investigation conducted within two years of the date of enrollment. Close contact is defined as \> 4 hours in a shared airspace during a one-week period. Among close contacts, a positive TST is defined as \> 5 mm induration after 5 TU of PPD placed intradermally using the Mantoux technique.
  2. TST converters--converting from a documented negative to positive TST within a two-year period. This is defined as persons with a tuberculin skin test of \> 10 mm within two years of a nonreactive test or persons with an increase of \> 10 mm within a two-year period.
  3. HIV-seropositive, TST positive (\> 5 mm induration) persons.
  4. Persons with \> 2 cm2 of pulmonary parenchymal fibrosis on chest X-ray, no prior history of TB treatment, \> 5 mm induration on TST, and 3 sputum cultures negative for M. tuberculosis on final report.
* HIV-seropositive close contacts of persons with culture-confirmed TB, regardless of TST status. In addition, HIV-seropositive close contacts of persons with culture-confirmed TB who have a documented history of completing an adequate course of treatment for active TB or latent TB infection, are also eligible.
* Willing to provide signed informed consent, or parental consent and participant assent.

EXCLUSION criteria:

* Current confirmed culture-positive or clinical TB
* Suspected TB (as defined by the site investigator)
* Tuberculosis resistant to isoniazid or rifampin in the source case
* A history of treatment for \> 14 consecutive days with a rifamycin or \> 30 consecutive days with INH during the previous 2 years.
* A documented history of a completing an adequate course of treatment for active TB or latent TB infection in a person who is HIV-seronegative.
* History of sensitivity/intolerance to isoniazid or rifamycins
* Serum aminotransferase aspartate (AST, SGOT) \> 5x upper limit of normal among persons in whom AST is determined
* Pregnant or nursing females
* Persons currently receiving or planning to receive HIV-1 protease inhibitors or nonnucleoside reverse transcriptase inhibitors in the first 90 days after enrollment.
* Weight \< 10.0 kg
D: Inclusion Criteria:

* Mother is HIV-infected. Hard copy documentation of the mother's HIV infection is unnecessary if a positive DNA PCR from her infant is available.
* Received Bacille Calmette-Guerin (BCG) vaccine up to and including the 30th day of life and at least 90 days prior to study entry
* Able to complete all study requirements
* Physician assessment of age-appropriate neurodevelopment in which the chronological age is corrected for gestational age for prematurely born infants
* Parent or legal guardian able and willing to provide signed informed consent
* Plan to live in the study area for at least 4 years
* For inclusion in HIV-infected stratum, infant must have a positive HIV-1 DNA PCR; for inclusion in HIV-uninfected stratum, infant must have a negative HIV-1 DNA PCR performed at \>= 4 weeks of age

Exclusion Criteria:

* Previous diagnosis of TB infection, TB disease or current treatment for TB infection or TB disease
* Previous receipt of INH
* Contact with a known acid fast bacilli (AFB) sputum smear or culture-positive case of TB before study entry
* Current acute or recurrent (3 or more prior episodes) lower respiratory tract disease
* Chronic persistent diarrhea
* Failure to thrive
* Contraindications for use of INH or TMP/SMX
* Require certain medications
* Known or suspected immune system diseases other than HIV
* Current or previous diagnosis of or treatment for cancer
* Current immunosuppressive therapy greater than 1 mg/kg/day of prednisone or equivalent
* Anticipated long-term oral or intravenous corticosteroid therapy (greater than 3 weeks). Those receiving nonsteroidal anti-inflammatory agents and inhaled corticosteroids are not excluded.
* Grade 3 or greater AST/SGOT, ALT/SGPT, ANC, hemoglobin, platelet count, rash, neuropathy, or myopathy at screening
* Any Grade 4 clinical or laboratory toxicity within 14 days prior to study entry
* Other acute or chronic conditions that, in the opinion of the investigator, may interfere with the study

Answer: D