Please select the eligibility criteria that correspond to the clinical trial below.
Title: Urgent Versus Post-Stabilization ART in HIV-1 Infected Children With Severe Co-Infections
Brief Summary: Design: Randomized clinical trial involving hospitalized HIV-1 infected children. Children will be randomized to randomized to urgent (\<48 hours) versus early antiretroviral therapy (7-14 days). This trial will be unblinded.

Population: Hospitalized HIV-1 infected children who are antiretroviral therapy (ART) naïve ≤ 12 years of age.

Sample size: 360 children will be randomized (180 per arm).

Treatment: All infants will be treated with ART according to World Health Organization (WHO) and Kenyan national guidelines.

Study duration: Enrollment into the study will occur over the course of 36-48 months and each infant will be routinely followed for a maximum of 6 months.

Study site: Kenyan hospitals.

Primary hypothesis:

HIV-1 infected children hospitalized with severe co-infection either may be unsalvageable due to too far advanced immunosuppression/co-infection or may benefit from urgent ART.

Secondary hypotheses:

Urgent ART during an acute infection could potentially result in increased risk of immune reconstitution inflammatory syndrome (IRIS) or drug toxicities/interactions.

Specific aims:

1. To compare the 6 month all-cause mortality rate, incidence of immune reconstitution inflammatory syndrome (IRIS), and incidence of drug toxicity in HIV-1 infected children (≤ 12 years old) presenting to hospital with a serious infection randomized to urgent (\<48 hours) versus early ART (7-14 days).
2. To determine co-factors for mortality, IRIS, and drug toxicity. Potential cofactors will include: baseline weight-for-age, height-for-age, weight-for-height (Z-scores), CD4, HIV-1 RNA, type of co-infection, age, rate of viral load and CD4 change following ART, immune activation markers, pathogen and HIV-1 specific immune responses.

Secondary aim: To determine etiologies of IRIS and to compare immune reconstitution to HIV, TB, EBV and CMV following ART overall and in each trial arm.


Options:
A: Inclusion Criteria:

* Aged ≤ 12 years old (reported)
* HIV-1 positive (for example, two rapid HIV-1 antibody tests for children \>18 months and not breastfeeding, or one HIV-1 DNA/RNA test for children ≤18 months or who are breastfeeding)
* Not currently receiving antiretroviral therapy (history of pMTCT does not affect eligibility)
* Eligible to receive ART, according to current WHO guidelines
* Caregiver plans to reside in study catchment area for at least 6 months (reported)
* Caregiver provides sufficient locator information

Exclusion Criteria:

* Suspected meningitis, any other central nervous system infection, or encephalitis
B: Inclusion Criteria:

* Age ≥18 years;
* HIV-1 infection as documented at any time prior to trial entry, as per national testing procedures;
* CD4 \<100 cells/mm3;
* No history of antiretroviral drug use (except transient ART for PMTCT);
* Able to correctly understand the trial and to sign the informed consent.

Exclusion Criteria:

* HIV-2 co-infection;
* Contra-indication to efavirenz;
* Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>5 times the upper limit of normal;
* Creatinine clearance \<50 ml/min;
* Overt evidence that TB treatment should be started immediately;
* History of TB treatment in the past 5 years;
* Ongoing TB chemoprophylaxis (isoniazid preventive therapy);
* Any condition that would lead to differ ART initiation (e.g. acute condition requiring investigations and/or treatment prior to ART initiation);
* Current pregnancy or breastfeeding.
C: Inclusion criteria:

1. Children aged 2 to 59 months
2. Newly hospitalized for severe pneumonia defined using WHO criteria as cough or difficulty in breathing with:

   1. Peripheral oxygen saturation \< 90% or central cyanosis, or
   2. Severe respiratory distress (e.g. grunting, nasal flaring, very severe chest indrawing), or
   3. Signs of pneumonia, defined as cough or difficulty in breathing with fast breathing (tachypnea) and/or chest indrawing, with any of the following danger signs:

      * Inability to breastfeed or drink,
      * Persistent vomiting
      * Lethargy or reduced level of consciousness
      * Convulsions,
      * Stridor in calm child
      * Severe malnutrition
3. Informed consent signed by parent/guardian

Exclusion criteria:

- Ongoing TB treatment or history of intake of anti-TB drugs in the last 6 months
D: Inclusion Criteria:

All HIV-infected men and women \> 18 years of age with newly diagnosed HIV at the 12 study clinics will be asked to participate in the study.

Exclusion Criteria:

* Patients will be excluded from participation if they have a current diagnosis of TB and/or if they are currently taking IPT, TB treatment and/or ART.
* Patients will also be excluded from participation if they cannot speak English or Chichewa;
* if they have a language or hearing impairment; or
* if they are prisoners.

Answer: A