Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Control Trial of Early vs Delayed ART in the Treatment of Cryptococcal Meningitis.
Brief Summary: Cryptococcal Meningitis continues to be one of the most devastating AIDS defining illness in sub-Saharan Africa. Despite the availability of azoles such as fluconazole for treatment, mortality remains high with some studies showing 100% mortality. The investigators designed a study to determine if timing of the initiation of antiretroviral therapy (ART) in patients with cryptococcal meningitis and HIV would improve survival. The investigators hypothesis was that early initiation of ART result in improved mortality for patients with HIV and cryptococcal meningitis.


Options:
A: Inclusion Criteria:

* HIV-infection, documented by ELISA
* Antiretroviral medication naïve (excluding mother-to-child transmission therapy)
* Age \>14 years
* Cryptococcal meningitis diagnosed by either culture or CSF cryptococcal antigen (CRAG)
* Ability and willingness of the participant or legal guardian/representative to give informed consent.
* Receiving amphotericin-based anti-fungal therapy

Exclusion Criteria:

* Study entry prior to receipt of \<7 days or \>11 days of amphotericin therapy
* History of prior, known cryptococcal meningitis
* Inability to take enteral medication
* Receiving chemotherapy or other immunosuppressant medications
* Cannot or unlikely to attend regular clinic visits
* Contraindication to immediate or delayed HIV therapy based on serious co-morbidities or co-infections, or laboratory values
* Pregnancy or Breastfeeding
* Female participants of childbearing potential who are participating in sexual activity that could lead to pregnancy must agree to use two reliable methods of contraception
B: INCLUSION CRITERIA:

* Signed informed consent
* HIV infection documented by a plasma HIV RNA viral load, rapid HIV test or any licensed\* ELISA test; and confirmed by another test using a different method including but not limited to a rapid HIV test, Western Blot, HIV culture, HIV antigen, or HIV pro-viral DNA at any time prior to study entry.
* Age greater than or equal to 18 years
* Karnofsky performance score greater than or equal to 80 (an indication that the participant can perform normal activities)
* Perceived life expectancy of at least 6 months
* For women of child-bearing potential, willingness to use contraceptives as described in the product information of the ART drugs they are prescribed
* Two CD4+ cell counts greater than 500 cells/mm(3) at least 2 weeks apart within 60 days before randomization

  * The term licensed refers to an FDA-approved kit or, for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country. Confirmation of the initial test result must use a test method that is different than the one used for the initial assessment.

EXCLUSION CRITERIA:

* Any previous use of ART or interleukin-2 (IL-2)
* Diagnosis of any clinical AIDS event before randomization (including esophageal candidiasis and chronic Herpes simplex infection)
* Presence of HIV progression such as oral thrush, unexplained weight loss, or unexplained fever
* Cardiovascular event (myocardial infarction, angioplasty, coronary-artery bypass grafting, stroke) within 6 months before randomization
* Non-AIDS-defining cancer, excluding basal and squamous cell skin cancer, within 6 months before randomization
* Dialysis within 6 months before randomization
* Diagnosis of decompensated liver disease before randomization
* Current imprisonment, or compulsory detention (involuntary incarceration) for treatment of a psychiatric or physical illness
* Current pregnancy or breastfeeding (a negative serum or urine pregnancy test is required within 14 days before randomization for women of child-bearing potential)
C: Note: Participants who enrolled in this study prior to Version 3.0 will be offered and allowed to switch to FTC/TDF if they wish. However, participants under the age of 18 cannot receive FTC/TDF through this study.

Inclusion Criteria for Step 1:

* HIV-1 infected
* Currently being treated for OI (including Pneumocystis carinii pneumonia \[PCP\]; cryptococcal meningitis; disseminated histoplasmosis; disseminated Mycobacterium avium complex \[MAC\]; cytomegalovirus \[CMV\] retinitis; CMV encephalitis; toxoplasmic encephalitis; other atypical non-tuberculous, non-MAC mycobacterial infections; or other serious, invasive BIs). Participants who have tuberculosis (TB) alone are ineligible for this study. Participants with bacterial pneumonia or serious BI must have a CD4 count less than 200 cells/mm3 within 30 days prior to study entry. Participants with other serious OIs, including other AIDS-defining and -related OIs for which appropriate therapy other than ART exists are eligible, pending investigator approval. Participants' current OI treatment must have been started within 14 days prior to study entry, but may have been discontinued prior to study entry.
* Able to take oral medications
* Parent or guardian willing to provide informed consent, if applicable
* Willing to use acceptable methods of contraception

Exclusion Criteria for Step 1:

* Any ART within 8 weeks prior to study entry
* 31 or more days of any ARV within 6 months prior to entry
* History of more than one virologic, immunologic, or clinical treatment failure while on a HAART regimen, or a history of more than one regimen change for unknown reasons
* Systemic cancer chemotherapy within 30 days prior to study entry
* Immunomodulators within 30 days prior to study entry, including growth factors, immune globulin, interleukins, and interferons (unless for hepatitis C virus or Kaposi's sarcoma)
* Investigational ARV agents at study entry
* Systemic investigational agents (except ARV drugs) within 30 days prior to study entry will be allowed at the study official's discretion
* Anticipated use of certain medications
* Kidney failure requiring dialysis
* Current drug or alcohol use that, in the opinion of the study official, would interfere with the study
* Treatment for current, first-treated, and diagnosed OI or BI for more than 14 days prior to study entry
* Known resistance to ART that prohibits administration of an effective ART regimen
* Current OI has recurred within 90 days prior to study entry. Recurrent BIs are not excluded.
* Pregnant or breastfeeding
D: Inclusion Criteria:

* HIV infection documented by a positive HIV antibody test at enrollment;
* Adult men and women (age\>18);
* Cryptococcal meningitis infection documented by a positive CSF CRAG or CSF identification of C. neoformans.
* Place of residence is located within a 50km radius of Harare.

Exclusion Criteria:

* Previous diagnosis (\>1 week) of and treatment for cryptococcal meningitis
* Currently on ARVs, or have been intermittently on and off ART in the past.
* Concurrent use of medications that affect the metabolism of fluconazole e.g., antiseizure medications, oral hypoglycaemic agents.
* History of cardiac failure and or predisposition to arrhythmias will be excluded.
* They are pregnant or active lactation women
* History of active hepatitis or hepatic or renal dysfunction will be excluded.

Answer: D