Tenofovir Disoproxil Fumarate to Treat Pediatric HIV

INCLUSION CRITERIA

HIV-infected children between the ages of 4 years and less than 18 years.

BSA greater than or equal to 0.50 (m(2))

An indication for treatment with antiretrovirals as defined by the 2001 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (one of the following):

Clinical symptoms associated with HIV infection (i.e., clinical categories A, B, or C);

Evidence of immune suppression indicated by CD4 T-lymphocyte count or percentage (i.e., immune category 2 or 3);

High or increasing HIV RNA copy number;

Rapidly declining CD4 T-lymphocyte number or percentage to values approaching those indicative of moderate immune suppression (i.e., immune category 2).

Children failing at least their second antiretroviral regimen as defined by the 2001 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (http://www.hivatis.org/) (one of the following):

Less than a 10-fold decrease from baseline viral load in patients on a HAART regimen (combination regimen that includes a PI and/or NNRTI) after 8-12 weeks of therapy;

Less than a 5-fold decrease in viral load from baseline in patients on non-HAART regimen (e.g., dual NRTI combinations);

Viral load not suppressed to undetectable levels after 4-6 months of antiretroviral therapy;

Repeated detection of HIV RNA in patients who initially responded to antiretroviral therapy with undetectable levels;

An increase in viral load of greater than 3-fold;

Change in immunologic classification;

For children in immunologic category 3, a decline of five percentiles or more in CD4 cell percentage;

A greater than 30% decline in absolute CD4 cell count;

Progressive neurodevelopmental deterioration;

Disease progression;

Intolerant to or showing evidence of toxicity from other antiretroviral treatments.

HIV RNA greater than or equal to 10,000 copies/mL within the past 3 months (may be from outside institution);

Ability to swallow tablets.

Sexually active patients must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.

Hematologic function: Total WBC greater than 1,500/mm(3), Absolute Neutrophil Count greater than 750/mm(3), hemoglobin greater 8.0 gm/dL and platelet count greater than 75,000/mm(3) at study entry.

Hepatic function: Liver transaminases must be less than or equal 3.0 times the upper limit of normal; lipase less than 1.5 times the upper limit of normal; Creatinine phosphokinase (CPK) less than 2.5 times the upper limit of normal.

Renal function: patients must have an age-adjusted normal serum creatinine OR a creatinine clearance greater than or equal to 70 mL/min/1.73.

Informed Consent: All patients or one of their parents or legal guardians (if the patient is less than 18 years old) must sign the study informed consent to document their understanding of the investigational nature and the risks of the study before any protocol-related studies are performed.

EXCLUSION CRITERIA

Therapeutic regimens including:

• Nephrotoxic agents: aminoglycoside antibiotics, IV amphotericin B, cidofovir, cisplatin, foscarnet, IV pentamidine, oral and IV vancomycin, oral and IV ganciclovir;
• Immunomodulating agents (within 30 days of entry), other than GCSF, erythropoeitin, corticosteroids, IVIG, or anti-D;
• Treatment with chemotherapeutic agents (including hydroxyurea) or radiation therapy within the past 6 weeks; or
• Current use, or use within the last 28 days, of any investigational agent.

Clinically significant, unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the Principal Investigator or Chairperson would compromise the patient's ability to tolerate this therapy or is likely to interfere with the study procedures or results

Weight less than 10 kg

Pregnant or breast feeding females will be excluded from this trial. Women of childbearing potential must be willing to agree to avoid becoming pregnant while on study and for 4 months afterwards.