Tenofovir Disoproxil Fumarate to Treat Pediatric HIV

NCT00024986 | Completed Phase 1

• 2 other identifiers: 02000602-C-0006
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test the safety, side effects and antiviral activity of different doses of tenofovir DF in children and adolescents with human immunodeficiency virus (HIV) infection. Tenofovir DF belongs to a group of drugs called nucleotide analog reverse transcriptase inhibitors. These drugs prevent the virus from replicating (making more copies of itself). HIV becomes resistant to many drugs used to fight the virus and these drugs become ineffective. In laboratory tests, tenofovir DF has remained effective against HIV longer than other anti-HIV medicines, and when resistance does develop, the virus may still be sensitive to other drugs. HIV-infected children between the ages of 4 and 18 years who weigh at least 10 kg (22 pounds) may be eligible for this study. They must be able to receive antiretroviral therapy and have completed at least two previous antiretroviral courses of treatment without benefit. Upon entering the study, participants will have physical, eye and neuropsychiatric examinations, blood tests, including tests to determine what anti-HIV drugs the patient is resistant to, an echocardiogram (echo), electrocardiogram (EKG), chest X-ray, head CT scan, skin tests, and special tests to examine the bones. These physical exams and tests will be repeated throughout the study to determine changes in health. Participants will continue their current anti-HIV therapy for 2 weeks and then stop all medicines for a 1-week 'washout' period. After the washout period, patients will begin taking tenofovir DF. For the first 2 days on the drug, a small blood sample (1/2 teaspoon) will be collected 11 times over a 48-hour period through. A heparin lock (a tube kept in place in a vein) may be put in place to avoid multiple needle sticks. Blood samples will be collected for another 4 days to measure how well tenofovir DF alone works against HIV before other drugs are added to the treatment regimen. After these first 6 days, at least two other anti-HIV drugs will be added. They will be selected based on the results of the earlier blood tests for resistance and on the child's medication history. After 3 days of combination therapy, patients will continue therapy on an outpatient basis. They will be seen in the clinic every 4 weeks at the start of the study and then every 12 weeks for physical exams, lab tests and other procedures as needed. The study will last approximately 48 weeks. Patients who benefit from therapy may be able to continue to receive tenofovir DF from the drug company sponsor or as part of another study, or the protocol for this study may be amended to lengthen the treatment period.

Conditions

HIV Infection

Keywords

HAART; Genotypic Resistance; Phenotypic Resistance; Immune Reconstitution; Bone Density; HIV; Children; Pediatric HIV Infection

Interventions

Tenofovir DF DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Palumbo PE, Raskino C, Fiscus S, Pahwa S, Fowler MG, Spector SA, Englund JA, Baker CJ. Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children. JAMA. 1998 Mar 11;279(10):756-61. doi: 10.1001/jama.279.10.756.

  PMID: 9508151 BACKGROUND

• Parkin NT, Lie YS, Hellmann N, Markowitz M, Bonhoeffer S, Ho DD, Petropoulos CJ. Phenotypic changes in drug susceptibility associated with failure of human immunodeficiency virus type 1 (HIV-1) triple combination therapy. J Infect Dis. 1999 Sep;180(3):865-70. doi: 10.1086/314928.

  PMID: 10438382 BACKGROUND

• Deeks SG, Hellmann NS, Grant RM, Parkin NT, Petropoulos CJ, Becker M, Symonds W, Chesney M, Volberding PA. Novel four-drug salvage treatment regimens after failure of a human immunodeficiency virus type 1 protease inhibitor-containing regimen: antiviral activity and correlation of baseline phenotypic drug susceptibility with virologic outcome. J Infect Dis. 1999 Jun;179(6):1375-81. doi: 10.1086/314775.

  PMID: 10228057 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 10, 2001
• First Posted: October 11, 2001
• Study Start: October 1, 2001
• Study Completion: September 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-09

Locations

US (1)