Know Cancer

forgot password

Therapeutic Drug Monitoring and Viral Resistance Testing in the Treatment of HIV-Infected Children

Phase 1
Not Enrolling
HIV Infections

Thank you

Trial Information

Therapeutic Drug Monitoring and Viral Resistance Testing in the Treatment of HIV-Infected Children

This is a single arm study to determine whether a novel dose adjustment strategy that
individualizes protease inhibitor dosing to maintain drug concentrations above
virologic-based threshold values (TDM) in pediatric patients with HIV is able to result in a
potentially clinically useful proportion of patients who achieve a targeted inhibitory
quotient (IQ). The study will consist of up to 34 children between 0 and 21 years of age
(minimum weight 10 kg). Patients will have viral resistance testing performed at baseline
and that information, combined with treatment history analysis and drug tolerability issues
will be used to design a combination antiretroviral regimen. After the new regimen is
started, pharmacokinetic monitoring will guide dose adjustments of protease inhibitors. An
algorithm will be followed to make dose adjustments based upon viral phenotype and drug
levels. The primary outcome measure will be the fraction of patients who attain adequate
protease inhibitor levels above target values. Secondary measures will include virologic
and immunologic benefits and evaluation of toxicity and tolerability.

Inclusion Criteria


HIV-infected children between the ages of 0 and 21 years

An indication for treatment with a PI containing antiretroviral regimen 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)

Age less than 12 months - regardless of clinical, immunologic, or virologic status

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 current treatment as defined by the 2001 Guidelines for the Use of
Antiretroviral Agents in Pediatric HIV Infection ( (one of the

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

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

A greater than 30 percentage decline in absolute CD4 cell count.

Progressive neurodevelopmental deterioration

Growth failure

Disease progression

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

HIV RNA greater than or equal to 5,000 copies per/ml within the past 3 months (may be from
outside institution).

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

Hematologic Function: Total WBC greater than 1,500/mm(3), Absolute Neutrophil Count
greater than 750/mm(3), hemoglobin greater than 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 to 3.0 times the upper
limit of normal; Lipase less than 1.5 times the upper limit normal; Creatine 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 70mL/min/1.73.


History of non-adherence that in the opinion of the PI or study chairperson makes it
unlikely that the patient will adhere to protocol.

Clinically significant, unrelated systemic illness (serious infections or significant
cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgement 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.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

March 2002

Completion Date:

April 2006

Related Keywords:

  • HIV Infections
  • Antiretrovirals
  • Adherence
  • Dose Adjustments
  • Genotypic Resistance
  • Phenotypic Resistance
  • HIV Infections
  • Acquired Immunodeficiency Syndrome



National Cancer Institute (NCI) Bethesda, Maryland  20892