A Pharmacokinetic (PK) Study of a Combination of Indinavir, Ritonavir, and Amprenavir
Status:
Completed
Trial end date:
2007-01-01
Target enrollment:
Participant gender:
Summary
When individuals who are infected with HIV are started on treatment with HIV medications, the
effect of these drugs only lasts for a limited period of time, often because of development
of drug resistance by the HIV virus. When this happens, such patients have to be switched to
different combinations of HIV medications. However, since the availability of new HIV drugs
that are active against resistant virus is limited, HIV care providers are resorting to
curtail medications that contain three or more protease inhibitors (PIs). The reason for this
is Norvir (ritonavir), a PI that has the ability to boost or increase the blood levels of
other PIs in a way that can sometimes overcome the resistance of HIV virus. In addition, it
may be more difficult for the virus to overcome two or more drugs with high blood levels,
than it is to overcome just one. For these reasons, many clinicians are now using Norvir in
combination with two other PIs, including Crixivan (indinavir) plus Lexiva (fosamprenavir),
for treating patients who have been exposed to many other HIV medications.
While this may be the case, researchers also know that when two or more PIs are combined, the
effects each drug may have on the blood level of other drugs could be different. For example,
researchers know from some recent studies that the combination of Norvir, Lexiva, and
Kaletra, another PI, leads to an unacceptably low level of both Kaletra and Lexiva. Because
researchers can not always assume that when multiple HIV medications are combined, the levels
will remain high enough to be effective, the investigators think it will always be reasonable
that, before any combination of drugs are used on HIV-infected patients, the effect a
combination has on the levels of each of the drugs in the combination should be investigated.
AIMS: The aim of this pilot study therefore is to examine the blood levels of Crixivan,
Lexiva, and Norvir when these three drugs are used together as part of a combination
treatment for HIV infection.
METHODS: Fifteen (15) HIV-infected volunteers already being treated with a Crixivan and
Norvir containing regimen will be recruited from the Grady Infectious Disease Clinic (IDP).
Lexiva will be added to this regimen for 5 days, at the end of which participants will be
admitted to the Grady General Clinical Research Center (GCRC) where blood samples will be
collected at 9 different time points over 12 hours for measurement of blood drug levels.
Pharmacokinetic Analysis: The blood concentrations of Crixivan, Lexiva, and Norvir will be
measured by a special technique known as reverse-phase high-performance liquid chromatography
with ultraviolet detection.
Statistical Analysis: The blood level information will be summarized by a statistical method.
The researchers will then compare the levels of Lexiva in this combination with historically
published levels of Lexiva in a study of Lexiva plus Norvir; and that of Crixivan in a study
of Crixivan plus Norvir. A difference of 30% or more in drug levels between this study and
historical reports will be considered a significant difference.