Pharmacokinetic Interaction between Antiretroviral and Cytotoxic therapy in HIV-infected patients - a pilot study

Due to an increased number of treatments with antineoplastic agents in
HIV-infected patients over the past decade, the urge to investigate drug-drug
interactions between cytotoxic and antiretroviral agents has become relevant.
As yet, there is little knowledge about the effects of NNRTIs and PIs on the
pharmacokinetics of the antineoplastic therapy and visa versa. The proposed
mechanism of such interactions is that NNTRIs and PIs induce or inhibit
respectively the CYP-enzymes and P-pg transporters, which results in altered
pharmacokinetics of the antineoplastic agents. This may lead to an altered
exposure and/or altered toxicity of the antineoplastic drug, which could be
clinical relevant because PK/PD correlations are found between antineoplastic
levels and the efficacy and toxicity. Thus far, no dose or HAART adjustments
are described for HIV-infected patients treated with antineoplastic agents and
HAART. Therefore, measuring serum levels of possibly affected drugs
(cyclophosphamide, etoposide, vinblastine and vincristine and their
metabolites) seems to be a fair surrogate parameter to monitor the efficacy
and/or toxicity of the antineoplastic therapy in the presence and absence of
NNRTIs and/or PIs.

1º Is there a significant difference of more than 10% in the pharmacokinetic
parameter AUC of the investigated antineoplastic drugs (as a surrogate
parameter for the efficacy) in the presence and absence of NNRTIs and/or PIs?
2º Are there clinically significant differences in toxicity of the investigated
antineoplastic drugs (measured by questionnaires and laboratory values) due to
drug-drug interactions between antineoplastic drugs, PIs and NNRTIs? Are dose
adjustments necessary for investigated antineoplastic drugs used in patients
co-treated with PI- or NNTRI-based HAART? And/or, is it necessary to avoid PIs
and NNTRIs when patients are treated with antineoplastic drugs?

A randomized, observational, crossover controlled clinical pilot study.

Patients will not have advantages of participation at this study. Patients will
temporarily switch of their regular HAART to II-based HAART. Theoretically,
II-based HAART has no interaction with antineoplastic agents and therefore the
chemotherapy will be the most optimal therapy, but it will be a switch of their
patient-tailored anti-HIV therapy. II-based HAART is generally well tolerated.
Switching or not-switching may either benefit or harm for this patient group. A
disadvantage of participation will be the extra blood drawing, which will be
per occurrence 6 extra tubes (approx. 40ml) and filling in the questionnaires.
The antineoplastic treatment of the patient shall not be changed by inclusion
in this study.