Medikamente für Reisende mit HIV – Medikamenteninteraktionen unter einer HIV-Therapie

Interaktionen in der HIV-Therapie finden größtenteils an den Isoenzymen des Cytochromsystems in der Leber statt. Etwa die Hälfte aller Medikamente wird über das Isoenzym CYP 3A4 abgebaut. Proteasehemmer (PI) inhibieren das Isoenzym CYP 3A4, nicht nukleosidale reverse Transkriptase-Inhibitoren (NNRTI) induzieren das Enzym. Daraus ergeben sich vielseitige Interaktionen zwischen der Begleitmedikation und der antiretroviralen Therapie (ART).

Die Arzneistoffe Mefloquin, Chinin und Lumefantrin zur Malariaprohylaxe und -behandlung werden über CYP 3A4 metabolisiert. Ihr Abbau wird theoretisch von PI gehemmt beziehungsweise von NNRTI beschleunigt. Interaktionen fallen bei Mefloquin eher gering aus. Das Interaktionspotenzial von Chinin wird zurzeit evaluiert. Der Hersteller stuft Lumefantrin aufgrund fehlender Daten und theoretischer Überlegungen zu erhöhten Spiegeln unter PI als kontraindiziert ein. Für Atovaquon wird diskutiert, ob die Dosis unter Lopinavir/ Ritonavir, Atazanavir/Ritonavir und Efavirenz ausreichend ist.

Das Interaktionspotenzial der Antibiotika ist gering. Die meisten Antibiotika werden renal ausgeschieden. Antiretrovirale Substanzen, die hepatisch abgebaut werden, haben dagegen ein hohes Interaktionspotenzial. Interaktionen treten mit den Makrolidantibiotika auf: Clarithromycin ist mit Atazanavir aufgrund der QT-Prolongation kontraindiziert. Ansonsten sind für Clarithromycin und Erythromycin Spiegelschwankungen unter einem PI und NNRTI zu beachten. Für Clindamycin gibt es keine Daten. Azithromycin ist interaktionsarm.

The cytochrom system is a major place for drug metabolism. At its isoenzyms a large part of drug-drug interactions in HIV-therapy take place. Half of all drugs are metabolised via the isoenzym CYP 3A4 including Protease inhibitors (PI) and Non-Nucleosid-Reverse Transcriptase Inhibitors (NNRTI). PI inhibit the isoenzym CYP-3A4. Drug levels of all other drugs metabolised via CYP-3A4 are reduced and the risk of toxicity is increased. NNRTI induce CYP-3A4 and increase metabolism of co-medication. This may lead to subtherapeutic drug levels of co-medication. Antimalaria drugs like Mefloquine, Quinine and Lumefantrin are also metabolized via CYP 3A4. The literature does not report any clinically significant drug-drug interactions between Mefloquine and ART. Drug-drug interaction with Quinine and antiretroviral therapy (ART) are evaluated. Lumefantrin is contraindicated because of missing PK data and theoretical considerations about increased Lumefantrin levels with PI. Atovaquone is not contraindicated with ART but reduced Atovaquone levels with Efavirenz, Lopinavir/Ritonavir and Atazanavir/Ritonavir lead to a discussion for dose modification.

The potential of drug-drug interactions between ART and antibiotics is low. Most antibiotics are eliminated by the kidney. One exception is macrolide. Clarithromycin is contraindicated with Atazanavir concerning QT-prolongation. Fluctuation in drug levels of Clarithromycin and Erythromycin occur with PI and NNRTI. There are no data about drug-drug interactions of ART and Clindamycin. Azithromycin has a low potential of drug-drug interactions in HIV-therapy and is recommended.

Key words

HIV - drug-drug interactions - malaria drugs - antibiotics

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