Malaria prophylaxis

The interactions between antiretroviral drugs and drugs available for malaria prophylaxis as chloroquine, mefloquine, doxycycline, and Malarone™ (atova-quone/proguanil), are inadequately evaluated.

In healthy volunteers taking mefloquine (Lariam™) together with ritonavir, a 30 % reduction of the steady-state plasma level of ritonavir was reported; however, me-floquine did not change the ritonavir level after single dose of ritonavir (Khaliq 2001). The explanation is probably a reduced bile production caused by meflo-quine. No relevant interactions seem to occur if mefloquine is coadministered with nelfinavir or indinavir (Schippers 2000).

Chloroquine is metabolized by CYP2D6, but also significantly excreted by the kidneys; explicit data on interactions of chloroquine with HIV drugs are lacking. In vitro, chloroquine inhibits HIV replication and shows synergistic effects together with protease inhibitors (Savarino 2001 and 2004). If this observation or the immunosuppressive effect of chloroquine has an impact on the clinical management of HIV infection is yet uncertain.

Clinical data on the interactions of atovaquone and proguanil with HIV drugs are missing. In vitro data indicate that ritonavir causes a reduced level of atovaquone and an increased level of proguanil. Atovaquone decreases the indinavir level by 20 % and increases the aciclovir level by 30 %.

Doxycycline is not metabolized by the cytochrome P450 system. Thus, relevant interactions with HIV drugs are not anticipated.

Available data and clinical experience indicate that mefloquine as well as doxycycline and chloroquine can be safely and effectively used in patients taking antiretro-viral therapy. Although clinical studies are lacking, the same applies for Malarone™. Thus, recommendations for malaria prophylaxis are not limited by concomitant HIV medication.

Common drugs for malaria stand-by treatment are chloroquine, mefloquine, Ma-larone™, and Riamet™ (artemether/lumefantrine). Both components of Riamet™ are substrates of CPY3A4; due to incalculable increases in drug exposure, Riamet™ is contraindicated with protease inhibitors (see Riamet™ product information). With this exception, HIV patients should follow the same recommendations as healthy travelers. However, mefloquine is often unfavorable because of frequent neurological comorbidity in HIV patients.

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