Antiretrovirals and antimalarials: a deadly mix?

July 8, 2014 — Pierre Lutgen

At the 15th International Workshop on Clinical Pharmacology of HIV on May 19, 2014 at the University of Nebraska, FA Fehintola showed that nevirapine co-prescribed with artemether-lumefantrine may reduce the artemether concentration in blood by 70%.
This is in line with similar results obtained in South Africa by T Kredo (Antimicrob Agents Chemother. 2011 Dec; 55(12):5616-23). Artemether and nevirapine are metabolized by the cytochrome P450 3A4 enzyme system, which nevirapine induces. They conclude that studies investigating the interaction of nevirapine and artemether-lumefantrine in HIV-infected patients with malaria are urgently needed.
Pauline Byakik at Makerere University also found that co-administration of coartem (AL) with efavirenz resulted in reduction in artemether, DHA, lumefantrine exposure. (J Antimicrob Chemother 2012, 67, 2213-2221).

The antagonistic effect has not only been seen for artemisinin derivatives but also for quinine pharmacokinetics in pregnant women with Malaria-HIV Co-Infection (K Kayentao, Am J Trop Med Hyg. 2014 Mar;90(3):530-4).
Also for malarone frequently taken by European travellers. Lower atovaquone/proguanil concentrations have been found in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir (van Luin M1, AIDS. 2010 May 15;24(8):1223-6).
A good summary of these recent studies is given by Van Geertruyden JP. (Clin Microbiol Infect. 2014 Apr;20(4):278-85). Possible pathophysiological, clinical and epidemiological interactions between human immunodeficiency virus (HIV) and tropical pathogens, especially malaria parasites, constitute a concern in tropical areas. Two decades of research have shown that HIV-related immunosuppression is correlated with increased malaria infection, burden, and treatment failure, and with complicated malaria, irrespective of immune status. The recent role out of antiretroviral therapies and new antimalarials, such as artemisinin combination therapies, raise additional concerns regarding possible synergistic and antagonistic effects on efficacy and toxicity.

Already in 2006 F Nosten and U d’Alessandro had claimed that it was urgent to study drug interactions betweeen antimalarials and antiretrovirals, especially during pregnancy ( Curr Drug Saf 2006, Jan 1-15). Not much has been done until 2012.
But over the last decade millions of antimalarial and antiretroviral drugs for billions of dollars have been sold on the African market.
Cui bono ?

Comment by Valentine Lah
9 July 2014
I personally know so many HIV/AIDS patients under antiretroviral
therapy who keep drinking artemisia tea because they feel better and
stronger with it. I do not think that would have been the case if
there was a negative interaction between ARVs and natural Artemisia.

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