Prophylactic Activity Of Hiv-Protease Inhibitors Against Malaria And Their Interaction With Antimalarial In Male Mice

ABSTRACT

Malaria and HIV/AIDS have a wide geographical overlap in several tropical

regions. This makes co-infection of the two diseases very common. Due to

enhanced global coverage of antiretroviral drugs (ARVs), HIV/AIDS patients

are under ARVs including protease inhibitors (PIs). Just like HIV, malaria

parasite also depend on proteases in their life cycle. Therefore, PIs against

HIV could offer some level of antimalarial activity by targeting the parasite

proteases. This study sought to investigate the antimalarial activity of HIV PIs

and their interaction with antimalarial drugs in mice models. The effective

dose 50 (ED50) for three PIs ritonavir, saquinavir and nelfinavir and the

antimalarial drugs artemether and lumefantrine was assessed using Peter’s 4-

day suppressive test against Plasmodium berghei. Chemosupression was

assessed on day 7, 10 and 13 after antimalarial and PIs treatment. Prophylactic

activity was assessed 2h, 3h and 5h post drug administration (pda). Interaction

of PIs with artemether and lumefantrine was also determined using the

suppression test. The ED50 was calculated using regression equation in

statistica software version 12.5. Student’s t-test was used to compare the mean

parasitaemia of the control and treatment groups. Drug interaction data was

analysed using one-way ANOVA and Tukey’s test. The analysis were done

using SPSS version 22. Artemether, lumefantrine, ritonavir, saquinavir and

nelfinavir had ED50 values of 1.04, 1.67, 3.84, 4.86 and 4.92 mg/kg,

respectively. Antimalarial drugs had significant (p < 0.05) chemosuppression

activity throughout and lumefantrine was more effective (67.7% - 84.5%) than

artemether (24.5% - 73.6%). For PIs, on day 10 pi, ritonavir had significant (p

< 0.05) antimalarial activity (24.5%) as compared to saquinavir (13.3%) and

nelfinavir (9.8%). For prophylactic activity ritonavir and nelfinavir had

significant (p < 0.05) parasitaemia suppression at 3h pda while for saquinavir

it was 5h pda. Drug interaction studies indicated that drug combination were

more effective than stand-alone but the suppression was only significant (p