The frequency of malaria is similar among women receiving either lopinavir/ritonavir or nevirapine-based antiretroviral treatment

Tina S Skinner-Adams, Alice S Butterworth, Kimberly A Porter, Ronald D'Amico, Fred Sawe, Doug Shaffer, Abraham Siika, Mina C Hosseinipour, Elizabeth Stringer, Judith S Currier, Tsungai Chipato, Robert Salata, Shahin Lockman, Joseph J Eron, Steven R Meshnick, James S McCarthy, Tina S Skinner-Adams, Alice S Butterworth, Kimberly A Porter, Ronald D'Amico, Fred Sawe, Doug Shaffer, Abraham Siika, Mina C Hosseinipour, Elizabeth Stringer, Judith S Currier, Tsungai Chipato, Robert Salata, Shahin Lockman, Joseph J Eron, Steven R Meshnick, James S McCarthy

Abstract

HIV protease inhibitors (PIs) show antimalarial activity in vitro and in animals. Whether this translates into a clinical benefit in HIV-infected patients residing in malaria-endemic regions is unknown. We studied the incidence of malaria, as defined by blood smear positivity or a positive Plasmodium falciparum histidine-rich protein 2 antigen test, among 444 HIV-infected women initiating antiretroviral treatment (ART) in the OCTANE trial (A5208; ClinicalTrials.gov: NCT00089505). Participants were randomized to treatment with PI-containing vs. PI-sparing ART, and were followed prospectively for ≥48 weeks; 73% also received cotrimoxazole prophylaxis. PI-containing treatment was not associated with protection against malaria in this study population.

Conflict of interest statement

Competing Interests: RDS is employed by Abbot Pharmaceuticals, the funder of this study. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors.

References

    1. Pisell TL, Hoffman IF, Jere CS, Ballard SB, Molyneux ME, et al. Immune activation and induction of HIV-1 replication within CD14 macrophages during acute Plasmodium falciparum malaria coinfection. Aids. 2002;16:1503–1509.
    1. Whitworth JA, Hewitt KA. Effect of malaria on HIV-1 progression and transmission. Lancet. 2005;365:196–197.
    1. Dooley KE, Flexner C, Andrade AS. Drug interactions involving combination antiretroviral therapy and other anti-infective agents: repercussions for resource-limited countries. J Infect Dis. 2008;198:948–961.
    1. German P, Greenhouse B, Coates C, Dorsey G, Rosenthal PJ, et al. Hepatotoxicity due to a drug interaction between amodiaquine plus artesunate and efavirenz. Clin Infect Dis. 2007;44:889–891.
    1. Abu-Raddad LJ, Patnaik P, Kublin JG. Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science. 2006;314:1603–1606.
    1. Otieno RO, Ouma C, Ong'echa JM, Keller CC, Were T, et al. Increased severe anemia in HIV-1-exposed and HIV-1-positive infants and children during acute malaria. Aids. 2006;20:275–280.
    1. Skinner-Adams TS, McCarthy JS, Gardiner DL, Hilton PM, Andrews KT. Antiretrovirals as antimalarial agents. J Infect Dis. 2004;190:1998–2000.
    1. Redmond AM, Skinner-Adams T, Andrews KT, Gardiner DL, Ray J, et al. Antimalarial activity of sera from subjects taking HIV protease inhibitors. Aids. 2007;21:763–765.
    1. Andrews KT, Fairlie DP, Madala PK, Ray J, Wyatt DM, et al. Potencies of human immunodeficiency virus protease inhibitors in vitro against Plasmodium falciparum and in vivo against murine malaria. Antimicrob Agents Chemother. 2006;50:639–648.
    1. Skinner-Adams TS, McCarthy JS, Gardiner DL, Andrews KT. HIV and malaria co-infection: interactions and consequences of chemotherapy. Trends Parasitol. 2008;24:264–271.
    1. Nathoo S, Serghides L, Kain KC. Effect of HIV-1 antiretroviral drugs on cytoadherence and phagocytic clearance of Plasmodium falciparum-parasitised erythrocytes. Lancet. 2003;362:1039–1041.
    1. Lockman S, Hughes MD, McIntyre J, Zheng Y, Chipato T, et al. Antiretroviral therapies in women after single-dose nevirapine exposure. N Engl J Med. 2010;363:1499–1509.
    1. Bell D, Wongsrichanalai C, Barnwell JW. Ensuring quality and access for malaria diagnosis: how can it be achieved? Nat Rev Microbiol. 2006;4:682–695.
    1. Iqbal J, Siddique A, Jameel M, Hira PR. Persistent histidine-rich protein 2, parasite lactate dehydrogenase, and panmalarial antigen reactivity after clearance of Plasmodium falciparum monoinfection. J Clin Microbiol. 2004;42:4237–4241.
    1. Swarthout TD, Counihan H, Senga RK, van den Broek I. Paracheck-Pf accuracy and recently treated Plasmodium falciparum infections: is there a risk of over-diagnosis? Malar J. 2007;6:58.
    1. Mermin J, Ekwaru JP, Liechty CA, Were W, Downing R, et al. Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study. Lancet. 2006;367:1256–1261.
    1. Peatey CL, Andrews KT, Eickel N, Macdonald T, Butterworth AS, et al. Antimalarial asexual stage-specific and gametocytocidal activity of HIV protease inhibitors. Antimicrob Agents Chemother 2009
    1. Skinner-Adams TS, Andrews KT, Melville L, McCarthy J, Gardiner DL. Synergistic interactions of the antiretroviral protease inhibitors saquinavir and ritonavir with chloroquine and mefloquine against Plasmodium falciparum in vitro. Antimicrob Agents Chemother. 2007;51:759–762.
    1. Lucia MB, Golotta C, Rutella S, Rastrelli E, Savarino A, et al. Atazanavir inhibits P-glycoprotein and multidrug resistance-associated protein efflux activity. J Acquir Immune Defic Syndr. 2005;39:635–637.
    1. Soyinka JO, Onyeji CO, Omoruyi SI, Owolabi AR, Sarma PV, et al. Pharmacokinetic interactions between ritonavir and quinine in healthy volunteers following concurrent administration. Br J Clin Pharmacol. 2010;69:262–270.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa