Efficacy of artemisinin-based combination therapy (ACT) in people living with HIV (PLHIV) diagnosed with uncomplicated Plasmodium falciparum malaria in Africa: a WWARN systematic review.

Publisher: BioMed Central Country of Publication: England NLM ID: 101139802 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2875 (Electronic) Linking ISSN: 14752875 NLM ISO Abbreviation: Malar J Subsets: MEDLINE

Original Publication: London : BioMed Central, [2002-

Malaria, Falciparum*/drug therapy ; Antimalarials*/therapeutic use ; HIV Infections*/drug therapy ; HIV Infections*/complications ; Artemisinins*/therapeutic use; Humans ; Africa/epidemiology ; Drug Therapy, Combination ; Treatment Outcome ; Plasmodium falciparum/drug effects ; Drug Combinations

Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
Background: Africa bears the highest double burden of HIV and malaria worldwide. In 2023, an estimated 25.9 million people were living with HIV (PLHIV), and 246 million malaria cases were diagnosed in Africa. Malaria patients co-infected with HIV are considered at a higher risk of failing malaria treatment, according to the World Health Organization (WHO) guidelines. This systematic literature review aims to assess the treatment outcomes following artemisinin-based combination therapy (ACT) in PLHIV.
Methods: The literature search was conducted up to April 2022 in the following databases: MEDLINE, EMBASE, Web of Science, Cochrane Central, WHO Global Index Medicus, Clinicaltrials.gov, and the WorldWide Antimalarial Resistance Network (WWARN) Clinical Trial Library. Studies describing any malaria treatment outcomes or anti-malarial drug exposure in PLHIV treated for uncomplicated Plasmodium falciparum malaria infection were eligible for inclusion.
Results: A total of 26 articles describing 19 studies conducted between 2003 and 2017 in six countries were included in this review; it represented 2850 malaria episodes in PLHIV across various transmission settings. The most studied artemisinin-based combination was artemether-lumefantrine (in 16 studies). PLHIV were treated with various antiretroviral therapy (ART) regimens, namely efavirenz (EFV), nevirapine (NVP), atazanavir-ritonavir (ATVr), lopinavir-ritonavir (LPV/r), and/or on prophylaxis with trimethoprim-sulfamethoxazole (TS), or were untreated (in 3 studies). There was no evidence of an increased risk of recrudescence in PLHIV compared to those without HIV. When treated with artemether-lumefantrine, PLHIV receiving LPV/r had a lower risk of malaria recurrence compared to PLHIV on NVP-based or EFV-based ART, or those without HIV. LPV/r increased lumefantrine exposure and EFV-treated patients had a reduced exposure to both artemether and lumefantrine; NVP reduced artemether exposure only.
Conclusions: Limited data on ACT outcomes or drug exposure in PLHIV in Africa remains a reality to date, and the effect of antivirals appears inconsistent in the literature. Considering the heterogeneity in study designs, these review's findings support conducting an individual patient data meta-analysis to explore the impact of antiretroviral therapy on anti-malarial treatment.
Trial Registration: The protocol for the original search was published on PROSPERO with registration number CRD42018089860.
(© 2025. The Author(s).)

PLOS Glob Public Health. 2023 Dec 1;3(12):e0002059. (PMID: 38039291)
Antimicrob Agents Chemother. 2013 Sep;57(9):4146-50. (PMID: 23774430)
PLoS One. 2017 Oct 24;12(10):e0186589. (PMID: 29065172)
Antimicrob Agents Chemother. 2018 Sep 24;62(10):. (PMID: 30082286)
J Acquir Immune Defic Syndr. 2009 Aug 1;51(4):424-9. (PMID: 19506482)
BMC Med Res Methodol. 2005 Apr 20;5:13. (PMID: 15840177)
Antimicrob Agents Chemother. 2020 Apr 21;64(5):. (PMID: 32071050)
Malar J. 2014 May 30;13:205. (PMID: 24885714)
N Engl J Med. 2014 Jul 31;371(5):411-23. (PMID: 25075834)
Lancet Infect Dis. 2011 Jul;11(7):541-56. (PMID: 21700241)
Antimicrob Agents Chemother. 2019 Jan 29;63(2):. (PMID: 30420479)
N Engl J Med. 2012 Nov 29;367(22):2110-8. (PMID: 23190222)
Clin Infect Dis. 2009 Dec 1;49(11):1629-37. (PMID: 19877969)
Antimicrob Agents Chemother. 2011 Nov;55(11):5073-7. (PMID: 21876053)
Malar J. 2019 May 24;18(1):180. (PMID: 31126288)
BMC Infect Dis. 2016 Jan 27;16:30. (PMID: 26818566)
Clin Infect Dis. 2005 Dec 1;41(11):1631-7. (PMID: 16267737)
J Acquir Immune Defic Syndr. 2020 Feb 1;83(2):140-147. (PMID: 31929402)
Malar J. 2010 Jun 23;9:177. (PMID: 20573194)
BMC Med Res Methodol. 2014 Dec 19;14:135. (PMID: 25524443)
J Antimicrob Chemother. 2021 Apr 13;76(5):1269-1272. (PMID: 33550391)
Am J Trop Med Hyg. 2013 Apr;88(4):736-43. (PMID: 23382157)
Clin Infect Dis. 2008 Apr 1;46(7):985-91. (PMID: 18444813)
Stat Med. 2007 Oct 30;26(24):4505-19. (PMID: 17348080)
AIDS Rev. 2007 Apr-Jun;9(2):88-98. (PMID: 17694676)
Clin Pharmacol Ther. 2015 Jul;98(1):87-95. (PMID: 25732044)
J Antimicrob Chemother. 2012 May;67(5):1217-23. (PMID: 22316571)
Pharmacogenet Genomics. 2020 Jul;30(5):96-106. (PMID: 32209837)
J Infect Dis. 2006 Oct 1;194(7):917-25. (PMID: 16960779)
J Clin Epidemiol. 2011 Dec;64(12):1311-6. (PMID: 21802902)
Pharmacogenomics J. 2016 Feb;16(1):88-95. (PMID: 25963334)
BMJ. 2016 Oct 12;355:i4919. (PMID: 27733354)
Malar J. 2014 Jan 28;13:32. (PMID: 24468007)
Front Cell Infect Microbiol. 2021 Apr 12;11:656938. (PMID: 33912477)
Clin Infect Dis. 2016 Aug 1;63(3):414-22. (PMID: 27143666)
Am J Trop Med Hyg. 2020 Jul;103(1):359-368. (PMID: 32431267)
Acta Trop. 2016 Jul;159:36-43. (PMID: 27001145)
Malar J. 2009 Nov 18;8:258. (PMID: 19922664)
Science. 1997 Jul 4;277(5322):112-6. (PMID: 9204894)
J Pharmacol Sci. 2020 Nov;144(3):95-101. (PMID: 32921396)
Clin Infect Dis. 2014 Aug 1;59(3):446-53. (PMID: 24759826)
J Infect Dis. 2006 Jan 1;193(1):9-15. (PMID: 16323126)
Open Forum Infect Dis. 2016 Dec 15;3(4):ofw217. (PMID: 28018925)
Am J Trop Med Hyg. 2004 Aug;71(2 Suppl):41-54. (PMID: 15331818)
BMJ. 2019 Aug 28;366:l4898. (PMID: 31462531)
J Antimicrob Chemother. 2012 Sep;67(9):2213-21. (PMID: 22687893)
Antimicrob Agents Chemother. 2011 Jun;55(6):2629-35. (PMID: 21383095)
Clin Infect Dis. 2014 Aug 15;59(4):509-16. (PMID: 24825870)
AIDS. 2006 Oct 24;20(16):1993-2004. (PMID: 17053345)
Malar J. 2019 Aug 20;18(1):277. (PMID: 31429785)
Malar J. 2015 Apr 25;14:179. (PMID: 25906774)
AIDS. 2007 Oct 1;21(15):2059-66. (PMID: 17885296)
Eur J Clin Pharmacol. 2021 Sep;77(9):1341-1348. (PMID: 33755736)

INV-004713 United States GATES Gates Foundation

Keywords: Anti-retroviral drugs; Artemisinin-based combination therapy; Drug-drug interactions; Human immunodeficiency virus; Malaria; People living with HIV

0 (Antimalarials)
0 (Artemisinins)
9RMU91N5K2 (artemisinin)
0 (Drug Combinations)

Date Created: 20250516 Date Completed: 20250516 Latest Revision: 20250604

20250605

PMC12083008

10.1186/s12936-025-05393-8

40380136