Antimalarial drug resistance markers in human immunodeficiency virus (HIV)-positive and HIV-negative adults with asymptomatic malaria infections in Port Harcourt, Nigeria

Trans R Soc Trop Med Hyg. 2021 May 8;115(5):531-537. doi: 10.1093/trstmh/trab061.

Abstract

Background: In Nigeria, indiscriminate use of antimalarial drugs may contribute to the threat of drug resistance, but this has not been evaluated among people living with human immunodeficiency virus (HIV).

Methods: HIV-positive adults attending a university hospital HIV clinic and HIV-negative adult volunteers from the university hospital community with a positive blood film were treated with artemether-lumefantrine. Parasite DNA from before and after treatment was polymerase chain reaction amplified to identify molecular markers of drug susceptibility.

Results: The pfcrt76T genotype was prevalent among both HIV-positive and HIV-negative participants (78.6% and 68.2%, respectively). Three new mutations in the pfmdr1 gene-F73S, S97L and G165R-and the uncommon pfdhps S436F variant were detected, whereas pfdhps K540E and pfdhfr I164L were absent. The A437G allele of pfdhps predominated (62/66 [94%]). The I431 V mutation was found in 19 of 66 pretreatment pfdhps sequences (28.8%). The pfmdr1 86N allele was significantly more common at day 3 post-treatment than at baseline (odds ratio 8.77 [95% confidence interval 1.21 to 380]).

Conclusions: We found evidence of continued chloroquine use among HIV-positive individuals. Selection for the pfmdr1 86N after artemether-lumefantrine treatment was observed, indicating a possible threat to antimalarial efficacy in the study area. The complexity of pfdhps haplotypes emphasises the need for careful monitoring of anti-folate susceptibility in Nigeria.

Keywords: HIV; antimalarial drugs; drug resistance; malaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimalarials* / pharmacology
  • Antimalarials* / therapeutic use
  • Artemether / therapeutic use
  • Artemether, Lumefantrine Drug Combination / therapeutic use
  • Drug Combinations
  • Drug Resistance / genetics
  • HIV
  • Humans
  • Malaria* / complications
  • Malaria* / drug therapy
  • Malaria, Falciparum* / complications
  • Malaria, Falciparum* / drug therapy
  • Malaria, Falciparum* / epidemiology
  • Nigeria
  • Plasmodium falciparum / genetics
  • Protozoan Proteins / genetics

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Drug Combinations
  • Protozoan Proteins
  • Artemether