Impact of Anthelmintic Therapy for Invasive Helminth Infection on Microbial Translocation, Inflammation, and Immune Response among Ugandans Living with HIV: A Randomized Proof of Concept Study.
Bożena M Morawski, Miya Yunus, Stefanie Sowinski, Grace Turyasingura, Anna Gabrielle Bottazzi, Claudia Muñoz-Zanzi, Kibirge Leonard, David R Boulware, Rojelio Mejia
Abstract
Open AccessMicrobial translocation drives chronic immune activation that is linked to HIV disease progression. Invasive parasitic gut nematodes induce microbial translocation and downregulate the expression of pro-inflammatory cytokines. We evaluated the impact of albendazole anthelmintic therapy on serum markers of microbial translocation and inflammation among helminth-infected Ugandans living with HIV. Participants were randomized to an immediate or delayed 400 mg of daily albendazole and followed for 1 month. Baseline stool analysis, conducted via multiparallel real-time quantitative polymerase chain reaction, determined the prevalence of parasitic infections. Baseline and follow-up blood draws evaluated soluble CD14 (sCD14), C-reactive protein (CRP), and 10 pro-inflammatory cytokines. Changes in biomarker concentrations over time and across randomization arms were evaluated using parametric and nonparametric tests. We enrolled 224 antiretroviral therapy-experienced Ugandan adults living with HIV. Twenty-four participants (10.7%) were infected with either Necator americanus or Strongyloides stercoralis (12 immediate arm; 12 delayed arm). At baseline, participants with current helminth infection had increased concentrations of CRP, interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor-α compared with uninfected participants. Among helminth-infected participants, those in the immediate therapy arm had nonsignificant higher mean sCD14 concentrations (1.40 µg/mL) at follow-up compared with participants in the delayed arm (95% CI: -0.17, 2.98; P = 0.06) with no significant differences observed in other biomarker concentrations. Increases in sCD14 following anthelmintic treatment in this cohort require further investigation in larger cohorts with longer follow-up durations. However, incorporating anthelmintic therapy into routine adult HIV care may provide subtle health benefits in this potentially vulnerable population.