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Low-Dose Aspirin Cuts Inflammation in Blood and HIV Target Cells in Female Genital Tract
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HIV Research for Prevention (HIVR4P), October 21-25, 2018, Madrid
Mark Mascolini
Low-dose aspirin lowered numbers of HIV-target CD4 cells in female genital tract and cut expression of activation markers in blood, according to results of a 76-woman study by researchers at the University of Manitoba and University of Nairobi [1]. Whether this activity against activation and target cell numbers can help prevent HIV infection remains unknown.
Researchers who conducted this study noted that most HIV prevention strategies (condoms, PrEP, microbicides) involve blocking the virus, while only one, medical male circumcision, removes target cells. HIV acquisition requires both a replication-competent virus and susceptible target cells (CD4+CCD5+ and Th17+). Inflammation, the investigators observed, involves activated CD4 cells migrating to tissue.
The Manitoba/Nairobi team hypothesized that blocking inflammation will lower numbers of HIV target cells in the female genital tract. They conducted this study to see whether oral administration of aspirin, an antiinflammatory drug, would reduce numbers of target cells and markers of inflammation. They chose aspirin because of its generally good safety profile, affordability, accessibility, and acceptability. Low-dose aspirin, 81 mg daily, is very safe. Preliminary community consultations in Kenya indicated its high acceptability because taking aspirin carries no stigma.
The study involved a cohort of low-HIV-risk women at a community clinic in Nairobi: 37 took 81 mg of aspirin daily for 6 weeks and 39 took 200 mg of hydroxychloroquine (HCQ) daily for 6 weeks. Women gave blood, cytobrush/scraper, and cervicovaginal lavage samples 5 to 7 days after menses before starting aspirin and HCQ, at treatment weeks 2 and 6, and after stopping treatment.
No drug-associated adverse events arose. Aspirin could be detected in genital tract samples of all aspirin-treated women at week 2 and of 80% of women at week 6.
From visit 1 (before treatment) to visit 3 (treatment week 6), blood samples showed that women taking aspirin had significant declines in the inflammation marker MCP-1 (P = 0.03), the HIV receptor CCR5 on CD4 cells (35% decline, P = 0.01), the acute activation marker CD69 on CD4 cells (P = 0.003), and the HIV target-cell indicator Th17 with the activation marker CD69 (28% decline, P = 0.02). In mucosal tissue women taking aspirin had significant drops in CD4 cells expressing CCR5 (P = 0.017) and CD4 Th17 target cells (P = 0.04). Lower aspirin levels correlated with more CCR5-expressing cells in tissue (r2 = -0.4325, P < 0.0001).
Further analysis at the National Microbiology Laboratory found no significant changes in the female microbiome with aspirin. These proteomic analyses confirmed decreased inflammatory proteins, decreased cell recruitment proteins, and increased tight junction proteins in the female genital tract with aspirin. Lactobacillus-dominant women were more sensitive to the antiinflammatory effects of aspirin.
The Manitoba/Nairobi team concluded that low-dose aspirin (1) decreases expression of CCR5 on target cells and activation markers in blood and (2) reduces the number of target cells (CCR5+ or Th17+) in the female genital tract. And aspirin tissue levels correlated with target-cell reduction.
The researchers plan to repeat these experiments in high-risk female sex workers for 6 months, determine aspirin's mechanisms of action, and design an efficacy trial to see if aspirin limits HIV transmission. They cautioned that low-dose aspirin therapy to thwart HIV must attain immune quiescence without inducing immune suppression.
Reference
1. Fowke K, Birse K, Mwangi L, et al. Reducing inflammation as a novel HIV prevention approach: aspirin reduces inflammation and HIV target cells at the female genital tract. HIV Research for Prevention (HIVR4P), October 21-25, 2018, Madrid. Abstract OA01.06.
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