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Low-Dose Aspirin or Hydroxychloroquine
Limits Activated Target Cells in Genital Tract
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HIV Research for Prevention (HIVR4P), October 17-19, 2016, Chicago
Mark Mascolini
Daily low-dose aspirin or hydroxychloroquine significantly reduced numbers of CCR5-expressing CD4 cells and lowered activation marker levels on CD4s in a pilot study in Nairobi women not engaged in sex work [1]. The study aimed to mimic the HIV-resistant "immune quiescence" observed in sex workers who resist HIV infection despite ongoing contact with the virus and lack of any preventive intervention.
Researchers from the University of Manitoba and the University of Nairobi have identified a group of HIV-exposed but persistently seronegative female sex workers in Nairobi. Their research defines a condition of low-level inflammation and immune activation in these women, which the investigators label "immune quiescence" [2,3]. They conducted this 77-woman trial to see if they could induce immune quiescence in HIV-negative women not engaged in sex work through daily low doses of a nonsteroidal antiinflammatory, either hydroxychloroquine (HCQ, Plaquenil) or acetylsalicylic acid (ASA, aspirin).
The Manitoba-Nairobi team hypothesized that daily oral administration of safe and affordable nonsteroidal antiinflammatories--the antimalarial HCQ or the analgesic ASA--will lower the number of activated (CCR5-, CD69-, or CD161-expressing) HIV target cells in the genital tract of women. They recruited 77 non-sex worker Nairobi women and assigned 40 to 81 mg of daily ASA for 6 weeks and 37 to 200 mg of daily HCQ for 6 weeks.
Three to 5 days after menses every month, the researchers collected samples of blood, cervical lavage, and cervical mononuclear cells. They used standard assays to analyze cell phenotypes and levels of cytokines or chemokines. And they measured ASA levels in blood and cervical lavage. The investigators reported findings at visit 1 (2 weeks before therapy began), visit 2 (2 weeks after therapy began), and visit 3 (6 weeks after therapy began).
Daily HCQ significantly lowered expression of the CCR5 HIV coreceptor on peripheral blood CD4 cells from visit 1 to visit 2 (P < 0.01) and from visit 1 to visit 3 (P < 0.05). HCQ also significantly lowered CCR5 coreceptor intensity on cervical mononuclear cells from visit 1 to visit 3 (P = 0.01) and from visit 2 to visit 3 (P = 0.005). And HQC significantly lowered expression of CD69, an acute activation marker, on cervical CD4 cells from visit 1 to visit 3 (P = 0.007).
Daily ASA significantly lowered CCR5 expression on blood CD4 cells from visit 1 to visit 2 (P = 0.006) and from visit 1 to visit 3 (P = 0.01). With daily ASA, levels of activation markers CD161 and CD69 also fell significantly in blood from visit 1 to visit 3 (P = 0.02) and from visit 2 to visit 3 (P = 0.002). Among women taking ASA, CCR5 expression on cervical mononuclear cells dropped significantly from visit 1 to visit 3 (P = 0.017) and from visit 2 to visit 3 (P = 0.03). Daily ASA also significantly lowered expression of the activation marker CD161 on cervical mononuclear cells from visit 1 to visit 3 (P = 0.03) and from visit 2 to visit 3 (P = 0.04).
ASA levels in blood and cervical lavage correlated inversely with CCR5 expression on CD4 cells, while ASA levels in blood correlated directly with number of activated (CD161+) CD4 cells.
The Manitoba-Nairobi team concluded that low-dose HCQ lowers expression of CCR5 and CD69 on genital tract CD4 cells, while low-dose aspirin lowers numbers of HIV target cells in the female genital tract. They suggested that future work should assess whether reducing numbers of HIV target cells leads to decreased HIV incidence. They proposed that such work might involve high-risk populations such as female sex workers and men who have sex with men.
References
1. Fowke KR, Mwangi L, Boily-Larouche G, et al. Can we prevent HIV infection by focusing on the HIV target cell rather than the virus? HIV Research for Prevention (HIVR4P 2016), October 17-19, 2016, Chicago. Abstract P19.25.
2. Card CM, Ball TB, Fowke KR. Immune quiescence: a model of protection against HIV infection. Retrovirology. 2013;10:141.
http://retrovirology.biomedcentral.com/articles/10.1186/1742-4690-10-141
3. Lajoie J, Kimani M, Plummer FA, et al. Association of sex work with reduced activation of the mucosal immune system. J Infect Dis. 2014;210:319-329. http://jid.oxfordjournals.org/content/210/2/319.long
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