The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1

Abstract

Immune activation associated with HIV-1 infection contributes to morbidity and mortality. We studied whether chloroquine, through Toll-like receptor (TLR) antagonist properties, could reduce immune activation thought to be driven by TLR ligands, such as gut-derived bacterial elements and HIV-1 RNAs. AIDS Clinical Trials Group A5258 was a randomized, double-blind, placebo-controlled study in 33 HIV-1-infected participants off antiretroviral therapy (ART) and 37 participants on ART. Study participants in each cohort were randomized 1:1 to receive chloroquine 250 mg orally for the first 12 weeks then cross over to placebo for 12 weeks or placebo first and then chloroquine. Combining the periods of chloroquine use in both arms of the on-ART cohort yielded a modest reduction in the proportions of CD8 T cells co-expressing CD38 and DR (median decrease = 3.0%, p = .003). The effect on immune activation in the off-ART cohort was likely confounded by increased plasma HIV-1 RNA during chloroquine administration (median 0.29 log 10 increase, p < .001). Transcriptional analyses in the off-ART cohort showed decreased expression of interferon-stimulated genes in 5 of 10 chloroquinetreated participants and modest decreases in CD38 and CCR5 RNAs in all chloroquine-treated participants. Chloroquine modestly reduced immune activation in ART-treated HIV-infected participants. Clinical Trials Registry Number: NCT00819390.

The Use of Antimalarial Drugs against Viral Infection

“…It was a randomized, double-blind, placebo-controlled study in 33 HIV-1-infected participants off antiretroviral therapy and 37 participants on antiretroviral therapy. CQ modestly reduced immune activation in antiretroviral therapy-treated HIV-infected participants [42].…”

“…Increased HIV-1 replication and decreased CD4 numbers [41] Chloroquine NCT00819390 Modest reduction in immune activation [42] Chloroquine NCT02004314…”

Immunosenescence and hurdles in the clinical management of older HIV-patients

“…In some studies this molecule was shown to reduce immune activation markers (i.e., IL-6, TNF-a and LPS) and CD8 T-cells expressing CD38CHLA-DRC and Ki-67, 158-161 while other researchers found no effect on immune-activation. [162][163][164] A possible target is also represented by TNF itself, which may be antagonized by several molecules currently in use for rheumatologic diseases. A study in rhesus macaques showed that adalimumab, a human anti-TNF monoclonal antibody, was able to reduce infiltration of polymorphonuclear cells into the T-cell zone of lymphoid tissues, diminishing also lymphoid tissue fibrosis; nevertheless, no effect on plasma immune activation was proven.…”

Systematic Review and Meta-analysis of the Safety of Chloroquine and Hydroxychloroquine From Randomized Controlled Trials on Malarial and Non-malarial Conditions

“…Out of 92 studies included, eight were on COVID-19 [21][22][23][24][25][26][27][28], 13 studies were on malaria [29][30][31][32][33][34][35][36][37][38][39][40][41], 11 on other infectious conditions [42][43][44][45][46][47][48][49][50][51][52][53], 31 were on rheumatology , four on dermatologic diseases [85][86][87][88], eight on cancer [89][90][91][92][93][94][95][96], ve were on metabolic disease [97][98][99][100][101],...…”