Abstract
Patients with visceral leishmaniasis (VL)–human immunodeficiency virus (HIV) coinfection experience increased drug toxicity and treatment failure rates compared to VL patients, with more frequent VL relapse and death. In the era of VL elimination strategies, HIV coinfection is progressively becoming a key challenge, because HIV-coinfected patients respond poorly to conventional VL treatment and play an important role in parasite transmission. With limited chemotherapeutic options and a paucity of novel anti-parasitic drugs, new interventions that target host immunity may offer an effective alternative. In this review, we first summarize current views on how VL immunopathology is significantly affected by HIV coinfection. We then review current clinical and promising preclinical immunomodulatory interventions in the field of VL and discuss how these may operate in the context of a concurrent HIV infection. Caveats are formulated as these interventions may unpredictably impact the delicate balance between boosting of beneficial VL-specific responses and deleterious immune activation/hyperinflammation, activation of latent provirus or increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a target molecule and a more detailed account of the immunological status induced by the coinfection as well as surrogate markers of cure and protection are still required. We do, however, argue that virologically suppressed VL patients with a recovered immune system, in whom effective antiretroviral therapy alone is not able to restore protective immunity, can be considered a relevant target group for an immunomodulatory intervention. Finally, we provide perspectives on the translation of novel theories on synergistic immune cell cross-talk into an effective treatment strategy for VL–HIV-coinfected patients.
Highlights
Visceral leishmaniasis (VL), called kala-azar, is a vectorborne protozoan infection caused by species of the Leishmania donovani complex, which mainly targets tissue macrophages of systemic organs, such as spleen, liver, and bone marrow [1]
There has been one case report on the use of rIL-2 in a VL–Human immunodeficiency virus (HIV)-coinfected patient failing to respond to anti-leishmanial and HIV treatment with low CD4 counts and incomplete HIV suppression despite ART use [77]
Genetic polymorphisms in the IL-10 gene promoter that lead to decreased IL-10 expression have been associated with more rapid disease progression in late stages of HIV infection, suggesting that the anti-inflammatory effects of IL-10 may be solely protective in the setting of chronic immune activation and blocking IL-10 function would only make sense in an acute setting [121]
Summary
Visceral leishmaniasis (VL), called kala-azar, is a vectorborne protozoan infection caused by species of the Leishmania donovani complex, which mainly targets tissue macrophages of systemic organs, such as spleen, liver, and bone marrow [1]. The evidence for beneficial effects of GM-CSF on HIV disease is limited, but GM-GSF adjuvant therapy could provide a potential value for treatment of neutropenic VL in stable ART patients.
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