Abstract
HIV-infected subjects under virological control still exhibit a persistent proinflammatory state. Thus, chronic HIV infection changes the host homeostasis towards an adapted immune response that may affect the outcome of coinfections. However, little is known about the impact of HIV infection on inflammatory amplification and clinical presentation in dengue. Platelets have been shown to participate in immune response in dengue and HIV. We hypothesized that altered platelet responses in HIV-infected subjects may contribute to altered inflammatory milieu and disease progression in dengue. We prospectively followed a cohort of 84 DENV-infected patients of whom 29 were coinfected with HIV under virological control. We report that dengue and HIV coinfection progress with reduced inflammation and milder disease progression with lower risk of vascular instability. Even though the degree of thrombocytopenia and platelet activation were similar between dengue-infected and HIV plus dengue-coinfected patients, plasma levels of the platelet-derived chemokines RANTES/CCL5 and PF4/CXCL4 were lower in coinfection. Consistently, platelets from coinfected patients presented defective secretion of the stored-chemokines PF4 and RANTES, but not newly synthesized IL-1β, when cultured ex vivo. These data indicate that platelets from HIV-infected subjects release lower levels of chemokines during dengue illness, which may contribute to milder clinical presentation during coinfection.
Highlights
With the emergence of combined antiretroviral therapy (ART) the epidemiology of human immunodeficiency virus (HIV) infection has changed in the last decades from high mortality by opportunistic infections in acquired immunodeficiency syndrome (AIDS) to long-term noninfectious comorbidities in subjects chronically infected with HIV1,2
Based on the review of the clinical charts from 55 dengue infected and 29 HIV plus dengue coinfected patients, we investigated the relationship between chronic HIV infection and severity of dengue illness (Fig. 1A and Table 1)
HIV plus dengue coinfected patients presented a trend towards protection against liver dysfunction (OR [95% confidence interval (CI)] = 0.1396 [0.0171–1.1421], p = 0.0491) and major bleeding (Gastrointestinal bleed, vaginal bleed and/or hematuria) (OR [95% CI] = 0.1429 [0.0175–1.1681], p = 0.0501) (Fig. 1A and Table 1)
Summary
With the emergence of combined antiretroviral therapy (ART) the epidemiology of human immunodeficiency virus (HIV) infection has changed in the last decades from high mortality by opportunistic infections in acquired immunodeficiency syndrome (AIDS) to long-term noninfectious comorbidities in subjects chronically infected with HIV1,2. Even though sustained virologic control is achieved through ART, higher rates of long-term comorbidities including cardiovascular diseases, HIV-associated neurocognitive disorders and non-AIDS cancers are still responsible for increased morbidity among HIV infected people[3,4,5,6,7]. The immune network and key cellular components involved in HIV-driven reprogramming of host homeostasis are highly complex, and little is known about the impact of chronic HIV infection on the pathogenesis and clinical presentation of endemic/epidemic infectious diseases, including dengue. We show that patients coinfected with HIV plus dengue progressed with milder clinical presentation compared to patients infected with DENV only. More benign disease progression in coinfected patients was associated with reduced levels of pro-inflammatory cytokines and platelet-derived chemokines. Platelets isolated from HIV plus dengue coinfected patients showed defective secretion of granule-stored chemokines when cultured ex vivo. These data suggest that platelet degranulation fatigue with reduced secretion of stored chemokines may contribute to reduced inflammatory response in HIV plus dengue coinfection
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