Decreased monocyte activation with daily acyclovir use in HIV-1/HSV-2 coinfected women

Redd, Andrew D.; Newell, Kevin; Patel, Eshan U.; Nalugoda, Fred; Ssebbowa, Paschal; Kalibbala, Sarah; Frank, Melanie A.; Tobian, Aaron A.R.; Gray, Ronald H.; Quinn, Thomas C.; Serwadda, David; Reynolds, Steven J.

doi:10.1136/sextrans-2014-051867

Cited by 10 publications

(5 citation statements)

References 14 publications

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“…CD4 + T-cell counts, HIV viral load (VL), soluble CD14 (sCD14) and high-sensitivity CRP (hs-CRP) measurements were determined biannually [35, 36] . CMV IgG antibody levels were measured at the baseline visit among all women, and at the 12- and 24-month follow-up visits among a sub-set of women who initiated ART during the study period.…”

Section: Methodsmentioning

confidence: 99%

Elevated cytomegalovirus IgG antibody levels are associated with HIV-1 disease progression and immune activation

Patel¹,

Gianella

Newell³

et al. 2017

Aids

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Objective To assess the association between CMV IgG antibody levels, HIV disease progression, and immune activation in sub-Saharan Africa. Design A prospective cohort study was conducted among women enrolled in a trial that was designed to determine the effect of acyclovir on HIV disease progression in Rakai, Uganda. Methods The primary endpoints were progression to a CD4+ T-cell count<250 cells/μL, non-traumatic death, or initiation of ART. CD4+ T-cell counts, HIV viral load, C-reactive protein, and soluble CD14 levels were assessed biannually for 24 months. CMV IgG antibody were measured at baseline among all women, and annually among a subset of women who initiated ART during the study. Results There were 300 HIV/CMV coinfected participants who contributed a total of 426.4 person-years with a median follow-up time of 1.81 years. Compared to the lowest CMV IgG tertile group at baseline, the highest CMV IgG tertile group was associated with an increased risk to reach a primary endpoint independent of acyclovir use, age, CD4+ T-cell count, and HIV viral load at baseline (adjHR=1.59;[95%CI=1.05-2.39];P=0.027). Among pre-ART visits (n=1,200), women in the highest baseline CMV IgG tertile had increasing annual rates of sCD14 and CRP levels, which was not observed for the low CMV IgG tertile group. Compared to pre-ART visits, CMV IgG antibody levels were higher post-ART initiation, and concurrent levels remained associated with sCD14 and CRP during suppressive ART (n=95). Conclusion The magnitude of the immune response to CMV was associated with HIV disease progression and immune activation in sub-Saharan Africa.

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Section: Methodsmentioning

confidence: 99%

Elevated cytomegalovirus IgG antibody levels are associated with HIV-1 disease progression and immune activation

Patel¹,

Gianella

Newell³

et al. 2017

Aids

Self Cite

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“…Redd et al tried to explore the effect of acyclovir on immune activation status in HIV-1/HSV-2 ART-naïve coinfected women and demonstrated a relatively small decrease of sCD14 but at a significantly faster rate in acyclovir treated compared to the untreated group, independently of HIV viral load and CD4+ cell count suggesting a role for monocyte activation during HSV-2 reactivation [79]. In ART treated patients though a randomized controlled trial of valacyclovir for 12 weeks to suppress HSV-2 showed no effect on cellular immune activation or systemic inflammatory markers suggesting that the overall impact on systemic immune activation of treated patients may be small or transient [80].…”

Section: Cryptococcusmentioning

confidence: 99%

HIV infection and immune activation

Boulougoura

Sereti

2016

Current Opinion in HIV and AIDS

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Purpose of review To explore new data from recent studies addressing the role of co-infections in immune activation in HIV-1 infected patients, with a focus on Immune Reconstitution Inflammatory Syndrome (IRIS), an aberrant inflammatory response occurring shortly after antiretroviral therapy (ART) initiation. Recent findings Chronic HIV infection is associated with a number of co-infections that contribute to immune activation in various settings including early after ART initiation in the most noticeable form of IRIS and also in chronic treated infection, with chronic viral infections like CMV and HCV or HBV contributing to immune activation and also morbidity and mortality. Expanding on older studies, the role of T cells in IRIS has been further elucidated with evidence of more pronounced effector activity in IRIS patients that may be leading to excessive tissue pathology. Newer studies are also continuing to shed light on the role of myeloid cells in IRIS as well as the contribution of antigen load in the syndrome. In addition, preliminary data are beginning to suggest a possible role of inflammasome formation in IRIS. In cryptococcal IRIS, the role of activated immune cells (T cell and myeloid) and biomarkers were evaluated in more detail at the site of infection (CSF). Finally, important differences of patients developing IRIS versus those who die from TB despite ART initiation were reported, a distinction that may have important implications for participant selection in studies aiming to prevent IRIS with immunosuppressive agents. Summary Better understanding of the role of opportunistic infections at ART initiation and IRIS pathogenesis will assist in improved strategies for prevention and treatment. The long-term consequences of IRIS remain unclear. Chronic viral coinfections with herpesviruses and HCV are important factors in persistent immune activation in chronic treated HIV.

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“…Herpes simplex virus 2 (HSV-2) coinfection may act as a cofactor for increased HIV replication, and the use of acyclovir/valacyclovir to target HSV-2 may have localized benefits on HSV-2 with mucosal level HIV suppression and decreased monocyte activation. 283,284 In a study of 291 men living with HIV in the MACS, infection with multiple herpes viruses was found to be associated with elevated coronary arterial calcium. However, HSV-2 seropositivity in this cohort had the strongest association with subclinical atherosclerosis, with a 4-fold increased risk.…”

Section: Figure 3 Proposed Model Of How Hiv and Other Chronic Persist...mentioning

confidence: 99%

Inflammation in HIV and Its Impact on Atherosclerotic Cardiovascular Disease

Obare,

Temu,

Mallal

et al. 2024

Circulation Research

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People living with HIV have a 1.5- to 2-fold increased risk of developing cardiovascular disease. Despite treatment with highly effective antiretroviral therapy, people living with HIV have chronic inflammation that makes them susceptible to multiple comorbidities. Several factors, including the HIV reservoir, coinfections, clonal hematopoiesis of indeterminate potential (CHIP), microbial translocation, and antiretroviral therapy, may contribute to the chronic state of inflammation. Within the innate immune system, macrophages harbor latent HIV and are among the prominent immune cells present in atheroma during the progression of atherosclerosis. They secrete inflammatory cytokines such as IL (interleukin)-6 and tumor necrosis-α that stimulate the expression of adhesion molecules on the endothelium. This leads to the recruitment of other immune cells, including cluster of differentiation (CD)8 + and CD4 + T cells, also present in early and late atheroma. As such, cells of the innate and adaptive immune systems contribute to both systemic inflammation and vascular inflammation. On a molecular level, HIV-1 primes the NLRP3 (NLR family pyrin domain containing 3) inflammasome, leading to an increased expression of IL-1β, which is important for cardiovascular outcomes. Moreover, activation of TLRs (toll-like receptors) by HIV, gut microbes, and substance abuse further activates the NLRP3 inflammasome pathway. Finally, HIV proteins such as Nef (negative regulatory factor) can inhibit cholesterol efflux in monocytes and macrophages through direct action on the cholesterol transporter ABCA1 (ATP-binding cassette transporter A1), which promotes the formation of foam cells and the progression of atherosclerotic plaque. Here, we summarize the stages of atherosclerosis in the context of HIV, highlighting the effects of HIV, coinfections, and antiretroviral therapy on cells of the innate and adaptive immune system and describe current and future interventions to reduce residual inflammation and improve cardiovascular outcomes among people living with HIV.

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Decreased monocyte activation with daily acyclovir use in HIV-1/HSV-2 coinfected women

Abstract: NCT00405821.

Cited by 10 publications

References 14 publications

Elevated cytomegalovirus IgG antibody levels are associated with HIV-1 disease progression and immune activation

Elevated cytomegalovirus IgG antibody levels are associated with HIV-1 disease progression and immune activation

HIV infection and immune activation

Inflammation in HIV and Its Impact on Atherosclerotic Cardiovascular Disease

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