Increased Risk of Anemia, Neutropenia, and Thrombocytopenia in People With Human Immunodeficiency Virus and Well-Controlled Viral Replication

2019 ◽  
Vol 220 (11) ◽  
pp. 1834-1842 ◽  
Author(s):  
Delal Akdag ◽  
Andreas Dehlbæk Knudsen ◽  
Rebekka Faber Thudium ◽  
Ditte Marie Kirkegaard-Klitbo ◽  
Chivit Nielsen ◽  
...  

Abstract Background Prior to the introduction of combination antiretroviral therapy (cART), cytopenias were common in people with human immunodeficiency virus (PWH), but it is unknown if well-controlled HIV infection is a risk factor for cytopenia. In this study we aimed to determine if HIV infection is an independent risk factor for anemia, neutropenia, lymphocytopenia, and thrombocytopenia. Methods PWH with undetectable viral replication and absence of chronic hepatitis infection (n = 796) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) study and matched uninfected controls from the Copenhagen General Population Study (n = 2388). Hematology was analyzed in venous blood samples. Logistic regression analyses adjusted for age, sex, ethnicity, smoking status, alcohol, and high-sensitivity C-reactive protein were performed to determine possible associations between HIV and cytopenias. Results PWH had a higher prevalence of anemia (6.9% vs 3.4%, P < .001), neutropenia (1.3% vs 0.2%, P < .001), and thrombocytopenia (5.5% vs 2.7%, P < .001) compared with uninfected controls. HIV was independently associated with anemia-adjusted odds ratio (aOR) of 2.0 (95% confidence interval [CI], 1.4–3.0); neutropenia aOR, 6.3 (95% CI, 2.0–19.6); and thrombocytopenia aOR, 2.7 (95% CI, 1.8–4.2). No association was found between HIV and lymphocytopenia. Conclusions Cytopenia is rare in people with well-controlled HIV, but HIV remains a risk factor for anemia, neutropenia, and thrombocytopenia and requires ongoing attention and monitoring.

Author(s):  
Rebekka F Thudium ◽  
Andreas D Knudsen ◽  
Jakob Hjorth Von Stemann ◽  
Malene Hove-Skovsgaard ◽  
Hedda Hoel ◽  
...  

Abstract Background Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 [IL-6], interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 [sCD14] and soluble CD163 [sCD163]) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH. Methods We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices. Results PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (−212 mL [95% confidence interval, −308 to −116 mL]), lower forced vital capacity (−208 mL [−322 to −93 mL]), and airflow limitation (aOR, 2.62 [1.58–4.36]) (all P &lt; .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005). Conclusion IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases.


2020 ◽  
Vol 223 (1) ◽  
pp. 94-100
Author(s):  
Andreas D Knudsen ◽  
Andreas Ronit ◽  
Thomas Kristensen ◽  
Magda Teresa Thomsen ◽  
Anne-Mette Lebech ◽  
...  

Abstract Background Pulmonary artery enlargement is a marker of pulmonary hypertension. We aimed to determine the proportion with pulmonary artery enlargement among well-treated persons with human immunodeficiency virus HIV (PWH) and uninfected controls. Methods PWH with a chest computed tomography were included from the ongoing Copenhagen Comorbidity in HIV Infection (COCOMO) study. Age and sex-matched uninfected controls were recruited from the Copenhagen General Population Study. Pulmonary artery enlargement was defined as a ratio of &gt;1 between the diameter of the main pulmonary artery (at the level of its bifurcation) and the diameter of the ascending aorta. Results In total, 900 PWH were included, and 44 (5%) had a pulmonary artery–aorta ratio (PA:A) &gt;1. After adjustment for age, sex, and body mass index, obesity (adjusted odds ratio, 4.33; 95% confidence interval, 1.76–10.65; P = .001) and injection drug use (IDU) (4.90; 1.00–18.46; P = .03) were associated with higher odds of having a PA:A &gt;1, and pulmonary indices and smoking status were not. HIV seropositivity was borderline associated with a PA:A &gt;1 (adjusted odds ratio, 1.89; 95% confidence interval, .92–3.85; P = .08). Conclusions A PA:A &gt;1 was common in PWH. Obesity and IDU were independently associated with this finding and HIV serostatus was borderline associated with it, but HIV-related factors were not. Increased awareness may be appropriate in obese PWH and those with IDU.


2007 ◽  
Vol 14 (9) ◽  
pp. 1102-1107 ◽  
Author(s):  
Richard M. Novak ◽  
Betty A. Donoval ◽  
Parrie J. Graham ◽  
Lucy A. Boksa ◽  
Gregory Spear ◽  
...  

ABSTRACT Innate immune factors in mucosal secretions may influence human immunodeficiency virus type 1 (HIV-1) transmission. This study examined the levels of three such factors, genital tract lactoferrin [Lf], secretory leukocyte protease inhibitor [SLPI], and RANTES, in women at risk for acquiring HIV infection, as well as cofactors that may be associated with their presence. Women at high risk for HIV infection meeting established criteria (n = 62) and low-risk controls (n = 33) underwent cervicovaginal lavage (CVL), and the CVL fluid samples were assayed for Lf and SLPI. Subsets of 26 and 10 samples, respectively, were assayed for RANTES. Coexisting sexually transmitted infections and vaginoses were also assessed, and detailed behavioral information was collected. Lf levels were higher in high-risk (mean, 204 ng/ml) versus low-risk (mean, 160 ng/ml, P = 0.007) women, but SLPI levels did not differ, and RANTES levels were higher in only the highest-risk subset. Lf was positively associated only with the presence of leukocytes in the CVL fluid (P < 0.0001). SLPI levels were lower in women with bacterial vaginosis [BV] than in those without BV (P = 0.04). Treatment of BV reduced RANTES levels (P = 0.05). The influence, if any, of these three cofactors on HIV transmission in women cannot be determined from this study. The higher Lf concentrations observed in high-risk women were strongly associated with the presence of leukocytes, suggesting a leukocyte source and consistent with greater genital tract inflammation in the high-risk group. Reduced SLPI levels during BV infection are consistent with an increased risk of HIV infection, which has been associated with BV. However, the increased RANTES levels in a higher-risk subset of high-risk women were reduced after BV treatment.


Author(s):  
Rebekka F Thudium ◽  
Nicolai L P Hughes ◽  
Shoaib Afzal ◽  
Yunus Çolak ◽  
Marco Gelpi ◽  
...  

Abstract Background Increased risk of asthma and chronic obstructive pulmonary disease has been reported in people living with human immunodeficiency virus (PLWH). Fraction of exhaled nitric oxide (FeNO) is a marker of eosinophilic airway inflammation. We assessed FeNO levels in PLWH and matched uninfected controls and investigated whether human immunodeficiency virus (HIV) status is independently associated with elevated FeNO. Methods FeNO was quantified by NIOX Vero and pulmonary function was assessed by spirometry in 432 PLWH from the Copenhagen Comorbidity in HIV Infection Study and in 1618 age- and sex-matched uninfected controls from the Copenhagen General Population Study. Elevated FeNO was defined as ≥25 parts per billion. Associations between FeNO and HIV status were adjusted for known potential confounders. Results Mean age of PLWH was 50.7 (standard deviation [SD], 11.1) years and 97.4% received combination antiretroviral therapy. PLWH had higher FeNO than uninfected controls (median, 17.0 [interquartile range {IQR}, 11.0–26.0] vs 13.0 [IQR, 9.0–19.0]; P &lt; .001). Also, PLWH had a higher prevalence of elevated FeNO than uninfected controls (27.5% vs 12.3%; P &lt; .001). This association remained after adjusting for age, sex, height, smoking status, use of airway medication, blood eosinophils, and immunoglobulin E (adjusted OR [aOR], 3.56 [95% CI, 2.51–5.04]; P &lt; .001). Elevated FeNO was associated with self-reported asthma (aOR, 2.65 [95% CI, 1.66–4.24]; P &lt; .001) but not with airflow limitation (aOR, 1.07 [95% CI, .71–1.62]; P = .745). Conclusions HIV status was independently associated with elevated FeNO, suggesting increased eosinophilic airway inflammation. The potential impact on chronic lung disease pathogenesis needs further investigation.


1992 ◽  
Vol 176 (4) ◽  
pp. 1197-1201 ◽  
Author(s):  
M H Malim ◽  
W W Freimuth ◽  
J Liu ◽  
T J Boyle ◽  
H K Lyerly ◽  
...  

The human immunodeficiency virus (HIV) Rev protein is essential for viral structural protein expression (Gag, Pol, and Env) and, hence, for viral replication. In transient transfection assays, mutant forms of Rev have been identified that inhibit wild-type Rev activity and therefore suppress viral replication. To determine whether such transdominant Rev proteins could provide long-term protection against HIV infection without affecting T cell function, T leukemia cell lines were stably transduced with a retroviral vector encoding a transdominant mutant of the Rev protein, M10. While all the M10-expressing cell lines remained infectable by HIV-1, these same cells failed to support a productive replication cycle when infected with a cloned isolate of HIV-1. In addition, two out of three M10-expressing CEM clones were also resistant to highly productive infection by a heterogeneous HIV-1 pool. Expression of M10 did not affect induction of HIV transcription mediated by the kappa B regulatory element or Tat. Importantly, constitutive expression of Rev M10 did not alter the secretion of interleukin 2 in response to mitogen stimulation of EL-4 and Jurkat cells. The inhibition of HIV infection in cells stably expressing a transdominant Rev protein, in the absence of any deleterious effect on T cell function, suggests that such a strategy could provide a therapeutic effect in the T lymphocytes of acquired immunodeficiency syndrome patients.


Author(s):  
Spiridenko G.Yu. ◽  
Petrov Yu.A. ◽  
Bragina T.V.

Currently, due to the increase in the incidence of HIV infection in women of reproductive age, the number of desired pregnancies in such patients has increased. This makes it necessary to study the pathological effect of the human immunodeficiency virus on the placenta, fetus and the female body as a whole. HIV belongs to retroviruses and contributes to the discoordination of a woman's immune mechanisms. Using the gp41 and gp120 glycoproteins, reverse transcriptase, integrase, and protease, the virus destroys CD4 cells and increases the viral load. It founded that the risk of infection of the fetus decreases from 45% to 1% with HIV infection before pregnancy and with antiretroviral therapy throughout its duration. Vertical infection is possible in the intrauterine, intranatal and postnatal periods, the main of which is the period of childbirth-up to 70%. Viral, maternal, placental, fetal, obstetric and neonatal factors contribute to an increased risk of transmission of the pathogen to the fetus. High viral load and antiretroviral therapy lead in the 3rd trimester of pregnancy to the development of chronic placental insufficiency due to the formation of focal and diffuse deciduitis, membranitis, intervillusitis and chorionamnionitis and damage to the hematoplacental barrier. Early diagnosis before 12 weeks of gestation, timely therapy with nucleoside and non-nucleoside reverse transcriptase inhibitors, as well as protease inhibitors during pregnancy, childbirth and in the postpartum period are the main aspects of preventing HIV infection and further disorders of the child's growth and development. The timely choice of the method of delivery, indications and contraindications to delivery through the natural birth canal helps to reduce the risk of infection in a particularly dangerous period - the intrapartum.


2019 ◽  
Vol 71 (6) ◽  
pp. 1438-1446 ◽  
Author(s):  
Rayoun Ramendra ◽  
Stéphane Isnard ◽  
John Lin ◽  
Brandon Fombuena ◽  
Jing Ouyang ◽  
...  

Abstract Background Cytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G (IgG) levels are associated with adverse health outcomes in elderly populations. Among people living with human immunodeficiency virus (PLWH), CMV seropositivity has been associated with persistent CD8 T-cell elevation and increased risk of developing non-AIDS comorbidities despite long-term antiretroviral therapy (ART). Herein, we investigated whether CMV seropositivity and elevation of anti-CMV IgG levels were associated with increased epithelial gut damage, microbial translocation, and systemic inflammation. Methods A total of 150 PLWH (79 ART-naive and 71 ART-treated) were compared to 26 without human immunodeficiency virus (HIV) infection (uninfected controls). Plasma markers of HIV disease progression, epithelial gut damage, microbial translocation, nonspecific B-cell activation, anti-CMV and anti–Epstein-Barr virus (EBV) IgG levels, and proinflammatory cytokines were measured. Results CMV seropositivity and elevated anti-CMV IgG levels were associated with markers of epithelial gut damage, microbial translocation, and inflammation in PLWH and participants without HIV infection. In contrast, total nonspecific IgG, immunoglobulin M, immunoglobulin A, and anti-EBV IgG levels were not associated with these markers. CMV seropositivity was associated with markers of epithelial gut damage, microbial translocation, and inflammation independent of sociodemographic and behavioral characteristics of the study population. Conclusions CMV-seropositive people with and without HIV had increased epithelial gut damage, microbial translocation, and inflammation. Furthermore, anti-CMV IgG levels were independently associated with increased epithelial gut damage and microbial translocation. CMV coinfection may partially explain persistent gut damage, microbial translocation, and inflammation in ART-treated PLWH.


2007 ◽  
Vol 82 (1) ◽  
pp. 538-545 ◽  
Author(s):  
Sumathi Sankaran ◽  
Michael D. George ◽  
Elizabeth Reay ◽  
Moraima Guadalupe ◽  
Jason Flamm ◽  
...  

ABSTRACT Gut-associated lymphoid tissue (GALT) is an early target for human immunodeficiency virus type 1 (HIV-1) infection and is a site for severe CD4+ T-cell depletion. HIV-associated enteropathy is well-documented in chronic HIV-1 infection. However, the initial host responses to HIV infection in GALT and the early molecular correlates of HIV enteropathogenesis have not been characterized during primary HIV infection. In this study, we provide evidence of viral replication in GALT resident CD4+ T cells and macrophages in primary-stage patients and identify early patterns of host mucosal responses and changes in the molecular microenvironment through gene expression profiling. High levels of viral replication in GALT and marked CD4+ T-cell depletion correlated with decreased expression levels of genes regulating epithelial barrier maintenance and digestive/metabolic functions. These changes coincided with a marked increase in the transcription of immune activation-, inflammation-, and apoptosis-associated genes. Our findings indicate that HIV-induced pathogenesis in GALT emerges at both the molecular and cellular levels prior to seroconversion in primary HIV infection, potentially setting the stage for disease progression by impairing the ability to control viral replication and repair and regenerate intestinal mucosal tissues.


Author(s):  
Amy Justice

Human Immunodeficiency Virus (HIV) infection, in the era of combination antiretroviral therapy, has become more common among middle-aged and older individuals. Diagnosis and rapid initiation of antiretroviral therapy to suppress the virus below detectable levels are urgent priorities in management. Once achieved, those ageing with HIV infection can expect to live many years, but they remain at increased risk for HIV-associated non-AIDS (HANA) conditions compared to demographically similar uninfected individuals. Because HANA conditions include several forms of cancer, cardiovascular disease, liver disease, and kidney disease, the clinical management of those ageing with HIV is complicated by multimorbidity and polypharmacy at an earlier age than those ageing without HIV infection. The study of ageing with HIV infection may improve our understanding of the effects of long-term viral infection on the ageing process.


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