The association between the ratio of monocytes: lymphocytes and risk of tuberculosis among HIV-infected postpartum women.
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ABSTRACT:
SUBMITTER: Naranbhai V
PROVIDER: S-EPMC4229408 | biostudies-literature | 2014 Dec
REPOSITORIES: biostudies-literature
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The association between the ratio of monocytes: lymphocytes and risk of tuberculosis among HIV-infected postpartum women.
Naranbhai Vivek V Moodley Dhayendre D Chipato Tsungai T Stranix-Chibanda Lynda L Nakabaiito Clemensia C Kamateeka Moreen M Musoke Philippa P Manji Karim K George Kathleen K Emel Lynda M LM Richardson Paul P Andrew Philip P Fowler MaryGlenn M Fletcher Helen H McShane Helen H Coovadia Hoosen M HM Hill Adrian V S AV
Journal of acquired immune deficiency syndromes (1999) 20141201 5
Recent human studies support historical animal studies that suggested an association between peripheral blood monocyte:lymphocyte (ML) ratio and tuberculosis (TB) disease. To evaluate generalizability of this finding, we modeled the association between peripartum ML ratio and incident TB disease within 18 months postpartum among 1202 HIV-infected women in South Africa, Tanzania, Uganda, and Zimbabwe. The ML ratio was associated with increased risk of TB disease independently to combination antir ...[more]
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Project description:BackgroundEight decades ago, the ratio of monocytes to lymphocytes (hereafter, the "ML ratio") was noted to affect outcomes of mycobacterial infection in rabbits. Recent transcriptomic studies support a role for relative proportions of myeloid and lymphoid transcripts in tuberculosis outcomes. The ML ratio in peripheral blood is known to be governed by hematopoietic stem cells with distinct biases.MethodsThe predictive value of the baseline ML ratio was modeled in 2 prospective cohorts of HIV-infected adults starting cART in South Africa (primary cohort, 1862 participants; replication cohort, 345 participants). Incident tuberculosis was diagnosed with clinical, radiographic, and microbiologic methods per contemporary guidelines. Kaplan-Meier survival analyses and Cox proportional hazards modeling were conducted.ResultsThe incidence rate of tuberculosis differed significantly by baseline ML ratio: 32.61 (95% confidence interval [CI], 15.38-61.54), 16.36 (95% CI, 12.39-21.23), and 51.80 (95% CI, 23.10-101.71) per 1000 patient-years for ML ratios of less than the 5th percentile, between the 5th and 95th percentiles, and greater than the 95th percentile, respectively (P = .007). Neither monocyte counts nor lymphocyte counts alone were associated with tuberculosis. After adjustment for sex, World Health Organization human immunodeficiency virus disease stage, CD4(+) T-cell counts, and previous history of tuberculosis, hazards of disease were significantly higher for patients with ML ratios of less than the 5th percentile or greater than the 95th percentile (adjusted hazard ratio, 2.47; 95% CI, 1.39-4.40; P = .002).ConclusionsThe ML ratio may be a useful, readily available tool to stratify the risk of tuberculosis and suggests involvement of hematopoietic stem cell bias in tuberculosis pathogenesis.
| S-EPMC3903371 | biostudies-literature
Project description:BACKGROUND:Recent transcriptomic studies revived a hypothesis suggested by historical studies in rabbits that the ratio of peripheral blood monocytes to lymphocytes (ML) is associated with risk of tuberculosis (TB) disease. Recent data confirmed the hypothesis in cattle and in adults infected with HIV. METHODS:We tested this hypothesis in 1,336 infants (540 HIV-infected, 796 HIV-exposed, uninfected (HEU)) prospectively followed in a randomized controlled trial of isoniazid prophylaxis in Southern Africa, the IMPAACT P1041 study. We modeled the relationship between ML ratio at enrollment (91 to 120 days after birth) and TB disease or death in HIV-infected children and latent Mycobacterium tuberculosis (MTB) infection, TB disease or death in HEU children within 96 weeks (with 12 week window) of randomization. Infants were followed-up prospectively and routinely assessed for MTB exposure and outcomes. Cox proportional hazards models allowing for non-linear associations were used; in all cases linear models were the most parsimonious. RESULTS:Increasing ML ratio at baseline was significantly associated with TB disease/death within two years (adjusted hazard ratio (HR) 1.17 per unit increase in ML ratio; 95% confidence interval (CI) 1.01 to 1.34; P = 0.03). Neither monocyte count nor lymphocyte counts alone were associated with TB disease. The association was not statistically dissimilar between HIV infected and HEU children. Baseline ML ratio was associated with composite endpoints of TB disease and death and/or TB infection. It was strongest when restricted to probable and definite TB disease (HR 1.50; 95% CI 1.19 to 1.89; P = 0.006). Therefore, per 0.1 unit increase in the ML ratio at three to four months of age, the hazard of probable or definite TB disease before two years was increased by roughly 4% (95% CI 1.7% to 6.6%). CONCLUSION:Elevated ML ratio at three- to four-months old is associated with increased hazards of TB disease before two years among children in Southern Africa. While significant, the modest effect size suggests that the ML ratio plays a modest role in predicting TB disease-free survival; its utility may, therefore, be limited to combination with existing tools to stratify TB risk, or to inform underlying pathophysiologic determinants of TB disease.
| S-EPMC4223414 | biostudies-literature
Project description:Data on the prognostic utility of interferon-gamma release assays (IGRAs) for active tuberculosis (TB) among human immunodeficiency virus 1 (HIV-1) infected individuals are limited.Samples from a perinatal cohort of HIV-1-infected women in Kenya, obtained during pregnancy, were tested using T-SPOT®.TB IGRAs to detect Mycobacterium tuberculosis-specific interferon-gamma (IFN-?) responses. IFN-? (cut-off values of >0, ?6 and ?10 spot-forming cells [SFC]/well) and CD4 cell count (cut-off values of <250 and <350 cells/l) were evaluated to determine sensitivity and specificity using a time-dependent receiver operating characteristic curve and positive predictive value (PPV) using the Kaplan Meier method for future TB within 1 year postpartum.Of 327 women, 9 developed TB within 1 year postpartum (incidence rate 3.5/100 person-years of follow-up, 95%CI 1.66.7). IFN-? ? 6 SFC/well was associated with an optimal trade-off between sensitivity (78%) and specificity (55%) and a PPV of 5.9%. In women with CD4 cell count of <250 cells/?l, the sensitivity and specificity of IFN- 6 SFC/well were respectively 89% and 63%, and the PPV was 19.2%.Among HIV-1 infected women, IFN-? response (?6 SFC/well) during pregnancy lacked a high PPV for postpartum TB, but had higher sensitivity and PPV among immunosuppressed women (CD4 cell count of <250 cells/?l).
| S-EPMC4339676 | biostudies-literature
Project description:BACKGROUND:The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS:In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS:A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS:The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).
| S-EPMC7051859 | biostudies-literature
Project description:Dual method use, use of condoms plus another effective contraceptive method, is important in settings with high rates of unintended pregnancy and HIV infection. We evaluated the association of HIV status with dual method use in a cohort of postpartum women. Women completed baseline surveys in the postpartum ward and telephone surveys about contraceptive use 3, 6, and 12 months later. Nonpregnant women who completed at least one follow-up survey were eligible for this secondary analysis. Prevalence ratios were calculated using generalized estimating equations. Of the 511 sexually active women who completed a follow-up survey, condom use increased from 17.6% to 27.7% and nonbarrier contraceptive use increased from 73.8% to 87.6% from 3 to 12 months after delivery. Dual method use increased from 1.0% to 18.9% at 3 to 12 months after delivery. Dual method use was negligible and comparable between HIV-infected and HIV-uninfected women at 3 months but significantly higher among HIV-infected women at 6 months (APR = 3.9, 95% CI 2.2, 7.1) and 12 months (APR = 2.7, 95% CI 1.7, 4.3). Dual method use was low but largely driven by condom use among HIV-infected women at 6 and 12 months after delivery.
| S-EPMC5540462 | biostudies-other
Project description:The ratio of monocytes and lymphocytes (ML ratio) in peripheral blood is associated with tuberculosis and malaria disease risk and cancer and cardiovascular disease outcomes. We studied anti-mycobacterial function and the transcriptome of monocytes in relation to the ML ratio. Mycobacterial growth inhibition assays of whole or sorted blood were performed and mycobacteria were enumerated by liquid culture. Transcriptomes of unstimulated CD14 + monocytes isolated by magnetic bead sorting were characterised by microarray. Transcript expression was tested for association with ML ratio calculated from leucocyte differential counts by linear regression. The ML ratio was associated with mycobacterial growth in vitro (β = 2.23, SE 0.91, p = 0.02). Using sorted monocytes and lymphocytes, in vivo ML ratio (% variance explained R(2) = 11%, p = 0.02) dominated over in vitro ratios (R(2) = 5%, p = 0.10) in explaining mycobacterial growth. Expression of 906 genes was associated with the ML ratio and 53 with monocyte count alone. ML-ratio associated genes were enriched for type-I and -II interferon signalling (p = 1.2 × 10(− 8)), and for genes under transcriptional control of IRF1, IRF2, RUNX1, RELA and ESRRB. The ML-ratio-associated gene set was enriched in TB disease (3.11-fold, 95% CI: 2.28-4.19, p = 5.7 × 10(− 12)) and other inflammatory diseases including atopy, HIV, IBD and SLE. The ML ratio is associated with distinct transcriptional and anti-mycobacterial profiles of monocytes that may explain the disease associations of the ML ratio.
| S-EPMC4740301 | biostudies-literature
Project description:Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown.We analyzed prospective data from 447 HIV-infected women (18-49 years) initiating ART in rural Uganda (2005-2012). Participants completed blood work and comprehensive questionnaires quarterly. Pregnancy status was assessed by self-report. Analysis time periods were defined as currently pregnant, postpartum (0-12 months post-pregnancy outcome), or non-pregnancy-related. Depression symptom severity was measured using a modified Hopkins Symptom Checklist 15, with scores ranging from 1 to 4. Probable depression was defined as >1.75. Linear regression with generalized estimating equations was used to compare mean depression scores over the 3 periods.At enrollment, median age was 32 years (interquartile range: 27-37), median CD4 count was 160 cells per cubic millimeter (interquartile range: 95-245), and mean depression score was 1.75 (s = 0.58) (39% with probable depression). Over 4.1 median years of follow-up, 104 women experienced 151 pregnancies. Mean depression scores did not differ across the time periods (P = 0.75). Multivariable models yielded similar findings. Increasing time on ART, viral suppression, better physical health, and "never married" were independently associated with lower mean depression scores. Findings were consistent when assessing probable depression.Although the lack of association between depression and perinatal periods is reassuring, high depression prevalence at treatment initiation and continued incidence across pregnancy and non-pregnancy-related periods of follow-up highlight the critical need for mental health services for HIV-infected women to optimize both maternal and perinatal health.
| S-EPMC4251908 | biostudies-literature
Project description:ObjectiveTo determine time from delivery to resumption of sexual activity and menses among HIV-infected women on antiretroviral treatment (ART) and HIV-uninfected women.MethodsHIV-infected women on ART and HIV-uninfected women were recruited from five health facilities at delivery and followed prospectively for a maximum of 1 year in Blantyre, Malawi from January 2016 to September 2017. Sociodemographic, clinical, and laboratory data were collected at delivery and 1.5, 3, 6, 9, and 12 months. Descriptive, time to event Kaplan-Meier, and multivariable Cox proportional hazards analyses were conducted.ResultsData on 878 women (460 [52.4%] HIV-uninfected and 418 [47.6%] HIV-infected, P=0.156) who attended at least one follow-up visit were analyzed. Among HIV-uninfected compared to HIV-infected women, respectively, the median number of days to resumption of sexual activity was 180 vs 181; to irregular menses was 82 vs 71; and to regular menses was 245 vs 366. In multivariable models, being married was associated with early resumption of sexual activity (hazard ratio [HR] 1.91, P<0.001), and being HIV-infected and use of an effective method of family planning were associated with later start of regular menses (HR<1.0, P<0.050).ConclusionCounseling of women on reproductive intentions should start early irrespective of HIV infection or use of ART.
| S-EPMC7152561 | biostudies-literature
Project description:People living with HIV (PLWH) have chronic immune activation and increased cardiovascular disease (CVD) risk. Activation of monocytes and T lymphocytes causes upregulation of glucose transporter-1 (GLUT1) for efficient function. PLWH have an increased percentage of GLUT1-expressing monocytes and T lymphocytes, but it is unclear if these cells are associated with CVD. We evaluated the expression of GLUT1 and CD38 on monocyte and T lymphocyte populations from HIV-infected women with subclinical CVD.Participants with more than 75th percentile (n?=?15) and less than 25th percentile (n?=?15) age-adjusted intima-media thickness (IMT) at the right common carotid artery and bifurcation were identified from the Women's Interagency HIV Study. Groups were matched by age, race/ethnicity, smoking status, and CD4 cell count. All women were receiving suppressive antiretroviral therapy except for one high and one low IMT participant. Monocyte and T lymphocyte populations were evaluated for GLUT1 and CD38 expression using flow cytometry.Intermediate monocytes from high IMT women had significantly increased expression of GLUT1 (310 MFI vs. 210 MFI, P?=?0.024) (66.4% vs. 48.5%, P?=?0.031) and CD38 (339 MFI vs. 211 MFI, P?=?0.002) (10.5% vs. 3.8%, P?=?0.0002) compared with women with low IMT. High and low IMT participants showed no differences in GLUT1 or CD38 expression on classical monocytes, nonclassical monocytes, CD4 and CD8 T lymphocytes.GLUT1-expressing intermediate monocytes are elevated in HIV-infected women with subclinical CVD. These cells may contribute to development of CVD in PLWH and could be a novel target to limit inflammation.
| S-EPMC5393043 | biostudies-literature
Project description:The effect that HIV type 1 (HIV) has on neurocognition is a dynamic process whereby peripheral events are likely involved in setting the stage for clinical findings. In spite of antiretroviral therapy (ART), patients continue to be at risk for HIV-associated neurocognitive disorders (HAND), which might be related to persistence of inflammation. In a yearly assessment of HIV DNA levels in activated monocytes, increased HIV DNA copies were found in patients with persistent HAND. Furthermore, activated monocytes from patients with high HIV DNA copies secreted more inflammatory cytokines. Since these activated monocytes traffic to the CNS and enter the brain, they may contribute to an inflammatory environment in the CNS that leads to HAND.
| S-EPMC3335340 | biostudies-literature