Effect of Antiretroviral Therapy on the Memory and Activation Profiles of B Cells in HIV-Infected African Women.
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SUBMITTER: Tanko RF
PROVIDER: S-EPMC5263028 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe impact of antiretroviral therapy (ART) initiation on the vaginal microbiome is unknown. This is of particular importance among women living in sub-Saharan Africa. Understanding this relationship could help elucidate if and how the host immune system interacts with the vaginal microbiome.MethodsThe vaginal microbiome of HIV-1/HSV-2-coinfected women (n = 92) in Uganda was evaluated from self-collected vaginal swabs 1 month pre-ART and at 4 and 6 months post-ART initiation. The vaginal microbiome was characterized by 16S rRNA gene-based sequencing and quantitative polymerase chain reaction. Vaginal community state types (CSTs) were identified using proportional abundance data. Changes in microbiome composition were assessed with permutational analyses of variance (PerMANOVA).ResultsFive vaginal CSTs were identified, which varied significantly by bacterial load (P < .01): CST-1 was characterized by Lactobacillus iners, CST-2 by Gardnerella, CST-3 by Gardnerella and Prevotella, CST-4 by Lactobacillus crispatus, and CST-5 was highly diverse. Vaginal microbiome composition also did not change significantly after ART initiation (P = .985). Immune reconstitution after ART initiation did not affect vaginal microbiome CST assignment (P = .722) or individual-level changes in bacterial load (log response ratio [interquartile range], -0.50 [-2.75 to 0.38] vs -0.29 [-2.03 to 1.42]; P = .40).ConclusionsThe vaginal microbiome of HIV-infected women was not affected by the initiation of ART or immune reconstitution in this observational study. Further research is needed to explore the long-term effects of ART treatment on the vaginal microbiome.
| S-EPMC6798248 | biostudies-literature
Project description:OBJECTIVES:To estimate age at attaining Tanner stages in Ugandan/Zimbabwean HIV-infected children initiating antiretroviral therapy (ART) in older childhood and investigate predictors of delayed puberty, particularly age at ART initiation. DESIGN:Observational analysis within a randomized trial. METHODS:Tanner staging was assessed every 24 weeks from 10 years of age, menarche every 12 weeks and height every 4-6 weeks. Age at attaining different Tanner stages was estimated using normal interval regression, considering predictors using multivariable regression. Growth was estimated using multilevel models with child-specific intercepts and trajectories. RESULTS:Median age at ART initiation was 9.4 years (inter-quartile range 7.8, 11.3) (n?=?582). At the first assessment, the majority (80.2%) were in Tanner stage 1; median follow-up with staging was 2.8 years. There was a strong delaying effect of older age at ART initiation on age at attaining all Tanner stages (P?<?0.05) and menarche (P?=?0.02); in boys the delaying effect generally weakened with older age. There were additional significant delays associated with greater impairments in pre-ART height-for-age Z-score (P?<?0.05) in both sexes and pre-ART BMI-for-age in girls (P?<?0.05). There was no evidence that pre-ART immuno-suppression independently delayed puberty or menarche. However, older children/adolescents had significant growth spurts in intermediate Tanner stages, and were still significantly increasing their height when in Tanner stage 5 (P?<?0.01). CONCLUSION:Delaying ART initiation until older childhood substantially delays pubertal development and menarche, independently of immuno-suppression. This highlights that factors other than CD4, such as pubertal development, need consideration when making decisions about timing of ART initiation in older children.
| S-EPMC4342414 | biostudies-literature
Project description:As antiretroviral therapy (ART) expands in resource-limited settings, understanding the impact of ART on pregnancy outcomes is critical. We analyzed women who became pregnant on ART while enrolled in a clinical trial (HPTN 052, ACTG A5208, and ACTG A5175); the majority of women were from Africa, with a median age of 29 years. Eligible women were on ART at conception and had a documented date of a last menstrual period and a pregnancy outcome. The primary outcome was non-live birth (stillbirth; spontaneous abortion; elective termination; or ectopic pregnancy) versus live birth. Preterm birth (<37 weeks completed gestation) was a secondary outcome. We used Cox proportional hazards regression models with time-varying covariates. 359 women became pregnant, of whom 253 (70%) met inclusion criteria: 127 (50%) were on NNRTI-based ART, 118 (47%) on PI-based ART, and 8 (3%) on 3-NRTIs at conception. There were 160 (63%) live births (76 term and 84 preterm), 11 (4%) stillbirths, 51 (20%) spontaneous abortions, 28 (11%) elective terminations, and 3 (1%) ectopic pregnancies. In multivariable analysis adjusted for region, parent study, and pre-pregnancy ART class, only older age was associated with increased hazard of preterm birth [HR: 2.49 for age 25-30 years; 95% CI: 1.18-5.26; p = 0.017]. Women conceiving on ART had high rates of preterm birth and other adverse pregnancy outcomes. Despite the benefits of ART, studies designed to investigate the effects of preconception ART on pregnancy outcomes are needed.
| S-EPMC6051581 | biostudies-literature
Project description:In epidemiologic studies, human immunodeficiency virus (HIV)-infected men on antiretroviral therapy (ART) are at higher risk of incident diabetes mellitus compared with women with similar treatment histories. We used metabolomics to determine whether a sex difference in plasma amino acids, acylcarnitines, and organic acids predictive of diabetes and impaired energy metabolism is present in HIV-infected persons on long-term ART.We enrolled 70 HIV-infected adults (43% women) on efavirenz, tenofovir, and emtricitabine (Atripla) with HIV-1 RNA <50?copies/mL for over 2 years. Half of the HIV-infected subjects were obese, and these were matched with 30 obese HIV-negative controls. All subjects had no history of diabetes, statin use, or heavy alcohol use. Fasting insulin sensitivity was measured using homeostatic model assessment 2 (HOMA2), and adipose tissue was measured using dual-energy x-ray absorptiometry (DEXA). Liquid chromatography/mass spectrometry was used to quantitate fasting plasma branched chain and aromatic amino acids predictive of incident diabetes, and C3 and C5 acylcarnitinines and organic acids indicative of impaired energy metabolism.HIV-infected women had more baseline risk factors for insulin resistance: women were older (46 vs 44 years) and had a longer ART duration (8.4 vs 5.1 years, P?<?0.05 for both) compared with men but had similar CD4+ count (median 701?cells/?L), smoking and hepatic C prevalence, and body mass index (BMI) (median 30.3?kg/m). However, women had higher insulin sensitivity compared with men (P?<?0.01), and lower plasma levels of isoleucine, leucine, valine, phenylalanine, and tyrosine (P?<?0.01 for all), and lower C3 and C5 acylcarnitines (P?<?0.01 for all), in multivariable regression models after adjusting for DEXA fat mass index, age, race, CD4+ count, smoking, and ART duration. In the obese HIV-infected subjects and HIV-negative controls, the relationship of sex and plasma metabolite levels did not significantly differ according to HIV-status.HIV-infected women on non-nucleoside reverse transcriptase inhibitor-based ART had superior glucose tolerance and lower plasma metabolites associated with the development of diabetes compared with men with similar metabolic disease risk profiles. The relationship between sex and plasma metabolite levels did not significantly differ according to HIV-status among obese subjects, suggesting the observed sex-differences may not be specific to HIV infection.
| S-EPMC4902518 | biostudies-literature
Project description:ObjectivesTo determine the incidence, clinical manifestations and risk factors for immune reconstitution inflammatory syndrome (IRIS) in young children initiating highly active antiretroviral therapy (HAART).DesignA prospective cohort of antiretroviral-naïve HIV-infected children less than 24 months of age enrolled in a treatment strategies trial in Johannesburg, South Africa.MethodsAmong 169 HIV-infected children initiating HAART, April 2005 to November 2006, the records of 83 children suspected to have IRIS within 6 months of starting treatment were reviewed to determine whether they met criteria for IRIS. Seven were excluded due to incomplete follow-up. Pretreatment and post-treatment characteristics of children with and without IRIS were compared.ResultsOverall, 34/162 (21%) children developed IRIS at a median of 16 days (range 7-115 days) post-HAART initiation. Bacille Calmette-Guérin reaction was most common occurring in 24/34 (71%) children, primarily injection site lesions and/or ipsilateral axillary lymphadenitis with abscess. Other IRIS conditions (not mutually exclusive) included Mycobacterium tuberculosis (n = 12), cytomegalovirus pneumonia (n = 1), Streptococcus pneumonia sepsis (n = 1), and severe seborrheic dermatitis (n = 1). Children with IRIS were younger (median age 7 vs. 10 months, P = 0.007) with a lower CD4 cell percentage (median 13.9 vs. 19.2, P = 0.009) at HAART initiation than controls. After 24 weeks on HAART, 62% of IRIS cases vs. 28% of controls had HIV RNA more than 400 copies/ml (P = 0.001), odds ratio = 2.88 (95% confidence interval = 1.14-7.29) after adjusting for baseline factors.ConclusionInfants and young children with advanced HIV disease initiating HAART are at high risk for developing IRIS, leading to additional morbidity and possibly impairing virologic response to antiretroviral treatment.
| S-EPMC2810152 | biostudies-literature
Project description:Type 2 diabetes mellitus incidence is increased in HIV-infected persons. We examined the associations of diabetes mellitus with known diabetes mellitus-risk alleles from the general population in the context of HIV infection, and explored effect modification by combination antiretroviral therapy (cART).The Women's Interagency HIV Study is a prospective cohort of HIV-infected women. Seventeen European-derived diabetes mellitus-risk polymorphisms were genotyped in the eligible participants of the Women's Interagency HIV Study. Analyses were run separately for non-African Americans (Whites, Hispanics, Asians, and other; n?=?378, 49 with incident diabetes mellitus) and African Americans (n?=?591, 49 with incident diabetes mellitus). Cox proportional-hazards models were fit to estimate hazard ratios for diabetes mellitus overall and within strata of cART.In non-African Americans, heterogeneity across cART regimen was observed for nine of the 14 polymorphisms (phet?<?0.05). One polymorphism was statistically significantly inversely associated with diabetes mellitus risk among women taking two nucleotide reverse transcriptase inhibitors (NRTIs) + non-nucleotide reverse transcriptase inhibitor (NNRTI). Five polymorphisms were statistically significantly associated with diabetes mellitus among women treated with at least two NRTIs?+?at least one protease inhibitor and one polymorphism was associated with diabetes mellitus among those treated with at least three NRTIs?±?NNRTI. The hazard ratio per risk allele for IGF2BP2 rs1470579 was 2.67 (95% confidence interval 1.67-4.31) for women taking cART with at least two NRTIs?+?at least one protease inhibitor and 2.45 (95% confidence interval 1.08-5.53) in women taking at least three NRTIs?±?NNRTI (phet?=?2.50?×?10?³). No such associations were observed in the African Americans.Genetic susceptibility to diabetes mellitus, based on the variants studied, is substantially elevated among HIV-infected women using cART containing three or more NRTI/protease inhibitor components. A personalized medicine approach to cART selection may be indicated for HIV-infected persons carrying these diabetes mellitus-risk variants.
| S-EPMC4269472 | biostudies-literature
Project description:BACKGROUND:While extensive research has explored pharmacokinetic interactions between antiretroviral therapy and hormonal contraception, few studies have examined whether these interactions affect clinical outcomes. To address this gap, we conducted a systematic review of the literature that describes hormonal contraceptive among HIV infected women who also antiretroviral therapy, focusing on papers that address clinically important outcomes such as pregnancy or ovulation. METHODS:An electronic literature search was conducted of PUBMED and OVID to identify all articles that addressed hormonal contraception co-administered with antiretroviral therapy published in English between 01 January 1990 and 30 October 2014. In addition, manual reference checks of all articles of interest were conducted to identify articles not captured in the electronic search. Our search criteria identified 405 records. The title and abstract of data reports retrieved via the search were reviewed to identify potential articles of interest. Those with any indication of the main outcomes of interest were considered for inclusion (N=162). Abstracts were then reviewed to identify those manuscripts that would merit a review of the full text version (N=64). Eight articles that addressed the outcomes of interest were identified. The Newcastle-Ottawa Scale was used to assess the quality of these articles. RESULTS:The studies reviewed were limited in a number of ways that precluded their providing a rigorous assessment of the efficacy of contraception when co-administered with antiretroviral therapy. DISCUSSION:None of the studies were of adequate quality to provide the guidance that providers and HIV infected women need when considering contraceptive options. High quality, well-powered studies are required to address the efficacy of hormonal contraception when co-administered with antiretroviral therapy.
| S-EPMC5611808 | biostudies-literature
Project description:Anaemia has been linked with mortality in HIV infection. The mechanism of anaemia in the era of contemporary antiretroviral therapy is not understood. The aim of this study was to describe the association between anaemia and markers of immune activation and inflammation in a cohort of HIV-infected adults on stable antiretroviral therapy.We performed a cross-sectional study of HIV-infected adults on antiretroviral therapy with HIV-1 RNA<1,000 copies/ml. Soluble and cellular markers of inflammation and immune activation were measured. Relationships between haemoglobin levels, anaemia (haemoglobin <13 g/dl for men and <12 g/dl for women) and mild anaemia (haemoglobin <14 g/dl for men and <13 g/dl for women) and these markers were explored using multivariable linear regression.Among the 147 participants, median age was 46 years, 78% were men, 68% were African American and 29% were Caucasian. Median body mass index (BMI) was 26.7 kg/m(2), nadir and current CD4(+) T-cell counts were 179 and 613 cells/mm(3), respectively, and 78% had HIV-1 RNA<50 copies/ml (range 20-600 copies/ml). Median (IQR) haemoglobin was 14.3 (13.1-15.1) g/dl; 14% were anaemic and 33% had at least mild anaemia. In multivariable analyses, mild anaemia was independently associated with female sex, older age, shorter duration of antiretroviral therapy, lower white blood cell count, higher platelet count, higher sCD14 and a greater number of CD14(dim)CD16(+) cells or 'patrolling' monocytes, which remained significant after further adjusting for race and BMI.Having haemoglobin <14 g/dl for men and <13 g/dl for women was independently associated with monocyte activation (sCD14 and CD14(dim)CD16(+) cells) in HIV-infected adults on stable antiretroviral therapy.
| S-EPMC4531107 | biostudies-literature
Project description:BackgroundHuman immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa.MethodsBeginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged >40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT).ResultsA total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01).ConclusionsPersistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region.
| S-EPMC4704672 | biostudies-literature
Project description:INTRODUCTION:The 2016 WHO consolidated guidelines on the use of antiretroviral drugs defines HIV virologic failure for low and middle income countries (LMIC) as plasma HIV-RNA ? 1000 copies/mL. We evaluated virologic failure and predictors in four African countries. MATERIALS AND METHODS:We included HIV-infected participants on a WHO recommended antiretroviral therapy (ART) regimen and enrolled in the African Cohort Study between January 2013 and October 2017. Studied outcomes were virologic failure (plasma HIV-RNA ? 1000 copies/mL at the most recent visit), viraemia (plasma HIV-RNA ? 50 copies/mL at the most recent visit); and persistent viraemia (plasma HIV-RNA ? 50 copies/mL at two consecutive visits). Generalized linear models were used to estimate relative risks with their 95% confidence intervals. RESULTS:2054 participants were included in this analysis. Viraemia, persistent viraemia and virologic failure were observed in 396 (19.3%), 160 (7.8%) and 184 (9%) participants respectively. Of the participants with persistent viraemia, only 57.5% (92/160) had confirmed virologic failure. In the multivariate analysis, attending clinical care site other than the Uganda sitebeing on 2nd line ART (aRR 1.8, 95% CI 1·28-2·66); other ART combinations not first line and not second line (aRR 3.8, 95% CI 1.18-11.9), a history of fever in the past week (aRR 3.7, 95% CI 1.69-8.05), low CD4 count (aRR 6.9, 95% CI 4.7-10.2) and missing any day of ART (aRR 1·8, 95% CI 1·27-2.57) increased the risk of virologic failure. Being on 2nd line therapy, the site where one receives care and CD4 count < 500 predicted viraemia, persistent viraemia and virologic failure. CONCLUSION:In conclusion, these findings demonstrate that HIV-infected patients established on ART for more than six months in the African setting frequently experienced viraemia while continuing to be on ART. The findings also show that being on second line, low CD4 count, missing any day of ART and history of fever in the past week remain important predictors of virologic failure that should trigger intensified adherence counselling especially in the absence of reliable or readily available viral load monitoring. Finally, clinical care sites are different calling for further analyses to elucidate on the unique features of these sites.
| S-EPMC6363169 | biostudies-literature