Human Immunodeficiency Virus Disease Progression Research Articles

Expert Consensus Statement on an Updated Definition of Unintended Weight Loss Among Persons With Human Immunodeficiency Virus in the Modern Treatment Era.

The era of modern antiretroviral therapy (ART) has markedly improved health and survival among persons with human immunodeficiency virus (HIV) (PWH). In the pre-ART era, wasting was associated with HIV disease progression to acquired immunodeficiency syndrome and death. Effective ART has reduced the prevalence and incidence of this pre-ART form of HIV-associated wasting. However, a subgroup of ART-treated virally suppressed PWH continue to lose weight, often accompanied by aging-related comorbidities and/or functional deficits. For this subgroup of patients, the older definition of HIV-associated wasting (HIVAW) cannot and should not be applied. An expert panel comprising the authors of this white paper convened to review the existing definition of HIVAW and to create an updated definition that they termed HIV-associated weight loss, based on clinically defined parameters among contemporary PWH receiving ART. Here, clinical features and laboratory biomarkers associated with HIV-associated weight loss are reviewed and approaches to screening and treatment are considered. Available management approaches, including the use of current US Food and Drug Administration-approved medications for HIVAW and other available therapies are discussed. The expert panel also identified knowledge gaps and provided recommendations for clinicians, payers, and researchers.

Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection.

Chronic Human Immunodeficiency Virus (HIV) infection remains a significant challenge to global public health. Despite advances in antiretroviral therapy (ART), which has transformed HIV infection from a fatal disease into a manageable chronic condition, a definitive cure remains elusive. One of the key features of HIV infection is chronic immune activation and inflammation, which are strongly associated with, and predictive of, HIV disease progression, even in patients successfully treated with suppressive ART. Chronic inflammation is characterized by persistent inflammation, immune cell metabolic dysregulation, and cellular exhaustion and dysfunction. This review aims to summarize current knowledge of the interplay between chronic inflammation, immune metabolism, and T cell dysfunction in HIV infection, and also discusses the use of humanized mice models to study HIV immune pathogenesis and develop novel therapeutic strategies.

Review on Bariatric Surgery in Human Immunodeficiency Virus Patients

Bariatric surgery (BS) is a surgical intervention that aims to reduce excess body weight and improve obesity-related comorbidities. Obesity is a growing health problem among patients with human im¬munodeficiency virus (HIV) infection, especially with the widespread use of antiretroviral therapy (ART). However, there is limited evidence on the safety and efficacy of bariatric surgery in this pop¬ulation. This review summarizes the current knowledge on bariatric surgery in HIV patients, focusing on the types of procedures, the impact on HIV-related outcomes, antiretroviral considerations, concerns, and possible complications. The available data suggest that bariatric surgery is safe and well tolerated in HIV-infected individuals and does not adversely affect HIV disease progression or virologic suppression. However, bariatric surgery may increase the risk of postoperative complications such as strictures and micronutrient deficiencies and may require adjustments in ART regimens due to altered pharmacokinetics. Therefore, careful selection of candidates, multidisciplinary collaboration, and close monitoring are essential for optimal outcomes. Further studies are needed to evaluate the long-term effects of bariatric surgery in HIV patients and to compare different surgical techniques.

Integrated analysis of gut and oral microbiome in men who have sex with men with HIV Infection.

Human immunodeficiency virus (HIV) infection leads to severe deficiency in host immunity by depletion of CD4+ T-cells, resulting in an imbalance between the human microbiome and host immune response. Alterations in both gut and oral microbiomes have been observed in people living with HIV (PLWH). However, the impact of an altered gut and oral microbiome on HIV disease progression and the relationship between them in PLWH have not been explored. In this longitudinal study, we enrolled acute HIV-infected men who have sex with men (MSM) (n = 15), chronic HIV-infected MSM (n = 15), and HIV-uninfected MSM controls (n = 15). We collected anal and throat swab samples at recruitment (W0) from all participants and at 12 wk after antiretroviral therapy (ART) (W12) from the patients and performed 16S rRNA gene sequencing of genomic DNAs extracted from these swabs. In HIV-infected individuals with CD4 T-cell counts < 350 cells/µL, the increase in abundance of Streptococcus in the oral microbiome was inversely correlated with that of Streptococcus in the gut microbiome (r = -0.490, P = 0.039). In addition, the lower CD4+ T-cell counts (<200 cells/µL) were associated with the higher abundance of Escherichia-Shigella and the lower abundance of Methylobacterium-Methylorubrum of the gut microbiome in HIV-infected individuals. We demonstrate the alteration of gut microbiome resulting from HIV infection and ART and the relationship between the gut and oral microbiome in PLWH and controls. These findings highlight the need for a better understanding of the interactions between the oral and gut microbiome and its potential role in HIV disease progression. IMPORTANCE Our longitudinal integrated study has shown the marked alterations in the gut and oral microbiome resulting from acute and chronic HIV infection and from antiretroviral therapy. Importantly, the relationship between oral and gut microbiomes in people living with acute and chronic HIV infection and "healthy" controls has also been explored. These findings might contribute to a better understanding of the interactions between the oral and gut microbiomes and its potential role in HIV disease progression.

Severe intestinal barrier damage in HIV-infected immunological non-responders

The intestinal epithelial barrier plays an important role during human immunodeficiency virus (HIV) disease progression. However, the extent to which the intestinal epithelial barrier is damaged in immunological non-responders (INRs) and immunological responders (IRs) is largely unknown. In this study, we investigated and compared the levels of intestinal gland damage and related molecules, including the tight junction protein claudin-1, apoptosis marker caspase-3, HIV DNA, CD4+ T cell count, and inflammation marker tumor necrosis factor-α (TNF-α) among the IRs (n = 10), INRs (n = 8), and healthy controls (HCs, n = 7). Intestinal damage was not completely restored in both INRs and IRs and was more serious in INRs than that in IRs. Moreover, intestinal damage was positively correlated with HIV DNA levels and negatively correlated with CD4+ T cell counts. These results provide insight into understanding the characteristics of intestinal epithelial barrier damage between IRs and INRs.

Comparison of the Biological Basis for Non-HIV Transmission to HIV-Exposed Seronegative Individuals, Disease Non-Progression in HIV Long-Term Non-Progressors and Elite Controllers.

HIV-exposed seronegative individuals (HESIs) are a small fraction of persons who are multiply exposed to human immunodeficiency virus (HIV), but do not exhibit serological or clinical evidence of HIV infection. In other words, they are groups of people maintaining an uninfected status for a long time, even after being exposed to HIV several times. The long-term non-progressors (LTNPs), on the other hand, are a group of HIV-infected individuals (approx. 5%) who remain clinically and immunologically stable for an extended number of years without combination antiretroviral therapy (cART). Meanwhile, elite controllers are comprise a much lower number (0.5%) of HIV-infected persons who spontaneously and durably control viremia to below levels of detection for at least 12 months, even when using the most sensitive assays, such as polymerase chain reaction (PCR) in the absence of cART. Despite the fact that there is no universal agreement regarding the mechanisms by which these groups of individuals are able to control HIV infection and/or disease progression, there is a general consensus that the mechanisms of protection are multifaceted and include genetic, immunological as well as viral factors. In this review, we analyze and compare the biological factors responsible for the control of HIV in these unique groups of individuals.

CRISPR and gene editing in HIV therapy: A scoping review

Human immunodeficiency virus (HIV) is nowadays one of the major health problems worldwide. Several strategies have been explored for the eradication of latent HIV-1 reservoirs, current antiretroviral therapy stops the progression of HIV disease, however, as new therapies are being developed, CRISPR (clustered regularly interspaced short palindromic repeats) systems have recently been used as a genome editing technique. CRISPR is becoming progressively one of the possible cures, although it remains experimental, for HIV in medical research. This systematic review summarizes literature evidence of CRISPR gene editing in HIV/AIDS therapy. This study also identifies the research gaps in the current literature, helping to guide future research.

SG-APSIC1042: Cutaneous cryptococcosis in patient with advanced HIV disease: Is it possible to give antifungal monotherapy?

Objectives:Cryptococcus infection is one of the major human immunodeficiency virus (HIV)–related opportunistic infections, and the CD4 count falls below 100 per µL. Primary treatment for HIV-associated cutaneous cryptococcosis is amphotericin B (AmB) plus flucytosine. Methods: We present the case of a man with advanced HIV disease who developed whole-body cutaneous lesions yet improved with high-dose fluconazole alone. Results: A 33-year-old Asian man with a medical history of pulmonary tuberculosis and cryptococcal meningitis with complete treatment, injection drug use, and HIV infection with default of antiretroviral treatments (ART) 3 years earlier, presented to the emergency department with fever, oral thrush, and 30-pound weight loss over 6 weeks. He also had plaques, multiple hard papulonodules with central ulceration, and macular skin lesions all over his body of varying size. Blood cultures were negative for bacteria growth, but fungal microscopy of the blood culture showed unspecific hypha. Histopathology examination of the skin biopsy showed a classic “soap bubble” appearance, which is associated with Cryptococcus infection. Laboratory values revealed anemia (8.6 g/dL), leukopenia (2.9 ×109/L), lymphopenia (58/µL), and thrombocytopenia (145 ×109/L). The CD4 cell count was 18/µL, and the serum viral load was 638.665 copies/mL. Lumbar puncture could not be performed due to patient refusal. Treatment with high-dose fluconazole (1,200 mg) for 3 months was initiated and is planned to continue with consolidation and maintenance dose. ART was administered 4 weeks after starting antifungal therapy. His fever resolved and slow regression of the skin lesions occurred after treatment was given. Conclusions: Cutaneous cryptococcosis was assessed by biopsy of the cutaneous lesion, which is essential to confirming the diagnosis. In the case of cryptococcosis, skin infection may indicate a further progression of advanced HIV disease. In HIV-infected patients with Cryptococcus findings in any part of the body, a lumbar puncture should be considered to rule out central nervous system infection. Although neither AmB nor flucytosine was given due to unavailability in this area, the patient improved. In resource-limited settings, high-dose fluconazole alone may be useful as an alternative treatment, although it is also very challenging.

Influence of genetic variability in toll-like receptors (TLR 2, TLR 4, and TLR 9) on human immunodeficiency virus-1 disease progression.

It has been demonstrated that toll-like receptors (TLR2), TLR4, and TLR9 which were initially known for recognizing bacterial products are involved in the detection of viral components. It was planned to undertake a prospective longitudinal study among ethnically homogeneous antiretroviral treatment and antitubercular treatment naïve human immunodeficiency virus (HIV)-positive patients representing the north Indian population. The aim of the study was to investigate the influence of TLR2, TLR4, and TLR9 polymorphism in HIV disease progression. The present study was designed to investigate genetic polymorphism in TLRs (TLR2, TLR4, and TLR9) among HIV-infected patients with and without TB coinfection. The study population consisted of two groups: (i) HIV-positive patients without TB infection and disease (n = 223, HIV-positive patients); (ii) HIV-positive patients with latent tuberculosis infection (LTBI) (n = 150, HIV-positive LTBI patients). These participants were of either gender between 18 and 60 years of age and treatment naïve for both TB and HIV. HIV-positive and HIV-positive LTBI patients were longitudinally followed up for t2 years to study HIV disease progression. On comparing TLR2 and TLR4 allelic and genotypic frequencies between 306 HIV-positive patients (no TB/AIDS) and 47 HIV-positive patients progressed to active TB/AIDS, no significant difference was observed between the two groups. The frequency of "A" allele in TLR9 was found to be significantly increased in 47 HIV-positive patients who progressed to active TB/AIDS (61.7%) as compared to 42.16% in 306 HIV-positive patients (no TB/AIDS), (P < 0.001). Furthermore, a significantly increased frequency of "AA" genotype in TLR9 was observed in 47 HIV-positive patients progressed to active TB/AIDS (55.32%) as compared to 20.26% in HIV-positive patients (no TB/AIDS). Findings of the present study revealed that genetic variability in TLR9 may influence HIV disease progression. The AA genotype in TLR9 may be associated with progression to TB/AIDS for 2 years in HIV-positive patients.

Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners.

Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection by various mechanisms, there is lack of information on the role of DUBs in virus regulation, which needs to be further investigated. Immunoblotting, real-time polymerase chain reaction, in vivo / in vitro deubiquitination, protein immunoprecipitation, immunofluorescence, and co-localization biological techniques were employed to examine the effect of ubiquitin-specific protease 3 (USP3) on APOBEC3G (A3G) stability and human immunodeficiency virus (HIV) replication. To analyse the relationship between USP3 and HIV disease progression, we recruited 20 HIV-infected patients to detect the levels of USP3 and A3G in peripheral blood and analysed their correlation with CD4 + T-cell counts. Correlation was estimated by Pearson correlation coefficients (for parametric data). The results demonstrated that USP3 specifically inhibits HIV-1 replication in an A3G-dependent manner. Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner. It also enhances the A3G messenger RNA (mRNA) level by binding to A3G mRNA and stabilizing it in an enzyme-independent manner. Moreover, USP3 expression was positively correlated with A3G expression ( r = 0.5110) and CD4 + T-cell counts ( r = 0.5083) in HIV-1-infected patients. USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G. Therefore, USP3 may be an important target for drug development and serve as a novel therapeutic strategy against viral infections.

Do correlates of white matter features differ between older men and women living with human immunodeficiency virus?

Given estrogen's role in human immunodeficiency virus (HIV) disease progression and the higher rates of neurocognitive decline in affected women, the purpose of this study was to assess whether the relationship of white matter features and reproductive hormone levels differed between men versus women (sex as a moderator), controlling for selected cardiometabolic risk factors, HIV-related health indicators, and demographics in an aging population of persons living with HIV (PLWH). Older PLWH (50 y and older; 44 women and 35 men; mean ± SD age, 59.8 ± 0.6 y; 55.7% women; 72.2% non-Hispanic Black) participated in a cross-sectional study involving a fasting blood draw and a demographic survey (visit 1) and a magnetic resonance imaging scan (visit 2) to determine white matter volume and white matter hyperintensity (WMH) volume. Associations between reproductive hormones (follicle-stimulating hormone [FSH], estradiol, testosterone, dehydroepiandrosterone sulfate [DHEA-S]) and white matter features were assessed in linear regression models. Covariates were age, body mass index, hypertension, diabetes, dyslipidemia, current smoking status, CD4 count, and cranial size. For white matter volume, a sexually dimorphic interaction was seen for DHEA-S (B = 21.23; P = 0.012) and observed for FSH (B = -22.97, P = 0.08) with a trend for significance after controlling for risk factors. In women, higher white matter volume was associated with higher DHEA-S (B = 13.89, P = 0.017) and lower FSH (B = 23.58, P = 0.01). No hormone associations were shown in men for white matter volume. For WMH volume, no significant interaction effects between sex and reproductive hormones were identified. For WMH, sex did not predict associations with reproductive hormones after controlling for risk factors. Although sexually dimorphic interactions of reproductive hormones and total white matter volume were demonstrated, our study findings do not support a role for sex-based differences in reproductive hormones as predictive correlates of WMH in a small sample of older PLWH.

Surrogate Biomarkers of Disease Progression in Human Pegivirus Seropositive Human Immunodeficiency Virus-Infected Individuals.

Scientific observations indicate that an actively prevailing systemic condition could alleviate the pathology of another disease. Human pegivirus (HPgV), a highly ubiquitous flavivirus is believed to be associated with slow human immunodeficiency virus (HIV) disease progression, and has seldom been linked to hepatic pathology. In this study, we investigated whether HPgV seropositivity had any impact on surrogate markers of HIV disease progression in a cohort of HIV-infected HPgV seropositive (n = 28) and seronegative (n = 12) individuals who were prospectively evaluated for absolute CD4+ T cell counts, plasma viral load (PVL), liver enzymes, and plasma cytokine levels. The HIV PVL was relatively lower in HPgV seropositive than in HPgV seronegative HIV-infected subjects. Clinical markers of hepatic injury were significantly low among HPgV seropositive HIV-infected participants. HPgV seropositive individuals showed significantly higher levels of interleukin-7 (IL-7), and although not significant, the levels of IL-6 were lower among HPgV seropositive subjects. Spearman correlation analysis showed that the absolute CD4+T cell count was inversely correlated with HIV PVL. Exposure to HPgV appears to have a positive prognostic impact on the levels of surrogate biomarkers of HIV disease progression.

Altered HIV-1 Viral Copy Number and Gene Expression Profiles of Peripheral (CEM CCR5+) and Mucosal (A3R5.7) T Cell Lines Co-Infected with HSV-2 In Vitro.

Co-infecting pathogens have been speculated to influence Human Immunodeficiency Virus (HIV) disease progression. Herpes Simplex Virus Type-2 (HSV-2), another sexually transmitted pathogen, is commonly observed in individuals with HIV-1. Some clinical studies have observed an increase in HIV-1 viral copy number in HSV-2 co-infected individuals. In vitro studies have also demonstrated an increase in the expression of HIV-1 co-receptors on immune cells infected with HSV-2. Although both the viruses show distinctive persistent infection, the influence of HSV-2 on HIV-1 is poorly understood. Here we present a comparative analysis of primary CD4+ T-cells and four different T-cell lines (PM-1, CEM CCR5+, MOLT4 CCR5+, and A3R5.7) to assess the influence of HSV-2 co-infection on HIV-1 replication in vitro. Cell lines indicating significant changes in HIV-1 viral copy number [CEM CCR5+ (0.61 Log10), A3R5.7 (0.78 Log10)] were further evaluated for the infectivity of HIV-1 virions and the changes in gene expression profiles of HSV-2/HIV-1 co-infected and mono-infected cells, which were further confirmed by qPCR. Significant changes in NUP, MED, and VPS mRNA expression were observed in the gene expression profiles in co-infected CEM CCR5+ and A3R5.7 cells. In both cell lines, it was observed that the WNT signaling, PI3 kinase, apoptosis, and T-cell activation pathways were negatively affected in co-infected cells. The data suggest that HSV-2 infection of T-cells may influence the expression of genes that have been previously shown to affect HIV-1 replication in vitro. This idea needs to be explored further to identify anti-viral targets for HSV-2 and HIV-1.

High burden of malaria among Malawian adults on antiretroviral therapy after discontinuing prophylaxis.

Many individuals living with the human immunodeficiency virus (HIV) infection and receiving antiretroviral therapy (ART) reside in areas at high risk for malaria but how malaria affects clinical outcomes is not well described in this population. We evaluated the burden of malaria infection and clinical malaria, and impact on HIV viral load and CD4 + cell count among adults on ART. We recruited Malawian adults on ART who had an undetectable viral load and ≥250 CD4 + cells/μl to participate in this randomized trial to continue daily trimethoprim-sulfamethoxazole (TS), discontinue daily co-trimoxazole, or switch to weekly chloroquine (CQ). We defined clinical malaria as symptoms consistent with malaria and positive blood smear, and malaria infection as Plasmodium falciparum DNA detected from dried blood spots (collected every 4-12 weeks). CD4 + cell count and viral load were measured every 24 weeks. We used Poisson regression and survival analysis to compare the incidence of malaria infection and clinical malaria. Clinicaltrials.gov NCT01650558. Among 1499 participants enrolled, clinical malaria incidence was 21.4/100 person-years of observation (PYO), 2.4/100 PYO and 1.9/100 PYO in the no prophylaxis, TS, and CQ arms, respectively. We identified twelve cases of malaria that led to hospitalization and all individuals recovered. The preventive effect of staying on prophylaxis was approximately 90% compared to no prophylaxis (TS: incidence rate ratio [IRR] 0.11, 95% confidence interval [CI] 0.08, 0.15 and CQ: IRR 0.09, 95% CI 0.06, 0.13). P. falciparum infection prevalence among all visits was 187/1475 (12.7%), 48/1563 (3.1%), and 29/1561 (1.9%) in the no prophylaxis, TS, and CQ arms, respectively. Malaria infection and clinical malaria were not associated with changes in CD4 + cell count or viral load. In clinically stable adults living with HIV on ART, clinical malaria was common after chemoprophylaxis stopped. However, neither malaria infection nor clinical illness appeared to affect HIV disease progression.

HIV Infection Progression Monitoring System Based on CD4 Counts and Wishart Distribution.

The human immunodeficiency virus (HIV) is a viral infection that destroys the human immune system, resulting in the acquired immunodeficiency syndrome (AIDS). The management and care of patients on antiretroviral therapy (ART) consumes a large portion of the health budget of many countries. ART improves the lives of the HIV patients. However, benefiting from the treatment remains to be low due to the nonadherence, adverse events, and treatment failure associated with the transmitted drug resistance mutations (TDRMs). Extra care is therefore required in prescribing switch of ART regimens for HIV-naive patients. We propose a disease monitoring system, which depends on how the HIV-naive patients respond to the ART regimen. We model cluster of differentiation 4 (CD4) counts data measured at every 3 months in a period of 48 weeks on a cohort of 87 HIV-naive patients on ART, from Zambia. We demonstrate how to apply the Bayesian Wishart distribution to model CD4 counts, leading to an informative HIV progression monitoring system. We found a steady increase in the average of the CD4 counts (from 219 to 315) for HIV-naive patients on the ART regimen. The average was still below the expected 500 CD4 counts for a normal person. The derived precision matrix shows an increase in probability of potency of the ART regimen, which ranges from 0.1261 to 0.8678. An early detection is crucial as it allows for timely switch of regimen from first to second line or to the third line. The proposed HIV disease progression monitoring system for HIV-naive patients on ART regimen that is based on CD4 counts could enable physicians make informed decisions on the management and care of the patients.

Higher Risk of Mortality and Virologic Failure in HIV-Infected Patients With High Viral Load at Antiretroviral Therapy Initiation: An Observational Cohort Study in Chongqing, China.

BackgroundViral load (VL) is a strong predictor of human immunodeficiency virus (HIV) disease progression. The aim of this study was to evaluate the effect of high baseline VL on antiretroviral therapy (ART) outcomes among HIV-infected patients.MethodsThis retrospective study observed HIV-infected patients who had baseline VL test at ART initiation between 2015 and 2019 in Chongqing, China. Cox proportional hazards regression and logistic regression models were used to evaluate the effects of baseline VL on Acquired immunodeficiency syndrome (AIDS)-related mortality and virologic failure, respectively.ResultsThe cohort included 7,176 HIV-infected patients, of whom 38.7% had a baseline VL ≥ 100,000 copies/mL. Of the patients who died during follow-up, 58.9% had a baseline VL ≥ 100,000 copies/mL. Compared with a baseline VL < 10,000 copies/mL, ART initiation at VL ≥ 100,000 copies/mL was significantly associated with the AIDS-related death (adjusted hazard ratio, AHR = 1.4) and virologic failure (adjusted odds ratio, AOR = 2.4). Compared with patients with a baseline VL < 10,000 copies/mL, patients on the recommended first-line regimen with a VL ≥ 100,000 copies/mL at ART initiaition had higher mortality rate (5.1 vs. 1.7 per 100 person-years), but there was no significant difference in the mortality accoding to the initial VL level among patients on second-line ART (2.8 vs. 2.7 per 100 person-years). ART initiation ≤ 30 days after HIV diagnosis was associated with a lower risk of AIDS-related death (AHR = 0.6).ConclusionsART initiation with VL ≥ 100,000 copies/mL was associated with a significantly greater risk of mortality and virologic failure. Optimizing the ART regimen and initiating ART early may help to reduce mortality effectively among patients with a high baseline VL. VL testing for all HIV patients is recommended at HIV diagnosis or on ART initiation.

Prevalence of anemia among people living with HIV: A systematic review and meta-analysis.

SummaryBackgroundAnemia is the most frequent hematologic abnormality among people living with human immunodeficiency virus (HIV) (PLWHIV) and is associated with HIV disease progression and higher risk of mortality of the patients. However, there is a wide variation of the prevalence of anemia among PLWHIV in different clinical settings. We aimed to obtain more precise estimates of prevalence of anemia and severity of anemia among PLWHIV, which may be important for patients, caregivers, researchers and health policy-makers.MethodsWe systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library for original articles reporting the prevalence of anemia defined using age and sex-specific hemoglobin levels according to World Health Organization criteria among PLWHIV from inception to August 31, 2021. We used DerSimonian-Laird random-effects meta-analyses to obtain pooled prevalence and 95% confidence intervals (CIs) of anemia and severity of anemia among PLWHIV. A univariable meta-regression has been conducted to assess the association between anemia prevalence and study characteristics, including study design, median year of sampling, geographical region, World Bank Income level, and proportion of antiretroviral therapy (ART).FindingsWe included 63 observational studies covering 110,113 PLWHIV. The pooled prevalence of anemia was 39.7% (95% CI: 31.4%-48.0%) for children living with HIV aged <15 years, 46.6% (95% CI: 41.9%-51.4%) for adults (men and non-pregnant women) living with HIV aged ≥15 years, and 48.6% (95% CI: 41.6%-55.6%) for pregnant women living with HIV. Among adults living with HIV, the pooled prevalence of severity of anemia was 21.6% (95% CI: 19.9%-23.3%), 22.6% (95% CI: 14.8%-30.4%), and 6.2% (95% CI: 4.4%-8.1%) for mild, moderate and severe anemia, respectively. Compared with East Africa, anemia prevalence among adults living with HIV was higher in Southern Africa (p = 0.033).InterpretationAnemia is prevalent among PLWHIV. Thus, policies, strategies, and programs should be considered to identify the predictors of anemia among PLWHIV to reduce the burden of anemia among patients in the ART era.

Measurement of Plasma Fibrinogen Levels, PT and APTT among HIV Infected Patients: A Critical Bio-Marker for Coagulation Dysfunctions

Background: The literature stated that Human immunodeficiency virus (HIV) infection led to activation of coagulation, and habitually linked with an augmented risk of venous and arterial thrombosis. So the purpose of the study was to determine the plasma fibrinogen level in Sudanese HIV-infected patients.&#x0D; Materials and Methods: A total of one hundred participants were recruited, and classified into two groups; the case group include (50) HIV patients, and the control group enrolled (50) healthy individuals. Three ml of blood was collected. Fresh Poor Plasma was prepared from citrated venous blood by centrifuged for 15 minutes at 3000 pm. Fibrinogen levels were measured by an automated coagulation analyzer (Thrombolyzer XRC Germany). Data were collected using a directly structured questionnaire. Data were analyzed using SPSS Version 21. &#x0D; Results: The present study showed that the mean of plasma fibrinogen levels was statistically significantly higher in HIV infection in comparison with those normal healthy control (470.50 ±67.75 vs 214.75±21.25 with P-value 0.00). There was a significantly decreased level of PT, and PTT among the HIV group comparing with the control (9.575±0.64, and 22.39±4.94) VS (12.483±0.72, and 30.78±3.55) consequently, (P-value ≤0.001). Fibrinogen levels were significantly increased with the progression of HIV disease (469.84 ±67.15, 472.74 ±87.75, 478.47 ±61.92) in stage I, stage II, and stage III respectively.&#x0D; Conclusions: An HIV-infected patient had elevated plasma fibrinogen levels, as well as other coagulation dysfunctions.

Mold, Mycotoxins and a Dysregulated Immune System: A Combination of Concern?

Fungi represent one of the most diverse and abundant eukaryotes on earth. The interplay between mold exposure and the host immune system is still not fully elucidated. Literature research focusing on up-to-date publications is providing a heterogenous picture of evidence and opinions regarding the role of mold and mycotoxins in the development of immune diseases. While the induction of allergic immune responses by molds is generally acknowledged, other direct health effects like the toxic mold syndrome are controversially discussed. However, recent observations indicate a particular importance of mold/mycotoxin exposure in individuals with pre-existing dysregulation of the immune system, due to exacerbation of underlying pathophysiology including allergic and non-allergic chronic inflammatory diseases, autoimmune disorders, and even human immunodeficiency virus (HIV) disease progression. In this review, we focus on the impact of mycotoxins regarding their impact on disease progression in pre-existing immune dysregulation. This is complemented by experimental in vivo and in vitro findings to present cellular and molecular modes of action. Furthermore, we discuss hypothetical mechanisms of action, where evidence is missing since much remains to be discovered.

Global Prevalence of Anemia and the Impact of Antiretroviral Therapy Among People Living With HIV: A Systematic Review and Meta-Analysis

Background: Anemia is the most frequent hematologic abnormalities among people living with human immunodeficiency virus (HIV) and is associated with HIV disease progression and high mortality of the patients. However, there is a wide variation of the prevalence of anemia among people living with HIV in different clinical settings and the impact of antiretroviral therapy (ART) on anemia is inconsistent. We aimed to obtain more precise estimates of prevalence of anemia and severity of anemia as well as the impact of ART among people living with HIV, which may be important for patients, caregivers, researchers and health policy-makers. Methods: We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library for original articles reporting the prevalence of anemia defined using age and sex-specific hemoglobin levels according to World Health Organization criteria among people living with HIV from inception to August 31, 2021. We used random effects meta-analyses to obtain pooled prevalence and 95% confidence intervals (CIs) of anemia and severity of anemia as well as odds ratio (OR) and 95% CI of association between ART and anemia among people living with HIV. Findings: We included 41 cross-sectional studies covering 143,357 people living with HIV. Among people living with HIV, the pooled prevalence of anemia was 47.30% (95% CI: 38.96%-55.63%) in overall, 42.77% (95% CI: 38.58%-47.96%) in males, and 48.61% (95% CI: 40.84%-58.37%) in females. The pooled prevalence of severity of anemia was 22.74% (95% CI: 20.76%-24.71%), 17.56% (95% CI: 12.74%-22.38%), and 4.33% (95% CI: 2.96%-5.69%) for mild, moderate and severe anemia, respectively. There was no significant association between ART and anemia (OR=0.80; 95% CI: 0.64, 1.01) among people living with HIV. Interpretation: Anemia is prevalent among people living with HIV and ART could not reduce the risk of anemia for patients. Thus, policies, strategies, and programs should be considered to identify the predictors of anemia among people living with HIV to reduce the burden of anemia among patients in the ART era. Funding Information: This work was supported by the National Natural Science Foundation of China (grant number: 71934002, 71874003) and National Key Research and Development Program of China (grant number: 2020YFC0846300). Declaration of Interests: The authors have no competing interests to declare.