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Nature Communications Mar 2022Ex-vivo gene therapy (GT) with hematopoietic stem and progenitor cells (HSPCs) engineered with integrating vectors is a promising treatment for monogenic diseases, but... (Meta-Analysis)
Meta-Analysis
Ex-vivo gene therapy (GT) with hematopoietic stem and progenitor cells (HSPCs) engineered with integrating vectors is a promising treatment for monogenic diseases, but lack of centralized databases is hampering an overall outcomes assessment. Here we aim to provide a comprehensive assessment of the short and long term safety of HSPC-GT from trials using different vector platforms. We review systematically the literature on HSPC-GT to describe survival, genotoxicity and engraftment of gene corrected cells. From 1995 to 2020, 55 trials for 14 diseases met inclusion criteria and 406 patients with primary immunodeficiencies (55.2%), metabolic diseases (17.0%), haemoglobinopathies (24.4%) and bone marrow failures (3.4%) were treated with gammaretroviral vector (γRV) (29.1%), self-inactivating γRV (2.2%) or lentiviral vectors (LV) (68.7%). The pooled overall incidence rate of death is 0.9 per 100 person-years of observation (PYO) (95% CI = 0.37-2.17). There are 21 genotoxic events out of 1504.02 PYO, which occurred in γRV trials (0.99 events per 100 PYO, 95% CI = 0.18-5.43) for primary immunodeficiencies. Pooled rate of engraftment is 86.7% (95% CI = 67.1-95.5%) for γRV and 98.7% (95% CI = 94.5-99.7%) for LV HSPC-GT (p = 0.005). Our analyses show stable reconstitution of haematopoiesis in most recipients with superior engraftment and safer profile in patients receiving LV-transduced HSPCs.
Topics: Genetic Therapy; Genetic Vectors; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Lentivirus
PubMed: 35288539
DOI: 10.1038/s41467-022-28762-2 -
The Lancet. Global Health Dec 2023People who inject drugs are disproportionately affected by HIV and hepatitis C virus (HCV) infections, while there is little global data on HIV and HCV testing and...
BACKGROUND
People who inject drugs are disproportionately affected by HIV and hepatitis C virus (HCV) infections, while there is little global data on HIV and HCV testing and treatment coverage of this population. We conducted a systematic review to evaluate country-level, regional, and global coverage of HIV and HCV testing and treatment among people who inject drugs.
METHODS
We did a systematic review, and searched bibliographic databases (MEDLINE, Embase, and PsycINFO) and grey literature for studies published between Jan 1, 2017, and April 30, 2022, that evaluated the proportion of people who inject drugs who received testing or treatment for HIV or HCV. For each country, we estimated the proportion of people who inject drugs tested for HIV antibodies in the past 12 months (recent), people who inject drugs ever tested for HCV antibodies and HCV RNA, people who inject drugs with HIV currently receiving antiretroviral therapy, and people who inject drugs with HCV ever receiving HCV antiviral treatment. Regional and global estimates, weighted by the population size of people who inject drugs, were generated where sufficient data were available. This study is registered with PROSPERO (CRD42020173974).
FINDINGS
512 documents reported data eligible for analyses, including 337 peer-reviewed articles, 27 conference abstracts or presentations, and 148 documents from grey literature or supplementary searches. Data of recent HIV antibody testing were available for 67 countries and ever having had HCV antibody testing were available for 49 countries. Globally, an estimated 48·8% of people who inject drugs were recently tested for HIV antibodies (95% uncertainty interval [UI] 43·3-54·2%; range 0·9-86·0%), and 47·1% had ever been tested for HCV antibodies (95% UI 43·4-51·0%; range 0·0-93·3%). HCV RNA testing data were available from three countries. Coverage of HIV antibody testing was high (>75%) in four countries and for HCV antibody testing in 15 countries. The estimated uptake of current HIV treatment (18 countries) ranged from 2·6% to 81·9%, and the estimated uptake of ever having HCV treatment (23 countries) ranged from 1·8% to 88·6% across countries. Uptake of HIV treatment was high in two countries, and of HCV treatment in one country.
INTERPRETATION
HIV and HCV testing and treatment uptake among people who inject drugs was highly variable, and suboptimal in most countries. Strategies to improve access to HIV and HCV care among people who inject drugs and the availability of public health surveillance are urgently required.
FUNDING
Australian National Health and Medical Research Council and UK National Institute for Health and Care Research Health Protection Research Unit in Behavioural Science and Evaluation.
Topics: Humans; Substance Abuse, Intravenous; HIV Antibodies; Hepatitis C Antibodies; Drug Users; Australia; Hepatitis C; HIV Infections; Hepacivirus; HIV-1; RNA
PubMed: 37973339
DOI: 10.1016/S2214-109X(23)00461-8 -
Journal of the International AIDS... Mar 2023In people living with human immunodeficiency virus (PLHIV), traditional cardiovascular risk factors, exposure to HIV per se and antiretroviral therapy (ART) are assumed... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
In people living with human immunodeficiency virus (PLHIV), traditional cardiovascular risk factors, exposure to HIV per se and antiretroviral therapy (ART) are assumed to contribute to cardiometabolic diseases. Nevertheless, controversy exists on the relationship of HIV and ART with diabetes. To clarify the relationship between HIV and type 2 diabetes, this review determined, in PLHIV in Africa, diabetes and prediabetes prevalence, and the extent to which their relationship was modified by socio-demographic characteristics, body mass index (BMI), diagnostic definitions used for diabetes and prediabetes, and HIV-related characteristics, including CD4 count, and use and duration of ART.
METHODS
For this systematic review and meta-analysis (PROSPERO registration CRD42021231547), a comprehensive search of major databases (PubMed-MEDLINE, Scopus, Web of Science, Google Scholar and WHO Global Health Library) was conducted. Original research articles published between 2000 and 2021 in English and French were included, irrespective of study design, data collection techniques and diagnostic definitions used. Observational studies comprising at least 30 PLHIV and reporting on diabetes and/or prediabetes prevalence in Africa were included. Study-specific estimates were pooled using random effects models to generate the overall prevalence for each diagnostic definition. Data analyses used R statistical software and "meta" package.
RESULTS
Of the 2614 records initially screened, 366 full-text articles were assessed for eligibility and 61 were selected. In the systematic review, all studies were cross-sectional by design and clinic-based, except for five population-based studies. Across studies included in the meta-analysis, the proportion of men was 16-84%. Mean/median age was 30-62 years. Among 86,412 and 7976 participants, diabetes and prediabetes prevalence rates were 5.1% (95% CI: 4.3-5.9) and 15.1% (9.7-21.5). Self-reported diabetes (3.5%) was lower than when combined with biochemical assessments (6.2%; 7.2%).
DISCUSSION
While not statistically significant, diabetes and prediabetes were higher with greater BMI, in older participants, urban residents and more recent publications. Diabetes and prediabetes were not significantly different by HIV-related factors, including CD4 count and ART.
CONCLUSIONS
Although HIV-related factors did not modify prevalence, the diabetes burden in African PLHIV was considerable with suboptimal detection, and likely influenced by traditional risk factors. Furthermore, high prediabetes prevalence foreshadows substantial increases in future diabetes in African PLHIV.
Topics: Male; Adult; Humans; Aged; Middle Aged; Prediabetic State; Diabetes Mellitus, Type 2; HIV; HIV Infections; Prevalence; Africa
PubMed: 36924213
DOI: 10.1002/jia2.26059 -
Environmental Science & Technology Nov 2021Enveloped viruses are characterized by a lipid-containing envelope that encapsulates the virion, and they have been the cause of major outbreaks and pandemics. Some... (Meta-Analysis)
Meta-Analysis
Enveloped viruses are characterized by a lipid-containing envelope that encapsulates the virion, and they have been the cause of major outbreaks and pandemics. Some enveloped viruses are excreted in feces and other bodily fluids of infected people and animals, raising the question of their fate in the aquatic environment. Consequently, we conducted a systematic review and meta-analysis of the decay rate constants () of enveloped viruses from 12 families (i.e., , (specifically Phi6), , , , , , , , , , ) in environmental waters and wastewater to evaluate their decay kinetics and identify the environmental and virus characteristics that influence . A total of 812 that met inclusion criteria were identified in the literature, with the number of for each family ranging from 0 to 560, and the virus family averaged values of ranging from 0.11 d and 1.85 d. Virus type (i.e., genus, species, subspecies, or subtype), method of virus enumeration (i.e., culture-based or (RT-)QPCR), and experimental water matrix type, temperature and sterility were found to have significant effects on . Additionally, enveloped viruses were found to have statistically significantly greater than nonenveloped viruses. Multiple linear regression models that allow prediction of log as a function of virus type, enumeration method, water temperature, and water type are provided for six virus families that had sufficient data available for model fitting (i.e., , Phi6, , , , ). Compiled log and multiple regression models can be used to inform management of human and animal waste, operation of water and wastewater facilities, and exposure risks to treatment plant workers and communities living in regions that lack treatment facilities. Given limited data available for some enveloped virus families with a potential water-related transmission route, there is need for additional data collection to aid academic researchers, public health agencies, and water and wastewater professionals involved in outbreak response.
Topics: Animals; Disease Outbreaks; Disinfectants; Humans; Pandemics; Viruses; Wastewater
PubMed: 34665598
DOI: 10.1021/acs.est.1c03977 -
The Lancet. Microbe May 2022HIV-1 pol sequences from antiretroviral therapy (ART)-naive and ART-experienced people living with HIV-1 are fundamental to understanding the genetic correlates and... (Review)
Review
HIV-1 pol sequences from antiretroviral therapy (ART)-naive and ART-experienced people living with HIV-1 are fundamental to understanding the genetic correlates and epidemiology of HIV-1 drug resistance (HIVDR). To assess the public availability of HIV-1 pol sequences and ART histories of the individuals from whom sequenced viruses were obtained, we performed a systematic review of PubMed and GenBank for HIVDR studies published between 2010 and 2019 that reported HIV-1 pol sequences. 934 studies met inclusion criteria, including 461 studies of ART-naive adults, 407 of ART-experienced adults, and 66 of ART-naive and ART-experienced children. Sequences were available for 317 (68·8%) studies of ART-naive individuals, 190 (46·7%) of ART-experienced individuals, and 45 (68·2%) of children. Among ART-experienced individuals, sequences plus linked ART histories were available for 82 (20·1%) studies. Sequences were available for 21 (29·2%) of 72 clinical trials. Among journals publishing more than ten studies, the proportion with available sequences ranged from 8·3% to 86·9%. Strengthened implementation of data sharing policies is required to increase the number of studies with available HIVDR data to support the enterprise of global ART in the face of emerging HIVDR.
Topics: Adult; Anti-HIV Agents; Child; Drug Resistance, Viral; HIV Infections; HIV Seropositivity; HIV-1; Humans; Mutation; Viral Load
PubMed: 35544100
DOI: 10.1016/S2666-5247(21)00250-0 -
The Journal of Infectious Diseases Nov 2023HIV poses significant challenges for vaccine development due to its high genetic mutation and recombination rates. Understanding the distribution of HIV subtypes... (Meta-Analysis)
Meta-Analysis
Geographic and Population Distributions of Human Immunodeficiency Virus (HIV)-1 and HIV-2 Circulating Subtypes: A Systematic Literature Review and Meta-analysis (2010-2021).
BACKGROUND
HIV poses significant challenges for vaccine development due to its high genetic mutation and recombination rates. Understanding the distribution of HIV subtypes (clades) across regions and populations is crucial. In this study, a systematic review of the past decade was conducted to characterize HIV-1/HIV-2 subtypes.
METHODS
A comprehensive search was performed in PubMed, EMBASE, and CABI Global Health, yielding 454 studies from 91 countries.
RESULTS
Globally, circulating recombinant forms (CRFs)/unique recombinant forms (URFs) accounted for 29% of HIV-1 strains, followed by subtype C (23%) and subtype A (17%). Among studies reporting subtype breakdowns in key populations, 62% of HIV infections among men who have sex with men (MSM) and 38% among people who inject drugs (PWIDs) were CRF/URFs. Latin America and the Caribbean exhibited a 25% increase in other CRFs (excluding CRF01_AE or CRF02_AG) prevalence between 2010-2015 and 2016-2021.
CONCLUSIONS
This review underscores the global distribution of HIV subtypes, with an increasing prevalence of CRFs and a lower prevalence of subtype C. Data on HIV-2 were limited. Understanding subtype diversity is crucial for vaccine development, which need to elicit immune responses capable of targeting various subtypes. Further research is needed to enhance our knowledge and address the challenges posed by HIV subtype diversity.
Topics: Male; Humans; HIV Infections; Homosexuality, Male; HIV-1; HIV-2; Genetic Variation; Phylogeny; Sexual and Gender Minorities; Prevalence; Genotype
PubMed: 37592824
DOI: 10.1093/infdis/jiad327 -
Women's Health (London, England) 2022Black cisgender women in the United States experience a disproportionate burden of human immunodeficiency virus acquisition. Pre-exposure prophylaxis is an effective... (Review)
Review
BACKGROUND
Black cisgender women in the United States experience a disproportionate burden of human immunodeficiency virus acquisition. Pre-exposure prophylaxis is an effective oral daily medication that reduces the risk of human immunodeficiency virus through sex by 99% when taken as prescribed. However, less than 2% of eligible Black cisgender women take pre-exposure prophylaxis. The purpose of this scoping review was to describe the types of research studies done in this area, gaps in knowledge, and potential areas of research needed to increase pre-exposure prophylaxis use among Black cisgender women in the United States.
METHODS
We conducted our search in MEDLINE (PubMed), Embase (Elsevier), CINAHL (EBSCOhost), PsycINFO (EBSCOhost), and Scopus (Elsevier) using a combination of keywords and database-specific subject headings for the following concepts: pre-exposure prophylaxis, African American/Black or minority, and women. We used the Joanna Briggs Institute's Reviewers' Manual process for Scoping Reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews to ensure comprehensive and standardized reporting of each part of the review.
RESULTS
Fifty-nine studies were included in the final review. Results of the study were classified according to the three phases of the Human Immunodeficiency Virus Prevention Cascade-demand side, supply side, and adherence and retention. The majority of studies ( = 24, 41%) were cross-sectional quantitative surveys and 43 (34%) focused on the demand-side phase of the Human Immunodeficiency Virus Prevention Cascade. Fifty-eight percent of studies either assessed women's pre-exposure prophylaxis knowledge, attitudes, and intentions to use, or assessed perceived barriers and facilitators. Seven studies (12%) tested pre-exposure prophylaxis uptake and adherence among Black cisgender women.
CONCLUSION
This review found multiple missed opportunities to increase women's demand for pre-exposure prophylaxis and health care provider screening and referral for pre-exposure prophylaxis. Additional studies are needed to effectively assess pre-exposure prophylaxis uptake and adherence among Black cisgender women.
Topics: Black People; Female; HIV; HIV Infections; Health Personnel; Humans; Pre-Exposure Prophylaxis; United States
PubMed: 35699104
DOI: 10.1177/17455057221103098 -
Epidemiology and Infection Mar 2024Migrants in Europe face a disproportionate burden of HIV infection; however, it remains unclear if this can be prevented through public health interventions in host... (Meta-Analysis)
Meta-Analysis Review
Migrants in Europe face a disproportionate burden of HIV infection; however, it remains unclear if this can be prevented through public health interventions in host countries. We undertake a systematic review and meta-analysis to estimate post-migration HIV acquisition (PMHA) as a proportion of all HIV cases in European migrants. MEDLINE, EMBASE, Global Health, HMIC, and Cochrane Library were searched with terms capturing 'HIV', 'migration', and 'Europe'. Data relating to the proportion of HIV acquired following migration were extracted and random-effects model (REM) meta-analysis was undertaken to calculate a pooled estimate for the proportion of PMHA in European countries. Subgroup meta-analysis was undertaken for PMHA by migrant demographic characteristics and host country. Fifteen articles were included for systematic review following retrieval and screening of 2,320 articles. A total of 47,182 migrants in 11 European countries were included in REM meta-analysis, showing an overall PMHA proportion of 0.30 (95% CI: 0.23-0.38). Subgroup analysis showed no significant difference in PMHA between host country and migrant demographic characteristics. This work illustrates that migrants continue to be at high risk of HIV acquisition in Europe. This indicates the need for targeted screening and HIV prevention interventions, ensuring resources are appropriately directed to combat the spread of HIV.
Topics: Humans; HIV Infections; HIV; Europe; Communicable Disease Control; Transients and Migrants
PubMed: 38425215
DOI: 10.1017/S0950268824000372 -
Acta Obstetricia Et Gynecologica... Feb 2022Antiretroviral therapy-naïve pregnant women living with HIV are at an increased risk for adverse pregnancy outcomes. It remains controversial whether this risk persists... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Antiretroviral therapy-naïve pregnant women living with HIV are at an increased risk for adverse pregnancy outcomes. It remains controversial whether this risk persists with antiretroviral therapy. We conducted a systematic review and meta-analysis to evaluate whether pregnant women living with HIV and receiving antiretroviral therapy antenatally, are at an increased risk of adverse outcomes compared with HIV-negative controls.
MATERIAL AND METHODS
We searched MEDLINE, Embase, International Pharmaceutical Abstracts, EBM Reviews, PubMed (non-MEDLINE records), EBSCO CINAHL Complete, Clarivate Web of Science, African Index Medicus, LILACS and Google Scholar for all observational studies comparing pregnant women living with HIV on antiretroviral therapy with HIV-negative controls from 1 January 1994 to 10 August 2021 with no language or geographic restrictions. Perinatal outcomes included preterm birth (PTB), low birthweight, small-for-gestational age and preeclampsia. Using a random-effects model we pooled raw data to generate odds ratio (OR) with 95% confidence intervals (CI) for each outcome. Sub-analyses for high and low resource countries and time of antiretroviral therapy initiation were performed. This systematic review and meta-analysis is registered with PROSPERO, number CRD42020182722.
RESULTS
Of the 7900 citations identified, 27 were eligible for analysis (12 636 pregnant women living with HIV on antiretroviral therapy and 7 812 115 HIV-negative controls). ORs (95% CI) of PTB (1.88 [1.63-2.17]), small-for-gestational age (1.60 [1.18-2.17]) and low birthweight (2.15 [1.58-2.92]) were significantly higher in pregnant women living with HIV than in HIV-negative women, while the risk of preeclampsia (0.86 [0.57-1.30]) was comparable. The risk of PTB and low birthweight was higher in both high resource and low resource countries, while the risk of small-for-gestational age was higher only in the former. Preconceptional antiretroviral therapy was associated with a higher risk of PTB compared with antenatal initiation.
CONCLUSIONS
Pregnant women living with HIV on antiretroviral therapy have an increased risk of PTB, low birthweight and small-for-gestational age in high resource countries, as well as PTB and low birthweight in low income countries compared with HIV-negative controls.
Topics: Antiretroviral Therapy, Highly Active; Female; HIV Infections; HIV-1; Humans; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Prenatal Care; Risk Factors
PubMed: 34704251
DOI: 10.1111/aogs.14282 -
Impact of disasters on blood donation rates and blood safety: A systematic review and meta-analysis.Vox Sanguinis Jun 2022Timely and adequate access to safe blood forms an integral part of universal health coverage, but it may be compromised by natural or man-made disasters. This systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Timely and adequate access to safe blood forms an integral part of universal health coverage, but it may be compromised by natural or man-made disasters. This systematic review provides an overview of the best available scientific evidence on the impact of disasters on blood donation rates and safety outcomes.
MATERIALS AND METHODS
Five databases (The Cochrane Library, MEDLINE, Embase, Web of Science and CINAHL) were searched until 27 March 2020 for (un)controlled studies investigating the impact of disasters on blood donation rates and/or safety. Risk of bias and overall certainty of the evidence were assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Eighteen observational studies were identified, providing very low certainty of evidence (due to high risk of bias, inconsistency and/or imprecision) on the impact of natural (12 studies) and man-made/technological (6 studies) disasters. The available evidence did not enable us to form any generalizable conclusions on the impact on blood donation rates. Meta-analyses could not detect any statistically significant changes in transfusion-transmissible infection (TTI) rates [hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1/2, human T-lymphotropic virus I and II (HTLV-I/II) and syphilis] in donated blood after a disaster, either in first-time or repeat donors, although the evidence is very uncertain.
CONCLUSION
The very low certainty of evidence synthetized in this systematic review indicates that it is very uncertain whether there is an association between disaster occurrence and changes in TTI rates in donated blood. The currently available evidence did not allow us to draw generalizable conclusions on the impact of disasters on blood donation rates.
Topics: Blood Donors; Blood Safety; Disasters; HIV Infections; HIV-1; Hepatitis C; Humans; Syphilis
PubMed: 35167126
DOI: 10.1111/vox.13255