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Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

Science Advances, Volume 8, Issue 47, November 2022.

AbstractWhen first approved, many hoped that the SARS-CoV-2 vaccine would provide long-term protection after a primary series. Waning of immunity and continued appearance of new variants has made booster inoculations necessary. The process is becoming increasingly similar to that used for annual updating of the influenza vaccine. The similarity has become even more apparent with selection of BA.4/BA.5 as the Omicron strain of the updated bivalent (Original + Omicron) Covid-19 vaccines. It is hoped that, if Covid-19 develops winter seasonality, SARS-CoV-2 vaccines will require only annual review to determine if updates are necessary. Recommendations on whom should receive the booster would be based on conditions at that time.

AbstractThe EPCR-rs867186-G allele has been linked to high plasma level of soluble-EPCR and controversially associated with either susceptibility or resistance to severe and cerebral malaria. In this study, quantitative-ELISA and sequencing were used to assess sEPCR levels and EPCR-rs867186 polymorphism in blood samples from Beninese children with different clinical presentations of malaria. Our findings show that sEPCR levels were higher at admission to hospital than during convalescence and that EPCR-rs867186-G-allele was associated with increased sEPCR plasma levels, severe malaria and mortality (p-values < .0001,  = .03 and = .04, respectively), suggesting a role of sEPCR in the pathogenesis of severe malaria.

AbstractIn the northeastern and upper Midwestern United States, Babesia microti and Borreliella burgdorferi use Ixodes scapularis ticks as vector and Peromyscus leucopus mice as major reservoir host. We previously established, in a 5-year field trial, that a reservoir-targeted OspA vaccine reduces the prevalence of B. burgdorferi-infected ticks. We accessed ticks and mouse blood samples collected during the trial, extracted DNA and amplified the B. microti 18S rRNA gene. Vaccine deployment reduced the prevalence of ticks coinfected with B. microti and that of mice infected with B. microti. Breaking the enzootic cycle of B. burgdorferi may reduce the incidence of babesiosis.

ABSTRACTBackgroundUndernutrition is the leading risk factor for tuberculosis (TB) globally. Its impact on treatment outcomes is poorly defined.MethodsWe conducted a prospective cohort analysis of adults with drug-sensitive pulmonary TB at five sites in the Regional Prospective Observational Research on Tuberculosis (RePORT) India consortium (2015-2019). Using multivariable Poisson regression, we assessed independent associations between unfavorable outcomes and nutritional status based on body mass index (BMI) nutritional status at treatment initiation, BMI prior to TB disease, stunting, and stagnant or declining BMI after two months of TB treatment. Unfavorable outcome was defined as a composite of treatment failure, death, or relapse within 6 months of treatment completion.FindingsSevere undernutrition (BMI < 16 kg/m2) at treatment initiation and severe undernutrition before the onset of TB disease were both associated with unfavorable outcomes (adjusted incidence rate ratio [aIRR]: 2.05; 95% confidence interval [CI]: 1.42-2.91 and 2.20; 95% CI: 1.16-3.94, respectively). Additionally, lack of BMI increase after treatment initiation was associated with increased unfavorable outcomes (aIRR: 1.81; 95% CI: 1.27-2.61). Severe stunting (height-for-age z-score < -3) was associated with unfavorable outcomes (aIRR: 1.52; 95% CI: 1.00-2.24). Severe undernutrition at treatment initiation and lack of BMI increase during treatment were associated with a four and five-fold higher rate of death, respectively.InterpretationsPremorbid undernutrition, undernutrition at treatment initiation, lack of BMI increase after intensive therapy, and severe stunting are associated with unfavorable TB treatment outcomes. These data highlight the need for addressing this widely prevalent TB comorbidity. Nutritional assessment should be integrated into standard TB care.

AbstractBackgroundLinezolid-induced myelosuppression limits optimal therapy in cardiosurgical patients with deep-seated infections at current doses.MethodsAdult patients who received a cardiac surgery intervention and linezolid for a documented or presumed serious Gram-positive infection were evaluated. Therapeutic monitoring data, dosing, concomitant medications, and other pertinent laboratory data were collected retrospectively. A population pharmacokinetic model was constructed to identify covariates and test potential drug-drug interactions that may account for interpatient variability. Simulations from the final model identified doses that achieve a target therapeutic trough concentration of 2-8 mg/L.ResultsThis study included 150 patients (79.3% male) with sepsis and hospital acquired pneumonia in 71.7% as the primary indication. The population had a median (min-max) age, body weight and estimated glomerular filtration rate (eGFR) of 66 (30–85) years, 76 (45–130) kg and 46.8 (4.9–153.7) mL/min, respectively. The standard linezolid dosage regimen achieved the therapeutic range in only 54.7% of patients. Lower than standard doses were necessary in the majority of patients (77%). A two-compartment Michaellis-Menten clearance model with weight, kidney function, and the number of interacting drugs were identified as covariates that best fit the concentration-time data. Cyclosporine had the greatest effect on lowering the maximum elimination rate (Vmax) of linezolid. Empiric linezolid doses of 300 to 450 mg every 12 hours based on eGFR and the number of interacting medications is suggested by this analysis.ConclusionsLower empiric linezolid doses in cardiosurgical patients may avoid toxicities. Confirmatory studies are necessary to verify these potential drug interactions.

AbstractBackgroundAn increase of infections after transrectal prostate biopsy (PB), related to an increasing number of patients with ciprofloxacin-resistant rectal flora, necessitates the exploration of alternatives for the traditionally standard used empirical prophylaxis with ciprofloxacin. We compared infectious complication rates after transrectal PB using empirical ciprofloxacin prophylaxis versus culture-based prophylaxis.MethodsIn this non-blinded, randomized trial, between April 4, 2018 to July 30, 2021, we enrolled 1538 patients from 11 Dutch hospitals undergoing transrectal PB. After rectal swab collection, patients were 1:1 randomized to receive empirical prophylaxis with oral ciprofloxacin (control group; CG), or culture-based prophylaxis (intervention group; IG). Primary outcome was any infectious complication within seven days post-biopsy. Secondary outcomes were infectious complications within 30 days, and bacteremia and bacteriuria within seven and 30 days post-biopsy. For primary outcome analysis, the Chi-square test stratified for hospital was used. Trial registration number: NCT03228108.ResultsData from 1288 patients (83.7%) were available for analysis (CG: 652 and IG: 636). Infection rates within seven days post-biopsy were 4.3% (n = 28) (CG) and 2.5% (n = 16) (IG) (p-value: 0.08; reduction: -1.8%; 95% CI -0.004 to 0.040). Ciprofloxacin-resistant bacteria were detected in 15.2% (n = 1288). In the CG, the presence of ciprofloxacin-resistant rectal flora resulted in a 6.2 fold higher risk of early post-biopsy infection.ConclusionsOur study supports the use of culture-based prophylaxis to reduce infectious complications after transrectal PB. Despite adequate prophylaxis, post-biopsy infections can still occur. Therefore, culture-based prophylaxis must be weighed against other strategies that could reduce post-biopsy infections.

Proceedings of the National Academy of Sciences, Volume 119, Issue 48, November 2022.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Abstract The Omicron transmission has infected nearly 600,000 people in Shanghai from March 26 to May 31, 2022. Combined with different control measures taken by the government in different periods, a dynamic model was constructed to investigate the impact of medical resources, shelter hospitals and aerosol transmission generated by clustered nucleic acid testing on the spread of Omicron. The parameters of the model were estimated by least square method and MCMC method, and the accuracy of the model was verified by the cumulative number of asymptomatic infected persons and confirmed cases in Shanghai from March 26 to May 31, 2022. The result of numerical simulation demonstrated that the aerosol transmission figured prominently in the transmission of Omicron in Shanghai from March 28 to April 30. Without aerosol transmission, the number of asymptomatic subjects and symptomatic cases would be reduced to 130,000 and 11,730 by May 31, respectively. Without the expansion of shelter hospitals in the second phase, the final size of asymptomatic subjects and symptomatic cases might reach 23.2 million and 4.88 million by May 31, respectively. Our results also revealed that expanded vaccination played a vital role in controlling the spread of Omicron. However, even if the vaccination rate were 100%, the transmission of Omicron should not be completely blocked. Therefore, other control measures should be taken to curb the spread of Omicron, such as widespread antiviral therapies, enhanced testing and strict tracking quarantine measures. This perspective could be utilized as a reference for the transmission and prevention of Omicron in other large cities with a population of 10 million like Shanghai.…

Abstract Background In order to verify the existence of an anthrax outbreak, determine its scope, grasp the epidemiological characteristics and find out the cause of the outbreak and recommend preventive and control measures. Methods Etiological hypothesis was developed through descriptive epidemiological methods. Hypotheses were tested by analyzing epidemiological methods by comparing the differences in the incidence of different exposure types. Nucleic acid detection and bacterial isolation and culture in the BSL-2 laboratories. SPSS 21 was used to conduct statistical analysis. Results A total of 126 family, workshop, shop environment samples and meat samples were collected, and 6 samples were collected from skin lesions of suspected cutaneous anthrax cases. 41 samples were positive by rPCR and 8 strains of Bacillus anthracis were cultivated. Participated in slaughtering, cutting beef of sick cattles was significantly associated with cutaneous anthrax (RR 3.75, 95% CI 1.08–13.07), this behavior is extremely dangerous. Conclusions Comprehensive analysis of laboratory results and epidemiological survey results and environmental assessments, we judge this epidemic to be an outbreak of cutaneous anthrax, associated with slaughtering and other processes from infected cattle imported from other province. …

Abstract Background Long-lasting insecticidal nets (LLINs) play a key role in reducing malaria transmission in endemic countries. In a previous study, the authors demonstrated a substantial decrease in the bioefficacy of LLINs for malaria prevention delivered to Papua New Guinea (PNG) between 2013 and 2019. This coincided with a rise in malaria cases in the country. The present study was aimed at determining the underlying cause of the reduced bioefficacy observed in these LLINs. The main hypothesis was that a change in the coating formulation of the respective LLIN product was responsible, and had led to significantly altered product properties and performance. Methods A set of PermaNet® 2.0 LLIN samples (n = 12) manufactured between 2007 and 2019 was subjected to combustion ion chromatography in order to understand the chemistry of the LLIN polymer coating formulation. In addition, World Health Organization (WHO) LLIN standard wash tests and cone bioassays were conducted to further characterize the change in product performance that occurred between 2012 and 2013. Results High polymer fluorine content (average 3.2 g/kg) was measured in PermaNet® 2.0 manufactured up to 2012, whereas nets which were manufactured after 2012 contained very little polymer fluorine (average 0.04 g/kg) indicating a coating formulation change from a fluorocarbon (FC)-based to a non-FC-based formulation. The coating formulation change as part of the manufacturing process thus resulted in a significant reduction in bioefficacy. In addition, the manufacturing change affected wash resistance leading to a faster reduction in 24 h mosquito mortality in the non-FC-coated product with consecutive washes. Conclusion A change in coating formulation of PermaNet® 2.0 resulted in reduced product performance in PNG. Post-2012 PermaNet® 2.0 LLINs should not be considered to be the same product as PermaNet® 2.0 LLINs produced prior to and in 2012. Coating formulation changes should be validated to not impact LLIN product performance. …

Tropical Medicine &International Health, Accepted Article.

Tropical Medicine &International Health, Accepted Article.

New England Journal of Medicine, Volume 387, Issue 21, Page 1969-1978, November 2022.

New England Journal of Medicine, Volume 387, Issue 21, November 2022.

New England Journal of Medicine, Volume 387, Issue 21, November 2022.

Abstract Objectives Previous studies have found declining incidence of tuberculosis (TB) in Bissau, Guinea-Bissau. This study aimed to report incidence rates of TB for the period 2004–2020, stratifying by sex, smear-status, and HIV-status, as well as describe developments in TB case fatality rate and diagnostic delay. Design and methods Data from the Bandim Health Project HDSS and the TB registry from Jan 1st, 2004 to Dec 31st, 2020 were used. Incidence rates were calculated for each year and for smear-positive, smear-negative, HIV-positive, HIV-negative, and unknown HIV-status. Incidence rate ratio and test for trend were done using a one-step Newton approximation to the log-linear Poisson regression coefficient. Results Overall TB incidence declined only slightly over the period from 294 per 100,000 in 2004 to 273 in 2020. TB/HIV coinfection declined from 108 in 2004 to 14 in 2020, as did incidence among females and smear-negative cases. Conclusions Incidence of PTB in Bissau, Guinea-Bissau is declining slowly, if at all. TB incidence among females, smear-negative TB, TB case fatality rate, and TB/HIV coinfection and diagnostic delay are declining. …

Introduction: Studies examining hospitalization among infants with HIV in resource-limited settings, in the context of early infant diagnosis and early antiretroviral therapy (ART) initiation, are limited.Methods: We used routinely collected data on infants who initiated ART aged 1 hospitalization. Median age at ART initiation decreased from 57 days (interquartile range [IQR] 22–74; 2013–2015) to 19 days (IQR 5–54; 2016–2017). Early neonatal hospitalization (age…

Objective: To characterize the prevalence of anemia and risk factors between 2007 and 2017 for moderate/severe anemia among people with HIV (PWH) in North America who have initiated antiretroviral therapy (ART).Design: Observational study of participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).Methods: We estimated the annual prevalence between 1 January 2007 and 31 December 2017 of mild (11.0–12.9 g/dl men, 11.0–11.9 g/dl women), moderate (8.0–10.9 g/dl regardless of sex) and severe (1 year of ART) (aPR = 1.66 [1.61–1.72]).Conclusion: The prevalence of anemia among PWH is reduced after ART initiation but remains high. Risk factors differ by sex and include comorbidities and HIV disease severity. The persistent, substantial prevalence of anemia among PWH merits further investigation, targeted screening, and clinical interventions.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objectives: Despite suppressive antiretroviral therapy (ART), HIV can persist in a diverse range of CD4+ T-cell subsets. Through longitudinal env sampling from people with HIV (PWH) on ART, we characterized the persistence and phenotypic properties of HIV envs over two time-points (T1 and T2).Methods: Longitudinal blood and lymphoid tissue samples were obtained from eight PWH on suppressive ART. Single genome amplification (SGA) was performed on env to understand the genetic diversity and degree of clonal expansions over time. A subset of envs were used to generate pseudovirus particles to assess sensitivity to autologous plasma IgG and broadly neutralizing antibodies (bNAbs).Results: Identical env sequences indicating clonal expansion persisted between T1 and T2 and within multiple T-cell subsets. At both time-points, CXCR4-tropic (X4) Envs were more prevalent in naive and central memory cells; the proportion of X4 Envs did not significantly change in each subset between T1 and T2. Autologous purified plasma IgG showed variable neutralization of Envs, with no significant difference in neutralization between R5 and X4 Envs. X4 Envs were more sensitive to neutralization with clinical bNAbs, with CD4+-binding site bNAbs demonstrating high breadth and potency against Envs.Conclusion: Our data suggest the viral reservoir in PWH on ART was predominantly maintained over time through proliferation and potentially differentiation of infected cells. We found the humoral immune response to Envs within the latent reservoir was variable between PWH. Finally, we identified coreceptor usage can influence bNAb sensitivity and may need to be considered for future bNAb immunotherapy approaches.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective: Prior genomewide association studies have identified variation in MHC Class I alleles and CCR5Δ32 as genetic predictors of viral control, especially in “elite” controllers, individuals who remain virally suppressed in the absence of therapy.Design: Cross-sectional genomewide association study.Methods: We analyzed custom whole exome sequencing and direct HLA typing from 202 ART-suppressed HIV+ non-controllers in relation to four measures of the peripheral CD4+ T cell reservoir: HIV intact DNA, total (t)DNA, unspliced (us)RNA, and RNA/DNA. Linear mixed models were adjusted for potential covariates including age, sex, nadir CD4+ T cell count, pre-ART HIV RNA, timing of ART initiation, and duration of ART suppression.Results: Previously reported “protective” host genetic mutations related to viral setpoint (e.g., among elite controllers) were found to predict smaller HIV reservoir size. The HLA “protective” B∗57:01 was associated with significantly lower HIV usRNA (q = 3.3x10−3), and among the largest subgroup, European ancestry individuals, the CCR5Δ32 deletion was associated with smaller HIV tDNA (p = 4.3x10−3) and usRNA (p = 8.7x10−3). In addition, genomewide analysis identified several SNPs in MX1 (an interferon stimulated gene) that were significantly associated with HIV tDNA (q = 0.02), and the direction of these associations paralleled MX1 gene eQTL expression.Conclusions: We observed a significant association between previously reported “protective” MHC class I alleles and CCR5Δ32 with the HIV reservoir size in non-controllers. We also found a novel association between MX1 and HIV total DNA (in addition to other interferon signaling relevant genes, PPP1CB, DDX3X). These findings warrant further investigation in future validation studies.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective(s): To describe the dynamics of neutralizing antibody (NAbs) response after yellow fever (YF) vaccine in young adults and adolescents with perinatally acquired HIV (pHIV).Design: A retrospective cross-sectional study at three time points around YF vaccination and a matched case-control comparison of NAbs titers several years after YF vaccination.Methods: We selected patients who had both documented YF vaccination and perinatally acquired HIV (n = 46). The NAbs titers were measured in plasma samples from the following three time points: during the two years before (TP0), within the year after (TP1) and more than one year after (TP2) administration of the YF vaccine. The impact of perinatal infection was assessed by comparing pHIV YF vaccinees with 44 controls infected with HIV during adulthood.Results: The median time between the YF vaccine and TP1 and TP2 was 123 days and 7,3 years respectively. After YF vaccination, 85% of vaccinees experienced seroconversion. The proportion of pHIV patients with NAbs above the protective threshold was stable between TP1 and TP2 (91% and 86% respectively) but levels of NAbs decreased significantly between TP1 and TP2 (p = 0.0122). The case-control analysis found slightly higher geometrical mean titers (GMT) in pHIV than patients infected during adulthood.Conclusions: Patients with pHIV showed high seroconversion rate and NAbs persistence at levels above the protective threshold after first YF vaccination. However, a decline in antibody levels over time suggests that at least one revaccination may be necessary to maintain circulating antibodies, contrary to recommendations for the general population.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Background: The impact of pre-antiretroviral treatment (ART) HIV-RNA on time to successful virological suppression and subsequent failure in HIV patients remains poorly investigated.Methods: We used the Swedish InfCareHIV database and the Danish HIV Cohort Study to evaluate impact of pre-ART HIV-RNA on primary virological suppression (HIV-RNA < 50 copies/ml) and risk of secondary virological failure (two consecutive HIV-RNA > 200 copies/ml or one >1000 copies/ml). The study included 3366 Swedish and 2050 Danish ART naïve individuals who initiated ART in the period 2000–2018. We used Kaplan–Meier estimates and Cox regression analyses to estimate absolute risks and hazard ratios.Results: In both cohorts, >95% of patients with a pre-ART HIV-RNA 1 000 000 copies/ml. Almost all patients obtained virological suppression after four years irrespective of pre-ART HIV-RNA. In contrast, we observed no substantial impact of pre-ART HIV-RNA on risk of virological failure once virological suppression was obtained.Conclusion: High pre-ART HIV-RNA is strongly associated with increased time to successful virological suppression, but pre-ART HIV-RNA has no impact on risk of subsequent virological failure.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objectives: Molecular epidemiology is a powerful tool to characterize HIV epidemics and prioritize public health interventions. Typically, HIV clusters are assumed to have uniform patterns over time. We hypothesized that assessment of cluster evolution would reveal distinct cluster behavior, possibly improving molecular epidemic characterization, towards disrupting HIV transmission.Design: Retrospective cohort.Methods: Annual phylogenies were inferred by cumulative aggregation of all available HIV-1 pol sequences of individuals with HIV-1 in Rhode Island (RI) between 1990 and 2020, representing a statewide epidemic. Molecular clusters were detected in annual phylogenies by strict and relaxed cluster definition criteria, and the impact of annual newly-diagnosed HIV-1 cases to the structure of individual clusters was examined over time.Results: Of 2,153 individuals, 31% (strict criteria) - 47% (relaxed criteria) clustered. Longitudinal tracking of individual clusters identified three cluster types: normal, semi-normal and abnormal. Normal clusters (83%-87% of all identified clusters) showed predicted growing/plateauing dynamics, with ∼3-fold higher growth rates in large (15%-18%) vs. small (∼5%) clusters. Semi-normal clusters (1%-2% of all clusters) temporarily fluctuated in size and composition. Abnormal clusters (11%-16% of all clusters) demonstrated collapses and re-arrangements over time. Borderline values of cluster-defining parameters explained dynamics of non-normal clusters.Conclusions: Comprehensive tracing of molecular HIV clusters over time in a statewide epidemic identified distinct cluster types, likely missed in cross-sectional analyses, demonstrating that not all clusters are equal. This knowledge challenges current perceptions of consistent cluster behavior over time and could improve molecular surveillance of local HIV epidemics to better inform public health strategies.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Introduction: Identifying genetic factors that influence HIV-pathogenesis is critical for understanding disease pathways. Previous studies have suggested a role for the human gene ten-eleven methylcytosine dioxygenase 2 (TET2) in modulating HIV-pathogenesis.Methods: We assessed whether genetic variation in TET2 was associated with markers of HIV-pathogenesis using both gene level and single nucleotide level association in 8512 HIV-positive persons across five clinical trial cohorts.Results: Variation at both the gene and SNP-level of TET2 was found to be associated with levels of HIV viral load (HIV-VL) consistently in the two cohorts that recruited antiretroviral-naïve participants. The SNPs occurred in two clusters of high linkage disequilibrium (LD), one associated with high HIV-VL and the other low HIV-VL, and were predominantly found in Black participants.Conclusion: Genetic variation in TET2 was associated with HIV-VL in two large ART-naïve clinical trial cohorts. The role of TET2 in HIV-pathogenesis warrants further investigation.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objectives: Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people living with HIV (PLWH). Our objective was to compare COVID-19 vaccine immunogenicity in PLWH to HIV-negative individuals.Design: In a Canadian multi-centre prospective, observational cohort of PLWH receiving ≥2 COVID-19 vaccinations, we measured vaccine-induced immunity at three and six months post 2nd and one month post 3rd doses.Methods: The primary outcome was the percentage of PLWH mounting vaccine-induced immunity (co-positivity for anti-IgG against SARS-CoV2 Spike(S) and receptor binding domain (RBD) proteins) six months post 2nd dose. Univariable and multivariable logistic regression were used to compare COVID-19-specific immune responses between groups and within sub-groups.Results: Data from 294 PLWH and 267 controls were analyzed. Immunogenicity was achieved in over 90% at each time point in both groups. The proportions of participants achieving comparable anti-RBD levels were similar between the group at each time point. Anti-S IgG levels were similar by group at month 3 post 2nd dose and one month post 3rd dose. A lower proportion of PLWH vs controls maintained vaccine-induced anti-S IgG immunity 6 months post 2nd dose (92% vs 99%; OR 0.14[95% CI 0.03, 0.80; p = 0.027)]. In multivariable analyses, neither age, immune non-response, multimorbidity, sex, vaccine type or timing between doses were associated with reduced IgG response.Conclusion: Vaccine-induced IgG was elicited in the vast majority of PLWH and overall similar between groups. A slightly lower proportion of PLWH vs controls maintained vaccine-induced anti-S IgG immunity 6 months post 2nd dose demonstrating the importance of timely boosting in this population.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Objectives: Increasing numbers of women living with HIV (WLHIV) worldwide receive combination antiretroviral therapy (cART) during pregnancy. We aimed to assess the risk of adverse perinatal outcomes in pregnant WLHIV receiving cART compared with pregnant WLHIV receiving zidovudine monotherapy.Design: Systematic review and meta-analysis.Methods: We searched four electronic literature databases (PubMed, CINAHL, Global Health, EMBASE) for studies published between 01 January 1980 to 20 April 2020 using a comprehensive search strategy. Studies reporting data on WLHIV receiving cART compared with WLHIV receiving monotherapy for 11 adverse perinatal outcomes were sought: preterm birth (PTB), very PTB, spontaneous PTB, low birthweight (LBW), very LBW, preterm and term LBW, small-for-gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Random-effects meta-analyses were conducted to calculate relative risk (RR) and 95% confidence intervals (95% CI).Results: We included 30 studies reporting on 317 101 women in 27 countries. WLHIV receiving cART were at increased risk of PTB (RR 1.32, 95% CI 1.18–1.46), LBW (1.35, 1.19–1.53), SGA (1.32, 1.13–1.53), VSGA (1.64, 1.34–2.02), and stillbirth (2.41, 1.83–3.17) compared to WLHIV receiving monotherapy. The significance of these results was maintained in subgroup analyses for studies conducted in low-and-middle-income countries and average quality studies. Additionally, WLHIV receiving nonnucleoside reverse transcriptase inhibitor-based cART were associated with increased risk of PTB, LBW, and stillbirth, while WLHIV receiving protease inhibitor-based cART were associated with increased risk of PTB, compared with WLHIV receiving monotherapy.Conclusion: Pregnant WLHIV receiving cART are associated with increased risk of adverse perinatal outcomes, compared with WLHIV receiving monotherapy.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective: To compare the estimated glomerular filtration rate (eGFR) using the creatinine equation (eGFRcreat) or the cystatin C equation (eGFRcys) in people with HIV (PWH) under antiretroviral drugs. We specifically included patients with an eGFRcreat around 60 ml/min/1.73 m2 to evaluate agreement on stage 2 and 3 chronic kidney disease (CKD) classification.Design: eGFRcreat, eGFRcys and resulting CKD staging were determined in 262 consecutive patients with HIV-1 (PWH) with a suppressed viral load (…

Objective: To evaluate HIV care continuum trends over time among women with HIV (WWH).Design: The Medical Monitoring Project (MMP) is a complex sample survey of adults with diagnosed HIV in the United States.Methods: We used 2015–2019 MMP data collected from 5139 adults with diagnosed HIV infection who identified as cisgender women. We calculated weighted percentages with 95% confidence intervals (CIs) for all characteristics and estimated annual percent change (EAPC) and the associated 95% CI to assess trends. EAPCs were considered meaningful from a public health perspective if ≥1% with p-values…

Objective: Liver disease is accelerated in people living with HIV (PLWH) with hepatitis B (HBV) coinfection. We hypothesised that liver fibrosis in HIV-HBV is triggered by increased hepatocyte apoptosis, microbial translocation and/or HIV/HBV viral products.Design: Sera from PLWH with HBV coinfection versus from those with HBV only or putative mediators were used to examine the pathogenesis of liver disease in HIV-HBV.Methods: We applied sera from PLWH and HBV coinfection versus HBV alone, or putative mediators (including HMGB1), to primary human hepatic stellate cells (hHSC) and examined pro-fibrogenic changes at the single cell level using flow cytometry. HMGB1 levels in the applied sera were assessed according to donor fibrosis stage.Results: Quantitative flow cytometric assessment of pro-fibrogenic and inflammatory changes at the single cell level revealed an enhanced capacity for sera from PLWH with HBV coinfection to activate hHSC. This effect was recapitulated by LPS, HIV-gp120, hepatocyte conditioned-media and the alarmin HMGB1. Induction of hepatocyte cell death increased their pro-fibrogenic potential, an effect blocked by HMGB1 antagonist glycyrrhizic acid. Consistent with a role for this alarmin, HMGB1 levels were elevated in sera from PLWH and hepatitis B coinfection compared to HBV alone and higher in those with HIV-HBV with liver fibrosis compared to those without.Conclusions: Sera from PLWH and HBV coinfection have an enhanced capacity to activate primary hHSC. We identified an increase in circulating HMGB1 which, in addition to HIV-gp120 and translocated microbial products, drove pro-fibrogenic changes in hHSC, as mechanisms contributing to accelerated liver disease in HIV-HBV.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective: Cervical cancer is a common preventable cancer among African women living with HIV (WLWH). Molecular diagnostics for high-risk human papillomavirus (HR-HPV) genotypes are standard components of cervical cancer screening in resource-rich countries but not in resource-limited settings. We evaluated HR-HPV genotypes among women with and without HIV in four African countries to inform cervical cancer preventive strategies.Methods: The African Cohort Study (AFRICOS) enrolled participants with and without HIV at 12 clinics in Tanzania, Kenya, Uganda and Nigeria. Cervical cytobrush specimens from women were genotyped for 14 HR-HPV types using the multiplex Seegene Anyplex real-time PCR assay. Robust Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with HR-HPV in WLWH.Results: From January 2015 to March 2020, 868 WLWH and 134 WLWoH were tested for HR-HPV with prevalence of 50.9% and 38.1%, respectively (p = 0.007). Among WLWH, 844 (97.4%) were ART-experienced and 772 (89.7%) virally suppressed ≦1000 copies/mL. The most frequent HR-HPV types among WLWH were HPV-16 (13.5%), HPV-52 (9.5%) and HPV-35 (9.3%). HR-HPV infection was more common among Tanzanian WLWH (adjusted RR: 1.23, 95% CI: 1.05–1.44, p = 0.012). Also, WLWH with CD4 T cells of…

Objective: To systematically assess the efficacy, safety, and tolerability of isoniazid preventive therapy (IPT) for tuberculosis (TB) in people living with human immunodeficiency virus (PLHIV).Design: Systematic review and meta-analysis.Methods: A thorough literature search was performed using PubMed, Cochrane CENTRAL, and Google Scholar from their inception to June 30, 2021. All randomized controlled trials (RCTs) investigating the efficacy, safety, or tolerability of IPT on PLHIV compared to placebo or active comparators were included in the study. The heterogeneity among the studies was identified by using the I2 statistic and Cochran's Q test.Results: Out of the 924 non-duplicate RCTs identified through database searching and other sources, 26 studies comprising 38005 patients were included. The overall effect estimate identified the reduction of active TB incidence (OR 0.69; 95% CI 0.57, 0.84; P …