After Antiretroviral Therapy Research Articles

Double-Negative T Cell Number and Phenotype Alterations Before and After Effective Antiretroviral Treatment in Persons Living with HIV.

Double-negative (DN) T cells represent a small and phenotypically heterogeneous population that display regulatory functions. In HIV infection, DN T cells are decreased in peripheral blood and have been negatively associated with T cell activation. This study was aimed at describing the dynamics and phenotypic characteristics of DN T cells in peripheral blood of people living with HIV (PLHIV) before and after antiretroviral therapy (ART) initiation. We included 41 newly diagnosed, ART-naive individuals with advanced HIV infection, who were followed up for 6 months after ART initiation. The control group included 34 people without HIV (PWHIV), on preexposure prophylaxis for HIV infection. DN T cells in peripheral blood were characterized by flow cytometry. The absolute counts of DN T cells were lower in PLHIV than in PWHIV (p = 0.0223), and were particularly low in individuals with advanced HIV disease (p = 0.0311). Activation of DN T cells before ART initiation was directly associated with viral load (VL) (p = 0.0081, r = 0.4083) and inversely associated with CD4+ T cell counts (p = 0.0004, r = -0.4041). Compared with PWHIV, DN T cells of PLHIV expressed higher levels of CD57 (p = 0.0019), Ki67 (p = 0.0065), PD-1 (p = 0.0187), and CD38/HLA-DR (p < 0.0001). After 6 months on ART, expression of Ki67, PD-1, and CD38/HLA-DR on DN T cells returned to similar levels to those observed in PWHIV (p > 0.05 in all cases). However, expression of CD57 decreased only in individuals that start ART with high VL (p = 0.0127). DN T cell counts are decreased in HIV infection. Low DN T cell counts remained despite ART-induced immune reconstitution and viremia control. DN T cell phenotype is altered during chronic untreated infection with a high proportion of proliferating, activated, exhausted, and senescent cells. Most markers return to levels similar to those observed in PWHIV after ART. The impact of altered phenotype of DN T and their regulatory functions warrants further exploration.

Rate, risk factors and estimations of time to develop severe acute malnutrition after children receiving antiretroviral therapy at selected health facilities in northwest Ethiopia.

Severe acute malnutrition (SAM) affects up to 50 % of children with HIV, especially those who reside in resource-constrained healthcare setting like Ethiopia. During subsequent follow-up of children factors related to incidence of SAM after antiretroviral therapy (ART) is set on, however, there is no prior evidence. An institution-based retrospective cohort study was employed among 721 HIV-positive children from 1 January to 30 December 2021. Data were entered using Epi-Data version 3.1 and exported to STATA version 14 for analysis. Bi-variable and multivariable Cox-proportional hazard models were employed at 95 % confidence intervals to identify significant predictors for SAM. According to this result, the overall mean (±sd) age of the participants was found to be 9⋅83 (±3⋅3) years. At the end of the follow-up period, 103 (14⋅29 %) children developed SAM with a median time of 30⋅3 (13⋅4) months after ART initiation. The overall incidence density of SAM was found to be 5⋅64 per 100 child (95 % CI 4⋅68, 6⋅94). Children with CD4 counts below the threshold [AHR 2⋅6 (95 % CI 1⋅2, 2⋅9, P = 0⋅01)], disclosed HIV status [AHR 1⋅9 (95 % CI 1⋅4, 3⋅39, P = 0⋅03)] and Hgb level ≤10 mg/dl [AHR 1⋅8 (95 % CI 1⋅2, 2⋅9, P = 0⋅03)] were significant predictors for SAM. Significant predictors of acute malnutrition were having a CD4 count below the threshold, children who had previously reported their HIV status, and having haemoglobin <10 mg/dl. To ensure better health outcomes, healthcare practitioners should improve earlier nutritional screening and consistent counselling at each session of care.

Cumulative Human Immunodeficiency Virus (HIV)-1 Viremia Is Associated With Increased Risk of Multimorbidity Among US Women With HIV, 1997-2019.

To evaluate the effect of cumulative human immunodeficiency virus (HIV)-1 viremia on aging-related multimorbidity among women with HIV (WWH), we analyzed data collected prospectively among women who achieved viral suppression after antiretroviral therapy (ART) initiation (1997-2019). We included WWH with ≥2 plasma HIV-1 viral loads (VL) <200 copies/mL within a 2-year period (baseline) following self-reported ART use. Primary outcome was multimorbidity (≥2 nonacquired immune deficiency syndrome comorbidities [NACM] of 5 total assessed). The trapezoidal rule calculated viremia copy-years (VCY) as area-under-the-VL-curve. Cox proportional hazard models estimated the association of time-updated cumulative VCY with incident multimorbidity and with incidence of each NACM, adjusting for important covariates (eg, age, CD4 count, etc). Eight hundred six WWH contributed 6368 women-years, with median 12 (Q1-Q3, 7-23) VL per participant. At baseline, median age was 39 years, 56% were Black, and median CD4 was 534 cells/mm3. Median time-updated cumulative VCY was 5.4 (Q1-Q3, 4.7-6.9) log10 copy-years/mL. Of 211 (26%) WWH who developed multimorbidity, 162 (77%) had incident hypertension, 133 (63%) had dyslipidemia, 60 (28%) had diabetes, 52 (25%) had cardiovascular disease, and 32 (15%) had kidney disease. Compared with WWH who had time-updated cumulative VCY <5 log10, the adjusted hazard ratio of multimorbidity was 1.99 (95% confidence interval [CI], 1.29-3.08) and 3.78 (95% CI, 2.17-6.58) for those with VCY 5-6.9 and ≥7 log10 copy-years/mL, respectively (P < .0001). Higher time-updated cumulative VCY increased the risk of each NACM. Among ART-treated WWH, greater cumulative viremia increased the risk of multimorbidity and of developing each NACM, and hence this may be a prognostically useful biomarker for NACM risk assessment in this population.

Longitudinal decline of plasma neurofilament light levels after antiretroviral initiation in people living with HIV.

This retrospective follow-up study aims to investigate the dynamic longitudinal change of plasma neurofilament light (NfL) levels after antiretroviral therapy (ART) initiation in a cohort of people living with human immunodeficiency virus (HIV) (PWH). We tested a convenience sample of 116 patients from the NORTHIV study. Plasma NfL levels-measured using Single molecule array (Simoa) technology-as well as other laboratory parameters were collected at baseline, weeks 4, 48, 96, and 144. Linear mixed-effects models were estimated to evaluate longitudinal change over time. Baseline CD4+ T-cell levels, CDC classification, and HIV RNA levels were considered. Models were adjusted by age, sex, treatment regimen, and baseline serum creatinine levels. Plasma NfL levels were higher at baseline and also declined faster during the follow-up for participants with CD4+ count <100 cells/µl compared with >100 cells/µl. No significant difference was found between the CD4+ strata 100-199 and 200-499/µl. Participants with CDC classification stages B and C had higher levels of plasma NfL at baseline, as well as faster decline compared with participants with stage A. No significant main effects or change over time was found in baseline HIV RNA levels, treatment regimen, or sex. Plasma NfL is a sensitive biomarker to assess ongoing central nervous system injury in PWH. Plasma NfL concentrations decline relatively fast following ART initiation and then stabilize after 48 weeks. Plasma NfL concentrations are associated with CD4+ count and stage of HIV disease. No correlations were seen with different ART regimens.

How soon should patients be eligible for differentiated service delivery models for antiretroviral treatment? Evidence from a retrospective cohort study in Zambia

ObjectivesPatient attrition is high the first 6 months after antiretroviral therapy (ART) initiation. Patients with <6 months of ART are systematically excluded from most differentiated service delivery (DSD) models, which...

Metabolism-dependent ferroptosis promotes mitochondrial dysfunction and inflammation in CD4+ T lymphocytes in HIV-infected immune non-responders.

HIV immune non-responders (INRs) are described as a failure to reestablish a pool of CD4+ Tlymphocytes (CD4 cells) after antiretroviral therapy (ART), which is related to poor clinical results. Ferroptosis is a newly discovered form of cell death characterised by iron-dependent lipid peroxidation and the accumulation of reactive oxygen species (ROS). The mechanism of unrecoverable CD4 cells in INRs and whether ferroptosis plays a role are not fully understood. Ninety-two people living with HIV (PLHIVs) who experienced four-year ART with sustained viral suppression, including 27 INRs, 34 partial responders (PRs), and 31 complete responders (CRs); and 26 uninfected control participants (UCs) were analysed for 16 immune parameters with flow cytometry. Then plasma lipid, iron and oxidation, and antioxidant indicators were detected by ELISA, and CD4 cells were sorted out and visualised under transmission electron microscopy. Finally, ferroptosis inhibitors were added, and alterations in CD4 cell phenotype and function were observed. We found decreased recent thymic emigrants (RTE), over-activation and over-proliferation phenotypes, diminished killing function, decreased IL-7R and more severe inflammation; increased lipid peroxidation in the mitochondria and disruptions of the mitochondrial structure, showing typical features of ferroptosis in CD4 cells in INRs. Additionally, ferroptosis inhibitors could reduce inflammation and repair mitochondrial damage. Meanwhile, ELISA results showed increased plasma free fatty acids (FFA) and an imbalance of oxidative and antioxidant systems in INRs. Flow cytometry results displayed alterations of both transferrin receptor (CD71) and lipid transporter (CD36) expressions on the surface of CD4 cells. Mechanistically, there was a stronger correlation between CD36 expression and mitochondrial lipid peroxidation production, ferroptosis makers, and inflammation indicators; while amino acid transporter (CD98) was more related to killing functions; and CD71 was more closely related to activation status in CD4 cells. Cellular metabolism was closely correlated with its diverse functions in INRs. Ferroptosis was observed in CD4 cells of INRs, and inhibiting ferroptosis through modulating mitochondrial disorders and inflammation may offer an alternative immunological strategy for reinvigorating CD4 cells in INRs. This research was supported by the 13th Five-year Plan, Ministry of Science and Technology of China (2018ZX10302-102), Beijing Municipal Administration of Hospitals' Ascent Plan (DFL20191802), and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX202126).

Association Between Body Mass Index Variation and Early Mortality Among 834 Ethiopian Adults Living with HIV on ART: A Joint Modelling Approach.

Body mass index (BMI) is a simple and cost-effective tool for monitoring the clinical responses of patients living with human immunodeficiency virus (HIV) after antiretroviral therapy (ART) initiation, especially in resource-limited settings where access to laboratory tests are limited. Current evidence on the association between longitudinal BMI variation and clinical outcomes among adults living with HIV receiving ART is essential to inform clinical guidelines. Therefore, this study examines the association between BMI variation and premature mortality in adults living with HIV on ART. An institution-based retrospective cohort study was conducted among 834 adults living with HIV receiving ART from June 2014 to June 2020 at Debre Markos Comprehensive Specialized Hospital in Northwest Ethiopia. We first identified predictors of mortality and BMI variation using proportional hazards regression and linear mixed models, respectively. Then, the two models were combined to form an advanced joint model to examine the effect of longitudinal BMI variation on mortality. Of the 834 participants, 49 (5.9%) died, with a mortality rate of 4.1 (95% CI 3.1, 5.4) per 100 person-years. A unit increase in BMI after ART initiation corresponded to an 18% reduction in mortality risk. Patients taking tuberculosis preventive therapy (TPT), mild clinical disease stage, and changing ART regimens were at lower risk of death. However, patients with ambulatory/bedridden functional status were at higher risk of death. Regarding BMI variation over time, patients presenting with opportunistic infections (OIs), underweight patients, patients who started a Dolutegravir (DGT)-based ART regimen, and those with severe immunodeficiency had a higher BMI increase over time. However, patients from rural areas and overweight/obese patients experienced a lower BMI increase over time. BMI improvement after ART initiation was strongly associated with a lower mortality risk, regardless of BMI category. This finding implies that BMI may be used as a better predictor tool for death risk in adults living with HIV in Ethiopia. Additionally, patients who took a DGT-based ART regimen had a higher BMI increase rate over time, which aligns with possible positive effects, such as weight gain, of the DGT-based ART regimen in developing countries.

Obesity-Related Single-Nucleotide Polymorphisms and Weight Gain Following First-Line Antiretroviral Therapy.

We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH). Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models. A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020). Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.

Impact of antiretroviral therapy in primary HIV infection on natural killer cell function and the association with viral rebound and HIV DNA following treatment interruption.

Natural Killer (NK) cells play a key role in controlling HIV replication, with potential downstream impact on the size of the HIV reservoir and likelihood of viral rebound after antiretroviral therapy (ART) cessation. It is therefore important to understand how primary HIV infection (PHI) disrupts NK cell function, and how these functions are restored by early ART. We examined the impact of commencing ART during PHI on phenotypic and functional NK cell markers at treatment initiation (baseline), 3 months, 1 year, and 2 years in seven well-characterised participants in comparison to HIV seronegative volunteers. We then examined how those NK cell properties differentially impacted by ART related to time to viral rebound and HIV DNA levels in 44 individuals from the SPARTAC trial who stopped ART after 48 weeks treatment, started during PHI. NK cell markers that were significantly different between the seven people with HIV (PWH) treated for 2 years and HIV uninfected individuals included NKG2C levels in CD56dim NK cells, Tim-3 expression in CD56bright NK cells, IFN-γ expressed by CD56dim NK cells after IL-12/IL-18 stimulation and the fraction of Eomes-/T-bet+ in CD56dim and CD56bright NK cells. When exploring time to viral rebound after stopping ART among the 44 SPARTAC participants, no single NK phenotypic marker correlated with control. Higher levels of IL-12/IL-18 mediated NK cell degranulation at baseline were associated with longer times to viral rebound after treatment interruption (P=0.028). Additionally, we found higher fractions of CD56dim NK cells in individuals with lower levels of HIV DNA (P=0.048). NKG2A and NKp30 levels in CD56neg NK cells were higher in patients with lower HIV DNA levels (p=0.00174, r=-0.49 and p=0.03, r= -0.327, respectively) while CD27 levels were higher in those with higher levels of HIV DNA (p=0.026). These data show NK cell functions are heterogeneously impacted by HIV infection with a mixed picture of resolution on ART, and that while NK cells may affect HIV DNA levels and time to viral rebound, no single NK cell marker defined delayed viral rebound.

Improvement of liver metabolic activity in people with advanced HIV after antiretroviral therapy initiation.

Objective:Evaluating hepatic metabolic changes in people with HIV (PWH) with advanced disease, before and after antiretroviral therapy (ART) initiation, using [18F]-fluorodeoxyglucose (FDG) PET-computed tomography (PET/CT). FDG PET/CT noninvasively quantifies glucose metabolism in organs.Design/methods:Forty-eight viremic PWH (CD4+ cell counts <100 cells/μl) underwent FDG PET/CT at baseline and approximately 6 weeks after ART initiation (short-term). Twenty-seven PWH participants underwent follow-up scans 2 years after treatment (long-term). FDG PET/CT scans from 20 healthy controls were used for comparison. Liver FDG uptake was quantified from the PET/CT scans. Imaging findings as well as clinical, laboratory, and immune markers were compared longitudinally and cross-sectionally to healthy controls.Results:Liver FDG uptake was lower at baseline and short-term in PWH compared with controls (P < 0.0001). At the long-term scan, liver FDG uptake of PWH increased relative to baseline and short-term (P = 0.0083 and 0.0052) but remained lower than controls’ values (P = 0.004). Changes in FDG uptake correlated negatively with levels of glucagon, myeloperoxidase, sCD14, and MCP-1 and positively with markers of recovery (BMI, albumin, and CD4+ cell counts) (P < 0.01). In multivariable analyses of PWH values across timepoints, BMI and glucagon were the best set of predictors for liver FDG uptake (P < 0.0001).Conclusion:Using FDG PET/CT, we found decreased liver glucose metabolism in PWH that could reflect hepatocytes/lymphocytes/myeloid cell loss and metabolic dysfunction because of inflammation. Although long-term ART seems to reverse many hepatic abnormalities, residual liver injury may still exist within 2 years of treatment initiation, especially in PWH who present with low nadir CD4+ cell counts.

Nutritional aberration and related morphological disorders among patients with human immunodeficiency virus infection on combination antiretroviral therapy (cART) in Ghana: A retrospective study

BackgroundMetabolic and nutritional abnormalities among people living with human immunodeficiency virus (PLHIV) have been reported due to either their HIV infection, primary malnutrition caused by insufficient intake or consequences of the ART regimen provided. This study investigated the prevalence and patterns of nutritional abnormalities including morphological changes among HIV patients under combination Antiretroviral Therapy (cART) in the Bia-West District of the Western North Region. MethodsWe employed a hospital-based retrospective longitudinal design. Records of 180 patients with HIV infection before and after antiretroviral therapy (ART) initiation were extracted at the Essam Government Hospital. Eligibility criteria included being on treatment without change in regimen for at least one year and without defaulting in scheduled visits. Data extracted included patients' demography, nutritional parameters and medication history. We assessed patients’ nutritional characteristics with the subjective global assessment (SGA) tool which includes five components of medical history (weight change, dietary intake, gastrointestinal symptoms, functional capacity & metabolic stress) and two components of physical examination (signs of fat loss and muscle wasting, alterations in fluid balance). ResultsMalnutrition, lipodystrophy and body wasting among HIV patients were 48.3% (36.5–62.4), 43.9% (32.6–57.7) and 33.3% (23.6–46.0) respectively. Incremental percentage trends of malnutrition (stage I- 7.4%, stage II -22.4%, stage III-24.7%) and lipodystrophy (Stage I - 22.2%, Stage II - 48.7%, Stage III - 51.9%) were significantly associated with worsening disease status. Patients on AZT+3TC + NVP combined regimen presented with the highest malnutrition [52.9% (28.5–76.1)], lipodystrophy [64.7% (38.6–84.7)] and loss of muscle mass [47.1% (23.9–71.5)]. Long-term ART use was significantly associated with high malnutrition rate (p= 0.02620) and increasing muscle mass loss (p = 0.0040). ConclusionHigh malnutrition, lipodystrophy and muscle wasting exist in PLHIV on cART in the Bia-West District. These adverse nutritional effects may be modulated by disease severity, ARV medication and duration.

A Heavy Burden: Preexisting Physical and Psychiatric Comorbidities and Differential Increases Among Male and Female Participants After Initiating Antiretroviral Therapy in the HIV Outpatient Study, 2008-2018.

Attention to non-AIDS comorbidities is increasingly important in the HIV care and management in the United States. We sought to assess comorbidities before and after antiretroviral therapy (ART) initiation among persons with HIV (PWH). Using the 2008-2018 HIV Outpatient Study (HOPS) data, we assessed changes in prevalence of physical and psychiatric comorbidities, by sex, among participants initiating ART. Cox proportional hazards models were fit to investigate factors associated with the first documented occurrence of key comorbidities, adjusting for demographics and other covariates, including insurance type, CD4+ cell count, ART regimen, and smoking status. Among 1,236 participants who initiated ART (median age 36 years, CD4 cell count 375 cells/mm3), 79% were male, 66% non-white, 44% publicly insured, 53% ever smoked, 33% had substance use history, and 22% had body mass index ≥30 kg/m2. Among females, the percentages with at least one condition were: at ART start, 72% had a physical and 42% a psychiatric comorbidity, and after a median of 6.1 years of follow-up, these were 87% and 63%, respectively. Among males, the percentages with at least one condition were: at ART start, 61% had a physical and 32% a psychiatric comorbidity, and after a median of 4.6 years of follow-up, these were 82% and 53%, respectively. In multivariable Cox proportional hazards analyses, increasing age and higher viral loads (VL) were associated with most physical comorbidities, and being a current/former smoker and higher VL were associated with all psychiatric comorbidities analyzed. HOPS participants already had a substantial burden of physical and psychiatric comorbidities at the time of ART initiation. With advancing age, PWH who initiate ART experience a clinically significant increase in the burden of chronic non-HIV comorbidities that warrants continued surveillance, prevention, and treatment.

Immune Mechanisms Underlying Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B Patients With Viral Coinfection.

It is considered that chronic hepatitis B patients have obtained functional cure if they get hepatitis B surface antigen (HBsAg) seroclearance after treatment. Serum HBsAg is produced by cccDNA that is extremely difficult to clear and dslDNA that is integrated with host chromosome. High HBsAg serum level leads to failure of host immune system, which makes it unable to produce effective antiviral response required for HBsAg seroclerance. Therefore, it is very difficult to achieve functional cure, and fewer than 1% of chronic hepatitis B patients are cured with antiviral treatment annually. Some chronic hepatitis B patients are coinfected with other chronic viral infections, such as HIV, HCV and HDV, which makes more difficult to cure. However, it is found that the probability of obtaining HBsAg seroclearance in patients with coinfection is higher than that in patients with HBV monoinfection, especially in patients with HBV/HIV coinfection who have an up to 36% of HBsAg 5-year-seroclerance rate. The mechanism of this interesting phenomenon is related to the functional reconstruction of immune system after antiretroviral therapy (ART). The quantity increase and function recovery of HBV specific T cells and B cells, and the higher level of cytokines and chemokines such as IP-10, GM-CSF, promote HBsAg seroclearance. This review summarizes recent studies on the immune factors that have influence on HBsAg seroconversion in the chronic hepatitis B patients with viral coinfection, which might provide new insights for the development of therapeutic approaches to partially restore the specific immune response to HBV and other viruses.

Gut-derived bacterial toxins impair memory CD4+ T cell mitochondrial function in HIV-1 infection.

People living with HIV (PLWH) who are immune nonresponders (INRs) are at greater risk of comorbidity and mortality than are immune responders (IRs) who restore their CD4+ T cell count after antiretroviral therapy (ART). INRs have low CD4+ T cell counts (<350 c/μL), heightened systemic inflammation, and increased CD4+ T cell cycling (Ki67+). Here, we report the findings that memory CD4+ T cells and plasma samples of INRs from several cohorts are enriched in gut-derived bacterial solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) that both negatively correlated with CD4+ T cell counts. In vitro PCS or IS blocked CD4+ T cell proliferation, induced apoptosis, and diminished the expression of mitochondrial proteins. Electron microscopy imaging revealed perturbations of mitochondrial networks similar to those found in INRs following incubation of healthy memory CD4+ T cells with PCS. Using bacterial 16S rDNA, INR stool samples were found enriched in proteolytic bacterial genera that metabolize tyrosine and phenylalanine to produce PCS. We propose that toxic solutes from the gut bacterial flora may impair CD4+ T cell recovery during ART and may contribute to CD4+ T cell lymphopenia characteristic of INRs.

A nomogram for predicting paradoxical immune reconstitution inflammatory syndrome associated with cryptococcal meningitis among HIV-infected individuals in China

BackgroundCryptococcal meningitis (CM) associated immune reconstitution inflammatory syndrome (CM-IRIS) is the second most common complication in HIV-infected individuals with cryptococcal meningitis, with a reported mortality rate ranging from 8 to 30%. Given the devastating consequences of CM-IRIS related intracranial neuroinflammation and its challenging in diagnosis, we conducted a study to explore the risk factors and the occurrence of paradoxical CM-IRIS in HIV-infected patients, which is of great value for prevention and clinical management.MethodsWe conducted a retrospective cohort study to identify the indicators associated with paradoxical CM-IRIS among 86 HIV-infected patients with CM using univariate and multivariate cox analysis. A nomogram was constructed using selected variables to evaluate the occurrence of paradoxical CM-IRIS at 6 months and 12 months after ART initiation. The discrimination and calibration of the nomogram were assessed by concordance index (C-index) and calibration plots. Decision curves analysis (DCA) were used to evaluate clinical effectiveness of the nomogram. Subsequently, to help clinicians recognize patients at high risk faster, patients were divided into high-risk and low-risk groups according to the best cutoff point identified by X-tile.ResultsOf 86 AIDS patients with CM, 22.1% experienced paradoxical CM-IRIS at a median of 32 days after antiretroviral therapy (ART) initiation. The occurrence of paradoxical CM-IRIS was associated with age, ART initiation within 4 weeks of antifungal treatment, a four-fold increase in CD4 T cell counts, C-reactive protein levels, and hemoglobin levels independently. These five variables were further used to construct a predictive nomogram. The C-index (0.876) showed the favorable discriminative ability of the nomogram. The calibration plot revealed a high consistency between the predicted and actual observations. DCA showed that the nomogram was clinically useful. Risk stratification based on the total score of the nomogram showed well-differentiated in the high-risk and low-risk groups. Clinicians should pay attention to patients with total points high than 273.ConclusionsWe identified the predictive factors of paradoxical CM-IRIS and constructed a nomogram to evaluate the occurrence of paradoxical CM-IRIS in 6 months and 12 months. The nomogram represents satisfactory performance and might be applied clinically to the screening and management of high-risk patients.

Viral and Host Biomarkers of HIV Remission Post Treatment Interruption.

HIV rebound/remission after antiretroviral therapy (ART) interruption is likely influenced by (a) the size of the inducible replication-competent HIV reservoir and (b) factors in the host environment that influence immunological pressures on this reservoir. Identifying viral and/or host biomarkers of HIV rebound after ART cessation may improve the safety of treatment interruptions and our understanding of how the viral-host interplay results in post-treatment control. Here we review the predictive and functional significance of recently suggested viral and host biomarkers of time to viral rebound and post-treatment control following ART interruption. There are currently no validated viral or host biomarkers of viral rebound; however, several biomarkers have been recently suggested. A combination of viral and host factors will likely be needed to predict viral rebound and to better understand the mechanisms contributing to post-treatment control of HIV, critical steps to developing a cure for HIV infection.

Weight change after antiretroviral therapy initiation among adults living with HIV in Northwest Ethiopia: a longitudinal data analysis

ObjectivesThe first objective was to explore weight change in the first 2 years after antiretroviral therapy (ART) initiation in adults living with HIV. The second objective was to identify the...

Integrase Inhibitor Use Associated with Weight Gain in Women and Incident Diabetes Mellitus.

Excessive weight gain associated with integrase strand transfer inhibitor (InSTI) antiretrovirals is an emerging issue; however, the metabolic consequences of this effect have not been established. Our objective was to evaluate for InSTI-emergent weight gain and potential associated type 2 diabetes mellitus (T2DM) among a diverse HIV patient cohort. For this retrospective cohort study, we obtained clinical warehouse data for HIV+ patients between fiscal years 2007-17. We compared patients initiated on an InSTI with those started on an alternate regimen. Our primary outcome was percentage weight change from baseline to 24 months postinitiation using the linear mixed-effects model fit by restricted maximum likelihood. Our secondary outcome was incident T2DM as defined by a new prescription for antihyperglycemic medication within 18 months after antiretroviral therapy (ART) start. Diabetes-free survival was estimated using the Kaplan-Meier method, log-rank test, and Cox proportional-hazards model. The cohort included 1,235 individuals initiating ART, 136 (11.0%) with an InSTI. InSTI use in women was significantly associated with greater weight gain compared with non-InSTIs (11.0%, 95% confidence interval, CI: 5.22 to 16.8, p < .01), after adjusting for potential confounding variables. In a univariate analysis, InSTI use was associated with more incident T2DM diagnoses compared with non-InSTI regimens (unadjusted hazard ratio = 3.27, p = .01), although incident T2DM was not associated with weight gain. InSTIs were significantly associated with weight gain among females. We also observed an increased risk of incident diabetes mellitus among both sexes, however, unrelated to weight changes. Further prospective studies will be necessary to confirm this finding and investigate its mechanism.

A model for predicting high BMI of people living with HIV after receiving antiretroviral therapy.

Objective:The objective of this study was to evaluate the characteristics of high body mass index (BMI) and normal weight people living with HIV after antiretroviral therapy (ART) and establish a model.Methods:A total of 290 people living with HIV after 1 year of ART treatment were enrolled and divided into two groups based on whether their BMI index was <24 or ⩾24 at week 48. The demographic, clinical data were collected and analyzed. Multivariable logistic regression analysis was performed. A model was established and use to predict the occurrence of certain diseases.Results:A total of 290 people living with HIV were included in this study; 200 had a normal BMI (BMI < 24) and 90 were high BMI (BMI ⩾ 24) after 1-year ART. Their baseline characteristics were significantly different in relation to age (p = 0.007), sex distribution (p = 0.040), ART regimen (p = 0.040), alanine aminotransferase levels (p < 0.001), and three major serum lipid levels: triglycerides (p < 0.001), cholesterol (p = 0.011), and low-density lipoprotein (p = 0.005). A multivariate logistic regression analysis resulted in the development of a model for the diagnosis of high BMI and hyperlipidemia. The model score is an independent risk factor for hyperlipidemia (odds ratio = 2.674, p = 0.001) and high BMI (p < 0.001). The model score is significantly correlated with the controlled attenuation parameter (CAP) value (r = 0.230, p < 0.001) and can be used to divide the severity of liver steatosis based on CAP value.Conclusions:This study demonstrated a easy-to-use model to detect high BMI, hyperlipidemia, and liver steatosis in people living with HIV without risk factors for BMI changing at baseline after 1 year of ART treatment.

Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease.

Low nadir CD4 T-cell counts in HIV+ patients are associated with high morbidity and mortality and lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of immune recovery of T cells and B cells in severely lymphopenic HIV+ patients have not been fully characterized. In a cohort of lymphopenic (CD4 T-cell count < 100/µL) HIV+ patients, we studied mononuclear cells isolated from peripheral blood (PB) and lymph nodes (LN) pre-ART (n = 40) and 6-8 weeks post-ART (n = 30) with evaluation of cellular immunophenotypes; histology on LN sections; functionality of circulating T follicular helper (cTfh) cells; transcriptional and B-cell receptor profile on unfractionated LN and PB samples; and plasma biomarker measurements. A group of 19 healthy controls (HC, n = 19) was used as a comparator. T-cell and B-cell lymphopenia was present in PB pre-ART in HIV+ patients. CD4:CD8 and CD4 T- and B-cell PB subsets partly normalized compared to HC post-ART as viral load decreased. Strikingly in LN, ART led to a rapid decrease in interferon signaling pathways and an increase in Tfh, germinal center and IgD-CD27- B cells, consistent with histological findings of post-ART follicular hyperplasia. However, there was evidence of cTfh cells with decreased helper capacity and of limited B-cell receptor diversification post-ART. In conclusion, we found early signs of immune reconstitution, evidenced by a surge in LN germinal center cells, albeit limited in functionality, in HIV+ patients who initiate ART late in disease.