After Antiretroviral Therapy Research Articles

Is stopping secondary prophylaxis safe in HIV-positive talaromycosis patients? Experience from Myanmar.

ObjectivesThe aim of the study was to determine whether it is safe to stop secondary prophylaxis in patients with talaromycosis after immune reconstitution with a sustained increase in CD4 count to ≥ 100 cells/µL after antiretroviral therapy (ART).MethodsA retrospective cohort analysis was performed in HIV‐infected patients treated for talaromycosis between June 2009 and June 2017 in Medical Action Myanmar (MAM) clinics.ResultsAmong a cohort of 5466 HIV‐infected patients, 41 patients were diagnosed with and treated for clinical talaromycosis. All the patients were on ART and had a CD4 count < 100 cells/µL. Of these 41 patients, 24 patients (71%) were skin smear positive for talaromycosis, while results were negative in 17 patients. Median CD4 count and haemoglobin concentration were 24 cells/µL and 7.7 g/dL, respectively. Seventy‐three per cent (30) were male. Among the 41 patients, 11 (27%) died and six (15%) were transferred to other centres. Twenty‐four patients (58% of the total diagnosed) stopped itraconazole secondary prophylaxis after starting active ART with CD4 counts > 100 cells/µL for at least 1 year. Throughout the duration of follow‐up post itraconazole cessation, the observed incidence of relapse was zero with a total follow‐up of 93.8 person‐years (95% confidence interval 0–4 per 100 person‐years). The median (25th, 75th percentile) duration of follow‐up post‐prophylaxis discontinuation was 2.8 (2.1, 6.3) years.ConclusionsSecondary prophylaxis can be safely stopped in patients with talaromycosis after immune reconstitution with a sustained increase in CD4 count to ≥ 100 cells/µL after highly active antiretroviral therapy.

Prevalence and risk factors of paradoxical tuberculosis associated immune reconstitution inflammatory syndrome among HIV-infected patients in Beijing, China

BackgroundIn this study, we aimed to describe the prevalence, clinical presentation and risk factors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) cases in China.MethodsWe performed a descriptive analysis of demographic and clinical data of HIV/TB coinfected patients receiving ART at Beijing Ditan Hospital between January 2014 and October 2018.ResultsOf 199 patients included, 45 (22.6%) developed paradoxical TB-IRIS, and 19 (9.5%) TB-IRIS cases presented miliary TB. The pre-ART CD4 count lower than 50 cells/mm3 was found to be significantly associated with development of TB-IRIS. Similarly, patients with higher than 4-fold increase in CD4 cell count after antiretroviral therapy (ART) had significantly higher odds of having TB-IRIS. When patients aged 25–44 years were utilized as the control group, youths (< 25 years old) were more likely to have miliary TB. No significant difference was observed in the intervals from initiation of ART to IRIS presentation between miliary and non-miliary group.ConclusionsIn conclusion, our data demonstrate that approximate one quarter of patients coinfected with TB and HIV develop paradoxical TB-IRIS after initial of ART therapy in China. Lower baseline CD4 count and rapid increase in CD4 count are the major risk factors associated with the occurrence of paradoxical TB-IRIS.

HIV-Resistant and HIV-Specific CAR-Modified CD4+ T Cells Mitigate HIV Disease Progression and Confer CD4+ T Cell Help In Vivo

HIV infection preferentially depletes HIV-specific CD4+ T cells, thereby impairing antiviral immunity. In this study, we explored the therapeutic utility of adoptively transferred CD4+ T cells expressing an HIV-specific chimeric antigen receptor (CAR4) to restore CD4+ T cell function to the global HIV-specific immune response. We demonstrated that CAR4 T cells directly suppressed in vitro HIV replication and eliminated virus-infected cells. Notably, CAR4 T cells containing intracellular domains (ICDs) derived from the CD28 receptor family (ICOS and CD28) exhibited superior effector functions compared to the tumor necrosis factor receptor (TNFR) family ICDs (CD27, OX40, and 4-1BB). However, despite demonstrating limited in vitro efficacy, only HIV-resistant CAR4 T cells expressing the 4-1BBζ ICD exhibited profound expansion, concomitant with reduced rebound viremia after antiretroviral therapy (ART) cessation and protection of CD4+ T cells (CAR−) from HIV-induced depletion in humanized mice. Moreover, CAR4 T cells enhanced the in vivo persistence and efficacy of HIV-specific CAR-modified CD8+ T cells expressing the CD28ζ ICD, which alone exhibited poor survival. Collectively, these studies demonstrate that HIV-resistant CAR4 T cells can directly control HIV replication and augment the virus-specific CD8+ T cell response, highlighting the therapeutic potential of engineered CD4+ T cells to engender a functional HIV cure.

PS-SiZer map to investigate significant features of body-weight profile changes in HIV infected patients in the IeDEA Collaboration.

We extend the method of Significant Zero Crossings of Derivatives (SiZer) to address within-subject correlations of repeatedly collected longitudinal biomarker data and the computational aspects of the methodology when analyzing massive biomarker databases. SiZer is a powerful visualization tool for exploring structures in curves by mapping areas where the first derivative is increasing, decreasing or does not change (plateau) thus exploring changes and normalization of biomarkers in the presence of therapy. We propose a penalized spline SiZer (PS-SiZer) which can be expressed as a linear mixed model of the longitudinal biomarker process to account for irregularly collected data and within-subject correlations. Through simulations we show how sensitive PS-SiZer is in detecting existing features in longitudinal data versus existing versions of SiZer. In a real-world data analysis PS-SiZer maps are used to map areas where the first derivative of weight change after antiretroviral therapy (ART) start is significantly increasing, decreasing or does not change, thus exploring the durability of weight increase after the start of therapy. We use weight data repeatedly collected from persons living with HIV initiating ART in five regions in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) worldwide collaboration and compare the durability of weight gain between ART regimens containing and not containing the drug stavudine (d4T), which has been associated with shorter durability of weight gain. Through simulations we show that the PS-SiZer is more accurate in detecting relevant features in longitudinal data than existing SiZer variants such as the local linear smoother (LL) SiZer and the SiZer with smoothing splines (SS-SiZer). In the illustration we include data from 185,010 persons living with HIV who started ART with a d4T (53.1%) versus non-d4T (46.9%) containing regimen. The largest difference in durability of weight gain identified by the SiZer maps was observed in Southern Africa where weight gain in patients treated with d4T-containing regimens lasted 59.9 weeks compared to 133.8 weeks for those with non-d4T-containing regimens. In the other regions, persons receiving d4T-containing regimens experienced weight gains lasting 38-62 weeks versus 55-93 weeks in those receiving non-d4T-based regimens. PS-SiZer, a SiZer variant, can handle irregularly collected longitudinal data and within-subject correlations and is sensitive in detecting even subtle features in biomarker curves.

Antiretroviral Therapy Initiation Is Associated With Decreased Visceral and Subcutaneous Adipose Tissue Density in People Living With Human Immunodeficiency Virus.

Adipose tissue (AT) alterations are common in people living with human immunodeficiency virus (PLWH). Decreases in AT density suggest disrupted adipocyte function/hypertrophy. We assessed changes in AT density after antiretroviral therapy (ART) initiation and associations with immunometabolic parameters. In a prospective randomized clinical trial of ART initiation, L4-L5 abdominal CT scans measured subcutaneous AT (SAT) and visceral AT (VAT) area and density in treatment-naive PLWH randomized to tenofovir-emtricitabine plus ritonavir-boosted atazanavir, ritonavir-boosted darunavir, or raltegravir. Linear regression models compared week 0 and week 96 levels, and 96-week changes, in SAT and VAT density (in Hounsfield units [HU]). Spearman correlations assessed relationships between AT density and immunometabolic parameters. Of the 228 participants, 89% were male and 44% were white non-Hispanic. Median age was 36 years, baseline HIV-1 RNA was 4.6 log10 copies/mL, and CD4+ T-cell count was 344 cells/μL. Over 96 weeks, SAT and VAT HU decreased significantly in all arms. Less dense week 96 SAT and VAT density correlated with higher high-density lipoprotein (HDL) cholesterol and adiponectin (r = 0.19-0.30) levels and lower interleukin 6, non-HDL cholesterol, triglyceride, leptin, and homeostatic model assessment of insulin resistance (r = -0.23 to -0.68) levels at week 96 after adjusting for baseline CD4+ T-cell count, HIV-1 RNA, and baseline AT area. Following virologic suppression, lower SAT and VAT density was associated with greater plasma measures of systemic inflammation, lipid disturbances, and insulin resistance independent of AT area, suggesting that changes in AT density with ART may lead to adverse health outcomes independent of AT quantity. NCT00851799.

Impact of Genetic and Nongenetic Factors on Body Mass Index and Waist-Hip Ratio Change in HIV-Infected Individuals Initiating Antiretroviral Therapy

ObjectiveThere is limited data on abdominal obesity and the influence of genetics on weight change after antiretroviral therapy (ART) initiation. We assessed body mass index (BMI) and waist hip ration (WHR) change over time in the Swiss HIV Cohort study (SHCS).MethodsMixed-effects models characterizing BMI and WHR change over time in 1090 SHCS participants initiating ART between 2005 and 2015 were developed and used to quantify the influence of demographics, clinical factors, and genetic background.ResultsIndividuals with CD4 nadir <100 cells/µL gained 6.4 times more BMI than individuals with ≥200, and 2.8 times more WHR than individuals with ≥100 (P < .001) during the first 1.5 and 2.5 years after ART initiation, respectively. The risk of being overweight or obese after 1.5 years increased with CD4 nadir <100 cells/µL compared to 100–199 (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.63–2.74) and ≥200 (OR, 1.69; 95% CI, 1.26–2.32), persisting after 10 years of ART. The risk of abdominal obesity after 2.5 years increased with CD4 nadir <100 compared to ≥100 (OR, 1.35; 95% CI, 1.17–1.54 [in men]; OR, 1.36; 95% CI, 1.18–1.57 [in women]), persisting after 10 years of ART. No significant differences were found across antiretroviral drug classes or genetic scores.ConclusionsThe risk of general and abdominal obesity increased with CD4 nadir <100 cells/µL. Based on our results, including the genetic background would not improve obesity predictions in HIV-infected individuals.

Cardiovascular Biomarker Profile on Antiretroviral Therapy Is Not Influenced by History of an IRIS Event in People With HIV and Suppressed Viremia.

Immune reconstitution inflammatory syndrome (IRIS) is characterized by release of proinflammatory cytokines and tissue inflammation occurring early after antiretroviral therapy (ART) initiation. The role of previous IRIS events in persistent chronic inflammation in people with HIV is currently unclear. In this retrospective analysis of 143 participants who maintained suppression of HIV viremia, we compared biomarkers related to inflammation, coagulation, and cardiovascular risk after 3 years on ART in participants with and without a history of IRIS. There was no evidence of higher levels of persistent chronic inflammation in people with HIV who had a history of an IRIS event. ClinicalTrials.gov Identifier . NCT00286767.

Broadly neutralizing antibodies for the treatment and prevention of HIV infection.

Several anti-HIV-1 broadly neutralizing antibodies (bNAbs) with exceptional breadth and potency, and targeting different HIV-1 envelope epitopes have entered clinical trials. bNAbs are being evaluated for their potential as long-acting alternatives to antiretrovirals in HIV-1 prevention and therapy, and for potential role in strategies aiming at long-term viral remission. Here, we discuss recent findings from bNAb clinical studies. bNAbs targeting distinct HIV-1 envelope epitopes have shown, in general, favorable safety profiles, and engineered bNAb variants have demonstrated improved pharmacokinetics. Single bNAb infusions transiently decreased viremia with subsequent selection of escape variants, while a combination of two bNAbs successfully maintained viral suppression in individuals harboring antibody-sensitive viruses after antiretroviral therapy (ART) was discontinued. Studies in animal models suggest that bNAbs can modulate immune responses and potentially interfere with the establishment or composition of the latent reservoir, and ongoing clinical studies aim to assess potential bNAb-mediated effects on HIV-1 persistence and host immune responses. Early clinical studies support additional evaluation of bNAbs. Antibodies may offer advantages over standard ART for HIV-1 prevention and therapy, and as components of immunologic strategies to achieve sustained virologic control. The evaluation of engineered bNAbs with multispecificity, extended half-lives and increased potency, as well as alternative bNAb-delivery systems are being pursued.

The effect of antiretroviral therapy on the frequency and severity of cardiac arrhythmias in HIV-infected patients

The aim to study the effects of ART on the incidence and severity of supraventricular ectopy (SVE) and ventricular ectopy (VE) in HIV-infected patients.Materials and methods. We analyzed the results of ambulatory monitoring ECG (AM ECG) in 43 HIV-infected patients before and after antiretroviral therapy (ART). The amount of serum high sensitivity C-reactive protein (hsCRP) was determined in all patients.Results. In all patients before prescribing ART and one year after ART, SVE was registered with varying severity, whereas SVE was registered in 28 (93.3 %) patients of the control group. VE was detected in 31 (72.1 %) patients before prescribing ART, 27 (62.5 %) patients after a year of receiving ART and 6 (20 %) patients in the control group. After analyzing the structure of SVE and VE, it was noted that in HIV-infected patients before ART, a greater number of SVE and VE was recorded, which were significantly decreased when the virological and immunological goals of ART were achieved. Patients showed an increase in the SDNN index to 148.3 ± 11.2 ms and SDANN to 133.3 ± 8.3 ms after effective ART. There were not significant changes in other time-domain heart rhythm variability (HRV) indicators (SDNN, SDNN-index, pNN50 and rMSSD) in this group. A decrease in the frequency and severity of SVE and VE as well as HRV profile improvement were registered with a decrease in the concentration of highly sensitive CRP from 19.1 ± 2.2 mg/l to 10.7 ± 1.3 mg/l (P ˂ 0.05).Conclusions. In HIV-infected patients, both supraventricular and ventricular ectopy are more pronounced and significantly more frequently recorded, including ectopic rhythms which are not peculiar to healthy people. In HIV-infected patients on antiretroviral therapy for 52 ± 4 weeks when viral load &lt;20 copies/ml and CD4 + T lymphocytes &gt;400 cells/ml are reached, the frequency of supraventricular and ventricular ectopy registration is significantly decreased. In HIV-infected patients, a decrease in supraventricular ectopy and ventricular ectopy intensity occurs coupled with a decrease in the level of hsCRP, as well as an improvement in the integral time and spectral indices of heart rate variability. This suggests that systemic inflammatory response and hypersympathicotonia are pathogenetic links of arrhythmogenesis in HIV-infected patients.

Therapeutic Vaccine in Chronically HIV-1-Infected Patients: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Trial with HTI-TriMix.

Therapeutic vaccinations aim to re-educate human immunodeficiency virus (HIV)-1-specific immune responses to achieve durable control of HIV-1 replication in virally suppressed infected individuals after antiretroviral therapy (ART) is interrupted. In a double blinded, placebo-controlled phase IIa multicenter study, we investigated the safety and immunogenicity of intranodal administration of the HIVACAT T cell Immunogen (HTI)-TriMix vaccine. It consists of naked mRNA based on cytotoxic T lymphocyte (CTL) targets of subdominant and conserved HIV-1 regions (HTI), in combination with mRNAs encoding constitutively active TLR4, the ligand for CD40 and CD70 as adjuvants (TriMix). We recruited HIV-1-infected individuals under stable ART. Study-arms HTI-TriMix, TriMix or Water for Injection were assigned in an 8:3:3 ratio. Participants received three vaccinations at weeks 0, 2, and 4 in an inguinal lymph node. Two weeks after the last vaccination, immunogenicity was evaluated using ELISpot assay. ART was interrupted at week 6 to study the effect of the vaccine on viral rebound. The vaccine was considered safe and well tolerated. Eighteen percent (n = 37) of the AEs were considered definitely related to the study product (grade 1 or 2). Three SAEs occurred: two were unrelated to the study product, and one was possibly related to ART interruption (ATI). ELISpot assays to detect T cell responses using peptides covering the HTI sequence showed no significant differences in immunogenicity between groups. There were no significant differences in viral load rebound dynamics after ATI between groups. The vaccine was safe and well tolerated. We were not able to demonstrate immunogenic effects of the vaccine.

All-cause mortality after antiretroviral therapy initiation in HIV-positive women from Europe, Sub-Saharan Africa and the Americas.

Women account for over half of persons living with HIV/AIDS globally. We examined geographic variation in all-cause mortality after antiretroviral therapy (ART) for women living with HIV (WLWH) worldwide. We pooled data from WLWH at least 18 years initiating ART 2000-2014 within COHERE (Europe) and IeDEA regions (East Africa, West Africa, South Africa, North America, Latin America/Caribbean). Mortality rates were calculated at 0-3, 3-6, 6-12, 12-24 and 24-48 months after ART, and mortality rate ratios were compared with European rates with piecewise exponential parametric survival models based on Poisson regression. One hundred ninety thousand, one hundred and seventy-five WLWH (16% Europe, 47% East Africa, 13% West Africa, 19% South Africa, 1% South America, 3% North America and 2% Central America/Caribbean) were included. The highest death rates occurred 0-3 months after ART [1.51 (95% CI 1.25-1.82) per 100 person-years in Europe, 12.45 (11.30-13.73), 14.03 (13.12-15.02) and 9.44 (8.80-10.11) in East, West and South Africa, and 1.53 (0.97-2.43), 7.83 (5.44-11.27) and 17.02 (14.62-19.81) in North, South America and Central America/Caribbean, respectively] and declined thereafter. Mortality in Europe was the lowest, with regional differences greatest in the first 3 months and smaller at longer ART durations [adjusted rate ratios 24-48 months after ART: 3.63 (95% CI 3.04-4.33), 5.61 (4.84-6.51) and 3.47 (2.97-4.06) for East, West and South Africa; 2.86 (2.26-3.62), 2.42 (1.65-3.55) and 2.50 (1.92-3.26) for North, South America and Central America/Caribbean, respectively]. Global variations in short-term and long-term mortality among WLWH initiating ART may inform context-specific interventions.

Factors associated with CD4+/CD8+ T lymphocyte ratio normalization in acquired immunodeficiency syndrome patients after antiretroviral therapy

Objective To investigate the factors associated with CD4+ /CD8+ T lymphocyte ratio normalization in acquired immunodeficiency syndrome (AIDS) patients after antiretroviral therapy (ART). Methods The data of 1 188 human immunodeficiency virus (HIV)/AIDS patients from the national ART reporting system in Yuxi City, Yunnan Province between January 1, 2006 and December 31, 2016 were retrospectively collected and analyzed. The rate of CD4+ /CD8+ T lymphocyte ratio normalization after ART was calculated by lifetable. Cox proportional hazard models were used to analyze the factors associated with CD4+ /CD8+ T lymphocyte normalization in AIDS patients after ART. The Wilcoxon rank sum test was used for comparison between groups. Results The follow-up time was 3.8 (1.0-10.8) years. CD4+ /CD8+ T lymphocyte ratio normalization was documented in 95 patients with the rate of 1.89 per 100 person-years (95% confidence interval(CI) 1.52-2.27) after ART. The average time from ART to CD4+ /CD8+ T lymphocyte ratio normalized was 9.4 years. The cumulative normalization rate was 0.02 for the first year, 0.06 for the third year, 0.11 for the fifth year, 0.19 for the seventh year and 0.37 for the ninth year. By Cox proportional hazard models, the probability of CD4+ /CD8+ T lymphocyte ratio normalization in patients infected HIV by heterosexual contacts was 3.709 (95%CI 1.781-7.726) times higher than those by intravenous injection. The probability of CD4+ /CD8+ T lymphocyte ratio normalization in patients with baseline CD4+ T lymphocytes of 350-499 and more than 500 cell/μL groups were 2.792 (95%CI 1.196-6.519) and 3.832 (95%CI 1.648-8.913) times higher than those with baseline CD4+ T lymphocytes less than 200 cell/μL, respectively. The probability of normalization after ART in patients with higher baseline CD4+ /CD8+ T lymphocyte ratio was higher than those with baseline CD4+ /CD8+ T lymphocyte ratio≤ 0.20 (hazard ratio>1, all P<0.01). Conclusion The CD4+ /CD8+ T lymphocyte ratio normalization in AIDS patients after ART is associated with baseline CD4+ T lymphocyte counts, baseline CD4+ /CD8+ T lymphocyte ratio and HIV transmission mode. Key words: Acquired immunodeficiency syndrome; CD4-positive T-lymphocytes; CD8-positive T-lymphocytes; Antiretroviral therapy; Influencing factors

Peripheral neuropathy in HIV patients on antiretroviral therapy: Does it impact function?

HIV-associated distal sensory polyneuropathy (DSP), with or without neuropathic symptoms, can develop after anti-retroviral therapy (ART). Symptoms frequently involve small fibres but reports on autonomic dysfunction in HIV-DSP are sparse. We studied an HIV-infected cohort after 5 years of ART, and report on the frequency and severity of autonomic symptoms and the impact of DSP on everyday function. This cross-sectional study comprised of participants from a community-based South African HIV-clinic. The Brief Peripheral Neuropathy Screen and reduced Total Neuropathy Score evaluated neuropathic symptoms/signs. DSP was defined as ≥2 symmetrical DSP-signs, and symptomatic DSP when accompanied by neuropathic symptoms. Autonomic symptoms questionnaires, heart rate variability and postural blood pressure changes were assessed. The Lower Extremity Functional Scale (LEFS) was completed. The 67 participants had a median age of 42 years and median ART exposure of 7 years with viral suppression in 84%. Most (81%) met our criteria for DSP and 36% had additional neuropathic symptoms. Autonomic symptoms and signs (above normative values) were present in 15% and more likely in those with symptomatic DSP (P < .001). Participants with DSP, even without symptoms, had lower LEFS scores (P ≤ .039) than those without. HIV-DSP is prevalent and impacts on daily living.

Immune Reconstitution Inflammatory Syndrome During the First Six Months of Receiving Antiretroviral in HIV-Infected Individuals: A Retrospective Cohort Study

Introduction: Immune reconstitution inflammatory syndrome (IRIS) is referred to as the flare up of an underlying, previously undiagnosed infection or the worsening of a previously treated infection soon after antiretroviral therapy (ART) is started. Information about the prevalence and associated risk factors for IRIS in resource-constrained countries like Tanzania where access to ART is increasing is scarce. Therefore, this study was conducted to determine the prevalence and risk factors associated with IRIS among patients attending care and treatment clinic at Muhimbili National Hospital (CTC-MNH). Methods: A retrospective cohort study was conducted in patients receiving highly active antiretroviral therapy (HAART) who attended CTC-MNH between July 2016 and June 2018. Mann Whitney test was used to compare median CD4+ cells count and viral load at baseline and after 6 months of treatment. Associated factors were analysed using multi-logistic regression. Statistics were done using GraphPad Prism 7 software and a p-value &lt; 0.05 was considered statistically significant. Results: Of 318 patients, 8.5% encountered IRIS. Compared to baseline readings, there were significant increases in CD4+ cells (P &lt; 0.0001) and decrease in viral load count (P &lt; 0.0001). Patients who did not adhere to HAART were more likely to develop IRIS [Adjusted Odds Ratio (AOR) = 4.2, 95% CI; 1.14-15.60, P = 0.03]. Conclusion: This study found relatively low prevalence of IRIS as compared to those reported elsewhere. Moreover, poor adherence to HAART was found to be a risk factor for IRIS.

Inflammatory biomarkers in HIV-infected children hospitalized for severe malnutrition in Uganda and Zimbabwe.

A proportion of HIV-infected children with advanced disease develop severe malnutrition soon after antiretroviral therapy (ART) initiation. We tested the hypothesis that systemic inflammation underlies the pathogenesis of severe malnutrition in HIV-infected children. Cross-sectional laboratory substudy in 613 HIV-infected children initiating ART in Uganda and Zimbabwe. We measured C-reactive protein (CRP), TNFα, IL-6 and soluble CD14 by ELISA in cryopreserved plasma at baseline (pre-ART) and week-4 (children with severe malnutrition only). Independent associations between baseline biomarkers and subsequent hospitalization for severe malnutrition were identified using multivariable fractional polynomial logistic regression. Compared with children without severe malnutrition (n = 574, median age 6.3 years, median baseline weight-for-age Z-score -2.2), children hospitalized for severe malnutrition post-ART (n = 39, median age 2.3 years, median baseline weight-for-age Z-score -4.8) had higher baseline CRP [median 13.5 (interquartile range 5.5, 41.1) versus 4.1 (1.4, 14.4) mg/l; P = 0.003] and IL-6 [median 9.2 (6.7, 15.6) versus 5.9 (4.6, 9.3) pg/ml; P < 0.0001], but similar overall TNFα, soluble CD14 and HIV viral load (all P > 0.06). In a multivariable model, higher pre-ART IL-6, lower TNFα and lower weight-for-age were independently associated with subsequent hospitalization for severe malnutrition. Between weeks 0 and 4, there was a significant rise in CRP, IL-6 and soluble CD14, and fall in TNFα and HIV viral load in children hospitalized for severe malnutrition (all P < 0.02). Pre-ART IL-6 and TNFα were more strongly associated with hospitalization for severe malnutrition than CD4 cell count or viral load, highlighting the importance of inflammation at the time of ART initiation in HIV-infected children.

Changes health-related quality of life in HIV-infected patients following initiation of antiretroviral therapy: a longitudinal study

BackgroundSeveral tools have been developed to evaluate HIV health-related quality of life (HRQoL) during and after antiretroviral therapy (ART). Few longitudinal studies evaluated the effect of ART on the quality of life of HIV patients. ObjectiveTo evaluate changes in HRQoL in HIV-infected individuals one year after initiating ART. MethodsA prospective study was conducted from May 2016 to July 2018. Data on clinical and sociodemographic characteristics of 91 HIV-infected patients were collected prior to initiation of ART and one year thereafter. Demographic and clinical data were collected and the questionnaires 36-item Short Form Health Survey (SF-36) and HIV/AIDS-targeted quality of life (HAT-QoL) were administered in both periods. Asymptomatic individuals, aged ≥18 years, were included in the study. Patients who discontinued treatment were excluded. The association between predictors of physical and mental HRQoL was analyzed by multiple linear regression analysis. ResultsPatients were predominantly male (78.0%), mean age 35.3 ± 10.7 years, with no stable relationship (80.2%), and no comorbidities (73.6%). Most of the SF-36 domains improved after one year, particularly Physical Function (p = 0.0001), General Health (p = 0.0001), Social Functioning (p = 0.0001), Mental Health (p = 0.001), and Mental Component Summary (p = 0.004). HAT-QoL domains improved in the Overall Function (p = 0.0001), Life Satisfaction (p = 0.0001), Provider Trust (p = 0.001), and Sexual Function (p = 0.0001) domains. Sex (p = 0.032), age (p = 0.001), income (p = 0.007), and stable relationship (p = 0.004) were good predictors of the Physical Component Summary. Sex (p = 0.002) and stable relationship (p = 0.038) were good predictors of the Mental Component Summary. SF-36 and HAT-QoL scales presented strong correlations, except for Medication Concerns (0.15–0.37), HIV Mastery (0.18–0.38), Disclosure Worries (−0.15 to 0.07), and Provider Trust (−0.07 to 0.15). ConclusionsART improved HRQoL after one year of use. The HAT-QoL and SF-36 correlated well and are good tools to evaluate HRQoL in HIV-infected patients on ART.

Timing of Antiretroviral Therapy and Systemic Inflammation in Sub-Saharan Africa: Results From the META Longitudinal Cohort Study

Chronic inflammation predicts complications in persons with human immunodeficiency virus infection. We compared D-dimer, soluble CD14, and interleukin 6 levels before and 12 months after antiretroviral therapy (ART) initiation, among individuals starting ART during earlier-stage (CD4 T-cell count >350/µL) or late-stage disease (CD4 T-cell count <200/µL). Female sex, older age, viral load, and late-stage disease were associated with pre-ART biomarkers (n = 661; P < .05). However, there were no differences in biomarkers by disease stage after 12 months of ART (n = 438; P > .05), owing to loss from observation and greater declines in biomarkers in late-stage initiators (P < .001). Earlier initiation of ART is associated with decreased inflammation, but levels seem to converge between earlier and later initiators surviving to 12 months.

Plasma Biomarkers of Human Immunodeficiency Virus-Related Systemic Inflammation and Immune Activation in Sub-Saharan Africa Before and During Suppressive Antiretroviral Therapy.

We evaluated immune biomarker profiles in human immunodeficiency virus (HIV)–infected adults (n = 398) from 5 African countries. Although all biomarkers decreased after antiretroviral therapy (ART) initiation, levels of C-X-C chemokine ligand 10 (CXCL10), lipopolysaccharide-binding protein, C-reactive protein, soluble CD163, and soluble scavenger receptor CD14 were significantly higher during ART than in an HIV-uninfected reference group (n = 90), indicating persistent monocyte/macrophage activation, inflammation, and microbial translocation. Before ART initiation, high HIV viral load was associated with elevated CXCL10 and tuberculosis coinfection was associated with elevated soluble CD14. High pre-ART levels of each biomarker strongly predicted residual immune activation during ART. Chemokine (C-C motif) ligand 2, lipopolysaccharide-binding protein, C-reactive protein, and interleukin 6 were differentially expressed between countries. Further research is needed on the clinical implications of residual immune dysregulation.

Survival after long-term ART exposure: findings from an Asian patient population retained in care beyond 5 years on ART.

This study investigated survival in people living with HIV being followed-up from 5 and 10 years after antiretroviral therapy (ART) initiation in a multi-country Asian cohort. We included patients in follow-up >5 years after ART initiation. Factors associated with mortality beyond 5 and 10 years on ART were analysed using competing risk regression with time-updated variables. Of 13,495 patients retained after 5 years on ART, 279 subsequently died (0.56/100 person-years). Increased mortality was associated with age >50 years (sub-hazard ratio [sHR] 2.24, 95% CI 1.58, 3.15, compared with ≤40 years), HIV exposure through injecting drug use (sHR 2.17, 95% CI 1.32, 3.56), HIV viral load ≥1,000 copies/ml: sHR 1.52, 95% CI 1.05, 2.21, compared with <400), regimen (second-line regimen: sHR 2.11, 95% CI 1.52, 2.94, and third-line regimen: sHR 2.82, 95% CI 2.00, 3.98, compared with first-line regimen), HBV coinfection (sHR 2.23, 95% CI 1.49, 3.33), fasting plasma glucose ≥126 mg/dl (sHR 1.98, 95% CI 1.22, 3.21, compared with <100 mg/dl) and estimated glomerular filtration rate <60 ml/min/1.73 m2 (sHR 2.57, 95% CI 1.56, 4.22). Decreased mortality was associated with transmission through male-to-male sexual contact (sHR 0.44, 95% CI 0.22, 0.88, compared with heterosexual transmission) and higher CD4+ T-cell count (200-349 cells/µl: sHR 0.27, 95% CI 0.20, 0.38, 350-499 cells/µl: sHR 0.10, 95% CI 0.07, 0.16 and ≥500 cells/µl: sHR 0.09, 95% CI 0.06, 0.13, compared with <200 cells/µl). Results after 10 years were similar, but most associations were weaker due to limited power. Next to preventing ART failure, HIV programmes should carefully monitor and treat comorbidities, including hepatitis, kidney disease and diabetes, to optimize survival after long-term ART exposure.

Highlights of the Conference on Retroviruses and Opportunistic Infections, 4–9 March 2019, Seattle, WA, USA

The 26th Conference on Retroviruses and Opportunistic Infections 2019 meeting (CROI 2019) took place on 4–9 March in Seattle, WA, USA. This meeting provides up-to-date information of outstanding quality on HIV prevention, treatment and cure research as well as comorbidities. The case of viraemia remission over 18 months after antiretroviral therapy (ART) discontinuation in a patient who had received stem cell transplantation, otherwise known as the ‘London Patient‘, was one of the highlights of the meeting and produced much excitement among attendees and the international press. There was ongoing new data regarding the issue of potential teratogenicity with integrase inhibitors as raised in May 2018 in a cohort in Botswana. Impressive novel preventative and therapeutic agents and options for HIV were also presented together with important issues in terms of clinical management, opportunistic infections, sexually transmitted infections and comorbidities such as ageing, cognitive dysfunction and weight gain.