The Risk of Malnutrition and Sarcopenia in Elderly People Living with HIV during the COVID-19 Pandemic.

Malnutrition is a risk factor of sarcopenia in the elderly. During the COVID-19 pandemic, limited transportation and supply chain disruptions restricted access to nutritious foods. We assessed the nutritional status and sarcopenia risk in older people living with HIV (PLWH) on combination antiretroviral therapy in Thailand. This study was a hospital-based cohort among virally suppressed older PLWH who came for routine HIV clinic visits. The mini nutritional assessment (MNA), body composition analysis and 5-time chair stand test (CST) were performed to assess the nutritional status, muscle mass and physical performance, respectively. A total of 177 PLWH were enrolled (57.60% male). The median age was 58 years (IQR 55-62 years). Thirty-five participants (19.8%) were at risk of developing sarcopenia, and 28.2% had abnormal nutritional status. Muscle mass correlated positively with nutritional scores (r = 0.355, p < 0.001) but negatively with 5-time CST duration (r = -0.173, p = 0.021). In the multivariate model, muscle mass was associated with age, sex, mid-arm circumference, calf circumference and 5-time CST duration. In a well-viral-suppressed older Asian PLWH cohort, given the positive correlation between nutritional status and muscle mass, the nutritional status of older PLWH should be routinely evaluated and monitored.

Long-term patient reported outcome measures and kneeling function in patients with tibial intramedullary nails.

INTRODUCTION: Anterior knee pain (AKP) is a common complaint following intramedullary nail (IMN) insertion for tibial shaft fractures. There is a lack of long-term patient reported outcome data following tibial IMN, with conflicting evidence of the role of nail protrusion on AKP. In this study, we assess the long-term patient reported outcome measures and kneeling function in patients with tibial IMNs and compare the results with IMN protrusion, measured radiologically. MATERIALS AND METHODS: A retrospective cohort of 128 patients, from a single UK centre, were invited to participate in the study, to complete a Kujala score, KOOS, EQ-5D-5L and a four-posture kneeling assessment. We report the outcomes of 45 patients at an average follow-up of 6.9 years. RESULTS: The mean Kujala score was 80.7. The mean KOOS score was 83.2, 83.9, 85.8, 70.7 and 72.8 for symptoms, pain, daily living, sport and quality of life, respectively. We found 20.5% of patients experienced daily AKP. Pain and fear of pain were the most common limiting factors in the kneeling assessment. No significant correlation was found between the KOOS or Kujala score and nail-plateau distance, nail-anterior cortex distance, or the overall nail prominence. CONCLUSION: AKP affects a subset of patients more than five years post-tibial IMN, limiting their ability to kneel and other functions of daily living. Tibial IMN prominence does not seem to be associated with AKP.

Framingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART.

INTRODUCTION: Immune dysregulation persists in people with HIV (PWH) on antiretroviral therapy (ART) and may lead to accelerated vascular ageing and cardiovascular disease (CVD). While delayed time to initiation of ART has been linked to worse cardiovascular outcomes, the effect of ART initiation during acute infection on these outcomes is not well understood. METHODS: Participants were enrolled from the SEARCH010/RV254 acute HIV (AHI) and HIV-NAT chronic HIV (CHI) cohorts in Thailand. Participants with 6-year follow-up and viral suppression (viral load < 50 copies/µL) at follow-up were included. Both unmatched cohorts and age and gender-matched cohorts were analysed. Demographics, HIV laboratories, and cardiovascular risk factors from enrolment and 6-year follow-up were obtained from electronic records. Framingham Risk Score (FRS), vascular age (VA), vascular age deviation (VAD), and 10-year atherosclerotic cardiovascular disease (ASCVD) risk were calculated from previously published equations. Vascular outcomes in AHI and CHI cohorts were compared, and univariable and multivariable linear regression analyses were used to investigate risk factors associated with worse vascular scores. RESULTS: In all, 373 AHI participants and 608 CHI participants were identified. AHI participants were of younger age, had a higher prevalence of syphilis and a lower prevalence of prior hepatitis B, tuberculosis, diabetes, and hypertension. Higher CD4 T-cell and lower CD8 T-cell counts were seen in the AHI cohort at enrolment and 6-year follow-up. In all participants, the AHI cohort had a lower median FRS (p < 0.001) and VA (p < 0.001), but higher VAD (p < 0.001). However, in matched cohorts, no differences were found in FRS-based outcomes. In all participants, higher VAD after 6 years of ART was associated with higher body mass index (p < 0.001) and higher CD4 count (p < 0.001), which persisted in multivariable analysis. When FRS components were analysed individually, CD4 count was associated only with male sex and cholesterol. CONCLUSIONS: We did not identify differences in FRS-based vascular outcomes at 6 years in matched cohorts of participants who started ART during AHI versus CHI. We identified a correlation between higher CD4 count and worse FRS-based vascular outcomes, which may be driven by underlying metabolic risk factors. Further study is needed to confirm these findings and evaluate underlying mechanisms.

The floating hip injury: a descriptive study and case-control analysis.

PURPOSE: A "floating hip" (FH) injury is a rare injury describing the simultaneous ipsilateral fracture of the femur and pelvis or acetabulum (P/A). We describe our experience with patients presenting with FH injuries and compare them to controls with similar P/A fractures but without femoral involvement. METHODS: Medical records and radiographs of FH patients and controls presenting to our tertiary centre between 2015 and 2020 were reviewed. Follow-up data from outpatient clinical records were also extracted. The control group were extensively matched by age, sex, body mass index, fracture classification and energy of injury. RESULTS: From 1392 recorded P/A fractures, 42 FH cases were identified (average age 39 years, 78.6% males). The most common femoral fracture was the midshaft (35.7%), followed by the neck of femur (26.2%). 90.5% of FH injuries were due to high-energy mechanisms. 64.3% of P/A fractures, and 100% of femoral fractures were managed surgically. Compared to controls, FH cases were more likely to have additional orthopaedic injuries (73.8% vs. 40.5%, p = 0.002), more total theatre admissions (mean 2.5 vs. 1.19, p < 0.001), longer hospital stays (28.3 vs. 14.9 days, p = 0.02), and a higher rates of post-op complications (53.8% vs. 20%, p = 0.025). CONCLUSIONS: We report differences in the presentation, management, and outcomes of FH injuries versus controls, even after extensive matching for confounders. These differences may inform future treatment strategies for the FH injury.

Investigating rates and predictors of viral blips, low-level viraemia and virological failure in the Australian HIV observational database.

OBJECTIVES: Australia has made significant progress towards achieving the UNAIDS's 95-95-95 cascade targets including HIV viral suppression. To investigate the burden of HIV viraemia, we assessed viral blips, low-level viraemia (LLV) and virologic failure (VF) in an Australian cohort. METHODS: We studied the proportion of people with viral suppression, viral blips, LLV and VF in the Australian HIV observational database (AHOD) between 2010 and 2021. The association between blips or LLV, and VF was investigated using Cox regression, and predictors of viral blips and LLV were assessed using repeated-measured logistic regression. RESULTS: Among 2544 AHOD participants who were in follow-up and on antiretroviral therapy (ART) from 1 January 2010 (88.7% male), 444 had experienced VF (incidence rate: 2.45 [95% CI: 2.23-2.69] per 100 person-years [PY]) during 18,125 PY of follow-up (a median of 7.6 years). The proportion of people with VF decreased over time, whereas rates of blips and LLV remained stable. Participants with blips (hazard ratio, 2.89; 95% CI: 2.31-3.61) and LLV (4.46; 95% CI: 3.38-5.89) were at increased risk of VF. Hepatitis B co-infection, longer documented treatment interruption duration, younger age and lower CD4 at ART initiation, and protease inhibitors-based initial regimen were associated with an increased risk of VF. Common predictors of blips and LLV such as higher HIV-1 RNA and lower CD4 at ART initiation, longer treatment interruption, more VL testing and types of care settings (hospitals vs. sexual health services) were identified. CONCLUSIONS: Blips and LLV predict subsequent VF development. We identified important predictors of HIV viraemia including VF among individuals on INSTI-based regimens to help direct HIV management plans.

AI-augmented clinical decision in paediatric appendicitis: can an AI-generated model improve trainees' diagnostic capability?

Accurate diagnosis of paediatric appendicitis remains a challenge due to its diverse clinical presentations and reliance on subjective assessments. The integration of artificial intelligence (AI) with an expert's ''clinical sense'' has the potential to improve diagnostic accuracy. In this study, we aimed to evaluate the effectiveness of the Artificial Intelligence Pediatric Appendicitis Decision-tree (AiPAD) model in enhancing the diagnostic capabilities of trainees and compare their performance with that of an expert supervisor. Between March 2019 and October 2022, we included paediatric patients aged 0-12 years who were referred for suspected appendicitis. Trainees collected clinical findings using five predefined parameters before ordering any imaging studies. The AiPAD model, which was blinded to the surgical team, made predictions from the supervisor's and trainees' findings independently. The diagnosis verdicts of the supervisor and the trainees were statistically evaluated in comparison to the prediction of the AI model, taking into account the revealed correct diagnosis. A total of 136 cases were included, comprising 58 cases of acute appendicitis (AA) and 78 cases of non-appendicitis (NA). The supervisor's correct verdict showed 91% accuracy compared to an average of 70% for trainees. However, if trainees were enabled with AiPAD, their accuracy would improve significantly to an average of 97%. Significantly, a strong association was observed between the expert's clinical sense and the predictions generated by AiPAD. CONCLUSION:  The utilisation of the AiPAD model in diagnosing paediatric appendicitis has significant potential to improve trainees' diagnostic accuracy, approaching the level of an expert supervisor. This hybrid approach combining AI and expert knowledge holds promise for enhancing diagnostic capabilities, reducing medical errors and improving patient outcomes. WHAT IS KNOWN: • Sharpening clinical judgement for pediatric appendicitis takes time and seasoned exposure. Traditional training leaves junior doctors yearning for a faster path to diagnostic mastery. WHAT IS NEW: • AI-generated models unlock the secrets of expert intuition, crafting an explicit guide for juniors to rapidly elevate their diagnostic skills. This leapfrog advancement empowers young doctors, democratizing medical expertise and paving the way for brighter outcomes in clinical training.

Clinical and laboratory features of COVID-19 illness and outcomes in immunocompromised individuals during the first pandemic wave in Sydney, Australia.

People with immunocompromising conditions are at increased risk of SARS-CoV-2 infection and mortality, however early in the pandemic it was challenging to collate data on this heterogenous population. We conducted a registry study of immunocompromised individuals with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection from March-October 2020 in Sydney, Australia to understand clinical and laboratory outcomes in this population prior to the emergence of the Delta variant. 27 participants were enrolled into the study including people with a haematologic oncologic conditions (n = 12), secondary immunosuppression (N = 8) and those with primary or acquired immunodeficiency (i.e. HIV; N = 7). All participants had symptomatic COVID-19 with the most common features being cough (64%), fever (52%) and headache (40%). Five patients demonstrated delayed SARS-CoV-2 clearance lasting three weeks to three months. The mortality rate in this study was 7% compared to 1.3% in the state of New South Wales Australia during the same period. This study provides data from the first eight months of the pandemic on COVID-19 outcomes in at-risk patient groups.

Impact of steatotic liver disease and non-alcoholic steatohepatitis on cognitive impairment in people living with HIV: A cross-sectional study.

INTRODUCTION: The link between fatty liver diseases and cognitive impairment among people living with HIV (PLWH) remains unclear. We investigated the association of steatotic liver disease (SLD), advanced liver fibrosis and non-alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis with cognitive impairment in PLWH. METHODS: Cognitive performance was assessed for PLWH aged ≥50 years on stable antiretroviral therapy (ART) with the Thai-validated version of the Montreal Cognitive Assessment (MoCA), and a cut-off of <25/30 was used to define cognitive impairment. SLD and NASH with significant activity and liver fibrosis were defined as having a controlled attenuation parameter value ≥248 dB/m and a FibroScan-AST (FAST) score ≥0.67, respectively. Multivariable logistic regression was employed to investigate the association of cognitive impairment with SLD or NASH. RESULTS: Of the 319 PLWH (63.3% male and 98% had HIV-1 RNA ≤50 copies/mL) included, 74 (38%) had SLD. NASH with significant activity and liver fibrosis was present in 66 (20.1%) participants. Some 192 (60.2%) participants had cognitive impairment. In a multivariable analysis, NASH with significant activity and liver fibrosis was significantly associated with cognitive impairment (adjusted odds ratio [aOR] 2.01, 95% CI 1.02-3.98, p = 0.04), after adjusting for HIV-related parameters, age, sex, body mass index, employment status, education, income level, smoking, alcohol use, diabetes mellitus, hypertension and HIV-related parameters. The association of a lone diagnosis of SLD and cognitive impairment was not statistically significant. CONCLUSIONS: NASH with significant activity and liver fibrosis was associated with lower cognitive performance, even after controlling for demographics and HIV disease parameters. Additional research is needed to better understand the underlying mechanisms.

Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis With Liver Fibrosis as Predictors of New-Onset Diabetes Mellitus in People With HIV: A Longitudinal Cohort Study.

BACKGROUND: We investigated the association between nonalcoholic fatty liver disease (NAFLD) plus or minus a concurrent diagnosis of nonalcoholic steatohepatitis (NASH) and incident diabetes mellitus (DM) and the risk factors associated with NAFLD or NASH development. METHODS: In this prospective study, we analyzed people with human immunodeficiency virus (HIV; PWH) aged ≥18 years without excessive alcohol consumption or hepatitis coinfections. NAFLD was defined as controlled attenuation parameter ≥248 dB/m, whereas NASH with significant disease activity and liver fibrosis was defined as a FibroScan-AST score ≥0.67. Cox proportional hazard regression was used to investigate the association between NAFLD with or without NASH and new-onset DM. RESULTS: Of 847 PWH, the median age at baseline was 45 years (interquartile range, 38-51; 43% female). Baseline NAFLD was associated with 2.8-fold higher risk of new-onset DM after adjusting for age, sex, family history of DM, antiretroviral therapy duration, smoking, statin use, stavudine/didanosine/zidovudine exposure, time-updated body mass index, hypertension, and dyslipidemia. Combined NAFLD and NASH at baseline had 3.1-fold higher new-onset DM risk. In separate analyses, baseline DM did not predict progression to NAFLD or NASH, but tenofovir alafenamide use was associated with an increased risk of NAFLD (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.02-4.02) or NASH development (2.31; 95% CI, 1.12-5.11). CONCLUSIONS: NAFLD alone or combined with NASH strongly predicts new-onset DM. This highlights the need for systematic risk assessments and management of NAFLD/NASH, as it may contribute to metabolic complications such as DM and subsequent cardiovascular diseases in PWH.

Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza.

BACKGROUNDAntibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT 006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalized with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B but showed no benefit for influenza A.METHODSTo probe potential mechanisms of Flu-IVIG utility, sera collected from patients hospitalized with influenza A or B viruses (IAV or IBV) were analyzed for antibody isotype/subclass and Fcγ receptor (FcγR) binding by ELISA, bead-based multiplex, and NK cell activation assays.RESULTSInfluenza-specific FcγR-binding antibodies were elevated in Flu-IVIG-infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcγR binding were associated with more favorable outcomes. Flu-IVIG therapy also improved the odds of a more favorable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcγR-binding antibody was associated with less favorable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favorable outcome in participants with low levels of anti-IAV Fc-functional antibody.CONCLUSIONThese detailed serological analyses provide insights into antibody features and mechanisms required for a successful humoral response against influenza, suggesting that IBV-specific, but not IAV-specific, antibodies with Fc-mediated functions may assist in improving influenza outcome. This work will inform development of improved influenza immunotherapies.TRIAL REGISTRATIONClinicalTrials.gov NCT02287467.FUNDINGFunding for this research was provided by subcontract 13XS134 under Leidos Biomedical Research Prime Contract HHSN261200800001E and HHSN261201500003I, NCI/NIAID.

Metabolic-Associated Fatty Liver Disease (MAFLD) is associated with immune activation, increased epicardial fat volume, and steatohepatitis among people with HIV in a Thai cohort.

INTRODUCTION: A change in terminology from fatty liver disease to metabolic-associated fatty liver disease (MAFLD), along with modified diagnostic criteria, was proposed in 2020, and data regarding MAFLD burden in people living with HIV are limited. We investigated associations between MAFLD and immune activation, cardiovascular disease (CVD) risks including epicardial fat volume, and steatohepatitis in an Asian cohort. METHODS: We evaluated CVD risk (epicardial fat tissue, coronary artery calcium [CAC] score, and 10-year atherosclerotic CVD [ASCVD] score) in people living with HIV aged >50 years. Individuals with excessive alcohol consumption and viral hepatitis infections were excluded. MAFLD diagnosis was based on 2020 International Consensus criteria. Non-alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis was defined as FibroScan-aspartate aminotransferase (FAST) score ≥0.67 and >0.35. Multivariate logistic regression models were used to investigate factors associated with MAFLD and NASH with significant activity and liver fibrosis. RESULTS: The median age was 54 years (interquartile range [IQR] 52-60) and current CD4 count was 613 (IQR 467-804) cells/mm3 . A total of 37% were female, and most (98%) people living with HIV were virally suppressed. The prevalence of MAFLD and non-alcoholic fatty liver disease was 35% and 38%, respectively. In multivariate analyses, higher body mass index, albumin, epicardial fat volume, and liver stiffness were significantly associated with MAFLD. A higher CD4/CD8 ratio was associated with a lower risk of MAFLD. People with HIV with MAFLD had higher odds of having NASH with significant activity and liver fibrosis (adjusted odds ratio 3.3; 95% confidence interval 1.6-6.6), and similar associations were also observed among different MAFLD categories. CONCLUSIONS: The complex relationship between MAFLD and immune activation, steatohepatitis, and epicardial fat tissue suggests an increased risk of advanced liver disease and CVDs beyond the traditional risk factors in people living with HIV with fatty liver disease.

CD4/CD8 Ratio Recovery Among People Living With HIV Starting With First-Line Integrase Strand Transfer Inhibitors: A Prospective Regional Cohort Analysis.

BACKGROUND: We evaluated trends in CD4/CD8 ratio among people living with HIV (PLWH) starting antiretroviral therapy (ART) with first-line integrase strand transfer inhibitors (INSTI) compared with non-INSTI-based ART, and the incidence of CD4/CD8 ratio normalization. METHODS: All PLWH enrolled in adult HIV cohorts of IeDEA Asia-Pacific who started with triple-ART with at least 1 CD4, CD8 (3-month window), and HIV-1 RNA measurement post-ART were included. CD4/CD8 ratio normalization was defined as a ratio ≥1. Longitudinal changes in CD4/CD8 ratio were analyzed by linear mixed model, the incidence of the normalization by Cox regression, and the differences in ratio recovery by group-based trajectory modeling. RESULTS: A total of 5529 PLWH were included; 80% male, median age 35 years (interquartile range [IQR], 29-43). First-line regimens were comprised of 65% NNRTI, 19% PI, and 16% INSTI. The baseline CD4/CD8 ratio was 0.19 (IQR, 0.09-0.33). PLWH starting with NNRTI- (P = 0.005) or PI-based ART (P = 0.030) had lower CD4/CD8 recovery over 5 years compared with INSTI. During 24,304 person-years of follow-up, 32% had CD4/CD8 ratio normalization. After adjusting for age, sex, baseline CD4, HIV-1 RNA, HCV, and year of ART initiation, PLWH started with INSTI had higher odds of achieving CD4/CD8 ratio normalization than NNRTI- (P < 0.001) or PI-based ART (P = 0.015). In group-based trajectory modeling analysis, INSTI was associated with greater odds of being in the higher ratio trajectory. CONCLUSIONS: INSTI use was associated with higher rates of CD4/CD8 ratio recovery and normalization in our cohort. These results emphasize the relative benefits of INSTI-based ART for immune restoration.

Association of Phenotypic Aging Marker with comorbidities, frailty and inflammatory markers in people living with HIV.

BACKGROUND: Aging characteristics in people living with HIV (PLWH) are heterogeneous, and the identification of risk factors associated with aging-related comorbidities such as neurocognitive impairment (NCI) and frailty is important. We evaluated predictors of novel aging markers, phenotypic age (PhenoAge) and phenotypic age acceleration (PAA) and their association with comorbidities, frailty, and NCI. METHODS: In a cohort of PLWH and age- and sex-matched HIV-negative controls, we calculated PhenoAge using chronological age and 9 biomarkers from complete blood counts, inflammatory, metabolic-, liver- and kidney-related parameters. PAA was calculated as the difference between chronological age and PhenoAge. Multivariate logistic regression models were used to identify the factors associated with higher (>median) PAA. Area under the receiver operating characteristics curve (AUROC) was used to assess model discrimination for frailty. RESULTS: Among 333 PLWH and 102 HIV-negative controls (38% female), the median phenotypic age (49.4 vs. 48.5 years, p = 0.54) and PAA (- 6.7 vs. -7.5, p = 0.24) was slightly higher and PAA slightly less in PLWH although this did not reach statistical significance. In multivariate analysis, male sex (adjusted odds ratio = 1.68 [95%CI = 1.03-2.73]), current smoking (2.74 [1.30-5.79]), diabetes mellitus (2.97 [1.48-5.99]), hypertension (1.67 [1.02-2.72]), frailty (3.82 [1.33-10.93]), and higher IL-6 levels (1.09 [1.04-1.15]), but not HIV status and NCI, were independently associated with higher PAA. PhenoAge marker discriminated frailty better than chronological age alone (AUROC: 0.75 [0.66-0.85] vs. 0.65 [0.55-0.77], p = 0.04). In the analysis restricted to PLWH, PhenoAge alone predicted frailty better than chronological age alone (AUROC: 0.7412 vs. 0.6499, P = 0.09) and VACS index (AUROC: 0.7412 vs. 0.6811, P = 0.34) despite not statistically significant. CONCLUSIONS: While PLWH did not appear to have accelerated aging in our cohort, the phenotypic aging marker was significantly associated with systemic inflammation, frailty, and cardiovascular disease risk factors. This simple aging marker could be useful to identify high-risk PLWH within a similar chronological age group.

Bone mineral density among virologically suppressed Asians older than 50 years old living with and without HIV: A cross-sectional study.

There are limited data regarding bone health in older people living with HIV (PWH), especially those of Asian ethnicity. We aimed to determine whether BMD in well-suppressed HIV-infected men and women aged ≥ 50 years are different from HIV-uninfected controls. In a cross-sectional study, BMD by dual-energy X-ray absorptiometry and calciotropic hormones were measured. A total of 481 participants were consecutively enrolled (209 HIV+ men, 88 HIV- men, 126 HIV+ women and 58 HIV- women). PWH were on average 2.5 years younger [men: 55.0 vs. 57.5 yr; women: 54.0 vs. 58.0 yr] and had lower body mass index (BMI) [men: 23.2 vs. 25.1 kg/m2; women: 23.1 vs. 24.7 kg/m2] compared to the controls. The median duration since HIV diagnosis was 19 (IQR 15-21) years in men and 18 (IQR 15-21) years in women. Three-quarters of PWH had been treated with tenofovir disoproxil fumarate-containing antiretroviral therapy for a median time of 7.4 (IQR 4.5-8.9) years in men and 8.2 (IQR 6.1-10) years in women. In an unadjusted model, HIV+men had significantly lower BMD (g/cm2) at the total hip and femoral neck whereas there was a tend toward lower BMD in HIV+women. After adjusting for age, BMI, and other traditional osteoporotic risk factors, BMD of virologically suppressed older PWH did not differ from participants without HIV (P>0.1). PWH had lower serum 25(OH)D levels but this was not correlated with BMD. In conclusion, BMD in well-suppressed PWH is not different from non-HIV people, therefore, effective control of HIV infection and minimization of other traditional osteoporosis risk factors may help maintain good skeletal health and prevent premature bone loss in Asian PWH. Clinical trial registration: Clinicaltrials.gov # NCT00411983.

Weight change with integrase strand transfer inhibitors among virally suppressed Thai people living with HIV.

BACKGROUND: We compared weight changes in virally suppressed people living with HIV (PLWH) switching to integrase strand transfer inhibitors (INSTIs) with those remaining on an INSTI or non-INSTI regimen. METHODS: PLWH aged ≥18 years with weight measurements available at baseline between 2001 and 2020 were included. Viral suppression was defined as having had a viral load <400 copies/mL for 6 months. Baseline was defined as the time of switching from a non-INSTI to an INSTI regimen whilst virally suppressed (switch group) or the time that viral suppression was achieved (remain groups). Generalized estimating equations adjusted for age, sex and baseline weight were used to model weight changes 6, 12, 18 and 24 months after baseline. RESULTS: A total of 1673 PLWH contributed 1952 episodes of viral suppression-143 (7.3%) episodes were among PLWH who had switched from a non-INSTI to an INSTI, 102 (5.2%) episodes were among PLWH who remained on an INSTI and 1707 (87.4%) episodes were among PLWH who remained on a non-INSTI. PLWH in the switch group had significantly greater weight gain than those in the remain groups at 6, 12 and 18 months after achieving viral suppression. By 24 months, weight change on all regimens started to converge. Tenofovir alafenamide use was not significantly associated with weight gain in adjusted models. CONCLUSIONS: Our findings suggest that the mechanisms of weight gain due to INSTI use go beyond their superior efficacy over other antiretrovirals in controlling HIV or the effect of the 'return-to-health' phenomenon. Further research is needed to understand the mechanisms of such weight gain.

Higher prevalence of QTc interval prolongation among virologically suppressed older people with HIV.

OBJECTIVE: To assess the prevalence, and factors associated with QTc interval prolongation, among 383 virologically suppressed people with HIV (PWH), without evidence of cardiovascular disease and active opportunistic infections in Thailand. DESIGN: Cross-sectional study. METHODS: Resting 12-lead digital ECGs were performed in 2019. QT interval corrected for heart rate (QTc) >450 ms in males and >460 ms in females was defined as QTc interval prolongation. We used multivariable logistic regression to investigate factors associated with QTc interval prolongation. RESULTS: Mean (standard deviation) age was 56 (5.5) years and 42% were female. The median current CD4+ was 619 (interquartile range [IQR] 487, 769) cells/mm 3 . The median duration of antiretroviral therapy (ART) was 11.9 (IQR 7.1-16.1) years. Commonly used ART were rilpivirine (37.9%), efavirenz (20.1%), atazanavir/ritonavir (15.7%), lopinavir/ritonavir (12.3%) and dolutegravir (5%). The prevalence of QTc interval prolongation was 22.7%. In multivariable analysis, older age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12, P  = 0.005), female sex (OR 1.69, 95% CI 1.01-2.82, P  = 0.046) and increasing BMI (OR 1.08, 95% CI 1.01-1.15, P  = 0.03) were associated with QTc interval prolongation. With every 1-year increase in age, the odds of QTc interval prolongation increased by 7%. CONCLUSIONS: In this well-suppressed aging Asian HIV cohort, the prevalence of QTc interval prolongation was relatively high, and associated with increasing age, female sex, and higher BMI. For PLWH with these characteristics, QTc interval should be monitored before and after initiating any medications known to prolong QTc intervals, to prevent fatal cardiac arrhythmias.

Incidence of active tuberculosis among people living with HIV receiving long-term antiretroviral therapy in high TB/HIV burden settings in Thailand: implication for tuberculosis preventive therapy.

INTRODUCTION: Among high tuberculosis (TB) and HIV burden countries in Asia, tuberculosis preventive therapy (TPT) in people living with HIV (PLWH) has been underutilized despite its proven benefits independent of antiretroviral therapy (ART). Therefore, we determined the incidence of active TB and mortality among 9179 adult PLWH who attended and received ART from 15 tertiary care hospitals across Thailand. METHODS: A retrospective study was conducted in 2018 using follow-up data from 1999 to 2018. The primary endpoint was incident TB disease after ART initiation. Factors associated with TB incidence were analysed using competing risk regression. The Kaplan-Meier method was used to estimate mortality after ART initiation. RESULTS: During a median of 5.1 years of ART (IQR 2.2-9.5 years), 442 (4.8%) PLWH developed TB (TB/HIV), giving an overall incidence of 750 (95% CI 683-823) per 100,000 persons-year of follow up (PYFU). In multivariate analysis, lower CD4 at ART initiation (≤100 cells/mm3 , adjusted sub-distribution hazard ratio [aSHR]: 2.08, 95% CI, 1.47-2.92; 101-200 cells/mm3 , aSHR: 2.21, 95% CI, 1.54-3.16; 201-350 cells/mm3 , aSHR: 1.59, 95% CI, 1.11-2.28 vs. >350 cells/mm3 ), male sex (aSHR: 1.40, 95% CI, 1.11-1.78), lower body weight (<50 kg, aSHR: 1.52, 95% CI, 1.17-1.95) and prior TB event (aSHR: 3.50, 95% CI, 2.72-4.52) were associated with TB incidence. PLWH with HIV RNA ≥50 copies/ml had 5-9 times higher risk of active TB disease higher than those with HIV RNA <50 copies/ml at the same CD4 level. The risk for developing TB was remarkably high during the initial period of ART (175,511 per 100,000 PYFU at<3 months) and was comparable to the general population after 10 years of ART (151 per 100,000 PYFU). TB/HIV had higher mortality (10% vs. 5%) and poorer HIV treatment outcomes: HIV RNA <50 copies/ml (63.8% vs. 82.8%), CD4 cells count (317 vs. 508 cells/mm3 ) at the most recent visit. CONCLUSIONS: In this high TB burden country, TB incidence was remarkably high during the first few years after ART initiation and thereafter decreased significantly. Rapid ART initiation and appropriate TPT can be potential key interventions to tackle the TB epidemic and reduce mortality among PLWH in TB/HIV high burden settings.

High Proportion of Blood-Borne and Sexually Transmitted Infections Among People Deprived of Liberty in a Central Male Prison in Thailand: A Cross-Sectional Study 2018-2019.

Data are lacking or outdated on burden of HIV, viral hepatitis infection, and sexually transmitted infections such as syphilis among people deprived of liberty in the Asia-Pacific region. We aimed to evaluate the proportion of viral hepatitis B (HBV), hepatitis C (HCV), HIV, and syphilis infections, and factors associated with HCV, HBV, and HIV infection in a central male prison. A cross-sectional study was performed among 1,028 people deprived of liberty from a central male prison in Bangkok, Thailand. People deprived of liberty were screened for HIV, HBV, HCV, and syphilis infections during 2018-2019. HBV and HCV were defined as positive hepatitis B surface antigen and positive anti-HCV antibody, respectively. Proportions (95% confidence interval [CI]) of infections were calculated based on the binomial distribution. HBV proportion was reported for different age groups. Risk factors associated with HCV infections were evaluated by logistic regression model. The median age was 38 (interquartile range, 32-50) years, and 6.9% reported use of injection drugs. The proportion of HIV, HBV, anti-HCV, HCV RNA, and syphilis was 2.9% (95% CI, 1.9-4.1), 6.4% (5-8.1), 5.9% (4.6-7.6), 4.2% (3-5.6), and 4.8% (3.5-6.3), respectively. One (0.1%), 7 (0.6%), and 2 (3%) were co-infected with HIV/HBV, HIV/HCV, and HDV/HBV, respectively. HBV proportion differed across age groups: 3.7% in <30 years, 7% in 31-40 years, 9.7% in 41-50 years, and 5.5% in >50 years. Factors associated with HCV infection were older age, lower education level, previous incarceration, and injection drug use. In multivariable models, older age was associated with HBV infection, and men having sex with men was associated with HIV infection. The proportion of blood-borne infections was higher among males than among the general population. HBV vaccination, routine HCV screening, and treatment with pan-genotypic direct-acting antivirals with minimal specialist requirements should be implemented in Thai prisons.

Higher epicardial fat in older adults living with HIV with viral suppression and relationship with liver steatosis, coronary calcium and cardiometabolic risks.

OBJECTIVES: HIV infection is associated with ectopic fat deposition, which leads to chronic inflammation and cardiometabolic dysregulation. We assessed the epicardial adipose tissue (EAT) volume and its associated factors among people with HIV (PWH). DESIGN: A cross-sectional study. METHODS: We conducted a cross-sectional study among PWH aged at least 50 years and age-matched and sex-matched HIV-negative older individuals in Bangkok, Thailand. Participants underwent a noncontrast, cardiac computed tomography (CT) scan to assess coronary artery calcium (CAC) score and EAT between March 2016 and June 2017. Multivariate linear regression analyses were used to investigate HIV-related factors, cardiac and metabolic markers associated with EAT volume. RESULTS: Median age was 55 years [interquartile range (IQR) 52-60] and 63% were men. Median duration of antiretroviral therapy (ART) was 16 years with 97% had HIV-1 RNA less than 50 copies/ml and median CD4 + cell count of 617 cells/µl. Median EAT volume was significantly higher in PWH [99 (IQR 75-122) cm 3 ] than HIV-negative individuals [93 (IQR 69-117) cm 3 ], P  = 0.022. In adjusted model, factors associated with EAT volume included male sex ( P  = 0.045), older age ( P  < 0.001), abnormal waist circumference ( P  < 0.001) and HOMA-IR ( P  = 0.01). In addition, higher CAC score was independently associated with EAT volume. Higher mean EAT volume was seen in PWH with severe liver steatosis than those without steatosis ( P  = 0.018). In adjusted PWH-only model, duration of HIV was significantly associated with higher EAT volume ( P  = 0.028). CONCLUSION: In an aging cohort, PWH had higher EAT volume than HIV-negative controls. EAT was also independently associated with central fat accumulation, insulin resistance, liver steatosis and CAC score.