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.

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.

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.

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.

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.

Weight changes, metabolic syndrome and all-cause mortality among Asian adults living with HIV.

OBJECTIVES: We investigated weight changes following antiretroviral therapy (ART) initiation, the development of metabolic syndrome (MetS) and its association with all-cause mortality among Asian adults living with HIV. METHODS: Participants enrolled in a regional Asian HIV-infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing-risk regression models were used to investigate the association of MetS with all-cause mortality. RESULTS: Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29-41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48-63) kg and 20.5 (18.4-22.9) kg/m2 , respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9-2.5 kg] and baseline HIV RNA ≥ 100 000 HIV-1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2-1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)-based ART (diff = 2.1 kg; 95% CI 0.7-3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05-1.32)/100 person-years (PY)]. The mortality rate was 0.7 (95% CI 0.6-0.8)/100 PY. MetS was not significantly associated with all-cause mortality in the adjusted model (P = 0.236). CONCLUSIONS: Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI-based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed.

Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries.

BACKGROUND: As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. METHODS: In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. FINDINGS: 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43-81]) of 18 835 at 1 year, 10 796 (62% [41-77]) of 17 553 at 2 years, and 9177 (59% [38-91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53-80]) of 225 418 at 1 year, 145 552 (72% [48-79]) of 201 238 at 2 years, and 115 260 (65% [43-69]) of 178 458 at 3 years after ART initiation. INTERPRETATION: Although adults with HIV are approaching the global target of 95% viral suppression, progress among children and adolescents is much slower. Substantial efforts are still needed to reach the viral suppression target for children and adolescents. FUNDING: US National Institutes of Health.

Brief Report: HCV Universal Test-and-Treat With Direct Acting Antivirals for Prisoners With or Without HIV: A Prison Health Care Workers-Led Model for HCV Microelimination in Thailand.

BACKGROUND: This study investigated the sustained virologic responses (SVRs) among prisoners with hepatitis C virus (HCV) using universal test-and-treat approach by prison health care workers in a central male prison in Thailand. METHODS: A universal HCV screening was conducted in a maximum-security central prison (Klong Prem Central Prison) in Thailand. HCV RNA-confirmed prisoners were treated with generic sofosbuvir/velpatasvir by prison health care workers, regardless of their HCV genotypes and duration of prison sentences. We evaluated the SVR rates at 12 weeks after completing direct acting antivirals (DAA) treatment. RESULTS: A total of 68 prisoners with detectable HCV RNA received DAA treatment. The median age and duration of prison sentences were 44 years (interquartile range, 41-53) and 25 (interquartile range, 19-33) years, respectively. Twenty-five percentage of the participants was coinfected with HIV, and 6% of the participants was coinfected with hepatitis B virus. Among all prisoners who received DAA treatment, 20 (29%) had genotype (GT)-1a, 3 (4%) had GT-1b, 22 (32%) had GT-3a, 3 (4%) had GT-3b, and 7 (10%) had GT-6. Overall, improvements in liver biomarkers were seen after HCV treatment, and SVR was achieved in 97% of the participants with per-protocol analysis and in 90% of the participants with intention-to-treat analysis. CONCLUSIONS: HCV treatment using DAA among prisoners through universal test-and-treat approach led by prison health care workers is highly effective and safe, and such model can potentially help to facilitate the goals of HCV microelimination among prisoners in Thailand.

Achieving consistency in measures of HIV-1 viral suppression across countries: derivation of an adjustment based on international antiretroviral treatment cohort data.

INTRODUCTION: The third of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets is to achieve a 90% rate of viral suppression (HIV viral load <1000 HIV-1 RNA copies/ml) in patients on antiretroviral treatment (ART) by 2020. However, some countries use different thresholds when reporting viral suppression, and there is thus a need for an adjustment to standardize estimates to the <1000 threshold. We aim to propose such an adjustment, to support consistent monitoring of progress towards the "third 90" target. METHODS: We considered three possible distributions for viral loads in ART patients: Weibull, Pareto and reverse Weibull (imposing an upper limit but no lower limit on the log scale). The models were fitted to data on viral load distributions in ART patients in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration (representing seven global regions) and the ART Cohort Collaboration (representing Europe), using separate random effects models for adults and children. The models were validated using data from the World Health Organization (WHO) HIV drug resistance report and the Brazilian national ART programme. RESULTS: Models were calibrated using 921,157 adult and 37,431 paediatric viral load measurements, over 2010-2019. The Pareto and reverse Weibull models provided the best fits to the data, but for all models, the "shape" parameters for the viral load distributions differed significantly between regions. The Weibull model performed best in the validation against the WHO drug resistance survey data, while the Pareto model produced uncertainty ranges that were too narrow, relative to the validation data. Based on these analyses, we recommend using the reverse Weibull model. For example, if a country reports an 80% rate of viral suppression at <200 copies/ml, this model estimates the proportion virally suppressed at <1000 copies/ml is 88.3% (0.800.56 ), with uncertainty range 85.5-90.6% (0.800.70 -0.800.44 ). CONCLUSIONS: Estimates of viral suppression can change substantially depending on the threshold used in defining viral suppression. It is, therefore, important that viral suppression rates are standardized to the same threshold for the purpose of assessing progress towards UNAIDS targets. We have proposed a simple adjustment that allows this, and this has been incorporated into UNAIDS modelling software.

HIV treatment outcomes among people who acquired HIV via injecting drug use in the Asia-Pacific region: a longitudinal cohort study.

INTRODUCTION: Data on HIV treatment outcomes in people who inject drugs (PWID) in the Asia-Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS-defining events and mortality among PWID receiving antiretroviral therapy (ART). METHODS: We investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression (VS, HIV viral load <1000 copies/mL) were assessed. Factors associated with mean CD4 changes were analysed using repeated measures linear regression, and combined AIDS event and mortality were analysed using survival analysis. RESULTS: Of 622 PWID from 12 countries in the Asia-Pacific, 93% were male and the median age at ART initiation was 31 years (IQR, 28 to 34). The median pre-ART CD4 count was 71 cells/µL. CD4 counts increased over time, with a mean difference of 401 (95% CI, 372 to 457) cells/µL at year-10 (n = 78). Higher follow-up HIV viral load and pre-ART CD4 counts were associated with smaller increases in CD4 counts. Among 361 PWID with ≥1 viral load after six months on ART, proportions with VS were 82%, 88% and 93% at 2-, 5- and 10-years following ART initiation. There were 52 new AIDS-defining events and 50 deaths during 3347 person-years of follow-up (PYS) (incidence 3.05/100 PYS, 95% CI, 2.51 to 3.70). Previous AIDS or TB diagnosis, lower current CD4 count and adherence <95% were associated with combined new AIDS-defining event and death. CONCLUSIONS: Despite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings.