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HCV RNA test determines current active infection and is a requirement prior to initiating HCV treatment. We investigated trends and factors associated with post-diagnosis HCV RNA testing rates prior to HCV treatment, and risk factors for first positive HCV RNA among people living with HIV (PLHIV) with HCV in the Asia-Pacific region. PLHIV with positive HCV antibody and in follow-up after 2010 were included. Patients were considered HCV-antibody positive if they ever tested positive for HCV antibody (HCVAb). Repeated measures Poisson regression model was used to analyse factors associated with post-diagnosis HCV RNA testing rates from positive HCVAb test. Factors associated with time to first positive HCV RNA from positive HCVAb test were analysed using Cox regression model. There were 767 HCVAb positive participants included (87% from LMICs) of whom 11% had HCV RNA tests. With 163 HCV RNA tests post positive HCVAb test, the overall testing rate was 5.05 per 100 person-years. Factors associated with increased testing rates included later calendar years of follow-up, HIV viral load ≥1000 copies/mL and higher income countries. Later calendar years of follow-up, ALT >5 times its upper limit of normal, and higher income countries were associated with shorter time to first positive HCV RNA test. Testing patterns indicated that uptake was predominantly in high income countries possibly due to different strategies used to determine testing in LMICs. Expanding access to HCV RNA, such as through lower-cost point of care assays, will be required to achieve elimination of HCV as a public health issue.
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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.
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COVID-19 , Infecciones por VIH , Desnutrición , Evaluación Nutricional , Estado Nutricional , SARS-CoV-2 , Sarcopenia , Humanos , Sarcopenia/epidemiología , Sarcopenia/etiología , Masculino , Femenino , Desnutrición/epidemiología , COVID-19/complicaciones , COVID-19/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Persona de Mediana Edad , Tailandia/epidemiología , Factores de Riesgo , Composición Corporal , Anciano , Pandemias , Estudios de CohortesRESUMEN
INTRODUCTION: Toxoplasma gondii can cause symptomatic toxoplasmosis in immunodeficient hosts, including in people living with human immunodeficiency virus (PLWH), mainly because of the reactivation of latent infection. We assessed the prevalence of toxoplasmosis and its associated risk factors in PLWH in the Asia-Pacific region using data from the TREAT Asia Human Immunodeficiency Virus (HIV) Observational Database (TAHOD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA) Asia-Pacific. METHODS: This study included both retrospective and prospective cases of toxoplasmosis reported between 1997 and 2020. A matched case-control method was employed, where PLWH diagnosed with toxoplasmosis (cases) were each matched to two PLWH without a toxoplasmosis diagnosis (controls) from the same site. Sites without toxoplasmosis were excluded. Risk factors for toxoplasmosis were analyzed using conditional logistic regression. RESULTS: A total of 269/9576 (2.8%) PLWH were diagnosed with toxoplasmosis in 19 TAHOD sites. Of these, 227 (84%) were reported retrospectively and 42 (16%) were prospective diagnoses after cohort enrollment. At the time of toxoplasmosis diagnosis, the median age was 33 years (interquartile range 28-38), and 80% participants were male, 75% were not on antiretroviral therapy (ART). Excluding 63 out of 269 people without CD4 values, 192 (93.2%) had CD4 ≤200 cells/µL and 162 (78.6%) had CD4 ≤100 cells/µL. By employing 538 matched controls, we found that factors associated with toxoplasmosis included abstaining from ART (odds ratio [OR] 3.62, 95% CI 1.81-7.24), in comparison to receiving nucleoside reverse transcriptase inhibitors plus non-nucleoside reverse transcriptase inhibitors, HIV exposure through injection drug use (OR 2.27, 95% CI 1.15-4.47) as opposed to engaging in heterosexual intercourse and testing positive for hepatitis B virus surface antigen (OR 3.19, 95% CI 1.41-7.21). Toxoplasmosis was less likely with increasing CD4 counts (51-100 cells/µL: OR 0.41, 95% CI 0.18-0.96; 101-200 cells/µL: OR 0.14, 95% CI 0.06-0.34; >200 cells/µL: OR 0.02, 95% CI 0.01-0.06), when compared to CD4 ≤50 cells/µL. Moreover, the use of prophylactic cotrimoxazole was not associated with toxoplasmosis. CONCLUSIONS: Symptomatic toxoplasmosis is rare but still occurs in PLWH in the Asia-Pacific region, especially in the context of delayed diagnosis, causing advanced HIV disease. Immune reconstitution through early diagnosis and ART administration remains a priority in Asian PLWH.
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Infecciones por VIH , Toxoplasmosis , Humanos , Masculino , Factores de Riesgo , Adulto , Femenino , Toxoplasmosis/epidemiología , Toxoplasmosis/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Asia/epidemiología , Estudios Retrospectivos , Estudios de Casos y Controles , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , ToxoplasmaRESUMEN
BACKGROUND: CD4 measurement is pivotal in the management of advanced HIV disease. VISITECT® CD4 Advanced Disease (AccuBio Limited, Alva, UK; VISITECT) is an instrument-free, point-of-care, semi-quantitative test allowing visual identification of a CD4 ≤200 cells/µl, or >200 cells/µl from finger-prick or venous blood. METHODS: As part of a diagnostic accuracy study of FUJIFILM SILVAMP TB LAM (clinicaltrials.gov: NCT04089423), people living with HIV of ≥18 years old were prospectively recruited in seven countries from outpatient departments if a tuberculosis symptom was present, and from inpatient departments. Participants provided venous blood for CD4 measurement using flow cytometry (reference standard) and finger-prick blood for VISITECT (index text), performed at point-of-care. Sensitivity, specificity, and positive and negative predictive values of VISITECT to determine a CD4 ≤200 cells/µl were evaluated. RESULTS: Among 1604 participants, the median flow cytometry CD4 was 367 (IQR 128-626) cells/µl and 521 (32.5%) had a CD4 ≤200 cells/µl. VISITECT sensitivity was 92.7% (483/521, 95% CI 90.1-94.7%) and specificity was 61.4% (665/1083, 95% CI 58.4-64.3%). For participants with a CD4 between 0-100, 101-200, 201-300, 301-500, and >500 cells/µl, VISITECT misclassified 4.5% (95% CI 2.5-7.2%), 12.5 (95% CI 8.0-18.2%), 74.1% (95% CI 67.0-80.5%), 48.0% (95% CI 42.5-53.6%), and 22.6% (95% CI 19.3-26.3%), respectively. CONCLUSIONS: VISITECT's sensitivity, but not specificity, met the World Health Organization's minimal sensitivity and specificity threshold of 80% for point-of-care CD4 tests. VISITECT's quality needs to be assessed and its accuracy optimized. VISITECT´s utility as CD4 triage test should be investigated.
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BACKGROUND: Semaglutide, a GLP-1 receptor agonist, is highly effective for decreasing weight. Concomitant loss of muscle mass often accompanies weight loss and may have consequences on muscle function. METHODS: This is a secondary analysis from the SLIM LIVER (ACTG A5371) study, a single-arm study of semaglutide in people with HIV (PWH) with metabolic dysfunction-associated steatotic liver disorder (MASLD). Participants received subcutaneous semaglutide for 24 weeks (titrated to 1 mg/week by week 4). Psoas volume and fat fraction were assessed from liver magnetic resonance imaging and physical function by 10-time chair rise test and 4m gait speed. Mean change from baseline to week 24 was estimated with linear regression modeling. RESULTS: 51 PWH enrolled; muscle measures were available from 46 participants. The mean age was 50 (standard deviation [SD] 11) years and BMI 35.5 (5.6) kg/m2, 43% were women, 33% Black, and 39% Hispanic/Latino. Psoas muscle volume decreased by 9.3% (95% confidence interval [CI]: -13.4, -5.2; p<0.001) over 24 weeks but psoas muscle fat did not significantly change (-0.42%, CI: -1.00, 0.17; p=0.16). Chair rise and gait speed had non-significant improvements of 1.27 seconds (CI: -2.7, 0.10) and 0.05 m/sec (CI: -0.01, 0.10), respectively (both p>0.07). The prevalence of slow gait speed (< 1 m/sec) decreased from 63% to 46% (p=0.029). CONCLUSIONS: In PWH receiving low-dose semaglutide for MASLD, despite decreased psoas muscle volume, there was no significant change in physical function. This suggests that function was maintained despite significant loss of muscle concomitant with weight loss.
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Sofosbuvir/Velpatasvir (SOF/VEL) is a combination drug used for chronic hepatitis C (HCV) infection. However, limited information exists regarding the pharmacokinetics of SOF/VEL and its metabolites in hemodialysis patients. We conducted a prospective investigation of the pharmacokinetic parameters of SOF/VEL after a single dose of SOF/VEL (400/100 mg) on days with and without dialysis in 12 Thai hemodialysis patients with chronic HCV infection, who had been undergoing hemodialysis for a duration of 0.5-20 years. Blood samples were collected before dose (0) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, and 12.0 h after dose. Dialysate samples were also collected before dose (0) and 1.0, 2.0, 3.0, and 4.0 h after dose. Plasma and dialysate samples were quantified for SOF and its metabolite, GS-331007, and VEL concentrations using a fully validated LCMS technique. In addition, a preliminary efficacy study was conducted using the proposed SOF/VEL dose reduction regimen in all patients. No differences in SOF/VEL PK parameters between on- and off-dialysis studies. On the contrary, GS-331007 exhibited a 30% reduction in the area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24h) on dialysis days compared with non-dialysis days (AUC0-24h ratio 0.68 vs. 1.04, respectively). The dialysis clearance of SOF and GS-331007 was 9.35 (8.72-15.11) and 8.89 (8.52-14.07) mL/min, respectively. Subsequently, an alternate-day regimen of SOF/VEL (400/100 mg) was administered for 12 weeks, resulting in an undetectable plasma HCV viral load without side effects. Further clinical studies are warranted to validate the efficacy and safety of our proposed dose reduction regimen.
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Antivirales , Carbamatos , Esquema de Medicación , Combinación de Medicamentos , Hepatitis C Crónica , Compuestos Heterocíclicos de 4 o más Anillos , Diálisis Renal , Sofosbuvir , Humanos , Sofosbuvir/farmacocinética , Sofosbuvir/administración & dosificación , Carbamatos/farmacocinética , Carbamatos/administración & dosificación , Masculino , Persona de Mediana Edad , Femenino , Compuestos Heterocíclicos de 4 o más Anillos/farmacocinética , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Antivirales/farmacocinética , Antivirales/administración & dosificación , Estudios Prospectivos , Anciano , Adulto , Resultado del Tratamiento , Hepacivirus/efectos de los fármacos , Hepacivirus/aislamiento & purificación , Bencimidazoles , BenzopiranosRESUMEN
Ravidasvir (RDV) is a novel NS5A inhibitor that exhibits potent pan-genotypic inhibition of hepatitis C virus (HCV) replication. Sofosbuvir (SOF) plus RDV was demonstrated to be efficacious and safe in adults with active HCV infection, including those living with HIV (LWHIV), in the STORM-C-1 trial. We assessed the population pharmacokinetics (PK) of RDV in a sub-study nested within STORM-C-1 conducted in Thailand and Malaysia. SOF (400 mg) plus RDV (200 mg) was administered orally once daily for 12 weeks to adults with chronic HCV infection, but without cirrhosis and for 24 weeks to those with compensated cirrhosis. Intensive and sparse PK samples were collected at 4, 8, and 12 weeks after treatment initiation. Population PK parameters of RDV and the impact of covariates were evaluated using nonlinear mixed-effects modeling. Five hundred ninety-four participants were included, 235 (40%) had compensated cirrhosis, and 189 (32%) were LWHIV. RDV plasma concentrations were best described by a two-compartment model with first-order elimination. Oral clearance (CL/F) and volume of distribution (Vd/F) parameters were allometrically scaled on fat-free mass. Concomitant antiretroviral treatment (ART) increased RDV CL/F by 30%-60%, with efavirenz-based ART having the largest impact. Females had 16% lower RDV CL/F than males, and higher albumin levels reduced RDV central volume of distribution. While several covariates impact RDV CL/F and Vd/F, the effect on RDV exposures was not clinically relevant based on the efficacy data reported in this diverse Asian adult population. There were no meaningful drug-drug interactions in adults LWHIV on ART.
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Antivirales , Infecciones por VIH , Hepatitis C Crónica , Valina , Humanos , Masculino , Femenino , Hepatitis C Crónica/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Antivirales/farmacocinética , Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Valina/farmacocinética , Valina/análogos & derivados , Sofosbuvir/farmacocinética , Sofosbuvir/uso terapéutico , Ciclopropanos , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Alquinos , Tailandia , Benzoxazinas/farmacocinética , Benzoxazinas/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Quimioterapia Combinada , BencimidazolesRESUMEN
In this randomised, controlled study in 14 low- and middle-income countries, individuals taking dolutegravir with darunavir/ritonavir for 48 weeks had a greater increase in systolic and diastolic blood pressure than individuals taking two nucleoside reverse transcriptase with darunavir/ritonavir. The difference remained significant after controlling for confounding factors including weight gain.
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There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation. Of 1637 participants considered for the analysis, 296 (18%) were tuberculosis positive by eMRS. Median age was 40 years, median CD4 cell count was 369 cells/ul, and 52% were female. Overall FujiLAM sensitivity was 54·4% (95% CI: 48·7-60·0), overall specificity was 85·2% (83·2-87·0) against eMRS. Sensitivity and specificity estimates varied between sites, ranging from 26·5% (95% CI: 17·4%-38·0%) to 73·2% (60·4%-83·0%), and 75·0 (65·0%-82·9%) to 96·5 (92·1%-98·5%), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Lot variability limited interpretation of FujiLAM test performance. Although results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. The trial is registered at clinicaltrials.gov (NCT04089423).
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Infecciones por VIH , Tuberculosis , Humanos , Femenino , Masculino , Adulto , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Estudios Prospectivos , Tuberculosis/diagnóstico , Persona de Mediana Edad , Sensibilidad y Especificidad , Mycobacterium tuberculosis/aislamiento & purificación , Lipopolisacáridos/orina , Esputo/microbiologíaRESUMEN
BACKGROUND: One month of daily rifapentine + isoniazid (1HP) is an effective, ultrashort option for TB prevention in people with HIV (PWH). However, rifapentine may decrease antiretroviral drug concentrations and increase the risk of virologic failure. ACTG A5372 evaluated the effect of 1HP on the pharmacokinetics of twice daily dolutegravir. METHODS: A5372 was a multicenter, pharmacokinetic study in PWH (≥18 years) already on dolutegravir-containing antiretroviral therapy with HIV RNA < 50 copies/mL. Participants received daily rifapentine/isoniazid (600mg/300mg) for 28 days as part of 1HP. Dolutegravir was increased to 50mg twice daily during 1HP and intensive pharmacokinetic sampling was performed on day 0 (before 1HP) and on the final day of 1HP treatment. RESULTS: Thirty-two participants (41% female; 66% Black/African; median (Q1, Q3) age 42 (34, 49) years) were included in the pharmacokinetic analysis. Thirty-one of 32 had HIV RNA levels <50 copies/mL at the end of 1HP dosing. One participant had an HIV RNA of 160 copies/mL at day 28, with HIV RNA <50 copies/mL upon repeat testing on day 42. The median (Q1, Q3) dolutegravir trough concentration was 1751 ng/mL (1195, 2542) on day 0 vs. 1987ng/mL (1331, 2278) on day 28 (day 28:day 0 GMR 1.05, [90% CI 0.93-1.2]; p = 0.43). No serious adverse events were reported. CONCLUSION: Dolutegravir trough concentrations with 50mg twice daily dosing during 1HP treatment were greater than those with standard dose dolutegravir once daily without 1HP. These pharmacokinetic, virologic, and safety data provide support for twice daily dolutegravir use in combination with 1HP for TB prevention.
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BACKGROUND: Non-sputum-based tests are needed to predict or diagnose tuberculosis (TB) disease in people living with HIV (PWH). The enzyme indoleamine 2, 3-dioxygenase-1 (IDO1) is expressed in tuberculoid granuloma and catabolizes tryptophan (Trp) to kynurenine (Kyn). IDO1 activity compromises innate and adaptive immune responses, promoting mycobacterial survival. The plasma Kyn-to-Trp (K/T) ratio is a potential TB diagnostic and/or predictive biomarker in PWH on long-term antiretroviral therapy (ART). METHODS: We compared plasma K/T ratios in samples from PWH, who were followed up prospectively and developed TB disease after ART initiation. Controls were matched for age and duration of ART. Kyn and Trp were measured at 3 timepoints; at TB diagnosis, 6 months before TB diagnosis and 6 months after TB diagnosis, using ultra performance liquid chromatography combined with mass spectrometry. RESULTS: The K/T ratios were higher for patients with TB disease at time of diagnosis (median, 0.086; IQR, 0.069-0.123) compared to controls (0.055; IQR 0.045-0.064; p = 0.006), but not before or after TB diagnosis. K/T ratios significantly declined after successful TB treatment, but increased upon treatment failure. The K/T ratios showed a parabolic correlation with CD4 cell counts in participants with TB (p = 0.005), but there was no correlation in controls. CONCLUSIONS: The plasma K/T ratio helped identify TB disease and may serve as an adjunctive biomarker for for monitoring TB treatment in PWH. Validation studies to ascertain these findings and evaluate the optimum cut-off for diagnosis of TB disease in PWH should be undertaken in well-designed prospective cohorts. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00411983.
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Infecciones por VIH , Tuberculosis , Humanos , Triptófano , Quinurenina , Estudios Prospectivos , Estudios de Casos y Controles , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Biomarcadores , Indolamina-Pirrol 2,3,-DioxigenasaRESUMEN
BACKGROUND: In people living with HIV-HBV, liver fibrosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fibrosis and biomarkers of inflammation, apoptosis, and microbial translocation. METHODS: In this observational cohort study adults living with HIV-HBV already on effective ART were recruited in Australia and Thailand and followed for 3 years including 6 monthly clinical review and blood tests and annual transient elastography. Differences in clinical and laboratory predictors of liver fibrosis progression were tested followed by regression analysis adjusted for CD4+ T-cells at study entry. A linear mixed model was fitted to longitudinal data to explore changes over time. FINDINGS: 67 participants (85% male, median age 49 y) were followed for 175 person-years. Median duration of ART was 10 years (interquartile range (IQR) 8-16 years). We found 11/59 (19%) participants during 3-years follow-up (6/100 person-years) met the primary endpoint of liver disease progression, defined as increased Metavir stage from baseline to final scan. In regression analysis, progressors compared to non-progressors had higher levels of high mobility group box 1 protein (HGMB1), (median (IQR) 3.7 (2.6-5.0) and 2.4 ng/mL (1.5-3.4) respectively, adjusted relative risk 1.47, 95% CI [1.00, 2.17]) and lower nadir CD4+ T-cell percentage (median 4% (IQR 2-8) and 11% (4-15) respectively (relative risk 0.93, 95% CI [0.88, 0.98]). INTERPRETATION: Progression in liver fibrosis occurs in people with HIV-HBV on suppressive ART. Fibrosis progression was associated with higher HMGB1 and lower percentage nadir CD4+ T-cell count, highlighting the importance of early initiation of HBV-active ART. FUNDING: This work was supported by NHMRC project grant 1101836; NHMRC practitioner fellowship 1138581 and NHMRC program grant 1149990. The funder had no role in study design, data collection, data analysis, interpretation, writing of this manuscript or decision to submit for publication.
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Coinfección , Infecciones por VIH , Adulto , Humanos , Masculino , Persona de Mediana Edad , Femenino , Virus de la Hepatitis B , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Progresión de la Enfermedad , Recuento de Linfocito CD4RESUMEN
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.
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Infecciones por VIH , Humanos , Masculino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Femenino , Adulto , Persona de Mediana Edad , Tailandia/epidemiología , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Carga Viral , Recuento de Linfocito CD4 , Medición de Riesgo , Estudios de Cohortes , Antirretrovirales/uso terapéutico , Fármacos Anti-VIH/uso terapéuticoRESUMEN
BACKGROUND: Isoniazid preventive therapy (IPT) is recommended for tuberculosis prevention yet data on the safety of first-trimester pregnancy exposure are limited. METHODS: Planned secondary analysis in a TB prevention trial of adverse pregnancy outcomes among participants assigned to 9-month IPT who became pregnant during (IPT-exposed) or after (unexposed) IPT. Regression models compared binary outcomes of a composite adverse outcome (any non-live birth, excluding induced abortion); preterm delivery <37 weeks; and low birth weight <2500â g) among exposure groups. Models were adjusted for latent TB infection, maternal age, CD4 count, and antiretroviral therapy (ART). RESULTS: In total, 128 participants had a known pregnancy outcome; 39 IPT-exposed and 89 unexposed. At pregnancy outcome, ART use was lower in IPT-exposed (79%) than unexposed women (98%). Overall, 29 pregnancies ended in a composite adverse outcome (25 spontaneous abortions, 2 stillbirths and 2 ectopic pregnancies), 15 preterm deliveries, and 10 infants with low birth weight. IPT was associated with the composite adverse outcome adjusting for covariates at enrollment (adjusted relative risk [aRR] 1.98; 95% confidence interval [CI] 1.15, 3.41), but the effect was attenuated when adjusted for covariates at pregnancy outcome (aRR 1.47; 95% CI .84, 2.55); IPT was not associated with preterm delivery (relative risk [RR] 0.87; 95% CI .32-2.42) or low birth weight (RR 1.01; 95% CI .29, 3.56). CONCLUSIONS: First-trimester IPT exposure was associated with nearly two-fold increased risk of fetal demise, mostly spontaneous abortion, though the association was attenuated when adjusted for covariates proximal to pregnancy outcome including ART use. Further study is needed to inform TB prevention guidelines.
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Aborto Espontáneo , Infecciones por VIH , Nacimiento Prematuro , Tuberculosis , Recién Nacido , Lactante , Embarazo , Femenino , Humanos , Isoniazida/efectos adversos , Resultado del Embarazo , Tuberculosis/tratamiento farmacológico , VIH , Primer Trimestre del Embarazo , Antituberculosos/efectos adversos , Nacimiento Prematuro/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Infecciones por VIH/complicaciones , Aborto Espontáneo/epidemiología , Aborto Espontáneo/inducido químicamenteRESUMEN
OBJECTIVE: To determine the performance of the baseline monocyte to lymphocyte ratio (MLR), baseline anemia severity and combination of these biomarkers, to predict tuberculosis (TB) incidence in people with HIV (PWH) after antiretroviral therapy (ART) initiation. DESIGN: Multicenter, retrospective cohort study. METHODS: We utilized the data from study A5175 (Prospective Evaluation of Antiretroviral Therapy in Resource-limited Settings: PEARLS). We assessed the utility of MLR, anemia severity and in combination, for predicting TB in the first year after ART. Cox regression was used to assess associations of MLR and anemia with incident TB. Harrell's C index was used to describe single model discrimination. RESULTS: A total of 1455 participants with a median age of 34 [interquartile range (IQR) 29, 41] were included. Fifty-four participants were diagnosed with TB. The hazard ratio (HR) for incident TB was 1.77 [95% confidence interval (CI) 1.01-3.07]; P â=â0.04 for those with MLR ≥0.23. The HR for mild/mod anemia was 3.35 (95% CI 1.78-6.29; P â<â0.001) and 18.16 (95% CI 5.17-63.77; P â<â0.001) for severe anemia. After combining parameters, there were increases in adjusted HR (aHR) for MLR ≥0.23 to 1.83 (95% CI 1.05-3.18), and degrees of anemia to 3.38 (95% CI 1.80-6.35) for mild/mod anemia and 19.09 (95% CI 5.43-67.12) for severe anemia. CONCLUSIONS: MLR and hemoglobin levels which are available in routine HIV care can be used at ART initiation for identifying patients at high risk of developing TB disease to guide diagnostic and management decisions.
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Anemia , Infecciones por VIH , Tuberculosis , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Monocitos/química , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Tuberculosis/complicaciones , Incidencia , Anemia/epidemiología , Anemia/complicaciones , Anemia/diagnóstico , Linfocitos , Hemoglobinas/análisis , Recuento de Linfocito CD4RESUMEN
OBJECTIVE: The objective of this study was to assess the pharmacokinetics, safety, and efficacy and confirm the dose of once-daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) during pregnancy. DESIGN: An open-label, multicenter, single-arm, phase 1b study (NCT03960645) was conducted in 33 virologically suppressed pregnant women with HIV-1. METHODS: Participants received B/F/TAF (50/200/25âmg) from the second or third trimester through â¼16âweeks postpartum. Steady-state maternal plasma pharmacokinetic samples were collected at the second and third trimesters and 6 and 12âweeks postpartum for BIC, FTC, and TAF. Neonates ( n â=â29) were followed from birth to 4-8âweeks with sparse washout pharmacokinetic sampling for BIC and TAF. The proportion of participants with HIV-1 RNA less than 50âcopies/ml at delivery (missingâ=âexcluded) was evaluated. RESULTS: Mean areas under the concentration-time curve over the dosing interval (AUC tau ) for BIC, FTC, and TAF were lower during pregnancy versus postpartum but were closer to AUC tau values for nonpregnant adults with HIV reported in other studies. Geometric least-squares mean ratios for BIC, FTC, and TAF AUC tau during pregnancy versus postpartum ranged from 41 to 45%, 64 to 69% and 57 to 78%, respectively. Mean BIC trough concentrations during pregnancy were more than 6.5-fold greater than the protein-adjusted 95% effective concentration. In neonates, the median BIC half-life was 43âh. Virologic suppression was maintained in all adult participants throughout the study, with no virologic failure or treatment-emergent resistance to HIV-1, no discontinuations because of adverse events, and no perinatal transmission. CONCLUSION: Exposures to BIC, FTC, and TAF were lower during pregnancy than postpartum. However, mean BIC trough concentrations were maintained at levels indicative of efficacious exposure, and FTC/TAF data were concordant with published literature in this population. Pharmacokinetic and safety data, combined with maintenance of robust virologic suppression, suggest that once-daily B/F/TAF without dose adjustment is appropriate during pregnancy.
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Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Fármacos Anti-VIH/efectos adversos , Combinación de Medicamentos , Emtricitabina , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Seropositividad para VIH/tratamiento farmacológico , Mujeres EmbarazadasRESUMEN
This study aimed to assess second-line antiretroviral therapy (ART) outcomes in a National HIV Treatment program. People living with HIV aged ≥18 years initiating first-line ART who switched to second-line protease inhibitor-based regimens from January 2008 to May 2019, with a minimum of 1-year follow-up were studied. The primary outcome was second-line treatment failure (two consecutive virological failure episodes (viral load ≥1000 copies/mL)). Of 318,506 PLH initiating ART, 29,015 (9.1%) switched to second-line regimens after a median (IQR) ART duration of 1.63 (0.60-3.59) years. Lost to follow-up (LTFU) occurred in 5316 (18.3%) of whom 1376 (5%) remained LTFU and alive; 4606 (15.9%) died. Cumulative second-line failure incidence was 9.8% at 6 years, more common in females, younger PLH those with lower switch CD4 cell counts. Multidisciplinary, innovative support systems are needed to improve second-line treatment outcomes, particularly those relating to modifiable risk factors.
Outcomes after switching to second line antiretroviral regimens in the Thai National Treatment programWe assessed the rates of virological failure, losses to follow-up and death in 29,015 people who switched to second line antiretroviral therapy in Thailand. The cumulative rate of virological failure was a 9.8% at 6 years, loss to follow-up occurred in 18.3% (5% who remained alive) and 15.9% died. Women and those with lower CD4 counts at switch had the highest risk of virological failure.
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Fármacos Anti-VIH , Infecciones por VIH , Femenino , Humanos , Adolescente , Adulto , Insuficiencia del Tratamiento , Tailandia/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Resultado del Tratamiento , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Carga Viral , Recuento de Linfocito CD4 , Fármacos Anti-VIH/uso terapéuticoRESUMEN
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.
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Disfunción Cognitiva , Infecciones por VIH , Enfermedad del Hígado Graso no Alcohólico , Humanos , Masculino , Femenino , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Estudios Transversales , Infecciones por VIH/complicaciones , Infecciones por VIH/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Hígado/patologíaRESUMEN
Long-term effect of Direct-acting antivirals (DAAs) on gut microbiota, short-chain fatty acids (SCFAs) and microbial translocation in patients with hepatitis C virus (HCV) infection who achieve sustained virological response (SVR) were limited. A longitudinal study of 50 patients with HCV monoinfection and 19 patients with HCV/HIV coinfection received DAAs were conducted. Fecal specimens collected at baseline and at week 72 after treatment completion (FUw72) were analyzed for 16S rRNA sequencing and the butyryl-CoA:acetateCoA transferase (BCoAT) gene expression using real-time PCR. Plasma lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP) were quantified by ELISA assays. SVR rates in mono- and coinfected patients were comparable (94% vs. 100%). The improvement of gut dysbiosis and microbial translocation was found in responders but was not in non-responders. Among responders, significant restoration of alpha-diversity, BCoAT and LBP were observed in HCV patients with low-grade fibrosis (F0-F1), while HCV/HIV patients exhibited partial improvement at FUw72. I-FABP did not decline significantly in responders. Treatment induced microbiota changes with increasing abundance of SCFAs-producing bacteria, including Blautia, Fusicatenibacter, Subdoligranulum and Bifidobacterium. In conclusion, long-term effect of DAAs impacted the restoration of gut dysbiosis and microbial translocation. However, early initiation of DAAs required for an alteration of gut microbiota, enhanced SCFAs-producing bacteria, and could reduce HCV-related complications.
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Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Humanos , Hepacivirus/genética , Antivirales/uso terapéutico , Disbiosis/complicaciones , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Estudios Longitudinales , ARN Ribosómico 16S , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Clostridiales , Coenzima A TransferasasRESUMEN
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.