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.

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.

Tenofovir alafenamide nephrotoxicity: a case report and literature review.

BACKGROUND: Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has become the preferred drug for the treatment of HIV-1 and chronic hepatitis B infection in clinical practice. Results from clinical trials showed that it had better renal and bone mineral outcomes compared to tenofovir disoproxil fumarate (TDF). However, as we have seen with TDF, side effects from the new medication can be more prevalent and recognized after extensive use in real world situations. Sporadic cases of acute kidney injury in patients using TAF have started to emerge. CASE PRESENTATION: We report a case of 49-year-old Thai, HIV treatment-experienced female with hypertension presented with worsening renal function after switching her antiretroviral regimen from TDF, emtricitabine (FTC), and lopinavir/ritonavir (LPV/r) to TAF, FTC and dolutegravir (DTG) for 3 months. Kidney biopsy showed distinctive picture of tenofovir nephrotoxicity with acute tubular injury and mitochondrial injury. The possible causes of acute kidney injury and nephrotoxicity from TAF for this patient were discussed. We have extensively reviewed all published case reports of TAF-associated nephrotoxicity and summarized the essential information in this article. CONCLUSION: Although TAF has less nephrotoxicity compared with TDF; renal function should always be monitored after the initiation of both drugs. Future large cohort studies are required to identify the risk factors of TAF-associated nephrotoxicity and to design an effective preventive strategy.

Incident Liver Cirrhosis, Associated Factors, and Cardiovascular Disease Risks Among People Living With HIV: A Longitudinal Study.

OBJECTIVES: We investigated the incidence and associated factors of liver cirrhosis and cardiovascular disease risks among people living with HIV (PLHIV) in a Thai cohort. DESIGN: A prospective cohort analysis. METHODS: Participants with at least one reliable transient elastography measurement during follow-up, who had pretreatment alanine transaminase, AST, and platelet count at HIV treatment initiation were included. Liver cirrhosis was defined as AST to Platelet Ratio Index >1.5 or fibrosis-4 (FIB-4) >3.25 or liver stiffness by transient elastography >12.5 kPa and confirmed by imaging or liver biopsy. Competing-risk regression was used to identify factors associated with liver cirrhosis. Time-updated 10-year atherosclerotic CVD (ASCVD) risks were compared between PLHIV with or without liver cirrhosis. RESULTS: A total of 1069 participants (33% women, 9% hepatitis C virus, and 16% hepatitis B virus) with the median age and CD4 at cART initiation of 32 years and 240 cells/mm3 were included. During 8232 person-years, 124 (12%) developed liver cirrhosis after a median of 6.9 (2.4-13.7) follow-up years [incidence, 1.5 (95% confidence interval: 1.3 to 1.8) per 100 person-years]. In multivariable analysis, the factors independently associated with liver cirrhosis were time-updated HIV viremia, hepatitis B virus, and hepatitis C virus coinfection, diabetes mellitus, high-density lipoproteins <40 mg/mL, and d4T exposure. The median time-updated 10-year ASCVD risk score was statistically higher among cirrhotic PLHIV vs. noncirrhosis [4.9% (interquartile range, 2.3-9.7) vs. 2.4% (interquartile range, 1.3-4.9), P < 0.001]. CONCLUSION: PLHIV with metabolic diseases were more likely to develop liver cirrhosis, independent of hepatitis coinfections, and ASCVD risks were higher among cirrhotic individuals.

Higher Proportion of Abnormal Nutritional Status Among Well-Suppressed HIV-Infected Elderly Asians Compared to HIV-Negative Individuals.

Older adults face physiological, psychological, social, and economic changes, which may impair nutritional status, making the body vulnerable to illness and adverse clinical outcomes. Little is known regarding the nutritional status among elderly people living with HIV (PLHIV). We aimed to study the prevalence of malnutrition and the associated factors in a Thai aging cohort. A cross-sectional study was conducted among PLHIV >50 years of age on long-term antiretroviral therapy and HIV-negative controls, frequency matched by sex and age in Bangkok, Thailand. Nutritional status was assessed by the Mini Nutrition Assessment (MNA) tool. Abnormal nutritional status was defined as MNA score <24 (malnutrition and at risk of malnutrition). Body composition was measured by bioelectrical impedance analysis using Body Composition Analyzer. Demographic and disease-related factors were assessed for their association with abnormal nutrition status using multivariable logistic regression. There were 349 PLHIV and 103 HIV-uninfected controls, with median age 55 years. The majority were male (63%) with median body mass index (BMI) of 23.4 kg/m2. PLHIV had lower BMI [median, 23.1 (IQR, 20.8-25.2) vs. 25.3 (22.3-28.7) kg/m2, p < .001], lower fat percent [22.8% vs. 26.3%, p < .001] and lower fat mass [14.2 vs. 16.9 kg, p < .001] and higher abnormal nutritional status (18.05% vs. 6.8%, p = .005) than controls. In the multivariate model, older age (adjusted odds ratio [aOR], 1.06, 95% confident interval [CI]: 1.01-1.12, p = .03), positive HIV status (aOR, 2.67, 95% CI: 1.07-6.65, p = .036), diabetes mellitus (aOR, 2.21, 95% CI: 1.003-4.87, p = .049), lower fat mass (aOR, 0.70, 95%CI: 0.57-0.86, p < .001), and lower BMI (aOR, 0.63, 95% CI: 0.51-0.78, p < .001) were independently associated with abnormal nutritional status. PLHIV had higher risks for abnormal nutritional status compared with HIV-uninfected individuals. Regular screening and monitoring of nutritional status among PLHIV may promote better health outcomes.

Interferon-Inducible Protein 10 and Disease Activity in Systemic Lupus Erythematosus and Lupus Nephritis: A Systematic Review and Meta-Analysis.

There is increasing evidence of a correlation between interferon-inducible protein 10 (IP-10) and disease activity of systemic lupus erythematosus (SLE) and lupus nephritis (LN). We conducted a comprehensive search on IP-10 using MEDLINE, Scopus, and Cochrane electronic databases from the beginning to the end of December 2017. All studies that compared serum and/or urine IP-10 between active SLE/LN patients and any control groups were identified and included in this systematic review and meta-analysis. The mean difference (MD) of IP-10 level among active SLE and LN patients, as well as the correlation of IP-10 with disease activity, were meta-analyzed using a random-effects model. From 23 eligible studies, 15 provided adequate data for meta-analysis. Serum IP-10 was significantly elevated in patients with active SLE compared to non-active SLE patients (MD 356.5 pg/mL, 95% CI 59.6 to 653.4, p = 0.019). On the other hand, the levels of serum IP-10 was not different between active LN and non-active LN. However, serum IP-10 was positively correlated with disease activity like SLE disease activity index (SLEDAI) (pooled r = 0.29, 95% CI 0.22 to 0.35, p < 0.001). Furthermore, urine IP-10 tended to be higher in patients with active LN compared to non-active LN patients but this did not reach statistical significance (MD 3.47 pg/mgCr × 100, 95% CI -0.18 to 7.12, p = 0.06). Nevertheless, urine IP-10 was positively correlated with renal SLEDAI (pooled r = 0.29, 95% CI 0.05 to 0.50, p = 0.019). In conclusion, serum and urine IP-10 levels may be useful in monitoring the disease activity of SLE and LN. Serum IP-10 was correlated with systemic disease whereas urine IP-10 was a useful biomarker for detecting active LN.