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Antibody-mediated rejection (ABMR) is an important barrier to achieve long-term kidney allograft survival. Human leukocyte antibody (HLA)-incompatibility and ABO-incompatibility are the two main mechanisms of ABMR. Nevertheless, the advances in managing ABMR have changed the paradigm for kidney transplantation. This review aimed to emphasize the HLA-incompatibility and ABO-incompatibility kidney transplant and update the management of ABMR.HLA-incompatibility kidney transplantation is a strong risk factor for ABMR. Donor-specific antibody (DSA) is a surrogate biomarker that prevents long-term allograft survival. The standard treatment for ABMR has unfavorable results. New drugs that target the B cell are a promising approach to treat ABMR. In the past, ABO-incompatibility kidney donor was an absolute contraindication but now, it is widely accepted as an alternative organ resource. The advancement of ABO antibody removal and B-cell depletion therapy has been successfully developed. ABO isoagglutination remains the main biomarker for monitoring ABMR during the transplantation process. C4d staining without inflammation of the kidney allograft is the marker for the accommodation process.With the shortage of organ donors, transplant experts have expanded the organ resources and learned how to overcome the immunological barriers by using novel biomarkers and developing new treatments that support long-term graft survival.

Risk factors and consequences of urinary tract infection (UTI) post-kidney transplant have been variously reported by studies that were heterogenous in immunosuppressants and prophylactic protocols. We aimed to clarify the risks and consequences of UTI in kidney transplant recipients with post-transplantation cotrimoxazole prophylaxis in the context of modern immunosuppression. This retrospective cohort included kidney transplant recipients receiving tacrolimus, mycophenolate, prednisolone, and cotrimoxazole for bacterial UTI prophylaxis. Recipients were categorized into non-UTI and UTI groups. Asymptomatic bacteriuria (ASB) was screened in the first 3 months and was evaluated for association with UTI. Of 348 kidney transplant recipients, 129 were in the UTI group and 219 in the non-UTI group. UTI risk factors were female sex, body mass index ≥ 25 kg/m2, human leukocyte antigen mismatch, and panel reactive antibody ≥ 50%. Recipients with recurrent UTI had inferior allograft function compared with non-UTI recipients. Patient survival was significantly lower in recipients with UTI in the first post-transplant month. Higher degree of immunosuppressions was associated with recurrent UTI and drug-resistant organisms. In conclusion, UTI continues to negatively affect graft function and survival of kidney transplant recipients. Treating ASB in the first 3 months did not reduce the UTI incidence in the first transplantation year.

Background There is little known about the contribution of microRNAs (miRNAs) in the recovery from acute kidney injury (AKI). This study aimed to discover and validate miRNA profiles for predicting renal recovery from severe AKI. Patients and methods A prospective observational study was conducted between June 2020 and January 2021. Urine and serum samples of participants with AKI stage 3 were collected from two groups: renal recovery and renal non-recovery. Transcriptomic analysis was performed using nCounter miRNA Expression Assay. Expression levels of candidate miRNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR). Results The discovery phase identified 18 and 11 differentially expressed miRNAs that were statistically significant between the two groups in urine and serum specimens, respectively. Top candidate miRNAs selected included miR-556-3p, miR-1915-3p, miR-4284, miR-32-5p, miR-96-5p, and miR-556-5p in urine, and miR-499b-5p, miR-30a-3p, miR-92b-3p and miR-770-5p in serum. This study enrolled 110 participants in the validation phase. The qRT-PCR analysis indicated that urine miR-556-3p was significantly higher in the renal recovery group than in the renal non-recovery group. Urine miR-556-3p alone predicted renal recovery with an area under the curve (AUC) of 0.64 (95%CI 0.52–0.75, p = 0.03). Combining the clinical model with urine miR-556-3p predicted renal recovery with an AUC of 0.83 (95%CI 0.75–0.92, p Conclusion This data provides evidence that microtranscriptome profiles of severe AKI patients with renal recovery differed from the non-recovery group. Urine miR-556-3p had the potential to improve the prediction of renal recovery from severe AKI.

In settings with high tuberculosis (TB) endemicity, various genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data. We show that the TB epidemic in Dar es Salaam is dominated by multiple genotypes introduced to Tanzania from different parts of the world during the last 300 years. The most common MTBC genotypes deriving from these introductions exhibited differences in transmission rates and in the duration of the infectious period, but little differences in overall fitness, as measured by the effective reproductive number. Moreover, measures of disease severity and bacterial load indicated no differences in virulence between these genotypes during active TB. Instead, the combination of an early introduction and a high transmission rate accounted for the high prevalence of L3.1.1, the most dominant MTBC genotype in our setting. Yet, a longer co-existence with the host population did not always result in a higher transmission rate, suggesting that distinct life-history traits have evolved in the different MTBC genotypes. Taken together, our results point to bacterial factors as important determinants of the TB epidemic in Dar es Salaam.Author summaryTuberculosis (TB) is the deadliest human infectious disease caused by one single agent, Mycobacterium tuberculosis (Mtb). The origins of Mtb have been traced to East Africa millennia ago, where it likely became adapted to infect and transmit in humans. Here we show that in Dar es Salaam, Tanzania, an East African setting with a very high burden of TB, infections are caused by distinct Mtb genotypes introduced in recent evolutionary times from different parts of the world. These genotypes differed in traits important to Mtb transmission in the Dar es Salaam host population; while some Mtb genotypes transmitted more efficiently during a certain period of time, others elicited that patients would be infectious for longer periods. These traits evolved independently in the different Mtb genotypes and could not be explained by the time of co-existence between the host population and the pathogen. This suggests that bacterial factors are important determinants of the TB epidemic. More generally, we demonstrate that distinct pathogenic life history characteristics can co-exist in one host population.

In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV.STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA12 IU/mL in Thailand and HCV RNA15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

Hepatitis C virus (HCV) prevalence is high among people living with HIV co-infected with HCV, people who inject drugs, men who have sex with men and inmates in correctional settings. The barriers to eliminate HCV among these key populations include diagnosis challenges, lack of awareness, discrimination and stigmatization. In addition, scaling up of HCV treatment has been a challenge in Asia–Pacific with the lack of national policies, targets and unavailability of appropriate direct-acting antivirals regimens. In order to achieve HCV micro elimination within these high-risk populations, novel strategies to improve the cascade of care from diagnosis to treatment with direct-acting antivirals, complemented by behavioral change interventions, harm reduction services for people who inject drugs, civil society led advocacy and policies from the government, will be necessary.

Kidney transplant recipients (KTRs) have a suboptimal immune response to COVID-19 vaccination due to the effects of immunosuppression, mostly mycophenolic acid (MPA). This study investigated the benefits of switching from the standard immunosuppressive regimen (tacrolimus (TAC), MPA, and prednisolone) to a regimen of mammalian target of rapamycin inhibitor (mTORi), TAC and prednisolone two weeks pre- and two weeks post-BNT162b2 booster vaccination. A single-center, opened-label pilot study was conducted in KTRs, who received two doses of ChAdOx-1 and a single dose of BNT162b2. The participants were randomly assigned to continue the standard regimen (control group, n = 14) or switched to a sirolimus (an mTORi), TAC, and prednisolone (switching group, n = 14) regimen two weeks before and two weeks after receiving a booster dose of BNT162b2. The anti-SARS-CoV-2 S antibody level after vaccination in the switching group was significantly greater than the control group (4051.0 [IQR 3142.0–6466.0] BAU/mL vs. 2081.0 [IQR 1077.0–3960.0] BAU/mL, respectively; p = 0.01). One participant who was initially seronegative in the control group remained seronegative after the booster dose. These findings suggest humoral immune response benefits of switching the standard immunosuppressive regimen to the regimen of mTORi, TAC, and prednisolone in KTRs during vaccination.

With the increased availability and efficacy of ART, co-morbidities are now one of the leading causes of death in HIV-positive individuals. One of these co-morbidities is co-infection with HBV.

IntroductionConventional markers are not reliable predictors of histological activity of lupus nephritis (LN). We aimed to examine the utility of urine γ-interferon-inducible protein (IP-10) in predicting LN flares, diagnosis of LN, and forecasting treatment response.MethodsSLE patients who fulfilled the ACR 1997 criteria with history of LN were enrolled. Urine IP-10 was measured at least once during routine quarterly visits, at the time of diagnosis of active LN, and monthly during induction therapy for 6 months.ResultsThere were 65 active LN and 46 inactive LN included. The mean urine IP-10 levels among the active and inactive LN were 2.69 (95%CI 2.53-2.86) and 2.18 (95%CI 1.96-2.39) log copies/mcg total RNA respectively (p-value < 0.0001). Clinicopathological discordance was observed in 9 of 55 (16%) biopsied patients (5 with proliferative LN without proteinuric flare and 4 with nephrotic-range proteinuria from glomerulosclerosis). Urine IP-10 predicted histological activity of LN with 91% accuracy, compared to 84% with proteinuric flare. Within two years, half of the clinically inactive LN patients with positive baseline urine IP-10 developed LN flare, whereas no flares were observed in patients with negative baseline urine IP-10. Urine IP-10 levels were not associated with treatment response at 6 months.ConclusionUrine IP-10 may reflect histological activity of LN more accurately than conventional markers, especially in patients with clinicopathologic discrepancy. Clinically inactive LN patients with positive urine IP-10 were at a higher risk of developing LN flare.Key messages-The majority of the studies on novel biomarkers in LN lacked renal biopsy and relied on clinical indicators to determine histological activity. As a result, the validity of these studies may be jeopardized.-According to this study, clinicopathological discordance was found in 16% of LN patients who underwent renal biopsy. Urine IP-10 outperformed urinary protein level in differentiating histologically active LN from inactive LN (accuracy 91% versus 84%).-Within two years, half of the clinically inactive LN patients who had positive urine IP-10 developed LN flares, whereas none of those who had negative urine IP-10 did.-Urine IP-10 may aid in the diagnosis of histologically active LN, particularly in patients with clinicopathologic discrepancy. Urine IP-10 monitoring in clinically inactive LN patients may predict the risk of future LN flares.

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.

ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low- and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml. We report here long-term outcomes over 144 weeks.Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow-up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow-up of ≥144 weeks), with HIV-1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow-up. Proportion of participants with HIV-1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow-up; mean CD4 count changes were estimated using loess regression.Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mmThird-line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second-line PI-based ART prior to the availability of dolutegravir.

OBJECTIVE: To assess recent trends in the monitoring of antiretroviral therapy (ART) and detection of ART failure in adult and pediatric HIV clinics. METHODS: We used data collected from 21 adult and 17 pediatric sites (across 13 and 6 countries/territories, respectively) in the International Epidemiology Databases to Evaluate AIDS – Asia-Pacific cohort. ART failure was defined as viral, immune, or clinical consistent with WHO guidelines. RESULTS: A total of 8,567 adults and 6,149 children contributed data. Frequency of CD4 count monitoring declined between 2010-2019 among adult sites (from 1.93 to 1.06 tests/person/year, a 45.1% decline) and pediatric sites (from 2.16 to 0.86 tests/person/year, a 60.2% decline) while rates of viral load monitoring remained relatively stable. The proportion of adult and pediatric treatment failure detected as immune failure declined (from 73.4% to 50.0% and from 45.8% to 23.1%, respectively) while the proportion of failure detected as viral failure increased (from 7.8% to 25.0% and from 45.8% to 76.9%, respectively). The proportion of ART failure detected as clinical failure remained stable among adult and pediatric sites. The largest shifts in ART monitoring and failure type occurred in lower middle-income countries. CONCLUSION: Although viral failure in our Asian cohort now comprises a larger portion of ART failure than in prior years, the diagnostic characteristics of immune and clinical failure, and recommendations on their management, remain important inclusions for regional ART guidelines.

Coronavirus disease 2019 (COVID-19) was first detected in December 2019. In March 2020, the World Health Organization declared COVID-19 a pandemic. People with underlying medical conditions may be at greater risk of infection and experience complications from COVID-19. COVID-19 has the potential to affect People living with HIV (PLWH) in various ways, including be increased risk of COVID-19 acquisition and interruptions of HIV treatment and care. The purpose of this review article is to evaluate the impact of COVID-19 among PLWH. The contents focus on 4 topics: (1) the pathophysiology and host immune response of people infected with both SARS-CoV-2 and HIV, (2) present the clinical manifestations and treatment outcomes of persons with co-infection, (3) assess the impact of antiretroviral HIV drugs among PLWH infected with COVID-19 and (4) evaluate the impact of the COVID-19 pandemic on HIV services.

The Bangkok International Symposium on HIV Medicine is the longest running HIV conference in the Asia-Pacific, that provides professional healthcare workers with the latest information on HIV and related fields. For the first time, this event was held as a virtual symposium due to the COVID-19 pandemic and registration was free to everyone. More than 1800 people viewed the symposium from 41 countries. The first sessions reviewed COVID-19 and had a panel representing physicians from Australia, Myanmar, Indonesia and Thailand, who shared experiences in managing HIV care during the pandemic. For the first time, we had sessions on the WHO’s vision for integrating HIV care delivery models, and a number of physicians shared the innovative models that have been developed in their clinics.

Background: There is a very high prevalence of subclinical vitamin K deficiency in patients requiring hemodialysis (HD), and this problem is associated with vascular calcification and arterial stiffness. Vitamin K2 (MK-7) supplementation can improve vitamin K status in HD patients. However, the benefits of vitamin K supplementation on arterial stiffness have still not been established. The present study was conducted to evaluate the efficacy of menaquinone-7 (MK-7) supplementation on arterial stiffness in chronic HD patients. Methods: This open-label multicenter randomized clinical trial was conducted in 96 HD patients who had arterial stiffness, defined by high carotid femoral pulse wave velocity (cfPWV ≥ 10 m/s). The patients were randomly assigned to receive oral MK-7 (375 mcg once daily) for 24 weeks (n = 50) or standard care (control group; n = 46). The change in cfPWV was the primary outcome. Results: Baseline parameters were comparable between the two groups. There was no significant difference in the change in cPWV at 24 weeks between the MK-7 group and standard care [−6.0% (−20.2, 2.3) vs. −6.8% (−19.0, 7.3), p = 0.24]. However, we found that MK-7 significantly decreased cPWV in patients with diabetes [−10.0% (−15.9, −0.8) vs. 3.8% (−5.8, 11.6), p = 0.008]. In addition, the MK-7 group had a lower rate of arterial stiffness progression, compared to controls (30.2% vs. 39.5%, p = 0.37), especially in diabetes patients (21.4% vs. 72.7%, p = 0.01). No serious adverse events were observed during the 24 weeks. Conclusion: Vitamin K supplements provided a beneficial impact in lowering the rate of arterial stiffness progression in chronic hemodialysis patients with diabetes. Possible benefits on cardiovascular outcomes require further investigation.