Clinical Characteristics of Refractory Coronavirus Disease 2019 in Wuhan, China.

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe adult respiratory syndrome coronavirus 2, occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. METHODS: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 1 January to 5 February. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy of treatment after hospitalization, and the differences between groups were compared. RESULTS: Compared with patients with general COVID-19 (45.2%), those with refractory disease were older, were more likely to be male, and had more underlying comorbid conditions, a lower incidence of fever, higher maximum temperatures among patients with fever, higher incidences of shortness of breath and anorexia, more severe disease assessment at admission, higher neutrophil, aspartate aminotransferase, lactate dehydrogenase, and C-reactive protein levels, lower platelet counts and albumin levels, and higher incidences of bilateral pneumonia and pleural effusion (P < .05). Patients with refractory COVID-19 were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment, including corticosteroids, antiviral drugs, and immune enhancers (P < .05). Considering the factors of disease severity at admission, mechanical ventilation, and intensive care unit transfer, patients with refractory COVID-19 were also more likely to be male, have manifestations of anorexia on admission, and receive oxygen, expectorant, and adjunctive agents (P < .05). CONCLUSION: In nearly 50% of patients with COVID-19 obvious clinical and radiological remission was not achieved within 10 days after hospitalization. Male, anorexia, and no fever at admission was predictive of poor treatment efficacy.

Combination antiretroviral therapy is associated with reduction in liver fibrosis scores in patients with HIV and HBV co-infection.

BACKGROUND: Liver fibrosis is common in individuals with HIV/HBV co-infection, but whether cART could reverses liver fibrosis is unclear. METHODS: This was a retrospective observational study. Binary logistic regression was used to assess predictors of liver fibrosis in individuals with HIV/HBV co-infection. Comparison of FIB-4 scores before and after cART were compared using X2 test and t test. RESULTS: Four hundred and fifty-eight individuals with HIV/HBV co-infection were included in this study. It was found that cART (HR 0.016, 95% CI: 0.009-0.136; P < 0.001) was one of protection factors to against liver fibrosis. Forty individuals who had normal levels of ALT, AST and PLT during the whole course of diseases were stratified into FIB-4 < 1.45 (n = 14), 1.45 ≤ FIB-4 ≤ 3.25 (n = 19) and FIB-4 > 3.25 (n = 7) groups by their FIB-4 scores before cART. In 1.45 ≤ FIB-4 ≤ 3.25 group, 57.9%(11/19) of the individuals dropped to FIB-4 < 1.45 group by cART; in FIB-4 > 3.25 group, 85.7%(6/79) dropped to 1.45 ≤ FIB-4 ≤ 3.25 group, while 14.3%(1/7) dropped to FIB-4 < 1.45 group. In cART-naive group, 1 year, 2-5 years and 5-10 years post-cART groups, FIB-4 scores were 4.29 ± 0.43, 3.63 ± 0.38, 2.90 ± 0.36 and 2.52 ± 0.38, respectively (P = 0.034); and the incidence of liver fibrosis were 7.38%(104/141), 63.6%(98/154), 60.8%(62/102) and 47.5%(29/61), respectively (P = 0.004). CONCLUSION: cART was associated with decreased FIB-4 scores and the benefit of cART in reversing liver fibrosis can sustain for a decade in patients with HIV/HBV co-infection.

Long-term observation on hepatitis B surface antigen seroclearance in therapy experienced HIV/HBV co-infected Chinese.

The aim of this retrospective study was to observe hepatitis B surface antigen (HBsAg) seroclearance and explore predictors of HBsAg loss in HIV/HBV-co-infected patients receiving long-term lamivudine or both tenofovir and lamivudine containing therapies. Quantification of HBsAg, hepatitis B e antigen and HBV DNA before and after initiation of HBV-active antiretroviral therapy in a total of 268 HIV/HBV-co-infected patients started treatment between 2005 and 2017 were performed. Over a median of 65.63 months of follow-up, 10 (3.7%) were observed HBsAg loss and the quantification of HBsAg in 7 (2.6%) patients were less than 50 IU/mL. With the prolongation of antiretroviral therapy duration time, the rates of HBsAg seroclearance tended to increase gradually, rising from 1.8% (3/163) during 2-4 years treatment to 29.4% (10/34) after antiretroviral therapy for up to 10 years. Lower baseline qHBsAg and HBV DNA levels and strong 12-month declines in qHBsAg were significantly associated with HBsAg seroclearance. The event of HBsAg seroclearance is uncommon among Chinese individuals with HIV/HBV co-infection who have been treated with anti-HBV containing antiretroviral therapy, and lifelong therapy for HBV is needed for HIV/HBV co-infected patients. Baseline qHBsAg and HBV DNA levels and qHBsAg decline rate were predictors for HBsAg seroclearance.

The role of methylprednisolone on preventing disease progression for hospitalized patients with severe COVID-19.

BACKGROUND: COVID-19 is a public health emergency that is spreading worldwide and seriously affecting the global economy. Data on the effectiveness and safety of the use of methylprednisolone for patients with severe COVID-19 remain limited. METHODS: In this retrospective study, epidemiological, clinical, laboratory, treatment and outcomes data of hospitalized patients with severe COVID-19 in Zhongnan Hospital of Wuhan University from January 1 to 7 March 2020, were collected. Binary logistic regression model was used to analyse risk factors for disease progression from severe COVID-19 illness to critical illness. The effectiveness and safety of the use of methylprednisolone for patients with severe COVID-19 disease were evaluated. RESULTS: The results of the multivariate analysis from 175 patients with severe COVID-19 indicate that the use of methylprednisolone was a protective factor against disease progression from severe to critical illness(P < .001; OR: 0.054 95% CI: 0.017-0.173). Among patients with severe COVID-19 aged < 65 years, both the proportion of patients who progressed to critical illness (42.2% vs 90.0%, P = .000) and the mortality(6.7% vs 30.0%, P = .002) were lower for patients in methylprednisolone group, compared with those in the non-methylprednisolone group, whereas no statistical differences between the methylprednisolone group and the non-methylprednisolone group were found among patients with COVID-19 older than 65 years. Moreover, both the levels of CD4+ T lymphocyte counts (646 vs 463/µL, P = .007) and IL-6 (241.9 vs 82.8 pg/mL, P = .025) were higher among patients with severe COVID-19 aged < 65 years, compared with those patients ≥ 65 years old. CONCLUSION: Data from the limited sample showed that the early use of low or medium doses of methylprednisolone has a positive effect for patients with severe COVID-19 younger than 65 years old, and excessive immune response and cytokine storm may be some of the reasons for the effectiveness.

Risk factors for delayed negative conversion of SARS-CoV-2 in patients with COVID-19 pneumonia: a retrospective cohort study.

The epidemic of coronavirus disease 2019 (COVID-19) began in China and had spread rapidly to many other countries. This study aimed to identify risk factors associated with delayed negative conversion of SARS-CoV-2 in COVID-19 patients. In this retrospective single-centre study, we included 169 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 15th January to 2nd March. The cases were divided into two groups according to the median time of SARS-CoV-2 negative conversion. The differences between groups were compared. In total, 169 patients had a median virus negative conversion time of 18 days (interquartile range: 11-25) from symptom onset. Compared with the patients with short-term negative conversion, those with long-term conversion had an older age, higher incidence of comorbidities, chief complaints of cough and chest distress/breath shortness and severer illness on admission, higher level of leucocytes, neutrophils, aspartate aminotransferase, creatine kinase and erythrocyte sedimentation rate (ESR), lower level of CD3+CD4+ lymphocytes and albumin and more likely to receive mechanical ventilation. In multivariate analysis, cough, leucocytes, neutrophils and ESR were positively correlated with delayed virus negative conversion, and CD3+CD4+ lymphocytes were negatively correlated. The integrated indicator of leucocytes, neutrophils and CD3+CD4+ lymphocytes showed a good performance in predicting the negative conversion within 2 weeks (area under ROC curve (AUC) = 0.815), 3 weeks (AUC = 0.804), 4 weeks (AUC = 0.812) and 5 weeks (AUC = 0.786). In conclusion, longer quarantine periods might be more justified for COVID-19 patients with cough, higher levels of leucocytes, neutrophils and ESR and lower levels of CD3+CD4+ lymphocytes.

Molecular diagnosis of central nervous system opportunistic infections and mortality in HIV-infected adults in Central China.

BACKGROUND: CSF PCR is the standard diagnostic technique used in resource-rich settings to detect pathogens of the CNS infection. However, it is not currently used for routine CSF testing in China. Knowledge of CNS opportunistic infections among people living with HIV in China is limited. METHODS: Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral and fungal etiologies. Pathogen-specific primers were used to detect DNA from cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and John Cunningham virus (JCV) via real-time polymerase chain reaction (PCR). RESULTS: Cryptococcal meningitis accounted for 63.0% (34 of 54) of all causes of meningitis, 13.0% (7/54) for TB, 9.3% (5/54) for Toxoplasma gondii. Of 54 samples sent for viral PCR, 31.5% (17/54) were positive, 12 (22.2%) for CMV, 2 (3.7%) for VZV, 1 (1.9%) for EBV, 1 (1.9%) for HHV-6 and 1 (1.9%) for JCV. No patient was positive for HSV. Pathogen-based treatment and high GCS score tended to have a lower mortality rate, whereas patients with multiple pathogens infection, seizures or intracranial hypertension showed higher odds of death. CONCLUSION: CNS OIs are frequent and multiple pathogens often coexist in CSF. Cryptococcal meningitis is the most prevalent CNS disorders among AIDS. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve the diagnosis of AIDS related OIs in resource-limited developing countries, but the cost-efficacy remains to be further evaluated.

Metagenomic next-generation sequencing versus traditional laboratory methods for the diagnosis of central nervous system opportunistic infections in HIV-infected Chinese adults.

To evaluate clinical value of metagenomic next-generation sequencing (mNGS) in people living with HIV/AIDS (PLWHA) who had CNS disorders. Cerebrospinal fluid (CSF) samples from 48 PLWHA presenting with CNS disorders were sequenced using mNGS and compared with clinical conventional diagnostic methods. In total, 36/48 ss(75%) patients were diagnosed with pathogen(s) infection by mNGS, and the positive detection proportion by mNGS was higher than that by clinical conventional diagnostic methods (75% vs 52.1%, X2 = 5.441, P = 0.020). Thirteen out of 48 patients (27.1%) were detected with 3-7 pathogens by mNGS. Moreover, 77 pathogen strains were detected, of which 94.8% (73/77) by mNGS and 37.0% (30/77) by clinical conventional methods (X2 = 54.206, P < 0.001). The sensitivity and specificity of pathogens detection by mNGS were 63.9% (23/36) and 66.7% (8/12), respectively, which were superior to that by clinical conventional methods (23/36 vs 9/25, X2 = 4.601, P = 0.032; 8/12 vs 5/23, X2 = 5.029, P = 0.009). The application of mNGS was superior for its ability to detect a variety of unknown pathogens and multiple pathogens infection, and relatively higher sensitivity and specificity in diagnosis of CNS disorders in PLWHA.

A case of hepatic tuberculosis with acquired immune deficiency syndrome.

Hepatic tuberculosis (TB) is a rare type of extrapulmonary TB. Due to the nonspecific clinical symptoms and imaging manifestations, hepatic TB with human immunodeficiency virus (HIV) infection is easy to be misdiagnosed. We report a case of hepatic TB with acquired immune deficiency syndrome (AIDS), which was initially misdiagnosed as general bacterial liver abscess even after the patient received needle biopsy. In subsequent process, pathogenic tests using washing solution of punctured liver tissue sample were proved feasible, convenient, and specific for pathogenic diagnosis in resource-limited areas of China. For liver abscess in patients with HIV, the pathogens are more complex than HIV negative patients. Some uncommon pathogens, such as TB and fungi, should also be taken into consideration. For the hepatic TB without abscess formation, pathogenic test using washing solution of punctured liver tissue sample should be attached importance.

Electrocardiogram manifestations of hyponatraemia.

Electrolytes play a vital role in myocardial electrophysiological activities in the human body. Electrolyte disturbances can affect depolarisation and repolarisation of myocardial cells and thus result in arrhythmia. The most common electrolyte disturbance among hospitalised patients is hyponatraemia. We report on a case of an acquired immune deficiency syndrome patient with decompensated cirrhosis, who developed sinus arrest from hyponatraemia. The electrocardiogram manifestations at different sodium concentrations were also recorded in subsequent therapeutic processes.

Clinical progression and changes of chest CT findings among asymptomatic and pre-symptomatic patients with SARS-CoV-2 infection in Wuhan, China.

OBJECTIVES: To analyze characteristics of asymptomatic/pres-ymptomatic patients with SARS-CoV-2 infection. METHODS: Chest computed tomography(CT), indicators for organ and coagulation function, inflammation cytokines, of asymptomatic/pre-symptomatic patients with SARS-CoV-2 infection were retrospectively analyzed in Zhongnan Hospital of Wuhan University from 20 December 2019, to 8 March 2020. RESULTS: The proportion of normal chest CT in asymptomatic and pre-symptomatic patients with SARS-CoV-2 infection were 35.4% (17/48) and 3.3%(2/61), respectively (P< 0.001). In 17 asymptomatic patients, their images of chest CT maintained normal during the whole course of diseases, while the normal images of chest CT in 2 pre-symptomatic patients progressed to abnormal later (P< 0.001). All the six asymptomatic patients with SARS-CoV-2 infection maintained unilateral lesion, while the proportion was 29.4%(5/17) in pre-symptomatic patients(P= 0.003). Compared with asymptomatic patients, pre-symptomatic COVID-19 patients had worse levels of Lymphocyte count (P= 0.001), Albumin (P= 0.045), Aspartate aminotransferase (P= 0.044), γ-glutamyl transpeptadase (P= 0.016), Globulin (P= 0.036), Creatinine (P= 0.021), Lactate dehydrogenase (P= 0.008), C-reactive protein (P< 0.001), Serum amyloid A (P< 0.001), and Erythrocyte sedimentation rate (P< 0.001). Except for above indicators, Alkaline phosphatase (P= 0.009), Procalcitonin (P= 0.010), and D-dimer(P< 0.001) increased further during periods of symptoms compared with those levels in pre-symptomatic period. CONCLUSION: In early stage after SARS-CoV-2 infection, images of chest CT and blood tests of asymptomatic patients were different from pre-symptomatic patients.

Clinical characteristics of COVID-19 patients with HIV coinfection in Wuhan, China.

BACKGROUND: Information about the impact of HIV coinfection on clinical characteristics of COVID-19 patients remains limited. METHODS: Maximum body temperatures, fever duration, chest CT and viral shedding, lymphocyte counts, and titer of SARS-CoV-2 antibody were compared between COVID-19 patients with and without HIV infection in Zhongnan Hospital of Wuhan University from January 20th to February 14th, 2020. RESULTS: Compared with 53 COVID-19 patients without HIV infection, the patients with SARS-CoV-2 and HIV coinfection had higher maximum body temperatures (38.7°C vs 37.6°C, P = 0.044), longer duration of fever (8.7 ± 4.5 vs 4.2 ± 2.1 days, P = 0.038), longer time to have improvement of chest CT images (22 vs 15 days from the onset of illness, P = 0.011), lower level of SARS-CoV-2 IgG (5.11 ± 32.33 vs 37.45 ± 15.48 AU/ml, P = 0.042). However, no statistically significant difference of duration of SARS-CoV-2 shedding in the two groups was found (12.3 ± 2.6 vs 13.4 ± 2.4 days, , P = 0.813). CONCLUSION: Lower level of CD4+ T lymphocyte counts caused by HIV infection itself might be one of reasons for relatively weak ability to produce SARS-CoV-2 specific antibodies. The effects of anti-HIV drugs in prevention and treatment of COVID-19 appears to be limited.

The indicative role of markers for liver injury on the severity and prognosis of coronavirus disease 2019 patients.

BACKGROUND: Liver injury in coronavirus disease 2019 (COVID-19) patients was poorly understood. METHODS: The markers of liver injury, severity of disease and prognosis among 495 COVID-19 patients in Zhongnan Hospital of Wuhan University from 1st January 2019 to 11th March 2019 were retrospectively analyzed. RESULTS: The levels of aspartate aminotransferase (AST) (50.1 ± 38.4 vs. 31.4 ± 39.1, P < 0.001), gamma-glutamyl transpeptidase (GGT) (70.3 ± 70.2 vs. 34.1 ± 34.7, P < 0.001) and fibrinogen-to-albumin-ratio (FAR) (13.4 ± 4.0 vs. 10.4 ± 3.4, P < 0.001) were greater than mild COVID-19 patients, whereas the levels of albumin(35.0 ± 6.2 vs. 39.9 ± 3.7, P < 0.001) and albumin/globulin (A/G) ratio (1.21 ± 0.24 vs. 1.50 ± 0.31, P < 0.001) were lower in severe COVID-19 patients. By comparing the changes of liver injury markers 7-10 days after hospitalization, the level of albumin deteriorated from 35.0 ± 6.2 to 30.20 ± 5.5 (P < 0.001), A/G ratio from 1.21 ± 0.24 to 1.06 ± 0.25 (P < 0.001), and FAR from 13.4 ± 4.0 to 15.4 ± 2.9(P < 0.001) in severe COVID-19 patients, while the changes of albumin, A/G ratio and FAR showed opposite patterns in mild COVID-19 patients. FAR > 12 [2.566 (1.410-4.670), P = 0.012) on admission and changes of albumin >5g/l [22.489 (6.422-78.757), P = 0.001] were two risk factors for death, and the sensitivity and specificity for the poor prognosis were 80.8% and 64.0%, 82.6% and 76.3%, respectively. CONCLUSION: The levels of AST, GGT, albumin and FAR are correlated with disease severity after severe acute respiratory syndrome coronavirus-2 infection. FAR > 12 on admission and changes of albumin > 5 g/l were good predictors for the prognosis of COVID-19 patients.

[Nevirapine related hepatotoxicity: the prevalence and risk factors in a cohort of ART naive Han Chinese with AIDS].

OBJECTIVE: To investigate the incidence of hepatotoxicity in acquired immunodeficiency syndrome (AIDS) patients on combined anti-retroviral therapy (cART) containing nevirapine (NVP) and to assess the risk factors and its impact on cART. METHODS: 330 AIDS patients from March 2003 to June 2008 at local county were enrolled and a retrospective study using Kaplan-meier survival and Multivariate logistic regression modeling was conducted. RESULTS: 267 out of 330 patients received NVP based cART and 63 cases received EFV-based cART. The deference of prevalences of hepatotoxicity between the two groups is statistically significant (Chi2 = 6.691, P = 0.01). 133 out of 267 (49.8%) patients on NVP based cART had at least one episode of ALT elevation during a median 21 months (interquartile ranges, IQR 6, 37) follow-up time, amounts for 28.5 cases per 100 person-years. Baseline ALT elevation (OR = 14.368, P = 0.017)and HCV co-infection (OR = 3.009, P = 0.000) were risk factors for cART related hepatotoxicity, while greatly increased CD4+ T(CD4) cell count was protective against hepatotoxicity development (OR = 0.996, P = 0.000). Patients co-infected with HCV received NVP-based cART had the higher probability of hepatotoxicity than those without HCV co-infection (Log rank: Chi2 = 16.764, P = 0.000). 23 out of the 133 subjects (17.3%) with NVP related hepatotoxicity discontinued cART temporarily or shifted NVP to efavirenz. CONCLUSION: NVP related hepatotoxicity was common among ARV naive HIV infected subjects in our cohort. Baseline ALT elevation and HCV co-infection were associated statistically with the development of hepatotoxicity. Hepatotoxicity led to discontinuing cART temporarily or switching to other regimens in some subjects. It suggested that NVP should be used with caution in patients co-infected with HCV among whom anti-HCV therapy before cART initiation may contribute to minimizing the probability of NVP associated hepatotoxicity.

Two outbreaks of SARS-CoV-2 in department of surgery in a Wuhan hospital.

The outbreak of SARS-CoV-2 in China, attracted a large number of medical staff to help in the city's hospitals and this put them at a high risk of infection. We describe twenty medical staff who were diagnosed with COVID-19 within one week in the department of surgery in a Wuhan hospital. Epidemiological investigation of these cases identified misdiagnosed patients (source of infection), an inappropriate clinical meeting and working without wearing face masks to be the causes of the outbreaks. This report emphasizes the importance of wearing a facemask and applying other standard infection control precautions to protect medical personnel from infection with the virus.

Clinical Characteristics and Outcomes of Older Patients with Coronavirus Disease 2019 (COVID-19) in Wuhan, China: A Single-Centered, Retrospective Study.

BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) emerged in Wuhan city and spread rapidly throughout China and the world. In this study, we aimed to describe the clinical course and outcomes of older patients with COVID-19. METHODS: This is a retrospective investigation of hospitalized older patients with confirmed COVID-19 at Zhongnan Hospital of Wuhan University from January 1, 2020, to February 10, 2020. RESULTS: In total, 203 patients were diagnosed with COVID-19, with a median age of 54 years (interquartile range, 41-68; range, 20-91 years). Men accounted for 108 (53.2%) of the cases, and 55 patients (27.1%) were more than 65 years of age. Among patients who were 65 years and older, the mortality rate was 34.5% (19/55), which was significantly higher than that of the younger patients at 4.7% (7/148). Common symptoms of older patients with COVID-19 included fever (94.5%; n = 52), dry cough (69.1%; n = 38), and chest distress (63.6%; n = 35). Compared with young patients, older patients had more laboratory abnormalities and comorbidities. Through a multivariate analysis of the causes of death in older patients, we found that males, comorbidities, time from disease onset to hospitalization, abnormal kidney function, and elevated procalcitonin levels were all significantly associated with death. CONCLUSIONS: In the recent outbreak of COVID-19, our local hospital in Wuhan found that patients aged 65 and older had greater initial comorbidities, more severe symptoms, and were more likely to experience multiorgan involvement and death, as compared to younger patients.

Clinical characteristics of four cancer patients with SARS-CoV-2 infection in Wuhan, China.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of pneumonia in Wuhan. The virus is highly infectious. Patients with cancer might be susceptible to the viral infection because of the immunosuppressive state cause by therapies on tumors. CASE PRESENTATION: We present the clinical features of four cancer patients who were infected with SARS-CoV-2 in late January of 2020 in our hospital. Cases 1 and 3 were diagnosed as mild and common type of coronavirus disease 2019 (COVID-2019) and survived from the viral infection. They acquired SARS-CoV-2 infection during their staying in hospital under radiotherapy and surgery of the tumors. Cases 2 and 4 suffered from severe type of COVID-19, and Case 2 was dead owning to the advanced age, uncontrolled chronic B cell lymphocytic leukemia and many other underlying diseases. The immunosuppressive state induced by liver transplantation and anti-rejection therapy might contribute to the severity of COVID-19 in Case 4, who suffered from hepatitis B related hepatocellular carcinoma. However, Case 4 was recovered from COVID-19 after a combination therapy against virus, bacteria and fungi, and also respiratory support. Nearly all patients showed a decrease in lymphocytes including total CD3+ T cells, B cells, and natural killer cells after infection of the virus. CONCLUSIONS: The severity of COVID-19 might be influenced by immune system state and underlying diseases in cancer patients. And the treatment of SARS-CoV-2 infection in cancer patients is challenged by the immunosuppressive state of these patients under chemotherapy or surgery.

Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response.

The central role of the cellular immune response in the control and clearance of the hepatitis B virus (HBV) infection has been well-established. The contribution of humoral immunity, including B cell and antibody responses against HBV, has been investigated for a long time but has attracted increasing attention again in recent years. The anti-HBs antibody was first recognized as a marker of protective immunity after the acute resolution of the HBV infection (or vaccination) and is now defined as a biomarker for the functional cure of chronic hepatitis B (CHB). In this way, therapies targeting HBV-specific B cells and the induction of an anti-HBs antibody response are essential elements of a rational strategy to terminate chronic HBV infection. However, a high load of HBsAg in the blood, which has been proposed to induce antigen-specific immune tolerance, represents a major obstacle to curing CHB. Long-term antiviral treatment by nucleoside analogs, by targeting viral translation by siRNA, by inhibiting HBsAg release via nucleic acid polymers, or by neutralizing HBsAg via specific antibodies could potentially reduce the HBsAg load in CHB patients. A combined strategy including a reduction of the HBsAg load via the above treatments and the therapeutic targeting of B cells by vaccination may induce the appearance of anti-HBs antibodies and lead to a functional cure of CHB.

Five-year follow-up observation of HIV prevalence in serodiscordant couples.

OBJECTIVES: To evaluate the rate of HIV seroconversion and the related risk factors among HIV discordant couples in Hubei Province, China. METHODS: HIV seroconversion rates and associated factors in discordant couples were identified during 2010-2012, based on existing data collected in serological and behavioral surveys between 2005 and 2007. RESULTS: At baseline, HIV transmission had occurred in 505 out of 1258 couples and the annual rate of HIV transmission was 6.3% in the absence of an intervention (40.14% after HIV exposure for 6.4 years). Five out of 753 discordant couples were found to have seroconverted during the 5-year follow-up observation after the implementation of interventions. Factors independently associated with HIV seroconversion included an HIV viral load >1000 copies/ml (odds ratio (OR) 18.706, 95% confidence interval (CI) 1.577-221.926), the index partner being on antiretroviral therapy (OR 0.019, 95% CI 0.002-0.180), and condom use in the past 6 months (OR 0.194, 95% CI 0.021-0.795). CONCLUSIONS: HIV-negative partners in serodiscordant couples were at risk of HIV infection if the index partner did not receive any intervention. It is strongly advised that existing interventions are used, such as couples consultations, condom use, and antiretroviral treatment, to minimize the risk of HIV transmission.

Impact of hepatitis B virus infection on HIV response to antiretroviral therapy in a Chinese antiretroviral therapy center.

BACKGROUND: Co-infection with hepatitis B virus (HBV) and HIV is common in China; however, the impact of HBV on long-term antiretroviral therapy (ART) outcomes has not been fully characterized. METHODS: Patients were classified as being HIV mono-infected (hepatitis B surface antigen (HBsAg)-negative) or HIV/HBV co-infected (HBsAg-positive). The effects of HBV on HIV virological response, changes in CD4 cell counts, hepatotoxicity, and mortality among Chinese patients receiving ART were evaluated. RESULTS: The HIV/HBV co-infection rate in our cohort was 9.9% (354/3562). Five hundred and fifty HIV mono-infected and 78 HIV/HBV co-infected individuals fulfilled the inclusion criteria. HIV/HBV co-infected individuals were less likely to achieve HIV-RNA suppression and a CD4 increase than HIV mono-infected individuals at 48 months post-ART. Greater hepatotoxicity and a more rapid occurrence of death were observed in HIV/HBV co-infected subjects. HBV-related mortality accounted for 84.2% (16/19) of the total deaths in HIV/HBV co-infected subjects. CONCLUSIONS: HBV co-infection can affect late immunological and virological responses to ART and increase the risk of hepatotoxicity. Mortality due to liver disease was high among HIV/HBV co-infected individuals in this study, despite HBV-active ART. As long as HIV/HBV co-infected persons need anti-HBV therapy, they should be recommended ART that includes agents with activity against both HIV and HBV, regardless of the CD4 cell count level.