Case Letter Severe trauma has high morbidity and mortality rates,being the leading cause of death in young adults.Among all traumas,tra ffi c injuries are particularly lethal.^([1-2]) The injury severity score(ISS) ca...Case Letter Severe trauma has high morbidity and mortality rates,being the leading cause of death in young adults.Among all traumas,tra ffi c injuries are particularly lethal.^([1-2]) The injury severity score(ISS) can be used to assess trauma severity,with ISS of<9,9–15,16–24,and≥25 indicating minor,moderate,severe,and critical trauma,respectively.The ISS is correlated with mortality,morbidity,and hospitalization duration after injury.^([3-4]) Here,we report one patient who was admitted to our emergency intensive care unit(EICU) due to traumatic liver rupture and traumatic myocardial infarction complicated with inferior vena cava(IVC) thrombosis.展开更多
Objective： To assess the efficacy and safety of Zhongyan-4 （中研-4号, ZY-4, a Chinese herbal preparation worked out according to the therapeutic principle of supplementing qi, nourishing Yin, clearing heat and detox...Objective： To assess the efficacy and safety of Zhongyan-4 （中研-4号, ZY-4, a Chinese herbal preparation worked out according to the therapeutic principle of supplementing qi, nourishing Yin, clearing heat and detoxication） in treating HIV/AIDS patients in the early or middle stage. Methods： Adopted was randomized double-blinded and placebo-parallel-controlled method, with 72 HIV/AIDS patients randomly divided into the ZY-4 group （36 patients） treated with ZY-4 and the control group （36 patients） treated with placebo. The treatment course was six months. The index of OD4^＋, OD8^＋ counts, body weight, clinical symptom scoring were estimated at 4 time points （0, 1, 3 and 6 month in the course）, and also the viral load before and after treatment. The whole course of observation was completed in 63 patients, 30 in the ZY-4 group and 33 in the control group. Results： OD4^＋ count in the ZY-4 group got elevated by 7.70 4±150.96/mm^3 on average, while that in the control group lowered by 27.33 4±85.28 /mm^3 . Fifteen out of the 30 patients in the ZY-4 group had their OD4^＋ count increased, which was evidently much higher than that in the control group （8/33, P〈0. 05）, suggesting that the efficacy of ZY-4 is superior to that of placebo in elevating OD4^＋ count. Moreover, ZY-4 showed actions in elevating OD45RA^＋ and OD8^＋ count, reducing HIV virus load, improving clinical symptom/sign and increasing body weight of patients. No obvious adverse reaction was found in the clinical trial. Conclusion： ZY-4 has an immunity-protective and/or rebuilding function in HIV/AIDS patients in the early and middle stage, and also shows effects in lowering viral load, increasing body weight and improving symptoms and signs to a certain degree.展开更多
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS).After over 26 years of efforts,there is still not a therapeutic cure or an effective vaccine agai...Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS).After over 26 years of efforts,there is still not a therapeutic cure or an effective vaccine against HIV/AIDS.The clinical management of HIV-1 infected people largely relies on antiretroviral therapy (ART).Although highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients,the huge burden of ART in developing countries,together with the increasing incidence of drug resistant viruses among treated people,calls for continuous efforts for the development of anti-HIV-1 drugs.Currently,four classes of over 30 licensed antiretrovirals (ARVs) and combination regimens of these ARVs are in use clinically including:reverse transcriptase inhibitors (RTIs) (e.g.nucleoside reverse transcriptase inhibitors,NRTIs;and non-nucleoside reverse transcriptase inhibitors,NNRTIs),protease inhibitors (PIs),integrase inhibitors and entry inhibitors (e.g.fusion inhibitors and CCR5 antagonists).Here,we intend to provide updated information of currently available antiretroviral drugs for ART to promote the development of novel anti-HIV-1 drugs.展开更多
The hepatitis C virus(HCV) infects approximately 3% of the world population or more than 185 million people worldwide. Each year, an estimated 350000-500000 deaths occur worldwide due to HCV-associated diseases includ...The hepatitis C virus(HCV) infects approximately 3% of the world population or more than 185 million people worldwide. Each year, an estimated 350000-500000 deaths occur worldwide due to HCV-associated diseases including cirrhosis and hepatocellular carcinoma. HCV is the most common indication for liver transplantation in patients with cirrhosis worldwide. HCV is an enveloped RNA virus classified in the genus Hepacivirus in the Flaviviridae family. The HCV viral life cycle in a cell can be divided into six phases:(1) binding and internalization;(2) cytoplasmic release and uncoating;(3) viral polyprotein translation and processing;(4) RNA genome replication;(5) encapsidation(packaging) and assembly; and(6) virus morphogenesis(maturation) and secretion. Many host factors are involved in the HCV life cycle. Chaperones are an important group of host cytoprotective molecules that coordinate numerous cellular processes including protein folding, multimeric protein assembly, protein trafficking, and protein degradation. All phases of the viral life cycle require chaperone activity and the interaction of viral proteins with chaperones. This review will present our current knowledge and understanding of the role of chaperones in the HCV life cycle. Analysis of chaperones in HCV infection will provide further insights into viral/host interactions and potential therapeutic targets for both HCV and other viruses.展开更多
Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden re...Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden restricted to the Western Pacific and sub-Saharan African regions.Amidst this is a growing burden of metabolic syndrome(MetS)worldwide.A disproportionate co-burden of human immunodeficiency virus(HIV)infection is also reported in sub-Saharan Africa,which poses a further risk of liver-related morbidity and mortality in the region.We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection.While the mechanistic association between CHB and MetS remains poorly resolved,the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB.Among HIV infected individuals,MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy(ART).It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection.However,this remains to be explored through rigorous longitudinal studies,especially in sub-Saharan Africa.Ultimately,there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV coinfected individuals.展开更多
The purpose of this study was to identify factors affecting the time to development of tuberculosis in the presence of competing risks. In this case death before developing tuberculosis was deemed a competing risk bec...The purpose of this study was to identify factors affecting the time to development of tuberculosis in the presence of competing risks. In this case death before developing tuberculosis was deemed a competing risk because it altered the occurrence of the outcome of interest being time to development of tuberculosis from baseline. We used data from a randomized longitudinal clinical trial study called the “Tshepo” study. The “Tshepo” study was a 3-year randomized clinical study following 650 ART-naïve adults (69.4% female) from Botswana who initiated first-line NNRTI-based ART. Participants were assigned in equal proportions (in an open-label, unblinded fashion) to one of 6 initial treatment arms and one of two adherence arms using permuted block randomization. Randomization was stratified by CD4+ cell count (less than 200 cells/mm<sup>3</sup>, 201 - 350 cells/mm<sup>3</sup>) and by whether the participants had an adherence assistant. Classical methods such as the Kaplan-Meier method and standard Cox proportional hazards regression were used to analyze survival data ignoring the competing event(s) which may have been inappropriate in the presence of competing risks. The idea was to use competing risk models to investigate how different treatment regimens affect the time to the development of TB and compare the results to those obtained using the classical survival analysis model which does not account for competing risks. Amongst 38 patients who died 15.8% of them developed tuberculosis whilst 84.2% of those who died did not develop the outcome of interest. The hazard ratio of treatment C was 1.069 implying that the risk of developing TB in patients taking treatment C is about 6.9% higher compared to those taking treatment A having adjusted for baseline age, baseline BMI, baseline CD4, Hemoglobin and gender. Similarly, after accounting for competing risks the hazard ratio for treatment C was about 1.89 implying that the risk of developing TB amongst those taking treatment C was about 89% higher as compared to those taking treatment A. From the obtained results it was thus concluded that the standard Cox model of time to event data in the presence of competing risks underestimated the hazard ratios hence when dealing with data with multiple failure events it is important to account for competing events.展开更多
Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonf...Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K(HML6) and HERV-K(HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K(HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are twoedged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.展开更多
Background: India has scaled up ART programme very rapidly. Though there are reports on retention of patients in the national programme, data on transfer out patients within the ART centers are scanty in India. Method...Background: India has scaled up ART programme very rapidly. Though there are reports on retention of patients in the national programme, data on transfer out patients within the ART centers are scanty in India. Methods: This is a retrospective study of patients receiving antiretroviral treatment between January 2006 and July 2013. The patients who were transferred out from the ART center at National AIDS Research Institute in Pune were included in the study. The data on whether they reached the respective ART centers were collected either by making telephonic calls to the patients and/or to the respective ART centers. Results: Of the total 3015 patients ever started on treatment from the ART center, 158 (5.24%) were transferred out to other ART centers. Of these, 123 (77.8%) patients reached other centres and they were “transferred in”. However, 15 (9.5%) did not reach to respective ART centers and information could not be obtained for 20 (12.7%) transferred out patients. The analysis showed that those who were not living with their partners were 4.53 times more likely to not to reach the preferred ART centre after taking transfer [OR, 95% CI: (1.24 - 16.51), p = 0.022]. Conclusion: Our data suggest that significant number of transfer out patients is lost in HIV treatment cascade. Considering the total PLHIV on treatment in the country, this group adds significantly to the burden of lost to follow up patients. It is important to strengthen the system of tracking the transfer out patients in the programme which will help in patching an important leak in the cascade of HIV care.展开更多
AIM： To undertake analysis of hepatitis A viral load, alanine aminotransferase （ALT）, and viral genotypes with duration of viremia, and to correlate these parameters with CD4^＋/ CD8^＋ lymphocyte populations that ...AIM： To undertake analysis of hepatitis A viral load, alanine aminotransferase （ALT）, and viral genotypes with duration of viremia, and to correlate these parameters with CD4^＋/ CD8^＋ lymphocyte populations that control cell-mediated immunity. METHODS： Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus （HAV） RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. RESULTS： Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis （s-AH） and the remainder had a self-limited acute hepatitis A （AHA）, with one patient with fulminant disease （encephalopathy Grade IV） dying on the 4^th d. The ALT level was significantly higher both in AHA （1070.9±894.3; P = 0.0014） and s-AH （1713.9±886.3; P = 0.001） compared to normal controls （23.6±7.2）. The prothrombin time in s-AH patients （21.0 ±2.0; P=0.02） was significantly higher than in AHA （14.3±1.1;P = 0.44）. The CD4^＋/CD8^＋ ratio in AHA patients （1.17 ＋ 0.11; P = 0.22） and s-AH （0.83 ＋ 0.12; P = 0.0002） were lower than seen in normal healthy controls （1.52）. Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15TM or 30^th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and AIT values collected during the entire course of the selflimited infection were directly correlated but this was not the case for s-AH patients.CONCLUSION： Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.展开更多
Under India’s National AIDS Control Program (NACP), WHO recommended strategy of using three rapid tests is adopted for diagnosis of HIV in an asymptomatic individual. Since the NACP has a stringent kit evaluation pro...Under India’s National AIDS Control Program (NACP), WHO recommended strategy of using three rapid tests is adopted for diagnosis of HIV in an asymptomatic individual. Since the NACP has a stringent kit evaluation procedure and due to the availability of newer third generation Rapid Diagnostic Tests (RDTs) it may be possible to adapt two test strategy for HIV diagnosis instead of the recommended three test strategy. The authors reviewed programmatic data on HIV testing to explore whether use of two rapid tests for HIV diagnosis as against three tests could be a feasible approach without compromising the quality and readability of testing. Data on the HIV diagnosis performed on serum specimens collected for the period of one year (2011-12) from 82 Integrated Testing and Counselling Centers (ICTCs) or Prevention of Parent to Child Transmission Centers (PPTCTs) associated with State reference Laboratories (SRLs) was analysed. Out of 654258 results that were analysed 25168 (3.84%) specimens were positives. It was observed that both two and three test algorithms provided similar results for majority (>99%) of the HIV positive specimens. Discordance was observed in labelling of specimen with inconclusive status (N = 21), however the true status of these samples could not be obtained. The analysis indicated that the use of two test algorithm will have programmatic benefits in terms of reduced financial burden to the programme and ease of procurement, shipment and storage before and after distribution without comprising the quality of the testing. The prospective study would confirm this observation.展开更多
This paper examines whether truckers have been over-stigmatized as HIV carriers in the country. Data were taken from cross-sectional surveys of clients of female sex workers conducted in 2006-2007 in 12 districts of t...This paper examines whether truckers have been over-stigmatized as HIV carriers in the country. Data were taken from cross-sectional surveys of clients of female sex workers conducted in 2006-2007 in 12 districts of the country. A total 4822 clients of female sex workers were covered in the survey. Low-income skilled/semi-skilled men, including non-agricultural/casual labor, and petty businessmen/small shop owners, have the largest share in the clients’ population. There was no significant difference between truckers and other sub-group of clients’ population in terms of consistent condom use with female sex workers and prevalence of HIV or STI. These evidences suggest that the contribution of truckers in HIV epidemic in India might to similar to other sub-groups of clients’ population. Thus, truckers might have been over-stigmatized as HIV carriers in the country. However, there is no doubt that truckers constitute an extremely important target group for the HIV prevention programs and these efforts must be continued to prevent new HIV infections in the country.展开更多
Background: HIV infected individuals are at increased risk of developing psychiatric comorbidities, particularly depression. Coping with a disease associated with significant morbidity, mortality and financial stress ...Background: HIV infected individuals are at increased risk of developing psychiatric comorbidities, particularly depression. Coping with a disease associated with significant morbidity, mortality and financial stress is likely to result in psychiatric morbidity even among caregivers, especially family members. However, there is scarcity of such data in HIV uninfected caregiver spouses. Material and Methods: Beck Depression Inventory (BDI-II), a diagnostic tool that measures depressive symptoms, was administered to HIV uninfected caregiver spouses of HIV infected individuals (n = 55) and HIV seronegative individuals from general population (n = 63) with similar demographic profile. Chisquare test was used for categorical data. Results: Caregiver spouses exhibited higher depressive symptoms on the BDI-II (mean score 5.25 vs. 3.03;p = 0.029) as compared to others. The scores tended to be higher on the majority of the items, with sadness (p = 0.032), punishment feeling (p = 0.024) and crying (p = 0.037) being statistically significant. Conclusions: Our results indicate that it is important to address the mental health needs of the spouses of HIV infected individuals as they may play a major role in their care and support in the Indian展开更多
To the Editor:Cardiovascular disease(CVD)has become the leading cause of mortality in people living with human immunodeficiency virus(PLWH).[1]Existing data on cardiac dysfunction in PLWH on long-term combination anti...To the Editor:Cardiovascular disease(CVD)has become the leading cause of mortality in people living with human immunodeficiency virus(PLWH).[1]Existing data on cardiac dysfunction in PLWH on long-term combination antiretroviral therapy(cART)mostly come from North America and Europe,[2,3]with limited information on Asian PLWH.Therefore,it is imperative to perform cardiac evaluations on those PLWH from a global health perspective,which will facilitate a better understanding of the changing nature of human immunodeficiency virus(HIV)-related CVD with the application of cART.This study aimed to determine echocardiographic abnormalities’prevalence in Chinese PLWH on long-term cART,compared with ART-na飗e PLWH and uninfected controls.展开更多
Background: Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achie...Background: Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen.Methods: This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People’s Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and analyzed.Results: Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (Q_(1)-Q_(3): 24.0-34.0 years);of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. Of those, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against protease inhibitor (PI) only.Conclusions: Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote HIV-preventive strategies in the MSM population. The extremely high prevalence of TDR mutation in this population implies the need for future pretreatment drug resistance surveillance.展开更多
Mutations in SARS-CoV-2 variants of concern(VOCs)have enhanced transmissibility and immune evasion with respect to current vaccines and neutralizing antibodies(NAbs).How naturally occurring spike mutations affect the ...Mutations in SARS-CoV-2 variants of concern(VOCs)have enhanced transmissibility and immune evasion with respect to current vaccines and neutralizing antibodies(NAbs).How naturally occurring spike mutations affect the infectivity and antigenicity of VOCs remains to be investigated.The entry efficiency of individual spike mutations was determined in vitro using pseudotyped viruses.BALB/c mice were immunized with 2-dose DNA vaccines encoding B.1.1.7,B.1.351,B.1.1.529 and their single mutations.Cellular and humoral immune responses were then compared to determine the impact of individual mutations on immunogenicity.In the B.1.1.7 lineage,Del69–70 and Del 144 in NTD,A570D and P681H in SD1 and S982A and D1118H in S2 significantly increased viral entry,whereas T716I resulted in a decrease.In the B.1.351 lineage,L18F and Del 242–244 in the NTD,K417N in the RBD and A701V in S2 also increased viral entry.S982A weakened the generation of binding antibodies.All sera showed reduced cross-neutralization activity against B.1.351,B.1.617.2(Delta)and B.1.1.529(Omicron BA.1).S982A,L18F,and Del 242–244 hindered the induction of cross-NAbs,whereas Del 69–70,Del144,R246I,and K417N showed the opposite effects.B.1.351 elicited adequate broad cross-NAbs against both B.1.351 and B.1.617.2.All immunogens tested,however,showed low neutralization against circulating B.1.1.529.In addition,T-cell responses were unlikely affected by mutations tested in the spike.We conclude that individual spike mutations influence viral infectivity and vaccine immunogenicity.Designing VOC-targeted vaccines is likely necessary to overcome immune evasion from current vaccines and neutralizing antibodies.展开更多
The pandemic of human immunodeficiency virus type one(HIV-1),the major etiologic agent of acquired immunodeficiency disease(AIDS),has led to over 33 million people living with the virus,among which 18 million are wome...The pandemic of human immunodeficiency virus type one(HIV-1),the major etiologic agent of acquired immunodeficiency disease(AIDS),has led to over 33 million people living with the virus,among which 18 million are women and children.Until now,there is neither an effective vaccine nor a therapeutic cure despite over 30 years of efforts.Although the Thai RV144 vaccine trial has demonstrated an efficacy of 31.2%,an effective vaccine will likely rely on a break-through discovery of immunogens to elicit broadly reactive neutralizing antibodies,which may take years to achieve.Therefore,there is an urgency of exploring other prophylactic strategies.Recently,antiretroviral treatment as prevention is an exciting area of pro-gress in HIV-1 research.Although effective,the im-plementation of such strategy faces great financial,political and social challenges in heavily affected re-gions such as developing countries where drug re-sistant viruses have already been found with growing incidence.Activating latently infected cells for thera-peutic cure is another area of challenge.Since it is greatly difficult to eradicate HIV-1 after the establish-ment of viral latency,it is necessary to investigate strategies that may close the door to HIV-1.Here,we review studies on non-vaccine strategies in targeting viral entry,which may have critical implications for HIV-1 prevention.展开更多
Antigen-presenting cells(APCs)may be resistant to SARS-CoV-2 infection but still contribute to viral pathogenesis.Lectins such as sialic acid-binding Ig-like lectin 1(Siglec-1/CD169)mediate the attachment of viruses t...Antigen-presenting cells(APCs)may be resistant to SARS-CoV-2 infection but still contribute to viral pathogenesis.Lectins such as sialic acid-binding Ig-like lectin 1(Siglec-1/CD169)mediate the attachment of viruses to APCs.Here,we show that APCs effectively capture SARS-CoV-2 within compartments via recognition of Siglec-1.This receptor interacts with sialylated gangliosides on membranes of SARS-CoV-2 variants.展开更多
文摘Case Letter Severe trauma has high morbidity and mortality rates,being the leading cause of death in young adults.Among all traumas,tra ffi c injuries are particularly lethal.^([1-2]) The injury severity score(ISS) can be used to assess trauma severity,with ISS of<9,9–15,16–24,and≥25 indicating minor,moderate,severe,and critical trauma,respectively.The ISS is correlated with mortality,morbidity,and hospitalization duration after injury.^([3-4]) Here,we report one patient who was admitted to our emergency intensive care unit(EICU) due to traumatic liver rupture and traumatic myocardial infarction complicated with inferior vena cava(IVC) thrombosis.
基金Supported by the Projects of Ministry of Science and Tech-nology for 10th Five-year Plan (2001BA701A18)
文摘Objective： To assess the efficacy and safety of Zhongyan-4 （中研-4号, ZY-4, a Chinese herbal preparation worked out according to the therapeutic principle of supplementing qi, nourishing Yin, clearing heat and detoxication） in treating HIV/AIDS patients in the early or middle stage. Methods： Adopted was randomized double-blinded and placebo-parallel-controlled method, with 72 HIV/AIDS patients randomly divided into the ZY-4 group （36 patients） treated with ZY-4 and the control group （36 patients） treated with placebo. The treatment course was six months. The index of OD4^＋, OD8^＋ counts, body weight, clinical symptom scoring were estimated at 4 time points （0, 1, 3 and 6 month in the course）, and also the viral load before and after treatment. The whole course of observation was completed in 63 patients, 30 in the ZY-4 group and 33 in the control group. Results： OD4^＋ count in the ZY-4 group got elevated by 7.70 4±150.96/mm^3 on average, while that in the control group lowered by 27.33 4±85.28 /mm^3 . Fifteen out of the 30 patients in the ZY-4 group had their OD4^＋ count increased, which was evidently much higher than that in the control group （8/33, P〈0. 05）, suggesting that the efficacy of ZY-4 is superior to that of placebo in elevating OD4^＋ count. Moreover, ZY-4 showed actions in elevating OD45RA^＋ and OD8^＋ count, reducing HIV virus load, improving clinical symptom/sign and increasing body weight of patients. No obvious adverse reaction was found in the clinical trial. Conclusion： ZY-4 has an immunity-protective and/or rebuilding function in HIV/AIDS patients in the early and middle stage, and also shows effects in lowering viral load, increasing body weight and improving symptoms and signs to a certain degree.
基金supported by HKU-UDF,HKSARG FHB/RFCID09080772the National Basic Research Program of China(2008ZX10001-011 and 2008ZX10001-015)
文摘Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS).After over 26 years of efforts,there is still not a therapeutic cure or an effective vaccine against HIV/AIDS.The clinical management of HIV-1 infected people largely relies on antiretroviral therapy (ART).Although highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients,the huge burden of ART in developing countries,together with the increasing incidence of drug resistant viruses among treated people,calls for continuous efforts for the development of anti-HIV-1 drugs.Currently,four classes of over 30 licensed antiretrovirals (ARVs) and combination regimens of these ARVs are in use clinically including:reverse transcriptase inhibitors (RTIs) (e.g.nucleoside reverse transcriptase inhibitors,NRTIs;and non-nucleoside reverse transcriptase inhibitors,NNRTIs),protease inhibitors (PIs),integrase inhibitors and entry inhibitors (e.g.fusion inhibitors and CCR5 antagonists).Here,we intend to provide updated information of currently available antiretroviral drugs for ART to promote the development of novel anti-HIV-1 drugs.
文摘The hepatitis C virus(HCV) infects approximately 3% of the world population or more than 185 million people worldwide. Each year, an estimated 350000-500000 deaths occur worldwide due to HCV-associated diseases including cirrhosis and hepatocellular carcinoma. HCV is the most common indication for liver transplantation in patients with cirrhosis worldwide. HCV is an enveloped RNA virus classified in the genus Hepacivirus in the Flaviviridae family. The HCV viral life cycle in a cell can be divided into six phases:(1) binding and internalization;(2) cytoplasmic release and uncoating;(3) viral polyprotein translation and processing;(4) RNA genome replication;(5) encapsidation(packaging) and assembly; and(6) virus morphogenesis(maturation) and secretion. Many host factors are involved in the HCV life cycle. Chaperones are an important group of host cytoprotective molecules that coordinate numerous cellular processes including protein folding, multimeric protein assembly, protein trafficking, and protein degradation. All phases of the viral life cycle require chaperone activity and the interaction of viral proteins with chaperones. This review will present our current knowledge and understanding of the role of chaperones in the HCV life cycle. Analysis of chaperones in HCV infection will provide further insights into viral/host interactions and potential therapeutic targets for both HCV and other viruses.
文摘Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden restricted to the Western Pacific and sub-Saharan African regions.Amidst this is a growing burden of metabolic syndrome(MetS)worldwide.A disproportionate co-burden of human immunodeficiency virus(HIV)infection is also reported in sub-Saharan Africa,which poses a further risk of liver-related morbidity and mortality in the region.We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection.While the mechanistic association between CHB and MetS remains poorly resolved,the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB.Among HIV infected individuals,MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy(ART).It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection.However,this remains to be explored through rigorous longitudinal studies,especially in sub-Saharan Africa.Ultimately,there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV coinfected individuals.
文摘The purpose of this study was to identify factors affecting the time to development of tuberculosis in the presence of competing risks. In this case death before developing tuberculosis was deemed a competing risk because it altered the occurrence of the outcome of interest being time to development of tuberculosis from baseline. We used data from a randomized longitudinal clinical trial study called the “Tshepo” study. The “Tshepo” study was a 3-year randomized clinical study following 650 ART-naïve adults (69.4% female) from Botswana who initiated first-line NNRTI-based ART. Participants were assigned in equal proportions (in an open-label, unblinded fashion) to one of 6 initial treatment arms and one of two adherence arms using permuted block randomization. Randomization was stratified by CD4+ cell count (less than 200 cells/mm<sup>3</sup>, 201 - 350 cells/mm<sup>3</sup>) and by whether the participants had an adherence assistant. Classical methods such as the Kaplan-Meier method and standard Cox proportional hazards regression were used to analyze survival data ignoring the competing event(s) which may have been inappropriate in the presence of competing risks. The idea was to use competing risk models to investigate how different treatment regimens affect the time to the development of TB and compare the results to those obtained using the classical survival analysis model which does not account for competing risks. Amongst 38 patients who died 15.8% of them developed tuberculosis whilst 84.2% of those who died did not develop the outcome of interest. The hazard ratio of treatment C was 1.069 implying that the risk of developing TB in patients taking treatment C is about 6.9% higher compared to those taking treatment A having adjusted for baseline age, baseline BMI, baseline CD4, Hemoglobin and gender. Similarly, after accounting for competing risks the hazard ratio for treatment C was about 1.89 implying that the risk of developing TB amongst those taking treatment C was about 89% higher as compared to those taking treatment A. From the obtained results it was thus concluded that the standard Cox model of time to event data in the presence of competing risks underestimated the hazard ratios hence when dealing with data with multiple failure events it is important to account for competing events.
文摘Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K(HML6) and HERV-K(HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K(HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are twoedged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.
文摘Background: India has scaled up ART programme very rapidly. Though there are reports on retention of patients in the national programme, data on transfer out patients within the ART centers are scanty in India. Methods: This is a retrospective study of patients receiving antiretroviral treatment between January 2006 and July 2013. The patients who were transferred out from the ART center at National AIDS Research Institute in Pune were included in the study. The data on whether they reached the respective ART centers were collected either by making telephonic calls to the patients and/or to the respective ART centers. Results: Of the total 3015 patients ever started on treatment from the ART center, 158 (5.24%) were transferred out to other ART centers. Of these, 123 (77.8%) patients reached other centres and they were “transferred in”. However, 15 (9.5%) did not reach to respective ART centers and information could not be obtained for 20 (12.7%) transferred out patients. The analysis showed that those who were not living with their partners were 4.53 times more likely to not to reach the preferred ART centre after taking transfer [OR, 95% CI: (1.24 - 16.51), p = 0.022]. Conclusion: Our data suggest that significant number of transfer out patients is lost in HIV treatment cascade. Considering the total PLHIV on treatment in the country, this group adds significantly to the burden of lost to follow up patients. It is important to strengthen the system of tracking the transfer out patients in the programme which will help in patching an important leak in the cascade of HIV care.
文摘AIM： To undertake analysis of hepatitis A viral load, alanine aminotransferase （ALT）, and viral genotypes with duration of viremia, and to correlate these parameters with CD4^＋/ CD8^＋ lymphocyte populations that control cell-mediated immunity. METHODS： Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus （HAV） RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. RESULTS： Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis （s-AH） and the remainder had a self-limited acute hepatitis A （AHA）, with one patient with fulminant disease （encephalopathy Grade IV） dying on the 4^th d. The ALT level was significantly higher both in AHA （1070.9±894.3; P = 0.0014） and s-AH （1713.9±886.3; P = 0.001） compared to normal controls （23.6±7.2）. The prothrombin time in s-AH patients （21.0 ±2.0; P=0.02） was significantly higher than in AHA （14.3±1.1;P = 0.44）. The CD4^＋/CD8^＋ ratio in AHA patients （1.17 ＋ 0.11; P = 0.22） and s-AH （0.83 ＋ 0.12; P = 0.0002） were lower than seen in normal healthy controls （1.52）. Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15TM or 30^th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and AIT values collected during the entire course of the selflimited infection were directly correlated but this was not the case for s-AH patients.CONCLUSION： Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.
文摘Under India’s National AIDS Control Program (NACP), WHO recommended strategy of using three rapid tests is adopted for diagnosis of HIV in an asymptomatic individual. Since the NACP has a stringent kit evaluation procedure and due to the availability of newer third generation Rapid Diagnostic Tests (RDTs) it may be possible to adapt two test strategy for HIV diagnosis instead of the recommended three test strategy. The authors reviewed programmatic data on HIV testing to explore whether use of two rapid tests for HIV diagnosis as against three tests could be a feasible approach without compromising the quality and readability of testing. Data on the HIV diagnosis performed on serum specimens collected for the period of one year (2011-12) from 82 Integrated Testing and Counselling Centers (ICTCs) or Prevention of Parent to Child Transmission Centers (PPTCTs) associated with State reference Laboratories (SRLs) was analysed. Out of 654258 results that were analysed 25168 (3.84%) specimens were positives. It was observed that both two and three test algorithms provided similar results for majority (>99%) of the HIV positive specimens. Discordance was observed in labelling of specimen with inconclusive status (N = 21), however the true status of these samples could not be obtained. The analysis indicated that the use of two test algorithm will have programmatic benefits in terms of reduced financial burden to the programme and ease of procurement, shipment and storage before and after distribution without comprising the quality of the testing. The prospective study would confirm this observation.
文摘This paper examines whether truckers have been over-stigmatized as HIV carriers in the country. Data were taken from cross-sectional surveys of clients of female sex workers conducted in 2006-2007 in 12 districts of the country. A total 4822 clients of female sex workers were covered in the survey. Low-income skilled/semi-skilled men, including non-agricultural/casual labor, and petty businessmen/small shop owners, have the largest share in the clients’ population. There was no significant difference between truckers and other sub-group of clients’ population in terms of consistent condom use with female sex workers and prevalence of HIV or STI. These evidences suggest that the contribution of truckers in HIV epidemic in India might to similar to other sub-groups of clients’ population. Thus, truckers might have been over-stigmatized as HIV carriers in the country. However, there is no doubt that truckers constitute an extremely important target group for the HIV prevention programs and these efforts must be continued to prevent new HIV infections in the country.
文摘Background: HIV infected individuals are at increased risk of developing psychiatric comorbidities, particularly depression. Coping with a disease associated with significant morbidity, mortality and financial stress is likely to result in psychiatric morbidity even among caregivers, especially family members. However, there is scarcity of such data in HIV uninfected caregiver spouses. Material and Methods: Beck Depression Inventory (BDI-II), a diagnostic tool that measures depressive symptoms, was administered to HIV uninfected caregiver spouses of HIV infected individuals (n = 55) and HIV seronegative individuals from general population (n = 63) with similar demographic profile. Chisquare test was used for categorical data. Results: Caregiver spouses exhibited higher depressive symptoms on the BDI-II (mean score 5.25 vs. 3.03;p = 0.029) as compared to others. The scores tended to be higher on the majority of the items, with sadness (p = 0.032), punishment feeling (p = 0.024) and crying (p = 0.037) being statistically significant. Conclusions: Our results indicate that it is important to address the mental health needs of the spouses of HIV infected individuals as they may play a major role in their care and support in the Indian
基金supported by the Special Research Fund for the Central High-level Hospitals of Peking Union Medical College Hospital(No.2022-PUMCH-D-008)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(No.2021-I2M-1-037)the National Key Technologies R&D Program for the 13th Five-year Plan(No.2017ZX102021-001).
文摘To the Editor:Cardiovascular disease(CVD)has become the leading cause of mortality in people living with human immunodeficiency virus(PLWH).[1]Existing data on cardiac dysfunction in PLWH on long-term combination antiretroviral therapy(cART)mostly come from North America and Europe,[2,3]with limited information on Asian PLWH.Therefore,it is imperative to perform cardiac evaluations on those PLWH from a global health perspective,which will facilitate a better understanding of the changing nature of human immunodeficiency virus(HIV)-related CVD with the application of cART.This study aimed to determine echocardiographic abnormalities’prevalence in Chinese PLWH on long-term cART,compared with ART-na飗e PLWH and uninfected controls.
基金This study was supported by the Shenzhen Science and Technology Program (Nos. JCYJ20210324131610027, JCYJ20210324131605015, JCYJ20190809170011461, and JCYJ20210324132012035)。
文摘Background: Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen.Methods: This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People’s Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and analyzed.Results: Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (Q_(1)-Q_(3): 24.0-34.0 years);of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. Of those, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against protease inhibitor (PI) only.Conclusions: Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote HIV-preventive strategies in the MSM population. The extremely high prevalence of TDR mutation in this population implies the need for future pretreatment drug resistance surveillance.
基金This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund(C7156-20GF to ZC and C1134-20GF)the Research Grants Council General Research Fund(GRF17117422)+5 种基金the Hong Kong Health and Medical Research Fund(COVID1903010-Project 4,COVID190123 and 19181012)the Shenzhen Science and Technology Program(JSGG20200225151410198 and JCYJ20210324131610027)HKU Development Fund and LKS Faculty of Medicine Matching Fund to AIDS Institutethe Hong Kong Innovation and Technology Fundthe Hong Kong Health@InnoHK,Innovation and Technology Commissiona generous donation from the Friends of Hope Education Fund.ZC’s team was also partly supported by the Theme-Based Research Scheme(T11-706/18-N and T11-709/21-N).
文摘Mutations in SARS-CoV-2 variants of concern(VOCs)have enhanced transmissibility and immune evasion with respect to current vaccines and neutralizing antibodies(NAbs).How naturally occurring spike mutations affect the infectivity and antigenicity of VOCs remains to be investigated.The entry efficiency of individual spike mutations was determined in vitro using pseudotyped viruses.BALB/c mice were immunized with 2-dose DNA vaccines encoding B.1.1.7,B.1.351,B.1.1.529 and their single mutations.Cellular and humoral immune responses were then compared to determine the impact of individual mutations on immunogenicity.In the B.1.1.7 lineage,Del69–70 and Del 144 in NTD,A570D and P681H in SD1 and S982A and D1118H in S2 significantly increased viral entry,whereas T716I resulted in a decrease.In the B.1.351 lineage,L18F and Del 242–244 in the NTD,K417N in the RBD and A701V in S2 also increased viral entry.S982A weakened the generation of binding antibodies.All sera showed reduced cross-neutralization activity against B.1.351,B.1.617.2(Delta)and B.1.1.529(Omicron BA.1).S982A,L18F,and Del 242–244 hindered the induction of cross-NAbs,whereas Del 69–70,Del144,R246I,and K417N showed the opposite effects.B.1.351 elicited adequate broad cross-NAbs against both B.1.351 and B.1.617.2.All immunogens tested,however,showed low neutralization against circulating B.1.1.529.In addition,T-cell responses were unlikely affected by mutations tested in the spike.We conclude that individual spike mutations influence viral infectivity and vaccine immunogenicity.Designing VOC-targeted vaccines is likely necessary to overcome immune evasion from current vaccines and neutralizing antibodies.
基金supported by Hong Kong Research Grant Council RGC762209/762811/762712,Hong Kong Research for the Control of Infectious Diseases(RFCID)12110952 and Hong Kong AIDS Trust Fund MSS183Rby the University De-velopment Fund and LKSFM Matching Fund of the University of Hong Kong to AIDS Institute and by the National Science and Tech-nology Major Project 2012ZX10001-009.The authors declare no conflict of interest.
文摘The pandemic of human immunodeficiency virus type one(HIV-1),the major etiologic agent of acquired immunodeficiency disease(AIDS),has led to over 33 million people living with the virus,among which 18 million are women and children.Until now,there is neither an effective vaccine nor a therapeutic cure despite over 30 years of efforts.Although the Thai RV144 vaccine trial has demonstrated an efficacy of 31.2%,an effective vaccine will likely rely on a break-through discovery of immunogens to elicit broadly reactive neutralizing antibodies,which may take years to achieve.Therefore,there is an urgency of exploring other prophylactic strategies.Recently,antiretroviral treatment as prevention is an exciting area of pro-gress in HIV-1 research.Although effective,the im-plementation of such strategy faces great financial,political and social challenges in heavily affected re-gions such as developing countries where drug re-sistant viruses have already been found with growing incidence.Activating latently infected cells for thera-peutic cure is another area of challenge.Since it is greatly difficult to eradicate HIV-1 after the establish-ment of viral latency,it is necessary to investigate strategies that may close the door to HIV-1.Here,we review studies on non-vaccine strategies in targeting viral entry,which may have critical implications for HIV-1 prevention.
基金The authors also acknowledge the crowdfunding initiative#Yomecorono(https://www.yomecorono.com).N.I.-U.is supported by the grant PID2020-117145RB-I00 from the Spanish Ministry of Science and InnovationJ.M.-P.is supported by the grant PID2019-109870RB-I00 from the Spanish Ministry of Science and Innovation and in part also by Grifols.The C.R.laboratory is funded by RTI2018-094445-B100(MCIU/AEI/FEDER,UE)+1 种基金The NHP study was primarily supported by a YNPRC Coronavirus Pilot Research Project Program grant to M.Pa.under award P51 OD11132,Emergent Venture Fast grant program to M.Pa.under awards#2206 and#2144,and William and Lula Pitts Foundation(to M.Pa.)X.M.-T.is supported by the Spanish Ministry of Science and Innovation and the European Regional Development Fund under agreement BES-2017-082900.The funders had no role in the study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Antigen-presenting cells(APCs)may be resistant to SARS-CoV-2 infection but still contribute to viral pathogenesis.Lectins such as sialic acid-binding Ig-like lectin 1(Siglec-1/CD169)mediate the attachment of viruses to APCs.Here,we show that APCs effectively capture SARS-CoV-2 within compartments via recognition of Siglec-1.This receptor interacts with sialylated gangliosides on membranes of SARS-CoV-2 variants.
