Objective To investigate the influence of hepatitis B virus (HBV) infection on efficacy of combined antiretroviral therapy (cART) in patients with acquired immunodeficiency syndrome (AIDS).Methods Seventy-eight subjects with human immunodeficiency virus (HIV)/HBV co-infection and 156 subjects with HIV mono-infection were included.CD4+ T cell count,HIV viral load,HBV-markers and liver functions were routinely tested.The differences in survival rate,as well as immunological and virological responses between the two groups (HIV/HBV co-infection group and HIV mono-infection group) during cART were compared.Categorical data were compared by Chisquare test,measurement data were compared by t test,and measurement data with abnormal distribution were compared by Mann-Whitney test.Results At month 42 of cART,HIV RNA levels and CD4+ T cell counts of the two groups were comparable.However,at month 48,54 and 60 of cART,the immunological and virological responses of HIV/HBV co-infection group were less favorable than those of HIV mono-infection group.At each time point of month 12,24,36,48 and 60 of cART,3 out of 13 subjects with HIV/HBV co-infection maintained hepatitis B e antigen (HBeAg)loss; the HBeAg seroconversion rates were 32.1％ (9/28),50.0％ (14/28),53.6％ (15/28),64.3％ (18/28) and 71.4％ (20/28),respectively (x2 =10.189,P=0.037) ; HBV DNA negative rates were 95.1％ (39/41),82.9％ (34/41),68.3％ (28/41),43.9％ (18/41) and 43.9％ (18/41),respectively (x2 =29.982,P=0.000); liver dysfunction rate was 32.1 ％ (25/78),51.4％ (38/74),33.8％ (22/65),47.9％ (23/48) and 6.7％ (3/45),respectively (x2 =28.053,P=0.000).Mortalities in HIV/HBV co-infected and HIV mono-infected individuals were 24.4％ (19/78) and 5.1 ％ (8/156),respectively (x2 =18.841,P＜0.01).Sixteen out of the 19 deaths (84.2 ％) in HIV/ HBV co-infected subjects died of end stage liver diseases.Conclusions HBV co-infection diminishes the long term efficacy of cART.End stage liver diseases are the primary cause of death in HIV/HBV co-infected subjects during cART.

Objective:To investigate the epidemic trend and risk change of acquired immunodeficiency syndrome (AIDS) complicated with malignant tumors after combination antiretroviral therapy (cART).Methods:The types of malignant tumors in patients with AIDS at different stages of cART were analyzed among anti-human immunodeficiency virus (HIV)-positive population in Hubei Province screened in National AIDS/HIV prevention and control information system from 1st January, 2004 to 31st December, 2018. The standardized incidence ratios(SIR) of malignant tumors in AIDS patients was analyzed based on the incidence of malignant tumors in the general population in Hubei Province or China in 2013. The changes in risks for development of malignant tumors in AIDS patients at different cART stages from 2004 to 2013 and 2014 to 2018 were compared.Chi-square test was used for statistical analysis.Results:Three hundred and twenty-three out of 22 994 AIDS patients were diagnosed with malignant tumors. Non-Hodgkin lymphoma(NHL) and cervical cancer were most common types in acquired immunodeficiency syndrome-defining cancers (ADC), while liver cancers and lung cancers were the most common types in non-acquired immunodeficiency syndrome-defining cancers (NADC). The overall risk of malignancy in AIDS patients was similar to that in the general population (SIR=1.06, χ2=0.62, P=0.426). However, the risks of Kaposi sarcoma, NHL, Hodgkin lymphoma, cervical cancer, and head and face cancers (excepting nasopharyngeal cancer) in AIDS patients were significantly higher than those in the general population (SIR=834.09, 9.65, 13.33, 5.22 and 2.94, respectively, χ2=11 747.27, 625.54, 56.65, 184.21 and 13.66, respectively, all P<0.01). The risks of lung cancer, colorectal anal cancer, stomach cancer and breast cancer in AIDS patients were significantly lower than those in the general population (SIR=0.33, 0.36, 0.43 and 0.45, respectively, χ2=33.43, 12.84, 9.01 and 7.21, respectively, all P<0.05). The SIR of cervical cancer, liver cancer and colorectal anal cancer from 2014 to 2018 were 4.06, 0.43 and 0.10, respectively, which were significantly lower than those from 2004 to 2013 (7.42, 1.96 and 0.84, respectively). The differences were all statistically significant ( χ2=5.39, 19.52 and 10.86, respectively, all P<0.05). Conclusions:At present, there are no significant differences of the incidences of malignant tumors between AIDS patients and general population, but the tumor types are different. The most common malignant tumors in this region are NHL and cervical cancer, which should be noted that HIV screening among patients with such tumors is conducive to comprehensive treatment to improve the efficacy.

@@

Objective:To summarize the clinical features and survival differences between human immunodeficiency virus (HIV)-positive and HIV-negative cervical cancer patients, and to explore the factors influencing the prognosis.Methods:The clinical data of patients with cervical cancer diagnosed and treated in Zhongnan Hospital of Wuhan University from January 2015 to January 2022 were retrospectively analyzed. There were 46 HIV-positive cases and 587 HIV-negative cases; all 46 HIV-positive patients had squamous cell carcinoma, while 504 HIV-negative patients had squamous cell carcinoma. According to age and clinical staging, 230 HIV-negative squamous cell carcinoma patients were screened to match with 46 HIV-positive squamous cell carcinoma patients according to 1∶5. The clinical features of HIV-positive and HIV-negative patients were compared in all matched patients with pathological type of squamous cell carcinoma; the Kaplan-Meire method was used to analyze the overall survival (OS) and the comparison of OS was made by using log-rank test. Multivariate Cox proportional risk model was used to analyze the independent factors affecting the OS of patients with cervical squamous cell carcinoma.Results:The differences in the age, pathological types, clinical staging between 46 HIV-positive patients and 587 HIV-negative patients were statistically significant (all P < 0.05). There were statistically significant differences in age and clinical staging between 46 HIV-positive squamous cell carcinoma patients and 504 HIV-negative squamous cell carcinoma patients (all P < 0.05). After 1∶5 matching, there were no statistically significant differences in the age, clinical staging between 46 patients with HIV-positive squamous cell carcinoma and 230 patients with HIV-negative squamous cell carcinoma. The OS of HIV-positive patients in the entire group,pathological type of squamous cell carcinoma or after pairing was worse than that of HIV-negative patients (all P < 0.001). The median OS time of HIV-positive patients was 63 months (95% CI 61-109 months), while the median OS time of HIV-negative patients was not reached (95% CI 165-178 months, 164-178 months, 143-173 months, respectively). Multivariate Cox regression analysis showed that clinical staging Ⅲ-Ⅳ was an independent risk factor for OS in patients with cervical squamous cell carcinoma (Ⅲ-Ⅳ vs. Ⅰ-Ⅱ: HR = 1.573, 95% CI 1.032-2.397, P = 0.035); HIV infection was an independent protective factor for OS (HIV-positive vs. HIV-negative: HR = 0.087, 95% CI 0.042-0.182, P < 0.001), indicating that HIV-positive patients had an advantage in OS compared to HIV-negative patients at the same age and clinical staging. Age was not an independent influencing factor for OS ( P > 0.05). Conclusions:The onset age of HIV-positive cervical cancer tends to be younger and the clinical staging is late when patients are diagnosed. HIV-positive patients have poor prognosis.

Objective:To analyze the clinical data of 203 discharged patients with corona virus disease 2019(COVID-19), and to investigate the predictors for the severe cases.Methods:Confirmed COVID-19 cases hospitalized at Zhongnan Hospital of Wuhan University from January 1 to February 1, 2020 were consecutively enrolled, who were divided into severe group and non-severe group.The clinical data of enrolled patients were collected and the clinical manifestations, laboratory results, imaging, treatments and prognosis of patients in the two groups were analyzed. Mann-Whitney U rank sum test and chi-square test were used for statistical analysis. Results:A total of 203 discharged patients with COVID-19 were enrolled. The common clinical manifestations included fever (89.2%, 181/203), dry cough (60.1%, 122/203), chest distress (35.5%, 72/203), shortness of breath(29.1%, 59/203)and myalgia or arthralgia (26.6%, 54/203). The time from disease onset to hospital admission was 5.8 days (1.0 to 20.0 days). Among 203 enrolled patients, 107(52.7%) were divided into severe group and 96(47.3%) were non-severe group. The age in severe group was 60 years (23 to 91 years), which was significantly older than non-severe group (47 years (20 to 86 years)), the difference was statistically significant ( Z=-6.12, P<0.01). There were 63.6%(68/107) patients in severe group with at least one underlying disease, which was significantly more than non-severe group (20.8% (20/96)), the difference was statistically significant ( χ2=37.60, P<0.01). The proportions of patients with increased white blood cells, decreased lymphocytes and albumin, elevated alanine aminotransferase, aspartate aminotransferase, creatinine, lactic acid dehydrogenase, creatine kinase, fasting blood glucose, D-dimer, erythrocyte sedimentation rate, C-reactive protein, interleukin-6, and procalcitonin in severe group were all higher. On admission, 172 patients (84.7%) had bilateral patchy shadows or ground glass opacity in the lungs on chest imaging study, 20(9.9%) presented pleural effusion. Fifty-five cases (27.1%) showed progressions of lung lesions on computed tomography (CT) rescan at an average interval of five days. Among 203 patients, 123(60.6%) were given oxygen therapy upon admission, 107(52.7%) were given short-term glucocorticoid therapy, and 131(64.5%) received antiviral therapy; and 26(12.8%) died. The hospital stay was 11.0 days (1.0 to 45.0 days). Conclusions:Fever is the most common symptoms in COVID-19 patients.Elderly and patients with underlying diseases are risk factors for progression to severe cases. The elderly patients should be strengthened early monitoring, paid attention to the control of underlying diseases, and reduce the occurrence of critical diseases.

The data of patients with HIV/AIDS from Hubei Province during 2004 to 2018 were obtained from the National AIDS Comprehensive Prevention and Control Information System. A total of 22 980 HIV-positive or AIDS patients were followed up for 113 164 person-years and 323 malignant tumors were diagnosed. Non-Hodgkin′s lymphoma (NHL), cervical cancer, liver cancer, lung cancer, and Kaposi sarcoma (KS) accounted for 70.0% (226/323) of all malignant tumors in this population. The average crude incidence and mortality of malignant tumors in HIV-infected patients were 285.43/100 000(269.11/100 000 in males and 325.87/100 000 in females), and 169.67/100 000(184.78/100 000 in males and 132.19/100 000 in females), respectively. The result indicates that the overall cancer incidence and mortality in HIV/AIDS population under widely implementation of combination anti-retroviral therapy (cART) are similar to those in the general population of the region. But the incidence and mortality of AIDS-related tumors such as KS, NHL, HD and cervical cancer are higher than those in general population, and attention should be given to screening of these malignancies in HIV/AIDS population.

Objective:To investigate the feasibility, efficacy and adverse reactions of programmed death-1(PD-1) inhibitors in patients with acquired immunodeficiency syndrome (AIDS) complicated with malignant tumor.Methods:From September 2020 to August 2021, patients with AIDS complicated with malignant tumor in Zhongnan Hospital of Wuhan University were enrolled. Data including basic information, laboratory test results, CD4 + T cell count, human immunodeficiency virus (HIV) viral load were collected. Patients were continuously administered intravenously PD-1 monoclonal antibody until disease progression or intolerant toxicity reaction occurred. Adverse reactions during treatment were recorded.And treatment outcomes were assessed once every 12 weeks after treatment. HIV viral load was measured after treatment once a week for four consecutive times, then once four weeks for two consecutive times, and then once every 12 weeks. Results:Ten patients were included in the study, including seven males and three females, three cases of Hodgkin′s lymphoma, two cases of cervical cancer and hepatocellular carcinoma respectively, one case of non-Hodgkin′s lymphoma, non-small cell lung cancer and anal cancer respectively. There were four patients with CD4 + T cell count of 100 to 200 cells/μL and two patients with CD4 + T cell count lower than 100 cells/μL. All patients had completed at least three cycles of treatment with PD-1 monoclonal antibody, HIV viral load remained lower than 20 copies /mL. Three cases achieved complete response and three cases achieved partial response. Adverse reactions were cutaneous capillary endothelial proliferation (CCEP) (seven cases), major bleeding (three cases), and hearing impairment (one case). Conclusions:PD-1 inhibitor has no adverse effect on the continuous suppression of HIV viral load and has an effect on tumor control, so it is a viable choice in AIDS patients complicated with tumor. However, due to its considerable adverse reactions, multidisciplinary cooperation is needed to reduce the risk of complications and deal with serious complications.

Objective:To investigate the pathogen spectrum of acquired immunodeficiency syndrome (AIDS) patients with pulmonary opportunistic infections in the local area, and to evaluate the clinical application of metagenomic next-generation sequencing (mNGS) in these patients.Methods:From January to December 2021, AIDS patients with pulmonary infections admitted to Zhongnan Hospital of Wuhan University were enrolled. Their bronchoalveolar lavage fluid (BALF) was subjected to mNGS and coventional pathogen detection.Routine pathogen detection methods included smear, culture, polymerase chain reaction (PCR), and immunochromatographic colloidal gold. Fisher′s exact probability method was used for statistical analysis.Results:A total of 69 patients were included, and all of them were tested positive for mNGS. Among them, 53 cases (76.8%) were positive for fungi and viruses, 40 cases (58.0%) were positive for bacteria (excluding Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM)), six cases were positive for MTB, 11 cases were positive for NTM, and seven cases were positive for other pathogens. Mixed infections with two or more pathogens were found in 89.9%(62/69) of the patients. Among the conventional pathogen detections of BALF, 79.7%(55/69) of the patients were positive for pathogens, including 42 cases positive for Pneumocystis jirovecii PCR, 16 cases positive for BALF culture, nine cases positive for MTB PCR, and five cases positive for Cryptococcus antigen. The total detection rate of mNGS was 100.0%(69/69), which was higher than that of the conventional pathogen detection rate of 79.7%(55/69), and the difference was statistically significant (Fisher′s exact probability method, P<0.001). The specificity of mNGS detection was 88.4%. Combining clinical and two detection methods, the top five pathogens were Pneumocystis jirovecii (62.3%(43/69)), Candida (29.0%(20/69)), MTB (20.3%(14/69)), NTM and Talaromyces marneffei (15.9%(11/69), each). Fifty-three patients (76.8%) had co-infection with virus. Conclusions:The main cause of pulmonary infection in AIDS patients in this area is mixed infection, and Pneumocystis jirovecii is the most common pathogen. mNGS could significantly improve the pathogen detection rate in AIDS patients with pulmonary infections.