Association of Body Composition and Other Clinical Factors with Incomplete Immune Response after Highly Active Antiretroviral Therapy.

Objective To explore whether baseline body composition and other clinical factors are associated with incomplete immune response after highly active antiretroviral therapy(HAART)in Chinese men with human immunodeficiency virus(HIV)or acquired immunodeficiency syndrome(AIDS).Methods A retrospective study was conducted among HIV/AIDS male patients who achieved viral suppression(maintained HIV-1 RNA levels<400 copies/ml)after a year of HAART between 2007 and 2015.Clinical,immunological,and virological data were collected from patients' files,including weight,height,and whole body composition measured within one month prior to staring HAART.Body mass index(BMI),lean mass index(LMI),fat mass index(FMI),and body bone mineral content/height were adjusted by height.According to whether the patients experienced incomplete immune responses(CD4 cell count<350 cells/µl)after a year of HAART,the patients were divided into two groups:the complete immune response(CD4 cell count≥350 cells/µl)and the incomplete immune response(CD4 cell count<350 cells/µl),respectively.Student's t test,chi-square test,and Wilcoxon rank test were used to assess differences between these two groups.Multiple Logistic regression analysis was used to assess factors associated with an incomplete immune response in patients with sustained viral suppression.Results Totally 84 HIV/AIDS male patients with viral suppression were included in this study.There were statistical differences between these two groups in terms of age(Z=-2.479,P=0.013),baseline BMI(t=2.030,P=0.045),LMI(t=2.200,P=0.029),and CD4 cell count(Z=6.416,P=0.000).However,there was no statistical differences in viral load,FMI,body bone mineral content/height,HAART duration,and HAART regimen(all P>0.05).BMI[OR=0.742,95% confidence interval(CI)=0.554-0.993,P=0.044],LMI(OR=0.459,95% CI=0.249-0.844,P=0.012),HAART duration(OR=10.161,95% CI=1.110-93.052,P=0.040),baseline CD4 cell count(OR=80.051,95% CI=8.396-762.563,P=0.000)were significantly associated with incomplete immune response.Age(OR=1.497,95% CI=0.213-10.505,P=0.685),viral load(OR=0.333,95% CI=0.071-1.572,P=0.164),FMI(OR=0.797,95% CI=0.546-1.164,P=0.240),body bone mineral content/height(OR=1.145,95% CI=0.037-35.676,P=0.938)and HAART regimen(OR=0.430,95% CI=0.159-1.159,P=0.095)were not associated with incomplete immune response.Conclusions Baseline CD4 cell count and HAART duration may affect immune response.Patients with higher baseline BMI or higher LMI may be less likely to develop incomplete immune response.Baseline FMI and body bone mineral content/height ratio are not associated with incomplete immune response.

[A clinical analysis of AIDS-related non-Hodgkin lymphoma in 5 patients and review of literature].

OBJECTIVE: To analyze the clinical characteristics of AIDS-related non-Hodgkin lymphoma (ARL) and review relative literature for the diagnosis and treatment of ARL. METHOD: The clinical data of ARL patients admitted to Peking Union Medical College Hospital from April 2009 to April 2011 were retrospectively analyzed. RESULTS: Five male ARL patients aged 32 to 65 years old were included in this retrospective study. Among them, two patients were found to be HIV-positive for the first time, three were on regular highly active anti-retroviral therapy (HAART) for 7 - 8 months before the emergence of lymphoma-related symptoms. CD(4)(+) T cell count was (69 - 232) × 10(6)/L at presentation. Two patients firstly presented with sore throat and throat ulcer, one with cervical nodules, one with pelvic mass, one with fever and edema in right thigh. Through pathological analysis, four patients had B cell-originated lymphoma, with one Burkitt lymphoma and three diffuse large B cell lymphomas; one patient had T-cell lymphoma. Four patients were treated with chemotherapy, with one complete remission, one relapse, one non-response, and one death. One patient had radiotherapy only and had progressed disease. Bone marrow suppression and gastrointestinal disturbance were the main adverse effects of chemotherapy. CONCLUSIONS: Lymphoma should be considered in any HIV-infected patients presented with unexplainable adenopathy, recurrent sore throat or throat ulcer, or fever of unknown origin. Biopsy should be rigorously carried out. Appropriate chemotherapy, together with HAART, may improve the prognosis greatly.

[The impact of highly active antiretroviral therapy on bone mineral density in human immunodeficiency virus infected patients].

OBJECTIVE: To evaluate the influence of highly active antiretroviral therapy (HAART)on bone mineral density(BMD) of human immunodeficiency virus (HIV) infected patients and correlating clinical factors. METHODS: The clinical data from 2007 to 2008 were analyzed, including 50 patients treated with HAART (named treated group), 12 HIV-infected antiretroviral-naive patients (named untreated group) and 20 healthy people (named control group). Lumbar, femoral neck, femur, femoral greater trochanter and whole body BMD were measured by dual energy X-ray absorptiometry. The data were respectively analyzed. RESULTS: There were 19(38.0%) patients with osteopenia and 1 (2.0%) patient with osteoporosis in the treated group. There were 6 (50.0%) patients with osteopenia and 2 (16.7%) patient with osteoporosis in the untreated group. There were 5 (25.0%) patients with osteopenia, no one with osteoporosis in the control group. The prevalence of osteopenia/osteoporosis was statistically higher in the untreated group than that in the control group (P=0.02). The BMD of femur, femoral neck and greater trochanter [(0.97±0.14), (0.91±0.13), (0.76±0.12) g/cm2] in the HIV-infected group (including the treated and untreated group) were significantly lower than that in the control group [(1.04±0.12), (0.98±0.14), (0.84 ± 0.11) g/cm2, P<0.05]. There were no significantly differences in the BMD between the untreated group and the treated group. In the treated group, osteopenia/osteoporosis correlated with body weight less than 60 kg (r=0.074, P=0.004) and the viral load before HAART (r=5.103, P=0.021). CONCLUSIONS: The prevalence of osteopenia and osteoporosis in antiretroviral-naive HIV-infected patients is higher. The BMD of HIV-infected patients are reduced compared with the healthy people. The BMD is similar among HIV-infected patients irrespective of antiretroviral treatment. Body weight less than 60 kg and the viral load before HAART are the risk factors of osteopenia/osteoporosis for the HIV-infected antiretroviral patients.

[Clinical features of respiratory failure secondary to hypothyroidism].

OBJECTIVE: To explore the clinical features of respiratory failure secondary to hypothyroidism. METHOD: We retrospectively analyzed the clinical data of 4 patients with respiratory failure secondary to hypothyroidism. RESULTS: Respiratory failure secondary to hypothyroidism usually happened in the aged patients, presenting as myxedema, disturbance of consciousness, anemia, and hyponatrium. Respiratory symptoms were rare. Type II respiratory failure might occur as disease progressed. The clinical presentation of hypothyroidism was atypical and easily neglected. The hypoxia and hypercapnia ameliorated after thyroid hormone therapy. CONCLUSION: Hypothyroidism is a rare reason of respiratory failure. The prognosis is good after hormone therapy and mechanical ventilation.

Baseline Naive CD4+ T-cell Level Predicting Immune Reconstitution in Treated HIV-infected Late Presenters.

BACKGROUND: Among HIV-infected patients initiating antiretroviral therapy (ART), early changes in CD4+ T-cell subsets are well described. However, HIV-infected late presenters initiating treatment present with a suboptimal CD4+ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events. Therefore, factors associated with CD4+ T-cell reconstitution need to be determined in this population, which will allow designing effective immunotherapeutic strategies. METHODS: Thirty-one adult patients with baseline CD4+ T-cell count <350 cells/mm3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing, China, from October 2002 to September 2013. Changes in T-cell subsets and associated determinants were measured. RESULTS: Median baseline CD4+ T-cell count was 70 cells/mm3. We found a biphasic reconstitution of T-cell subsets and immune activation: a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years. Baseline CD4+ T-cell count >200 cells/mm3 in comparison to CD4+ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution (77.8% vs. 27.3% respectively; P = 0.017) and normalized CD4/CD8 ratio. We showed that the baseline percentage of naive CD4+ T-cell was a predictive marker for complete immune reconstitution (area under receiver operating characteristic curve 0.907), and 12.4% as cutoff value had a sensitivity of 84.6% and a specificity of 88.2%. CONCLUSIONS: Baseline naive CD4+ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy. Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.

Prevalence of thrombocytopenia among Chinese adult antiretroviral-naïve HIV-positive patients.

BACKGROUND: The prevalence of thrombocytopenia among Chinese antiretroviral therapy (ART)-naïve HIV-infected adults has not been well-described. The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-naïve HIV-infected adults. METHODS: We performed a cross-sectional study of Chinese adult ART-naïve HIV-infected patients from September 2005 through August 2014. Socio-demographic variables and laboratory results including platelets, CD4+ cell count, and viral load were obtained from medical records. Factors and outcomes associated with thrombocytopenia were assessed using logistic regression. RESULTS: A total of 1730 adult ART-naïve HIV-infected patients was included. The mean age was 38 years. The prevalence of thrombocytopenia was 4.5%. There were significant differences in the prevalence of thrombocytopenia between patients <30 years of age (2.8%) and 30-39 years (4.0%) compared with patients greater than 50 years (7.0%) (P = 0.006 and P = 0.044, respectively). The prevalence of thrombocytopenia was also significantly different between patients with CD4+ counts of 200-349 cells/mm 3 (3.3%) and >350 cells/mm 3 (2.8%) compared with patients with CD4+ counts of 50-199 cells/mm 3 (7.1%) (P = 0.002 and P = 0.005, respectively). The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab) seropositivity (10.2% for HCV-Ab positive vs. 3.9% for HCV-Ab negative, P = 0.001). We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection: Blood transmission (10.7%) versus men who have sex with men (3.9%) (P = 0.002) and versus heterosexual transmission (3.9%) (P = 0.001). In binary logistic regression analyses, age ≥ 50 years, HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm 3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]: 1.167, 5.281, P = 0.018), 2.091 (95% CI: 1.078, 4.055, P = 0.029) and 2.259 (95% CI: 1.028, 4.962, P = 0.042), respectively. CONCLUSIONS: Thrombocytopenia is not common among adult ART-naïve HIV-infected patients in China. Older age (age over 50 years), HCV-Ab positivity and lower CD4+ cell count are associated with an increased risk of thrombocytopenia. Therefore, early diagnosis and treatment of thrombocytopenia in these patients are necessary.

Impact of baseline CD4(+) T cell counts on the efficacy of nevirapine-based highly active antiretroviral therapy in Chinese HIV/AIDS patients: a prospective, multicentric study.

BACKGROUND: CD4(+) T cell counts have been used as the indicator of human immunodeficiency virus type 1 (HIV-1) disease progression and thereby to determine when to start highly active antiretroviral therapy (HAART). Whether and how the baseline CD4(+) T cell count affects the immunological and viral responses or adverse reactions to nevirapine (NVP)-containing HAART in Chinese HIV-1 infected adults remain to be characterized. METHODS: One hundred and ninety-eight HIV-seropositive antiretroviral therapy (ART)-naive subjects were enrolled into a prospective study from 2005 to 2007. Data were analyzed by groups based on baseline CD4(+) T cell counts either between 100 - 200 cells/microl or 201 - 350 cells/microl. Viral responses, immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 52, 68, 84, 100. RESULTS: Eighty-six and 112 subjects ranged their CD4(+) T cell counts 100 - 200 cells/microl and 201 - 350 cells/microl, respectively. The pre-HAART viral load in CD4 201 - 350 cells/microl group was significantly lower than that in CD4 100 - 200 cells/microl group (P = 0.000). After treatment, no significant differences were observed between these two groups either in the plasma viral load (pVL) or in the viral response rate calculated as the percentage of pVL less than 50 copies/ml or less than 400 copies/ml. The CD4(+) T cell counts were statistically higher in the 201 - 350 group during the entire follow-ups (P < 0.01) though CD4(+) T cell count increases were similar in these two groups. After 100-week treatment, the median of CD4(+) T cell counts were increased to 331 cells/microl for CD4 100 - 200 cells/microl group and to 462 cells/microl for CD4 201 - 350 cells/microl group. Only a slightly higher incidence of nausea was observed in CD4 201 - 350 cells/microl group (P = 0.05) among all adverse reactions, including rash and liver function abnormality. CONCLUSIONS: The pVLs and viral response rates are unlikely to be associated with the baseline CD4(+) T cell counts. Initiating HAART in Chinese HIV-1 infected patients with higher baseline CD4(+) T cell counts could result in higher total CD4(+) T cell counts thereby achieve a better immune recovery. These results support current guidelines to start HAART at a threshold of 350 cells/microl.

[Construction of eukaryotic expression vector of short hairpin RNA for transforming growth factor-beta1].

OBJECTIVE: To construct the plasmid containing short hairpin RNA (shRNA) of TGF-beta1 expression vector. METHODS: Short chain oligonucleotide was designed according to the TGF-beta1 mRNA sequence provided by Genebank, then DNA segment was gained through annealing after chemosynthesis, and then was cloned to pWH1 vector. The recombinant TGF-beta1 shRNA expression vector was evaluated by using enzyme cutting. At last, the constructed TGF-beta1 expression vector was transfected into salivary gland mucoepidermoid carcinoma (Ms) cells by Lipofectomine TM 2000, and its effect on TGF-beta1 expression was observed by RT-PCR and immunohistochemistry. RESULTS: Successful construction was identified by enzyme cutting and the constructed plasmid was called pWH1-TGF-beta1. The shRNA and it inhibited the TGF-beta1 mRNA and protein expression effectively. CONCLUSION: The constructed TGF-beta1 shRNA expression vector can block the TGF-beta1 expression in salivary gland mucoepidermoid carcinoma cells.