The predictive role of CD4+ cell count and CD4/CD8 ratio in immune reconstitution outcome among HIV/AIDS patients receiving antiretroviral therapy: an eight-year observation in China.

BACKGROUND: The immune reconstitution after initiation of highly active antiretroviral therapy (HAART) among HIV-infected individuals substantially affects patients' prognosis. However, the dynamic characteristics and predictors of reconstitution outcome remain unclear. METHODS: In this study, the HIV/AIDS patients with sustained virological suppression (viral load < 50 copies/ml) after HAART were enrolled. The patients were subgrouped into immunological non-responders (INRs) (< 200 cells/µl), immunological inadequate responders (IIRs) (200 ~ 500 cells/µl) and immunological responders (IRs) (> 500 cells/µl) according to the CD4 cell count after two-year HAART. The immune reconstitution data based on the CD4+ and CD8+ cell counts with 8-year follow-up were collected for analysis. RESULTS: The CD4+ cell counts in the immunological responders (IRs) were significantly higher than in the immunological non-responders (INRs) and immunological inadequate responders (IIRs) (P <  0.001). The overall CD4+ cell count and CD4/CD8 ratio in the IRs increased faster than the IIRs and INRs. The CD4+ cell count growth at 0.5 year and 1 year after HAART in the IRs was significantly higher than the IIRs and INRs. The ROC curve demonstrated that 1 year CD4+ cell count had the highest predictive value, with the best cut-off value of 188 cells/µl, the predictive sensitivity was 81.0%, the predictive specificity was 85.2%, false positive rate was 14.8%, false negative rate was 19.0%, positive predictive value (IR) was 63.0%, negative predictive value (INR) was 93.5%. CONCLUSIONS: Taken together, our findings suggest that early initiation of HAART can reduce the immune reconstitution failure. The combination of baseline CD4+ cell count and baseline CD4/CD8 ratio may serve as a valid predictor of immune reconstitution prognosis after HAART.

Evaluating anemia in HIV-infected patients using chest CT.

Objective: The aim of this study was to investigate the role of the Hounsfield unit value of chest CT non-contrast enhanced scan in evaluating the severity of anemia in HIV-infected patients. Methods: Patients with HIV infection combined with anemia admitted to the Kunming Third People's Hospital were retrospectively collected and divided into mild anemia, moderate anemia, and severe anemia groups by peripheral hemoglobin (HB) content and calculated the ratio of ventricular septum density (VSD) to left ventricular density (LVD) and VSD to right ventricular density (RVD); then, the above patients were divided into the critical value group and the non-critical value group according to HB and compared the differences of LVD, RVD, VSD/LVD, and VSD/RVD in the two groups of patients. Results: A total of 126 patients were included, with a mean age of 47.9 ± 11.1 years; 43 cases were in the mild anemia group, 59 cases were in the moderate anemia group, and 24 cases were in the severe anemia group; the differences in LVD, RVD, VSD/LVD, and VSD/RVD were significant in the three groups; VSD/LVD was an independent predictor for the diagnosis of anemia critical value in the non-critical value group vs critical value group by multifactorial binary logistic regression analysis, and the ROC was plotted using VSD/LVD with an area under the curve of 0.731. Conclusions: The measurement of cardiac cavity density and ventricular septal density under CT plain film scan has a high accuracy in evaluating the severity of anemia in patients with HIV infection and can quickly determine the severity of HIV infection in the early stage and treat it as soon as possible.

gp120-derived amyloidogenic peptides form amyloid fibrils that increase HIV-1 infectivity.

Apart from mediating viral entry, the function of the free HIV-1 envelope protein (gp120) has yet to be elucidated. Our group previously showed that EP2 derived from one ß-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity. Importantly, gp120 contains ~30 ß-strands. We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils, thereby promoting viral infection. Peptide array scanning, enzyme degradation assays, and viral infection experiments in vitro confirmed that many ß-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity. These gp120-derived amyloidogenic peptides, or GAPs, which were confirmed to form amyloid fibrils, were termed gp120-derived enhancers of viral infection (GEVIs). GEVIs specifically capture HIV-1 virions and promote their attachment to target cells, thereby increasing HIV-1 infectivity. Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity. GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents. Notably, endogenous GAPs and GEVIs were found in the lymphatic fluid, lymph nodes, and cerebrospinal fluid (CSF) of AIDS patients in vivo. Overall, gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics.

A Real-world Evidence-based Management of HIV by Differential Duration HAART Treatment and its Association with Incidence of Oral Lesions.

BACKGROUND: The efficacy of highly active antiretroviral therapy (HAART) can be estimated by the immunological response and the incidence of opportunistic infections. OBJECTIVE: This study aimed at evaluating the effectiveness of different durations of HAART in terms of immunological response markers (CD4 count and CD4/CD8 ratio) along with disease progression markers (incidence of oral lesions) in Chinese patients with HIV. METHODS: This single-center, retrospective, and real-world study included patients with HIV, grouped into a treatment group and treatment-naïve group, of which the former was further divided into 6, 12, and 18 months based on the treatment duration. The CD4 and CD8 cell counts were analyzed by the FACSCalibur flow cytometry. Kruskal-Wallis test was applied to determine the outcome of different duration of HAART. Oral examination was carried out according to the WHO type IV examination. RESULTS: In 246 patients with HIV, CD4 counts increased significantly post-HAART compared to pre-HAART in all three treatment groups (P<.001), while CD8 count decreased significantly (P<.05) in all three treated groups. A significant association of HAART with the CD4/CD8 ratio was observed (P<.001). A significant increase in CD4 count was observed between 12-months and 18-months treatment groups (P<.05). The occurrence of oral lesions reduced significantly in the treatment group. CONCLUSION: We observed a better response to the HAART regimen with 18-months of duration than 12-months and 6-months therapies and reduction in oral lesions.

Excessive mechanical strain accelerates intervertebral disc degeneration by disrupting intrinsic circadian rhythm.

Night shift workers with disordered rhythmic mechanical loading are more prone to intervertebral disc degeneration (IDD). Our results showed that circadian rhythm (CR) was dampened in degenerated and aged NP cells. Long-term environmental CR disruption promoted IDD in rats. Excessive mechanical strain disrupted the CR and inhibited the expression of core clock proteins. The inhibitory effect of mechanical loading on the expression of extracellular matrix genes could be reversed by BMAL1 overexpression in NP cells. The Rho/ROCK pathway was demonstrated to mediate the effect of mechanical stimulation on CR. Prolonged mechanical loading for 12 months affected intrinsic CR genes and induced IDD in a model of upright posture in a normal environment. Unexpectedly, mechanical loading further accelerated the IDD in an Light-Dark (LD) cycle-disrupted environment. These results indicated that intrinsic CR disruption might be a mechanism involved in overloading-induced IDD and a potential drug target for night shift workers.

[Effect of nutritional support on immunity function in the acquired immune deficiency syndrome patients].

OBJECTIVE: To investigate the effect of nutritional support on immunity function in the acquired immune deficiency syndrome (AIDS) patients. METHODS: Sixty-five AIDS patients were randomly divided into treatment group (n=35) and control group (n=30). In the treatment group, the patients received enteral nutrition (EN) treatment or EN supplemented with parenteral nutrition (EN+PN) on top of routine treatment according to the daily condition of the sufferers. The control group received routine treatment only. CD3, CD4 and CD8 cell, CD4/CD8, C3, C4, immunoglobulin G (IgG), IgM, IgA were determined on the 0 and 30th day of the treatment, and they were analyzed with covariance analysis. RESULTS: CD4 cell in the treatment group was significantly raised compared with before examination (P<0.05). Other immunity indexes were not correlated. All clinical indexes showed no change in the control group (all P>0.05). CONCLUSION: The nutritional support can raise the immunity function in the AIDS patient.

Clinical analysis of HIV/AIDS patients with drug eruption in Yunnan, China.

Drug eruption is the most common clinical presentation in patients with HIV/AIDS. The systemic clinical and risk factors associated with drug eruption remain unknown. A retrospective analysis in HIV/AIDS patients with drug eruption was carried out with demographic data, epidemiological data, clinical characteristics, laboratory data and follow-up data. The risk factors correlated with prognosis were assessed by case control analysis. A total of 134 out of 1817 HIV/AIDS patients (7.4%) presented drug eruptions. The major class of sensitizing drug was HAART drugs (47.7%), followed by antibiotics (47.0%). Nevirapine (39.6%) was the most common sensitizing drug in the HAART regimens. The patients received HAART or had allergic history were prone to develop drug eruption. The alanine aminotransferase, albumin, globulin, creatinine, blood urea nitrogen (BUN), lymphocytes, red blood cells (RBC) and eosinophils of the drug eruption patients were significantly different the control patients. The allergic history, opportunistic infection, viral load, CD4 cell count, high globulin and low albumin were the risk factors correlated with death in HIV/AIDS patients with drug eruption. It is proposed that patients with higher viral loads, higher globulin levels and lower white blood cells (WBC) should be given special attention for the prevention of complications and death.

[Incidence of oral hairy leukoplakia in human immunodeficiency virus-seropositive adult patients in Yunnan, China].

OBJECTIVE: To study the incidence rates, clinical characteristics of oral hairy leukoplakia (OHL) and its relation to the immune status in a sample of human immunodeficiency virus (HIV)-infected adults in Yunan, China. METHODS: 1 060 adult patients with HIV from January 2008 to June 2010 were evaluated. The age, gender, education grade, diagnosis time of HIV-infected, route of transmission, xerostomia, oral candidiasis, high active antiretroviral therapy and CD4 lymphocytes counts. The occurrence of OHL was recorded by oral examination. The relationship of CD4 lymphocytes counts and the incidence of OHL were analyzed by statistical methods. RESULTS: There were 94 OHL patients in 1 060 HIV patients (8.9%). The average age of the OHL patients was (39.33 +/- 10.45) years old. 90% OHL was found on the two lateral aspect of the tongue. The CD4 lymphocytes of 70.2% OHL patients were less than 200 mm-3. CONCLUSION: OHL is a frequent finding in patients with indicates severe immunosuppression and associated with the reduction of CD4 lymphocytes.