The Difference Of PT, aPTT, Fibrinogen, D-Dimer Activities In HIV Patients With CD4 Count Of 200 uL

ABSTRACT Introduction: HIV is a developing disease that has been a global problem. The progress of HIV infection is characterized by decreased CD4 count. Hemostasis disorder is often found in patients with HIV, where the formed virus-antibody complex can activate the coagulation system, beginning from the activation of the Hageman factor (Factor XII) into the active form (Factor XIIa). This factor will activate the fibrinolysis process. Fibrin polymer is broken down into fragments X and Y. Fragment Y is further broken down into Fragment D and E, which is known as D-dimer. Objective: To determine the difference of PT, aPTT, Fibrinogen, and D-Dimer in HIV patients with a CD4 lymphocyte count of < 200/µL and > 200/µL in H. Adam Malik General Hospital Medan. Hypothesis: There is a difference of PT and aPTT activities in HIV patients with a CD4 count of < 200 cells/µL and ≥ 200 cells/µL and a difference of D-dimer and fibrinogen levels in HIV patients with a CD4 count of < 200/µL and > 200/µL in H. Adam Malik General Hospital Medan. Methods: This study was conducted in the Clinical Pathology Laboratory, Department of Internal Medicine, H. Adam Malik General Hospital. Samples were collected with a consecutive sampling method which included patients diagnosed with HIV in H. Adam Malik General Hospital Medan from September 2019 to July 2020 who fulfilled the inclusion and exclusion criteria. Thirty-eight patients were divided into two groups, i.e., HIV patients with a CD4 count of < 200/µL and HIV patients with a CD4 lymphocyte count of > 200/ µL. Results: Mann-Whitney test was used to assess the comparison of PT and aPTT values between HIV patients with a CD4 count of < 200 cells/µL and ≥ 200 cells/µL. The result was significant with a p-value = 0.002, which means that there is a significant difference in PT and aPTT values between HIV patients with a CD4 count of < 200 cells/µL and ≥ 200 cells/µL. An Independent T-test was used to assess the difference in fibrinogen level between HIV patients with a CD4 count of < 200/µL and > 200/µL, which resulted in p-value = 0.032. This means that there is a significant difference in fibrinogen levels between HIV patients with a CD4 count of < 200/µL and > 200/µL. Mann-Whitney test was used to determine the comparison in D-dimer level between HIV patients with a CD4 count of < 200/µL and > 200/µL, which showed a p-value = 0.002. This indicated a significant difference in D-dimer level between HIV patients with a CD4 count of < 200/µL and > 200/µL. Conclusion: The lower the CD4 lymphocyte count, the higher the activities of PT, aPTT, fibrinogen, and D-dimer in HIV patients. Keywords: HIV, PT, aPTT, D-Dimer, Fibrinogen, Hemostasis

Impact of the COVID-19 pandemic: Community and hospital shared pharmaceutical care model. Satisfaction and acceptability of patients with HIV infection on antiretroviral treatment

Background. The health crisis due to the COVID-19 pandemic is a challenge in the dispensing of outpatient hospital medication (OHM). Models of Antiretroviral Therapy (ART) based on community pharmacy support (ARTCP) have proven to be successful. The aim was to evaluate the degree of satisfaction, acceptability and limitations of the implementation of ARTCP, in the context of a pandemic, in our environment. Methods. Descriptive cross-sectional study carried out in a Barcelona hospital, during the months of July-November 2020. A telephone survey was carried out via a questionnaire on the quality dimensions of the model (degree of satisfaction, acceptability) and associated inconveniences. Data collected: demographics, antiretroviral treatment (ART), concomitant medication, drug interactions (DDIs), CD4 lymphocyte count and plasma viraemia. Data analysis included descriptive statistics. Results. A total of 533 (78.0%) HIV patients receiving ART were included. 71.9% (383/533) of these patients were very satisfied and 76.2% preferred attending the community pharmacy rather than the hospital. The mean satisfaction rating was 9.3 (DS: 1.4). The benefits reported were: 1) proximity to home (406: 76.1%); 2) lower risk of contagion of COVID-19 (318: 59.7%); 3) shorter waiting time (201: 37.1%); 4) time flexibility (104: 19.5%); 5) reduction of financial expenses (35: 6.57%). A total of 11 (2%) patients reported no benefit. Only 22.9% reported disadvantages associated with ARTCP: 1) lack of privacy (65: 12.2%); 2) lack of coordinationorganization (57: 10.7%). Conclusion. The COVID-19 pandemic has had an impact on the provision of pharmaceutical care for HIV patients. The ARTPC model has proved efficient, with patients reporting a high degree of satisfaction.

Surgical treatment of patients with HIV-associated respiratory tuberculosis and different immune status

The objective of the study: to evaluate the impact of HIV infection on the nature and results of surgical interventions in respiratory tuberculosis (RTB) patients with the relevance of their immune status.Subjects and Methods. An ambispective observational study with continuous sampling included 565 patients above 18 years old who underwent surgical interventions. The study participants were divided into RTB+HIV Group (90 patients) with HIV-associated respiratory tuberculosis and RTB Group which included 475 HIV negative patients with respiratory tuberculosis. In RTB+HIV Group, patients were divided into three subgroups: with CD4-lymphocyte count below 200 cl/μL (n = 41), 200-499 cl/μL (n = 26), and 500 or more cl/μL (n = 23).Results. Compared to RTB Group, RTB+HIV Group was found to have less frequent resection surgery (24%; p < 0.0001; OR = 3.0) with acomparable frequency of collapsed surgery (4%; p > 0.05) and much more frequent thoracic diagnostic surgery (11%; p < 0.0001; OR = 10.6) and extrathoracic surgery (50%; p < 0.0001; OR = 6.8). In RTB+HIV Group, patients with CD4-lymphocyte count below 200 cells/μL (46%; p < 0.05) who had no resection surgery predominated, and the rate of collapsed surgery was 2.4% (p < 0.0001). There were no statistically significant differences in the incidence of postoperative complications for each individual type of surgery when stratifying participants by CD4-lymphocyte count in the intergroup comparison, as well as in RTB+HIV Group.

Validation of New International Prognostic Scores, Including Baseline Peripheral Blood Variables, in Patients with Diffuse Large B-Cell Lymphoma and HIV Infection Treated with R-CHOP and Combined Antiretroviral Therapy. Retrospective Study from Spanish Lymphoma Group Geltamo

Background Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of HIV-associated lymphoma. Since the introduction of combined antiretroviral therapy (cART), the prognosis of HIV-related DLBCL has substantially improved, resembling that of the general population. However, non-Hodgkin lymphoma still remains the first cause of AIDS-related deaths. The International Prognostic Index (IPI) is the most widely used score for DLBCL and it has been validated in the rituximab era (R-IPI). However, it has limited accuracy to identify a very high-risk prognostic subset. Although IPI has been demonstrated to be useful for predicting prognosis in HIV-related DLBCL, new scores subsequently developed, such as National Cancer Comprehensive Network IPI (NCCN-IPI), GELTAMO-IPI and a new score, which includes data from peripheral blood count, have not been applied in the HIV setting. The aim of this study was to assess the prognostic significance of the new variables -beta2-microglobulin (β2M), lymphocyte/monocyte (L/M) ratio and red blood cell width (RDW)- and to validate the new scores in a series of homogeneously treated HIV-related DLBCL patients. Methods Retrospective multicentric study of patients with HIV infection diagnosed with DLBCL in 16 hospitals from GELTAMO group in Spain, from 1998 to 2020. All patients were treated with R-CHOP and cART +/- radiotherapy. The main clinical and biological variables were collected. Peripheral absolute neutrophil, lymphocyte and monocyte counts were studied, including L/M ratio and CD4 + lymphocyte count. Moreover, HIV load, serum lactate dehydrogenase (LDH), β2M and RDW were evaluated. Univariable and multivariable analysis were performed using the binary logistic regression model for complete response (CR) rate and Cox proportional-hazards regression model for overall survival (OS) and progression-free survival (PFS). Survival curves were plotted by the Kaplan-Meier method and compared by the log-rank test. The discrimination power of IPI, aaIPI (age-adjusted IPI), R-IPI, NCCN-IPI, GELTAMO-IPI and the new score including L/M ratio (L Bento et al., Br J Haematol. 2020) was assessed by the C-index. Results One hundred and five patients were retrospectively analysed with a median follow up of 7.08 (0.36-25.21) years. The characteristics of the patients are summarized in Table 1. In the univariable analysis, performance status ≥2, extranodal sites ≥2, lymphocytopenia and low L/M ratio were associated with shorter OS and shorter PFS probabilities. Neutropenia was also associated with lower OS and advanced Ann Arbor stage was associated with lower PFS. On the other hand, monocytosis, low CD4 + lymphocyte count, positive HIV load and high values of serum LDH, RDW and β2M had no prognostic impact. By multivariable analysis, only L/M ratio &lt;3 emerged as an unfavourable prognostic factor for OS and PFS, with harzard ratios (HR) (95%CI) of 2.515 (1.256;5.039) and 2.563 (1.314;5), respectively (Figure 1). With the aim of validating the prognostic power of each score system, the patients were divided in two groups: patients corresponding with low or intermediate-low risk versus those with intermediate-high or high risk. R-IPI, NCCN-IPI and the new score including L/M ratio showed significant differences in two groups for CR rate, OS and PFS. IPI also significantly discriminated the groups for PFS. NCCN-IPI was the strongest score to discriminate OS with a C-index of 0.638, and the new score including L/M ratio was the best one for CR rate and PFS discrimination, with a C-index of 0.669 and 0.666 respectively. Conclusions Lymphocyte/monocyte ratio is a strong prognostic factor, which can be used in patients with DLBCL and HIV infection. NCCN-IPI and the new score including L/M ratio provided the best discriminative capacity to predict prognosis in patients with HIV-related DLBCL treated with R-CHOP and cART. Supported in part by Gilead Sciences S.L., Spain (GLD19/00121); 2017 SGR288 (GRE) from CERCA Programme/Generalitat de Catalunya, and by funds from Josep Carreras International Foundation and "la Caixa" Foundation. Figure 1 Figure 1. Disclosures Lopez-Guillermo: Roche, Gilead/Kite, Celgene, Novartis, Janssen, AbbVie, Spectrum: Consultancy, Honoraria, Research Funding. Salar: Janssen: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Gilead: Research Funding. de la Cruz Vicente: Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ferrer Lores: Janssen: Membership on an entity's Board of Directors or advisory committees. Abrisqueta: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Roche: Consultancy, Honoraria; BMS: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria. Sancho: Roche, Janssen, Celgene-BMS, Gilead, Novartis, Takeda: Honoraria, Speakers Bureau; Roche, Janssen, Celgene-BMS, Gilead, Novartis, Incyte, Beigene: Speakers Bureau. Ribera: SHIRE: Consultancy, Speakers Bureau; ARIAD: Consultancy, Research Funding, Speakers Bureau; TAKEDA: Consultancy, Research Funding, Speakers Bureau; NOVARTIS: Consultancy, Speakers Bureau; AMGEN: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau. Navarro: NOVARTIS, Roche: Honoraria; EUSA Pharma: Consultancy; GILEAD, EUSA Pharma: Research Funding.

Predictors for tuberculosis co-infection in people living with HIV/AIDS

Background/aim: Tuberculosis (TB) is one of the most common chronic infectious conditions causing mortality and se- vere outcomes, particularly in people living with HIV/AIDS (PLWHA). In this study, we aimed to determine the prevalence and predictors of TB among PLWHA. Materials and methods: We conducted a retrospective and single-center study of adults (≥18 years) PLWHA registered at our tertiary teaching and research hospital between 2000 and 2016. Results: A total of 711 PLWHA were included. Of whom, 633 (89.0%) were male. Mean age was 36.53 ±11.55 years (range, 17-79). Thirty-eight (5.3%) patients were diagnosed with active TB. TB development was associated with low CD4+ lymphocyte count (p<0.001), high viral load (p=0.040) and alcohol consumption (p=0.004) but no association with age (p=0.392), gender (p=0.928) and duration since anti-retroviral therapy initiation (p=0.788) was found. Also, a receiver operating characteristic analysis showed that the area under the curves of CD4+ lymphocyte count as a predictor for TB development in PLWHA was 0.717 (p<0.001). Conclusion: There are still clinical challenges to predict TB diagnosis. However, CD4+ lymphocyte count and viral load may be considered as valuable predictors for TB development. Also, community strategies to reduce harmful effect of alco- hol use should be developed. Keywords: Tuberculosis; HIV viral load; CD4 cell counts.

The Evaluation of the Factors Affecting Mortality in Cases of HIV-infected Pneumocystis Jiroveci Pneumonia

Objective: Pneumocystis jiroveci pneumonia (PJP) is a common opportunistic infection in human immunodeficiency virus (HIV) infection cases. This study aimed to investigate the mortality rate and the factors affecting mortality in HIV-infected PJP cases followed in our clinic. Methods: In this study HIV (+) cases followed up in our clinic between 2012-2019 were included. Age, sex, comorbidity status, LDH, CD4, lymphocyte, albumin, values, and blood gas results of these patients were recorded at the time of diagnosis. Results: Twenty-eight patients with the diagnosis of HIV-infected PJP were included in the study. The mean age of the patients was 45.7 years, and the male ratio was 78.6% (18/28). The overall hospital mortality rate was 35.7% (10/28) among the cases. Conclusions: As a result, performing studies involving many patients may be beneficial in these patients for diagnosis, follow-up and early treatment.

Nationwide surveillance of AIDS-defining illnesses among HIV patients in Japan from 1995 to 2017

Objectives The accurate prevalence of acquired immunodeficiency syndrome (AIDS)-defining illnesses (ADIs) in human immunodeficiency virus (HIV)-infected patients has not been well investigated. Hence, a longitudinal nationwide surveillance study analyzing the current status and national trend of opportunistic complications in HIV-infected patients in Japan is warranted. Methods A nationwide surveillance of opportunistic complications in HIV-infected patients from 1995 to 2017 in Japan was conducted. An annual questionnaire was sent to 383 HIV/AIDS referral hospitals across Japan to collect information (CD4+ lymphocyte count, time of onset, outcome, and antiretroviral therapy [ART] status) of patients diagnosed with any of 23 ADIs between 1995 and 2017. Results The response and case capture rates of the questionnaires in 2017 were 53% and 76%, respectively. The number of reported cases of opportunistic complications peaked in 2011 and subsequently declined. Pneumocystis pneumonia (38.7%), cytomegalovirus infection (13.6%), and candidiasis (12.8%) were associated with the cumulative incidence of ADIs between 1995 and 2017. The mortality rate in HIV-infected patients with opportunistic complications substantially decreased to 3.6% in 2017. The mortality rate was significantly higher in HIV patients who received ART within 14 days of diagnosis of complications than in those who received ART 15 days after diagnosis (13.0% vs. 3.2%, p < 0.01). Conclusions We have demonstrated a 23-year trend of a newly diagnosed AIDS status in Japan with high accuracy. The current data reveal the importance of Pneumocystis pneumonia as a first-onset illness and that early initiation of ART results in poor outcomes in HIV patients in Japan.

Chronic obstructive pulmonary disease in patients infected with human immunodeficiency virus

The aim of the study was to examine the role of COPD in the structure of respiratory diseases in HIV patients and the course of these comorbidities among hospitalized patients with HIV infection.Methods. A continuous longitudinal retrospective study was conducted in the Holy Great Martyr George the Victorious Novokuznetsk City Clinical Hospital No.2 and included all HIV patients with respiratory diseases (n = 185) hospitalized in the therapeutic department in 2017 – 2018. About 2% of population in the Kemerovo region (with the population 2.7 million people) is known to be HIV-infected. The regional COPD incidence is 124.7/100 000.Results. COPD was diagnosed in 19 (10.3%) of all HIV patients hospitalized with respiratory diseases. 73.7% of patients with COPD were aged ≤ 40 years, the mean age was 37.6 ± 5.0 years. All patients (100.0%) were known to have smoking and intravenous drug use as potential risk factors for the development and progression of COPD. The ART coverage was low (21.1%). 68.5% of patients with COPD had severe bronchial obstruction with a decrease in FEV1 < 50% of predicted values (GOLD grades III – IV). 73.7% of the patients were assigned to COPD group B, the rest 26.3% – to group D. In 31.6% of patients, the main cause of hospitalization was COPD itself, in 68.4% – COPD combined with other lung diseases (community-acquired pneumonias, septic embolism, tuberculosis and pneumocystosis). The CD4-lymphocyte count in cases of COPD combined with other respiratory diseases (median 214.0 cell/μl) was lower than in COPD as the only respiratory disease (median 495.5 cells/μl) (p = 0,014).Conclusion. The socio-economic significance of both HIV-infection and COPD argues the further study of the course and treatment of COPD in persons with HIV-infection.

Independent predictors of forecasting the course of congenital HIV infection in children

The purpose is to characterize the clinical and laboratory parameters in children with different rates of congenital HIV infection progression and, based on the data obtained, to develop independent predictors of forecasting the course of the disease.Research methods. The comparison of clinical, immunological and virological parameters in 91 children with HIV infection with rapid (26%) and slow progression of the disease (74%) was carried out. The criterion for the rapid progression of HIV infection was considered the development of the AIDS clinic in the first two years of life.Results. Testing of clinical, immunological and virological parameters in a multivariate logistic regression model revealed independent predictors of rapid progression in children aged 6 months — HIV blood viral load more than 1 00 000 cop./ml (odds ratio OR 23.9; 95% confidence interval 95% CI 4.6—71.8; P < 0.001) and a decrease of blood CD4-lymphocytes less than 25% (OR 6.3; 95% CI 1.2—33.4; P = 0.029). The predictor «HIV blood viral load more than 100 000 cop./ml» was characterized by a higher sensitivity (91.3%), specificity (97.1 %) compared to the indicator «CD4 lymphocyte count less than 25%» (88.2% and 86.9%).Conclusion. In 26% of children with HIV infection, there is a rapid progression of the disease with the development of AIDS clinic during the first two years of life. The independent predictors of forecasting an unfavorable course of the disease are HIV blood viral load of more than 1 00 000 cop./ml and a decrease in CD4 lymphocytes in the blood of less than 25% at the age of 6 months. The level of viremia seems to be more preferable for predicting the course of HIV infection in children due to its high sensitivity and specificity.