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

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.

Respiratory virus-associated infections in HIV-infected adults admitted to the intensive care unit for acute respiratory failure: a 6-year bicenter retrospective study (HIV-VIR study)

Introduction Acute respiratory failure is the main reason for admission to the intensive care unit (ICU) in HIV-infected adults. There is little data about the epidemiology of respiratory viruses in this population. Methods HIV-infected adults admitted to two intensive care units over a 6-year period for an acute respiratory failure and explored for respiratory viruses with multiplex polymerase chain reaction (mPCR) were retrospectively selected. Objectives were to describe the prevalence of respiratory viruses, coinfections with non-viral pathogens, and hospital outcome. Results A total of 123 episodes were included. An HIV infection was newly diagnosed in 9% of cases and 72% of the population were on antiretroviral therapy. Real-time mPCR tests identified at least one respiratory virus in the respiratory tract of 33 (27%) patients, but with a non-viral copathogen in two-thirds of cases. Rhinovirus was predominant, documented in 15 patients, followed by Influenza and Respiratory Syncytial Viruses (both n = 6). The prevalence of respiratory virus-associated infection did not vary along with the level of the CD4 T-cell deficiency, except for Rhinovirus which was more prevalent in patients with a CD4 lymphocyte count below 200 cells/µL (n = 13 (20%) vs. n = 2 (4%), p < 0.01). In multivariate analysis, respiratory virus-associated infection was not associated with a worse prognosis. Conclusions Viruses are frequently identified in the respiratory tract of HIV-infected patients with acute respiratory failure that requires ICU admission, but with a non-viral copathogen in two-thirds of cases. Rhinovirus is the predominant viral specie; its prevalence is highest in patients with a CD4 lymphocyte count below 200 cells/µL.

Immunologic Response of HIV-Infected Children to Different Regimens of Antiretroviral Therapy: A Retrospective Observational Study

Background. Both abacavir- (ABC-) based and zidovudine- (AZT-) based regimens are widely utilized for managing HIV infection in children. Unfortunately, there is a lack of data regarding their immunological response and associated risk factors in Ethiopia. Methods. A retrospective hospital-based cohort study was conducted on HIV-infected children in Jimma Medical Center (JMC). A total of 179 records were reviewed by including data from November 2015 to April 2017. Data were collected on sociodemographic, clinical characteristics of patients and drug-related variables. Data analysis was done using STATA 13.1. Mixed-effect linear regression was performed to assess the difference in CD4+ changes between groups adjusting for baseline characteristics. The change in predicted CD4 count attributed to each regimen was also assessed by marginal analysis. P<0.05 for slope of the random-effect linear regression was used as an indicator for the presence of association. Result. Of 179 patients, 98 (54.7%) were females. The mean (±SD) duration of follow-up was 939.8 ± 478.3 and 984.92 ± 453.1 days for ABC and AZT groups, respectively. AZT group had a significant CD4+ count gain per visit compared with their ABC counterparts ((β = 20.51, 95% CI [6.37–34.65]), P=0.004) over time. The regimen AZT + 3TC + LPV/r tended to have an excellent predicted CD4+ lymphocyte count change relative to all other regimens, while ABC + 3TC + LPV/r had the least immunologic recovery (margins 338.0 cells/mm3 versus 249.13 cells/mm3 (P<0.001)). Baseline CD4+ lymphocyte count, ART group, WHO clinical stages, and viral load were independent predictors for CD4+ change overtime. Conclusion. AZT-based regimens seem to have better immunological response compared to ABC-based regimens. Immunologic response was described worse in patients with a viral load of >1000copies/ml, low baseline CD4+ count, advanced WHO clinical stages, and ABC-containing regimens. Further study is needed to clarify these aspects.

Interventions to improve medication adherence in adolescents with HIV: a systematic review and meta-analysis

As of 2017, 1.8 million people living with HIV (PLWH) were adolescents between ages 10 and 19, accounting for 5% of all PLWH and 590,000 people between the ages 15 and 24 were newly infected with HIV. Between 2004 and 2011, AIDS-related deaths increased 50% among adolescents, and optimal adolescent adherence to antiretroviral treatment (ART) is estimated at only 62% of adolescents worldwide. While there have been great strides toward achieving the UNAIDS 90-90-90 goals, adolescents remain a group lacking appropriate resources and research to achieve these. This review analyzes current interventions aimed toward increasing adolescent ART adherence. Systematic searches of EMBASE, PubMed and PsycINFO were performed using the keywords ‘adolescent HIV medication adherence interventions’. The Gain Score effect size was calculated for studies reporting the Cohen’s d and variance to include both prestudy and poststudy values. A random-effects model analyzed intervention significance. Authors were contacted to obtain additional data values and study clarification. Twelve studies met inclusion criteria for meta-analysis. There were no significant differences seen between control and intervention groups in medication adherence (z=−1.4714, p<0.1412), viral load (z=−0.1946, p<0.8547) or CD4+ lymphocyte count (z=0.2650, p<0.7910). There was no significant difference between studies in increasing medication adherence. Results indicate that interventions did not improve medication adherence in adolescents with HIV. However, the paucity of quantitative research available speaks to a need for more quantitative intervention studies and standardization of measures of intervention efficacy.

Mathematical temporal prediction of CD4+ lymphocytes in HIV/AIDS patients in antiretroviral treatment

Background: The measurement of CD4 + lymphocyte count through flow cytometry, is necessary for the following up of HIV-infected patients in antiretroviral therapy, however, populations in low-income countries are limited to this test. For this, values of leukocytes and CD4 + lymphocytes counts greater than 500, between 200 and 500 and lesser than 200 cells were taken from 250 HIV-infected individuals in sequential dates up to three years. Then, temporal series of 12 prototypical patients were analyzed in search of predictive patterns between CD4 + lymphocytes and leukocytes, and then, these patterns were applied with the remaining data in a blind study in order to calculate the probability of success of the methodology for each range and its combinations, as well as sensitivity and specificity values.Results: Five patterns with predictive percentages greater than 99% were found for the distinct conditions of the methodology, with sensitivity and specificity values of 99%.Conclusions: A predictive theoretical simplification was achieved between leukocytes counts and CD4 + lymphocytes. This method could be useful to improve the surveillance and survival of HIV-infected individuals in low-income countries where flow cytometry cannot be afforded.

Preventive measures to avoid vertical transmission in untreated pregnant women with HIV/AIDS

The HIV/AIDS during pregnancy has high morbidity and mortality, without optimal prevention and treatment. The advanced stage cases are found in developing countries due to late detection, but, also in developed countries due to immigration; therefore, the professionals should know the management steps for these patients. The implementation of specific interventions can reduce vertical transmission incidence until 1%–8%. It is presented a case of a pregnant woman with AIDS detected during first hospitalisation, due to a ventilatory failure by opportunistic germs; at the delivery the specific interventions were implemented, being able to eliminate vertical transmission to the newborn. This article explains the four main aspects to be considered for reducing vertical transmission (detection of HIV, viral load levels-CD4 lymphocyte count, way and moment of childbirth and antiretroviral therapy) and shares experiences of the management of an advanced case, in order to help professionals to handle these cases and its complications.