Mechanisms of immune aging in HIV

Massive CD4+ T-cell depletion as well as sustained immune activation and inflammation are hallmarks of Human Immunodeficiency Virus (HIV)-1 infection. In recent years, an emerging concept draws an intriguing parallel between HIV-1 infection and aging. Indeed, many of the alterations that affect innate and adaptive immune subsets in HIV-infected individuals are reminiscent of the process of immune aging, characteristic of old age. These changes, of which the presumed cause is the systemic immune activation established in patients, likely participate in the immuno-incompetence described with HIV progression. With the success of antiretroviral therapy (ART), HIV-seropositive patients can now live for many years despite chronic viral infection. However, acquired immunodeficiency syndrome (AIDS)-related opportunistic infections have given way to chronic diseases as the leading cause of death since HIV infection. Therefore, the comparison between HIV-1 infected patients and uninfected elderly individuals goes beyond the sole onset of immunosenescence and extends to the deterioration of several physiological functions related to inflammation and systemic aging. In light of this observation, it is interesting to understand the precise link between immune activation and aging in HIV-1 infection to figure out how to best care for people living with HIV (PLWH).

Joint Modeling of Longitudinal Ordinal Data on Quality of Life and Survival

<p>Joint models for longitudinal and survival data have been widely discussed in the literature. This thesis proposes a joint model using a stereotype model for the longitudinal ordinal responses and a Cox proportional hazards model for survival time. Our current joint model has a new feature since no literature has examined the joint model under the stereotype model. The stereotype model can improve the fit by adding extra score parameters, but it still has the advantage of requiring only a single parameter to describe the effect of a predictor on the item response levels. We give an example to model longitudinal ordinal data and survival data for patients being followed up after treatments. The main focus is on modeling both the quality of life data and the survival data simultaneously with a goal of understanding the association between the two processes over time. These two models are linked through a latent variable that characterizes the quality of life of an individual and is assumed to underlie the hazard rate. In other words, the latent variable serves as a shared variable in the joint model. We present the joint model in two different aspects: one based on a Bayesian approach and the other one a semiparametric approach using the EM algorithm. For the Bayesian approach, the latent variable is treated as a continuous variable and is assumed to have a multivariate normal distribution. The partial survival likelihood function is used in the survival component of the Bayesian joint model, while the full likelihood function is considered in the semiparametric joint model. In the latter approach the baseline hazard is assumed to be a step function and has no parametric form. The latent variable in the semiparametric joint model is then treated as a discrete variable. We illustrate our methodologies by analyzing data from the Staccato study, a randomized trial to compare two treatment methods, for Human Immunodeficiency Virus (HIV) infection of Thai patients on Highly Active Antiretroviral Therapy (HAART), in which the quality of life was assessed with a HIV Medical Outcome Study (MOS-HIV) questionnaire. Furthermore, we extend the study further to the case of multiple failure types in the survival component. Thus, the extension of the joint model consists of the stereotype model and the competing risks model. The Bayesian method is employed to estimate all unknown parameters in this extended joint model. The results we obtained are consistent for both the Bayesian joint model and the semiparametric joint model. Both models show that patients who had a better quality of life were associated with a lower hazard of HIV progression. Patients on continuous treatment also had a lower hazard of HIV progression compared with patients on CD4-guided interruption treatment.</p>

Joint Modeling of Longitudinal Ordinal Data on Quality of Life and Survival

<p>Joint models for longitudinal and survival data have been widely discussed in the literature. This thesis proposes a joint model using a stereotype model for the longitudinal ordinal responses and a Cox proportional hazards model for survival time. Our current joint model has a new feature since no literature has examined the joint model under the stereotype model. The stereotype model can improve the fit by adding extra score parameters, but it still has the advantage of requiring only a single parameter to describe the effect of a predictor on the item response levels. We give an example to model longitudinal ordinal data and survival data for patients being followed up after treatments. The main focus is on modeling both the quality of life data and the survival data simultaneously with a goal of understanding the association between the two processes over time. These two models are linked through a latent variable that characterizes the quality of life of an individual and is assumed to underlie the hazard rate. In other words, the latent variable serves as a shared variable in the joint model. We present the joint model in two different aspects: one based on a Bayesian approach and the other one a semiparametric approach using the EM algorithm. For the Bayesian approach, the latent variable is treated as a continuous variable and is assumed to have a multivariate normal distribution. The partial survival likelihood function is used in the survival component of the Bayesian joint model, while the full likelihood function is considered in the semiparametric joint model. In the latter approach the baseline hazard is assumed to be a step function and has no parametric form. The latent variable in the semiparametric joint model is then treated as a discrete variable. We illustrate our methodologies by analyzing data from the Staccato study, a randomized trial to compare two treatment methods, for Human Immunodeficiency Virus (HIV) infection of Thai patients on Highly Active Antiretroviral Therapy (HAART), in which the quality of life was assessed with a HIV Medical Outcome Study (MOS-HIV) questionnaire. Furthermore, we extend the study further to the case of multiple failure types in the survival component. Thus, the extension of the joint model consists of the stereotype model and the competing risks model. The Bayesian method is employed to estimate all unknown parameters in this extended joint model. The results we obtained are consistent for both the Bayesian joint model and the semiparametric joint model. Both models show that patients who had a better quality of life were associated with a lower hazard of HIV progression. Patients on continuous treatment also had a lower hazard of HIV progression compared with patients on CD4-guided interruption treatment.</p>

Studi Literatur: Status Infeksi Tuberkulosis dan Progresi Penyakit HIV

One factor that affects HIV development is co-infected TB. HIV and TB both play a role in reducing the function of the immune system. The purpose of this study was to see the relationship between the status of TB infection in HIV+ patients with HIV progression to AIDS. Research articles were identified from the four databases PubMed, BMC Public Health, Science Direct and ProQuest. The review was conducted to synthesize findings on the published articles between January 2010- October 2020 with the research protocol and research evaluation using PRISMA. A total of 6 articles meet the inclusion and exclusion criteria. The results of the analysis found there were 4 articles that discussed TB / HIV with CD4 and were entirely significant. Two articles noted a CD4 decline in TB / HIV groups and the other two found an increase in CD4. Although there is an increase, compared to NONTP groups, CD4 counts in TB / HIV coinfection tend to be lower. On viral load, two articles noted a decline, but only one article mentioned a significant difference but did not compare with the NONTP group. HIV progressions became AIDS recorded in two articles and found a risk of development in TB / HIV groups was higher than the NONTP group. TB infections in HIV sufferers affect HIV development through immune system interactions. Further research on HIV development tuberculosis infection into AIDS needs to examine related tuberculosis type or location. Abstrak: Salah satu faktor yang memengaruhi perkembangan HIV adalah koinfeksi TB. HIV dan TB keduanya berperan dalam menurunkan fungsi sistem kekebalan. Tujuan penelitian ini adalah untuk melihat hubungan status infeksi TB pada pasien HIV+ dengan progresi HIV menjadi AIDS. Artikel penelitian diidentifikasi dari empat database PubMed, BMC Public Health, Sciencedirect dan ProQuest. Review dilakukan untuk mensintesis temuan pada artikel yang dipublikasi antara Januari 2010- Oktober 2020 dengan protokol dan evaluasi penelitian menggunakan PRISMA. Total 6 artikel yang memenuhi kriteria inklusi dan eksklusi. Hasil analisis menemukan ada 4 artikel yang membahas TB/HIV dengan CD4 dan seluruhnya signifikan. Dua artikel mencatat adanya penurunan CD4 pada kelompok TB/HIV dan dua lainnya menemukan peningkatan CD4. Meski terjadi peningkatan, dibandingkan dengan kelompok non TB, jumlah CD4 pada koinfeksi TB/HIV cenderung lebih rendah. Pada viral load, dua artikel mencatat adanya penurunan, namun hanya satu artikel yang menyebutkan adanya perbedaan signifikan namun tidak membandingkan dengan kelompok non TB. Progresi HIV menjadi AIDS dicatat pada dua artikel dan ditemukan risiko pengembangan pada kelompok TB/HIV lebih tinggi dibandingkan kelompok non TB. Infeksi TB pada penderita HIV berpengaruh terhadap perkembangan HIV melalui interaksi sistem imun. Penelitian lebih lanjut mengenai infeksi tuberkulosis perkembangan HIV menjadi AIDS perlu meneliti terkait jenis atau lokasi tuberkulosis.

Depresi dan Progresi Penyakit HIV

Depression is a common problem that occurs in people with HIV. Depression in HIV patients is associated with adherence to antiretroviral therapy (ARV), the possibility of HIV transmission, virologic failure and progression of disease to AIDS. However, there is contradictory evidence that overlaps based on previous studies. This study aims to investigate the relationship between depression and HIV disease progression. This study uses PICOS in the literature search. The literature search used 3 databases, SpringerLink, BMC Public Health and PubMed. Literature study search used 5 keywords “Depression”, “HIV Progression” “low CD4”, “Viral load counts” and “HIV-related death”. A total of 1,763 articles were found and identified. Transparency of the identification process to find articles analyzed using PRISMA diagrams. Assessment of study quality using STROBE and Tool To Assess Risk of bias in Cohort Studies. This study reviewed 4 articles that fit the criteria of inclusion and exclusion. This study shows depression plays a role in HIV disease progression. 75 percent of the articles showed significant association between depression and CD4 cell decline, increased viral load and risk of death. Both depressive symptoms and depressive disorder (MDD) play a role in CD4 cell decline and viral load increase over a 4-6 year period. Depressive symptoms in newly diagnosed HIV represent an 8-12 percent higher risk of death within 2 years. For this reason, it’s necessary to screen for depression before conducting a VCT test to provide initial data on the mental health of HIV patients and to determine depression management programs in HIV patients. Abstrak: Depresi merupakan masalah umum yang terjadi pada penderita HIV. Depresi pada penderita HIV dikaitkan dengan kepatuhan terapi antiretroviral (ARV), kemungkinan penularan HIV, kegagalan virologi dan perkembangan penyakit menjadi AIDS. Namun, terdapat bukti kontradiktif yang saling tumpang tindih berdasarkan penelitian terdahulu. Studi ini bertujuan mencari hubungan depresi dan progresi penyakit HIV. Studi ini menggunakan PICOS dalam pencarian literatur. Pencarian literatur menggunakan 3 database, Springerlink, BMC Public Health dan PubMed dengan menggunakan 5 kata kunci “Depression”, “HIV Progression” “low CD4”, “Viral load counts” dan “HIV-related death”. Sebanyak 1.763 artikel ditemukan dan diidentifikasi. Transparansi proses identifikasi menggunakan diagram PRISMA. Penilaian kualitas studi menggunakan STROBE dan Tool To Assess Risk of bias in Cohort Studies. Studi ini meninjau 4 artikel yang sesuai kriteria inklusi dan eksklusi. Studi ini menunjukan depresi berperan terhadap progresi penyakit HIV. 75 persen artikel menunjukan hubungan yang signifikan antara depresi dengan penurunan sel CD4, peningkatan viral load maupun risiko kematian. Gejala depresi maupun gangguan depresi (MDD) memiliki peran dalam penurunan sel CD4 dan peningkatan viral load dalam periode 4-6 tahun. Gejala depresi pada penderita baru menunjukan 8-12 persen risiko kematian yang lebih tinggi dalam kurun waktu 2 tahun. Untuk itu, diperlukan adanya skrining depresi sebelum melakukan tes VCT sebagai baseline data kesehatan mental pasien HIV dan penentuan program penanganan depresi pada penderita HIV.

Relations of Antiretroviral Combinations to CD4 Levels of HIV TB Patiens in RSUD H.Abdul Manap Jambi

The cases of Human Immunodeficiency Virus (HIV) infection are increasing every year. This case is a disease that is very rapidly transmitted throughout the world. HIV increases the risk of developing tuberculosis (TB) and conversely TB infection increases HIV progression. In 2017, it is estimated that 10 million people have HIV TB. Combination of antiretrovirals is the basis for the management of antiretroviral therapy for HIV / AIDS patients, because it can reduce resistance, suppress HIV replication effectively so that transmission, opportunistic infections and other complications. The purpose of this study was to determine the relationship between antiretroviral combinations and CD4 levels in outpatient HIV TB patients at RSUD H. Abdul Manap Jambi. This study is a retrospective cohort study using medical records of outpatient HIV TB patients at RSUD H. Abdul Manap Jambi based on inclusion and exclusion criteria. Based on research conducted on outpatient HIV TB patients at Abdul Manap Hospital, Jambi, it was found that there was no relationship between antiretroviral combinations and CD4 levels in HIV TB patients, marked by Asimp.Sig 0.778> 0.05.

Role of detection of lipoarabinomannan (LAM) in urine for diagnosis of pulmonary tuberculosis in HIV patients: Egyptian experience

Background Tuberculosis remains a worldwide problem fueled by the HIV epidemic. TB infection impacts HIV progression and mortality even with treatment. Egypt has increasing HIV prevalence, although still in low prevalent areas. Results Urinary LAM was positive in 22 (95.7%) of TB patients and 1 (1.9%) of non TB group. Sensitivity was 95.7%, specificity 98.1%, positive and negative predictive values were 95.7% and 98.1% respectively, with accuracy 97.4%. Urinary LAM ELISA assay has the highest sensitivity (95.7%) in relation to other tests used for TB detection in HIV patients and its concentration was highly correlated to CD4 cell count and the extent of radiological changes. Conclusion The use of urinary LAM in HIV patients is rapid, safe, available, and helpful tool for ruling in TB especially for those who cannot expectorate, critically ill, with low CD4, or presented by multiple system affection.

Examining HIV progression mechanisms via mathematical approaches

The progression of HIV infection to AIDS is unclear and under examined. Many mechanisms have been proposed, including a decline in immune response, increase in replication rate, involution of the thymus, syncytium inducing capacity, activation of the latently infected cell pool, chronic activation of the immune system, and the ability of the virus to infect other immune system cells. The significance of each mechanism in combination has not been studied. We develop a simple HIV viral dynamics model incorporating proposed mechanisms as parameters that are allowed to vary. In the entire parameter space, we derive two formulae for the basic reproduction number (R0) by considering the infection starting with a single infected CD4 T cell and a single virion, respectively. We show that both formulae are equivalent. We derive analytical conditions for the occurrence of backward and forward bifurcations. To investigate the influence of the proposed mechanisms to the HIV progression, we perform uncertainty and sensitivity analysis for all parameters and conduct a bifurcation analysis on all parameters that are shown to be significant, in combination, to explore various HIV/AIDS progression dynamics.