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The post-antiretroviral therapy era has transformed HIV into a chronic disease and non-HIV comorbidities (i.e., cardiovascular and mental diseases) are more prevalent in PLWH. The source of these non-HIV comorbidities aside from traditional risk factor include HIV infection, inflammation, distorted immune activation, burden of chronic diseases, and unhealthy lifestyle like sedentarism. Exercise is known for its beneficial effects in mental and physical health; reasons why exercise is recommended to prevent and treat difference cardiovascular and mental diseases in the general population. This cumulative thesis aimed to comprehend the relation exercise has to non-HIV comorbidities in German PLWH. Four studies were conducted to 1) understand exercise effects in cardiorespiratory fitness and muscle strength on PLWH through a systematic review and meta-analyses and 2) determine the likelihood of German PLWH developing non-HIV comorbidities, in a cross-sectional study. Meta-analytic examination indicates PLWH cardiorespiratory fitness (VO2max SMD = 0.61 ml·kg·min-1, 95% CI: 0.35-0.88, z = 4.47, p < 0.001, I2 = 50%) and strength (of remark lowerbody strength by 16.8 kg, 95% CI: 13–20.6, p< 0.001) improves after an exercise intervention in comparison to a control group. Cross-sectional data suggest exercise has a positive effect on German PLWH mental health (less anxiety and depressive symptoms) and protects against the development of anxiety (PR: 0.57, 95%IC: 0.36 – 0.91, p = 0.01) and depression (PR: 0.62, 95%IC: 0.41 – 0.94, p = 0.01). Likewise, exercise duration is related to a lower likelihood of reporting heart arrhythmias (PR: 0.20, 95%IC: 0.10 – 0.60, p < 0.01) and exercise frequency to a lower likelihood of reporting diabetes mellitus (PR: 0.40, 95%IC: 0.10 – 1, p < 0.01) in German PLWH. A preliminary recommendation for German PLWH who want to engage in exercise can be to exercise ≥ 1 time per week, at an intensity of 5 METs per session or > 103 MET·min·day-1, with a duration ≥ 150 minutes per week. Nevertheless, further research is needed to comprehend exercise dose response and protective effect for cardiovascular diseases, anxiety, and depression in German PLWH.
The human immunodeficiency virus (HIV) has resisted nearly three decades of efforts targeting a cure. Sustained suppression of the virus has remained a challenge, mainly due
to the remarkable evolutionary adaptation that the virus exhibits by the accumulation of drug-resistant mutations in its genome. Current therapeutic strategies aim at achieving and maintaining a low viral burden and typically involve multiple drugs. The choice of optimal combinations of these drugs is crucial, particularly in the background of treatment failure having occurred previously with certain other drugs. An understanding of the dynamics of viral mutant genotypes aids in the assessment of treatment failure with a certain drug
combination, and exploring potential salvage treatment regimens.
Mathematical models of viral dynamics have proved invaluable in understanding the viral life cycle and the impact of antiretroviral drugs. However, such models typically use simplified and coarse-grained mutation schemes, that curbs the extent of their application to drug-specific clinical mutation data, in order to assess potential next-line therapies. Statistical
models of mutation accumulation have served well in dissecting mechanisms of resistance evolution by reconstructing mutation pathways under different drug-environments. While these models perform well in predicting treatment outcomes by statistical learning, they do not incorporate drug effect mechanistically. Additionally, due to an inherent lack of
temporal features in such models, they are less informative on aspects such as predicting mutational abundance at treatment failure. This limits their application in analyzing the
pharmacology of antiretroviral drugs, in particular, time-dependent characteristics of HIV therapy such as pharmacokinetics and pharmacodynamics, and also in understanding the impact of drug efficacy on mutation dynamics.
In this thesis, we develop an integrated model of in vivo viral dynamics incorporating drug-specific mutation schemes learned from clinical data. Our combined modelling
approach enables us to study the dynamics of different mutant genotypes and assess mutational abundance at virological failure. As an application of our model, we estimate in vivo
fitness characteristics of viral mutants under different drug environments. Our approach also extends naturally to multiple-drug therapies. Further, we demonstrate the versatility of our model by showing how it can be modified to incorporate recently elucidated mechanisms of drug action including molecules that target host factors.
Additionally, we address another important aspect in the clinical management of HIV disease, namely drug pharmacokinetics. It is clear that time-dependent changes in in vivo
drug concentration could have an impact on the antiviral effect, and also influence decisions on dosing intervals. We present a framework that provides an integrated understanding
of key characteristics of multiple-dosing regimens including drug accumulation ratios and half-lifes, and then explore the impact of drug pharmacokinetics on viral suppression.
Finally, parameter identifiability in such nonlinear models of viral dynamics is always a concern, and we investigate techniques that alleviate this issue in our setting.
Die Autoren untersuchten mit Hilfe einer Fragebogenstudie das Sexualverhalten von StudentenInnen und KrankenpflegeschülernInnen unter der Bedrohung durch AIDS(n = 593). Als Ergebnis lässt sich festhalten, dass unterschiedliche Personengruppen mit unterschiedlichen Einstellungen, mit unterschiedlichem Wissen über HIV und AIDS, mit unterschiedlichem Sexualverhalten sowie einem unterschiedlichen Grad von persönlicher Betroffenheit auf differenzierte Weise angesprochen und zur Prävention angeleitet werden müssen. Die berufliche Nähe zu HIV und AIDS hat keinen Einfluss auf die sexuellen Einstellungen und Verhaltensweisen. Nur durch eine Selbststeuerung kann einer Gefahrensituation, wie sie eine mögliche HIV-Infektion darstellt, begegnet werden. Von daher muss neben der persönlichen Betroffenheit auch die Einsicht gegeben sein, dass ich mich als Individuum eigenständig vor dieser Gefahr schützen kann. Ferner muss dieses Verhalten in die eigene Lebenswelt eingepasst und von der eigenen sozialen Umgebung getragen werden. Präventionsbemühungen müssen auf kompetenzsteigernde, ressourcenorientierte und differenzierte Maßnahmen setzen. Ansätze von Furchtappellen und Lustfeindlichkeit wirken kontraproduktiv. Eine Beschränkung der Prävention auf individuumzentrierte Maßnahmen ist wenig effektiv, sofern gesellschaftliche und strukturelle Bedingungen ausgeblendet werden. Ziel von Sexualpädagogik und AIDS-Präventionsarbeit muss es daher sein, eine von allen geteilte Kommunikationsstruktur für Intimität zu entwickeln.