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Introduction: The most significant clinical challenges in people living with HIV/AIDS (PLWHA) are decline in CD4+ T helper cells and abnormal weight reduction. Consequently, PLWHA who are on Anti-Retroviral Therapy (ART) or Highly Active Anti-Retroviral Therapy (HAART) are usually predisposed to coronary artery diseases due to abnormal weight gain (lipohypertrophy), though with improved and unstable Cluster of Differentiation 4 (CD4) counts.The main aim of this study was to compare the effects of 6 weeks progressive resistance exercise (PRE) and moderate intensity aerobic exercise (MIAE) on CD4 count, and weight of PLWHA in Alex-Ekwueme Federal University Teaching Hospital Ebonyi State., Method: The study adopted quasi experimental research design. The population of the study was 60 Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome patients that attended HIV clinics at Alex-Ekwueme Federal University Teaching Hospital Abakaliki (AE-FUTHA) which formed 58 sample sizes for this study.Simple random sampling technique was adopted for the study and flow cytometry, Heel Densitometer (X-rite 331C), and Omron BF 400 were the instrument used for data collection of CD4 counts and weight respectively; and they are standardized hence not validated. Mean, standard deviation and Analysis of Co-variance (ANCOVA) were used to analyze the data obtained. The reliability coefficient obtained from the pilot study was 0.848 and 0.994 for CD4 and WEIGHT respectively., Results: The major findings revealed a significant difference after 6 weeks' PRE and MIAE on CD4 and Weight of PLWHA., Conclusion: Health promotion policy maker's arm of the government and Healthcare givers should integrate and enforce the use of exercises either as a single regimen or combined exercises into the management plan of PLWHA for greater boost in absolute CD4 count bearing in mind that both have positive effects. Physiotherapist should be integrated in the managements of PLWHA for appropriate prescription and education of therapeutic exercises for body weight., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The residual life of a patient with human immunodeficiency virus (HIV) is of major interest to patients and their physicians. While existing analyses of HIV patient survival focus mostly on data collected at baseline, residual life analysis allows for dynamic analysis based on additional data collected over a period of time. As survival times typically exhibit a right-skewed distribution, the median provides a more useful summary of the underlying distribution than the mean. In this paper, we propose an efficient inference procedure that fits a semiparametric quantile regression model assessing the effect of longitudinal biomarkers on the residual life of HIV patients until the development of dyslipidemia, a disease becoming more prevalent among those with HIV. Methods: For estimation of model parameters, we propose an induced smoothing method that smooths nonsmooth estimating functions based on check functions. For variance estimation, we propose an efficient resampling-based estimator. The proposed estimators are theoretically justified. Simulation studies are used to evaluate their finite sample performances, including their prediction accuracy. We analyze the Korea HIV/AIDS cohort study data to examine the effects of CD4 (cluster of differentiation 4) cell count on the residual life of HIV patients to the onset of dyslipidemia. Results: The proposed estimator is shown to be consistent and normally distributed asymptotically. Under various simulation settings, our estimates are approximately unbiased. Their variances estimates are close to the empirical variances and their computational efficiency is superior to that of the nonsmooth counterparts. Two measures of prediction performance indicate that our method adequately reflects the dynamic character of longitudinal biomarkers and residual life. The analysis of the Korea HIV/AIDS cohort study data shows that CD4 cell count is positively associated with residual life to the onset of dyslipidemia but the effect is not statistically significant. Conclusions: Our method enables direct prediction of residual lifetimes with a dynamic feature that accommodates data accumulated at different times. Our estimator significantly improves computational efficiency in variance estimation compared to the existing nonsmooth estimator. Analysis of the HIV/AIDS cohort study data reveals dynamic effects of CD4 cell count on the residual life to the onset of dyslipidemia. [ABSTRACT FROM AUTHOR]

Background: The number of elderly people living with HIV (EPLHIV) has increased significantly as a result of antiretroviral treatment (ART) and this has brought about a variety of psychosocial challenges that have an impact on their quality of life (QoL). Various psychosocial interventions have been tried or implemented in Sub-Saharan Africa (SSA) to improve QoL of EPLHIV. However, there is paucity of data on the types and effectiveness of these interventions. This systematic review, therefore, aims to explore available psychosocial interventions in SSA and their effectiveness in improving the QoL of EPLHIV. Methods: We will search PubMed, PsycINFO, LILACS, Cochrane Library, Google Scholar, HINARI, Africa Journals Online, Scopus and Web of Science to retrieve publications on psychosocial interventions implemented to improve QoL of EPLHIV from inception of the identified databases to 31st December 2023 without language restrictions. Also, supplementary sources such as conference proceedings, preprint repositories, databases of dissertations, as well as WHO and governmental databases can be explored for additional studies. For unpublished studies, trial registries and experts would be contacted, and reference lists of retrieved papers will be manually searched. Retrieved studies will be deduplicated using Mendeley and exported to Rayyan. At least two reviewers will independently select studies, extract data and assess the quality of the included studies using validated tools. Dichotomous outcomes data will be assessed and reported as odds ratio (OR) or risk ratio (RR) and for continuous outcomes, mean difference (MD) will be used; all reported with their 95% confidence interval (CI). Heterogeneity will be explored graphically by inspecting the overlapping of CIs and assessed quantitatively using the I2 statistic. Expected outcomes: This systematic review will be the first to rigorously identify psychosocial intervention on QoL of EPLHIV in SSA and assess their effectiveness with the aim to provide regional and country- specific data that will inform the selection and implementation of appropriate and socially acceptable policies across countries in SSA. Key findings of the review are expected to contribute critical evidence on availability, types and effectiveness of psychosocial interventions for improving quality of life of vulnerable elderly persons in SSA living with HIV. Furthermore, the review will explore any variation and possible correlates of psychosocial interventions by age, sex, CD4 count (if available), setting and geographic location within SSA that will provide healthcare professionals with reliable evidence, with the ultimate goal of inspiring countries in SSA to adopt innovative interventions to improve HIV care. Trial registration: Systematic review registration: The systematic review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO), with registration ID CRD42021278218. [ABSTRACT FROM AUTHOR]

Aspergillus spp. are ubiquitous and cause severe infections in immunocompromised patients. Less is known about its incidence and prognosis in patients with HIV/AIDS. We reviewed the mortality of invasive aspergillosis in HIV/AIDS patients. Pubmed, Embase and Medline databases were used to search for articles. Studies were excluded if they contained other aspergillosis risk factors, no original or patient survival data or were not in English. From 747 articles published, 54 studies and case reports were identified following reading, published between 1985 and 2021, with 54% papers prior to 2000 reporting 853 patients from 16 countries, none from Africa. 707 (83%) patients died with an average time from diagnosis to death of 77.5 days. Postmortem diagnosis was seen in 21% of deaths recorded. A national series from France of 242 cases of invasive aspergillosis diagnosed in life recorded a 3 month mortality of 68% pre-ART, falling to 31% after introduction of ART and voriconazole. CD4 count was recorded in 39 studies and ranged from 2 to >1000 cells/mm3; only 8 patients (1.8%) had a CD4 > 100 cells/mm3. Aspergillosis occurs in patients with HIV/AIDS and associated with high mortality but its slow progression should allow diagnosis and treatment with improved outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: The extracellular matrix surrounding or infiltrating tumor tissues, tumor cells, endothelial cells, immune cells, fibroblasts, macrophages, as well as soluble molecules like cytokines and growth factors secreted by these cells, constitute the complex biological structure known as the tumor microenvironment (TME). The cellular and non-cellular components of TME have a role in the development of tumors and the immune response, which offers novel insights for targeted therapies. Depleting existing cells, stopping them from being attracted to tumor locations, and reprogramming them into antitumor subtypes are the three primary categories of therapeutic approaches. TME exhibits complicated connections between Hodgkin/Reed–Sternberg cells and microenvironment and plays a crucial role in classical Hodgkin lymphoma (CHL) as well. Numerous studies have demonstrated that an extensive understanding of the CHL microenvironment, including the identification of all cellular components and variables implicated in the pathogenesis, is essential for improving prognostic stratification and developing innovative targeted treatments. Although classical Hodgkin lymphoma (CHL) is typically curable, 15–25% of individuals eventually experience a relapse and pass away from their disease. In CHL, the cellular microenvironment is constituted by few percent of H/RS (Hodgkin/Reed–Sternberg) tumor cells surrounded from a heterogeneous infiltration of inflammatory cells. The interplay of H/RS cells with other immune cells in the microenvironment may provide novel strategies for targeted immunotherapies. In this paper we analyzed the microenvironment content in CHL patients with responsive disease (RESP) and patients with relapsed/refractory disease to treatment (REL). Our results indicate the increase of CD68+ and CD163+ macrophages, the increase of PDL-1+ cells and of CD34+ microvessels in REL patients respective to RESP patients. In contrast we also found the decrease of CD3+ and of CD8+ lymphocytes in REL patients respective to RESP patients. Finally, in REL patients our results show the positive correlation between CD68+ macrophages and PDL-1+ cells as well as a negative correlation between CD163+ and CD3+. [ABSTRACT FROM AUTHOR]

Background: The association structure linking the longitudinal and survival sub-models is of fundamental importance in the joint modeling framework and the choice of this structure should be made based on the clinical background of the study. However, this information may not always be accessible and rationale for selecting this association structure has received relatively little attention in the literature. To this end, we aim to explore four alternative functional forms of the association structure between the CD4 count and the risk of death and provide rationale for selecting the optimal association structure for our data. We also aim to compare the results obtained from the joint model to those obtained from the time-varying Cox model.Methods: We used data from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) AIDS Treatment programme, the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) study, an open-label, three armed randomised, controlled trial between June 2005 and July 2010 (N=642). In our analysis, we combined the early and late integrated arms and compared results to the sequential arm. We utilized the Deviance Information Criterion (DIC) to select the final model with the best structure, with smaller values indicating better model adjustments to the data.Results: Patient characteristics were similar across the study arms. Combined integrated therapy arms had a reduction of 55% in mortality (HR:0.45, 95% CI:0.28-0.72) compared to the sequential therapy arm. The joint model with a cumulative effects functional form was chosen as the best association structure. In particular, our joint model found that the area under the longitudinal profile of CD4 count was strongly associated with a 21% reduction in mortality (HR:0.79, 95% CI:0.72-0.86). Where as results from the time-varying Cox model showed a 19% reduction in mortality (HR:0.81, 95% CI:0.77-0.84).Conclusions: In this paper we have shown that the "current value" association structure is not always the best structure that expresses the correct relationship between the outcomes in all settings, which is why it is crucial to explore alternative clinically meaningful association structures that links the longitudinal and survival processes. [ABSTRACT FROM AUTHOR]

Computer searches of the PubMed, Cochrane Library, and Embase databases for randomized controlled studies on the effects of intensive nutrition on clinical outcomes in patients with severe craniocerebral injury were conducted from the time of database creation to June 11, 2022, along with manual searches of the relevant literature. Two investigators independently screened the literature, extracted data, and evaluated the risk of bias of the included studies before the effect sizes were combined using RevMan 5.3 statistical software provided by the Cochrane Collaboration Network, and publication bias was detected using Stata 12.0 software. Meta-analysis showed that total protein levels were higher in the intensive nutrition group than in the regular nutrition group (WMD = 4.96 g/L (1.57-8.34), P < 0.001); IgA levels were significantly higher in the intensive nutrition group than in the regular nutrition group (SMD = 0.79 (0.51-1.07), P < 0.001 ; SMD = 0.98 (0.58-1.38), P < 0.001); IgG levels were significantly higher in the fortified group than in the regular group (SMD = 0.98 (0.58-1.38), P < 0.001); CD4/CD8 was significantly higher in the fortified patients than in the regular patients with a combined effect size of WMD = 0.33 (0.18-0.48) (P < RR = 0.45 (0.27-0.75), P = 0.002). The results show that effective support of early enteral nutrition can reduce the occurrence of gastrointestinal complications in patients, give them a better adaptation process to the gastrointestinal tract, and ensure the degree of tolerance of their gastric mucosa, thus absorbing more nutrition. Fortification significantly reduced the incidence of gastric retention in patients with craniocerebral injury (RR = 0.19 (0.07-0.49), P < 0.001). In the subgroup analysis of the three groups, it was shown that, depending on the starting time, the total protein level and IgG level were better in the early nutrition at 24 h than in the late nutrition above 24h and that, depending on the starting dose, the total protein level, IgA, IgG, and CD4/CD8 were better in the intervention at doses above 30 mL/h, using the starting dose of 30 mL/h as the cut-off point. In the subgroup analysis based on different nutrition methods (enteral and parenteral nutrition), IgA levels and the incidence of bloating and diarrhea were better than those of parenteral nutrition in the indicators of enteral nutrition. [ABSTRACT FROM AUTHOR]

This paper presents an innovative Bayesian method for assessing the status and progression of HIV infection using biomarkers such as the CD4 count and viral load variables. A distribution of viral loads in subjects starting antiretroviral treatment and followed over time may show a mixture of two subgroups: one subgroup representing "non-progressor" subjects and another subgroup of "progressor" subjects. In modeling these groups, we use a mass point and a right-skewed continuous distribution in which trajectories of repeated observations of viral load exhibit multiphasic features along with a gradual transition period. The commonly used method for describing these phasic patterns is a bent-cable model with a quadratic function for modeling the gradual transition phase. A quadratic function may be too restrictive for adequately modeling the transition period. Thus, we we extend the bent-cable model within the context of a two-component Tobit growth model by relaxing the assumption of a quadratic function for a gradual transition period and accounting for measurement errors in CD4 count. The proposed methods are demonstrated using real data from an AIDS clinical study. [ABSTRACT FROM AUTHOR]

Background: HIV treatment and care services were scaled up in 2007 in India with objective to increase HIV-care coverage. CD4 count based criteria was mainly used for treatment initiation with increasing threshold in later years. Therefore, this paper aimed to evaluate the survival by varying CD4 criteria for antiretroviral treatment (ART) initiation among of HIV-positive patients, and independent factors associated with the mortality.Methods: This retrospective cohort study included 127 949 HIV-positive patients aged ≥15 years, who initiated ART between 2007 and 2013 in Andhra Pradesh state, India. The patient's demographic and clinical characteristics were extracted from the patient's health records from electronic Computerized Management Information System Software (CMIS). Incidence of mortality/100 person-years was calculated for CD4 and treatment initiation categories. Kaplan-Meier and multivariable Cox-regression analyses were used to explore the association.Results: Median CD4 count was 172 (inter-quartile range (IQR) = 102-240) at the time of treatment initiation, and 19.3% of them had ≤ 100 CD4 count. Incidence of mortality for the period 2007-08 (CD4 ≤ 200 cells/mm3) was 8.5/100 person-years compared to 6.4/100 person-years at risk for the period 2012 onwards (CD4 ≤ 350 cells/mm3). Earlier thresholds for treatment initiation showed higher risk of mortality (2007-08 (CD4 ≤ 200 cells/mm3), adjusted hazard ratio (HR): 1.86, 95% confidence interval (CI): 1.68-2.07; 2009-11 (CD4 ≤ 250 cells/mm3), HR = 1.67, 95% CI = 1.51-1.85) compared to 2012 onwards (CD4 ≤ 350 cells/mm3) criteria for treatment initiation.Conclusions: Increasing CD4 threshold for treatment initiation over time was independently associated with lower risk of mortality. More efforts are required to detect and treat early, monitoring of follow-ups, promote health education to improve ART adherence, and provide supportive environment that encourages HIV-infected patients to disclose their HIV status in confidence. [ABSTRACT FROM AUTHOR]

Objectives: HIV virological failure remains a major threat to programme success in sub‐Saharan Africa. While HIV drug resistance (HIVDR) and inadequate adherence are the main drivers of virological failure, the individual, clinical and health system characteristics that lead to poor outcomes are not well understood. The objective of this paper is to identify those characteristics among people failing first‐line antiretroviral therapy (ART). Methods: We enrolled a cohort of adults in HIV care experiencing virological failure on first‐line ART at five sites and used standard statistical methods to characterize them with a focus on three domains: individual/demographic, clinical, and health system, and compared each by country of enrolment. Results: Of 840 participants, 51% were women, the median duration on ART was 3.2 years [interquartile range (IQR) 1.1, 6.4 years] and the median CD4 cell count prior to failure was 281 cells/µL (IQR 121, 457 cells/µL). More than half of participants [53%; 95% confidence interval (CI) 49–56%] stated that they had > 90% adherence and 75% (95% CI 72–77%) took their ART on time all or most of the time. Conversely, the vast majority (90%; 95% CI 86–92%) with a completed genotypic drug resistance test had any HIV drug resistance. This population had high health system use, reporting a median of 3 (IQR 2.6) health care visits and a median of 1 (IQR 1.1) hospitalization in the preceding 6 months. Conclusions: Patients failing first‐line ART in sub‐Saharan Africa generally report high rates of adherence to ART, have extremely high rates of HIV drug resistance and utilize significant health care resources. Health systems interventions to promptly detect and manage treatment failure will be a prerequisite to establishing control of the HIV epidemic. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the heterogeneity of change of posttraumatic growth (PTG) among people living with HIV (PLWH) in a 1-year prospective study. The goal was also to identify sociodemographic and clinical covariates and differences in baseline coping strategies. Particularly, time since diagnosis and positive reframing coping were of special interest. The sample consisted of 115 people with medically confirmed diagnosis of HIV infection. The participants filled out paper-and-pencil questionnaires three times with an interval of 6 months, including also sociodemographic and clinical data. Four trajectories of PTG were identified: curvilinear, low stable, high stable, and rapid change. Participants' gender, education level, CD4 count and time since HIV diagnosis occurred to be significant covariates of class membership. Positive reframing and self-distraction differentiated only between the high stable and the rapid change trajectory, with lower values in the latter. The study results call for attention to the complexity of PTG patterns in a face of struggling with HIV infection. Specifically, interventions in clinical practice should take into account the fact that there is no single pattern of PTG that fits all PLWH and that these differences may be related to the sociodemographic and clinical characteristics as well as to coping strategies representing meaning-making mechanism. [ABSTRACT FROM AUTHOR]

Marginal structural models (MSMs) with inverse probability weighted estimators (IPWEs) are widely used to estimate causal effects of treatment sequences on longitudinal outcomes in the presence of time‐varying confounding and dependent censoring. However, IPWEs for MSMs can be inefficient and unstable if weights are estimated by maximum likelihood. To improve the performance of IPWEs, covariate balancing weight (CBW) methods have been proposed and recently extended to MSMs. However, existing CBW methods for MSMs are inflexible for practical use because they often do not handle dependent censoring, nonbinary treatments, and longitudinal outcomes (instead of eventual outcomes at a study end). In this paper, we propose a joint calibration approach to CBW estimation for MSMs that can accommodate (1) both time‐varying confounding and dependent censoring, (2) binary and nonbinary treatments, (3) eventual outcomes and longitudinal outcomes. We develop novel calibration restrictions by jointly eliminating covariate associations with both treatment assignment and censoring processes after weighting the observed data sample (i.e., to optimize covariate balance in finite samples). Two different methods are proposed to implement the calibration. Simulations show that IPWEs with calibrated weights perform better than IPWEs with weights from maximum likelihood and the "Covariate Balancing Propensity Score" method. We apply our method to a natural history study of HIV for estimating the effects of highly active antiretroviral therapy on CD4 cell counts over time. [ABSTRACT FROM AUTHOR]

Missing response problem is ubiquitous in survey sampling, medical, social science and epidemiology studies. It is well known that non-ignorable missing is the most difficult missing data problem where the missing of a response depends on its own value. In statistical literature, unlike the ignorable missing data problem, not many papers on non-ignorable missing data are available except for the full parametric model based approach. In this paper we study a semiparametric model for non-ignorable missing data in which the missing probability is known up to some parameters, but the underlying distributions are not specified. By employing Owen (1988)'s empirical likelihood method we can obtain the constrained maximum empirical likelihood estimators of the parameters in the missing probability and the mean response which are shown to be asymptotically normal. Moreover the likelihood ratio statistic can be used to test whether the missing of the responses is non-ignorable or completely at random. The theoretical results are confirmed by a simulation study. As an illustration, the analysis of a real AIDS trial data shows that the missing of CD4 counts around two years are non-ignorable and the sample mean based on observed data only is biased. [ABSTRACT FROM AUTHOR]

Background: CD4 cell counts is widely used as a biomarker for treatment progression when studying the efficacy of drugs to treat HIV-infected patients. In the past, it had been also used in determining eligibility to initiate antiretroviral therapy. The main aim of this was to model the evolution of CD4 counts over time and use this model for an early prediction of subject-specific time to cross a pre-specified CD4 threshold. Methods: Hospital based retrospective cohort study of HIV-infected patients was conducted from January 2009 to December 2014 at University of Gondar hospital, Northwest Ethiopia. Fractional polynomial random effect model is used to model the evolution of CD4 counts over time in response to treatment and to estimate the individual probability to be above a pre-selected CD4 threshold. Human subject research approval for this study was received from University of Gondar Research Ethics Committee and the medical director of the hospital. Results: A total of 1347 patients were included in the analysis presented in this paper. The cohort contributed a total of 236.58 per 100 person-years of follow-up. Later the data were divided into two periods: the first is the estimation period in which the parameters of the model are estimated and the second is the prediction period. Based on the parameters from the estimation period, model based prediction for the time to cross a threshold was estimated. The correlations between observed and predicted values of CD4 levels in the estimation period were 0.977 and 0.982 for Neverapine and Efavirenz containing regimens, respectively; while the correlation between the observed and predicted CD4 counts in the prediction period are 0.742 and 0.805 for NVP and EFV, respectively. Conclusions: The model enables us to estimate a subject-specific expected time to cross a CD4 threshold and to estimate a subject-specific probability to have CD4 count above a pre-specified threshold at each time point. By predicting long-term outcomes of CD4 count of the patients one can advise patient about the potential ART benefits that accrue in the long-term. [ABSTRACT FROM AUTHOR]

HIV damages the immune system by targeting the CD4 cells. Hence CD4 count data modeling is important in the analysis of HIV infection. This paper considers a semiparametric mixed effects model for the analysis of CD4 longitudinal data. The model is a natural extension to the linear mixed and semiparametric models that uses parametric linear model to present the covariate effects and an arbitrary nonparametric smooth function to model the time effect and account for the within subject correlation using random effects. We approximate the nonparametric function by the profile kernel method, and make use of the weighted least squares to estimate the regression coefficients. Under some regularity conditions, the asymptotic normality of the resulting estimator is established and the performance is compared with the backfitting method. Although, two estimators share the same asymptotic variance matrix for independent data, it is shown that, backfitting often produces larger bias and variance than the profile-kernel method, asymptotically. Consequently, the use of backfitting method is no longer advised in semiparametric mixed effect longitudinal model. For practical implementation and also improve efficiency, the estimation of the covariance function is accomplished using an iterative algorithm. Performance of the proposed methods are compared through a simulation study and the analysis of CD4 data. [ABSTRACT FROM AUTHOR]

In this paper, we provide a unified framework for two-sample t-test with partially paired data. We show that many existing two-sample t-tests with partially paired data can be viewed as special members in our unified framework. Some shortcomings of these t-tests are discussed. We also propose the asymptotically optimal weighted linear combination of the test statistics comparing all four paired and unpaired data sets. Simulation studies are used to illustrate the performance of our proposed asymptotically optimal weighted combinations of test statistics and compare with some existing methods. It is found that our proposed test statistic is generally more powerful. Three real data sets about CD4 count, DNA extraction concentrations, and the quality of sleep are also analyzed by using our newly introduced test statistic. [ABSTRACT FROM AUTHOR]

In this paper, we investigate an in-host model for the viral dynamics of HIV-1 infection and its interaction with the CTL immune response. The model is sufficiently general to allow nonlinear forms for both viral infection and CTL response. Threshold parameters are identified that completely determine the global dynamics and outcomes of the virus-target cell-CTL interactions. Impacts of key parameter values for CTL functions and viral budding rate on the HIV-1 viral load and CD4 count are investigated using numerical simulations. Results support clinical evidence for important differences between HIV-1 nonprogressors and progressors. [ABSTRACT FROM AUTHOR]

Background: The benefit of a given treatment can be evaluated via a randomized clinical trial design. However, protocol deviations may severely compromise treatment effect since such deviations often lead to missing values. The assumption that methods of analysis can account for the missing data cannot be justified and hence methods of analysis based on plausible assumptions should be used. An alternative analysis to the simple imputation methods requires unverifiable assumptions about the missing data. Therefore sensitivity analysis should be performed to investigate the robustness of statistical inferences to alternative assumptions about the missing data., Aims: In this paper, we investigate the effect of tuberculosis pericarditis treatment (prednisolone) on CD4 count changes over time and draw inferences in the presence of missing data. The data come from a multicentre clinical trial (the IMPI trial)., Methods: We investigate the effect of prednisolone on CD4 count changes by adjusting for baseline and time-dependent covariates in the fitted model. To draw inferences in the presence of missing data, we investigate sensitivity of statistical inferences to missing data assumptions using the pattern-mixture model with multiple imputation (PM-MI) approach. We also performed simulation experiment to evaluate the performance of the imputation approaches., Results: Our results showed that the prednisolone treatment has no significant effect on CD4 count changes over time and that the prednisolone treatment does not interact with time and anti-retroviral therapy (ART). Also, patients' CD4 count levels significantly increase over the study period and patients on ART treatment have higher CD4 count levels compared with those not on ART. The results also showed that older patients had lower CD4 count levels compared with younger patients, and parameter estimates under the MAR assumption are robust to NMAR assumptions., Conclusions: Since the parameter estimates under the MAR analysis are robust to NMAR analyses, the process that generated the missing data in the CD4 count measurements is missing at random (MAR). The implication is that valid inferences can be obtained using either the likelihood-based methods or multiple imputation approaches.

Background: Antiretroviral therapy has prolonged the lives of those with human immunodeficiency virus (HIV), but the effects of chronic infection on their health-related quality of life (HRQoL) remain a concern. Numerous instruments have been developed to measure HRQoL, yet evidence of their cross-cultural equivalence and continued applicability is limited. We adapted the WHOQOL-HIV BREF to French and assessed its psychometric properties in a sample of community-dwelling adults living with HIV who were mostly virally suppressed.Methods: We conducted a cross-sectional study within the ANRS CO3 Aquitaine cohort from July 2018 to May 2019. Five hundred eighty-six participants were consecutively enrolled at their HIV-consultations and completed either a web-based (n = 406) or paper self-administered assessment (n = 180). The means and standard deviations for items and domains were computed and the presence of floor and ceiling effects assessed. We evaluated internal consistency by calculating Cronbach's alpha coefficients per domain. We assessed construct validity by performing a Confirmatory Factor Analysis (CFA). Concurrent, convergent and discriminant validity were assessed with Pearson's correlations and known-group validity was assessed according to CD4 cell count, viral load, Centers for Disease Control and Prevention clinical categories for HIV, and hospitalization of more than 48 h within 2 years of the most recent consultation using one-way analysis of variance and independent t-tests.Results: Five hundred eighty-six PLWH were included in this analysis. Their median age was 55; 73% were male; 85% were of French descent; 99% were on ART and 93% were virally suppressed. We found floor effects for one and ceiling effects for 11 items. Four of the six domains showed good internal consistency (α range: 0.63-0.79). CFA showed that the WHOQOL-HIV BREF's six-domain structure produced an acceptable fit (SRMR = 0.059; CFI = 0.834; RMSEA = 0.07; 90% CI: 0.06-0.08). It showed good concurrent, convergent and discriminant validity. There was some evidence of known-group validity. The personal beliefs domain had the highest score (15.04 ± 3.35) and the psychological health domain had the lowest (13.70 ± 2.78).Conclusions: The French WHOQOL-HIV BREF has acceptable measurement properties. Its broad conceptualisation of HRQoL, going beyond physical and mental health, may be of particular value in our older, treatment-experienced and virally suppressed population.Trial Registration: ClinicalTrials.gov NCT03296202 (Archived by WebCite at http://www.webcitation.org/6zgOBArps ). [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a new human infectious disease. The etiology for this outbreak is a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus far, related research on COVID-19 is still in preliminary stage. This paper summarized the latest outcomes of corresponding study from Chinese centers and clarified the hematopoietic abnormality caused by SARS-CoV-2 and potential mechanism. Lymphopenia was common in the early stage after the onset of COVID-19. A significant decrease was observed in peripheral CD4+ and CD8+ T lymphocytes. As the illness progressed, neutrophilia emerged in several cases, and patients with severe critical pulmonary conditions showed higher neutrophils than common type. Thrombocytopenia was resulting from the consumption and/or the reduced production of platelets in damaged lungs. Anemia was not observed notably, but the decrease in hemoglobin was frequent. The activation of monocyte-macrophage system aggravates the immune damage of lung and other tissues, which leads to the increase of D-dimer, prothrombin time, and platelet consumption. [ABSTRACT FROM AUTHOR]

Introduction: Combination antiretroviral therapy has become the standard care of human immunodeficiency virus (HIV)-infected patients and has further led to a dramatically decreased progression probability to acquired immune deficiency syndrome (AIDS) for patients under such a therapy. However, responses of the patients to this therapy have recorded heterogeneous complexity and high dynamism. In this paper, we simultaneously model long-term viral suppression, viral rebound, and state-specific duration of HIV-infected patients. Methods: Full-parametric and semi-parametric Markov multistate models were applied to assess the effects of covariates namely TB co-infection, educational status, marital status, age, quality of life (QoL) scores, white and red blood cell parameters, and liver enzyme abnormality on long-term viral suppression, viral rebound and state-specific duration for HIV-infected individuals before and after treatment. Furthermore, two models, one including and another excluding the effect of the frailty, were presented and compared in this study. Results: Results from the diagnostic plots, Akaike information criterion (AIC) and likelihood ratio test showed that the Weibull multistate frailty model fitted significantly better than the exponential and semi-parametric multistate models. Viral rebound was found to be significantly associated with many sex partners, higher eosinophils count, younger age, lower educational level, higher monocyte counts, having abnormal neutrophils count, and higher liver enzyme abnormality. Furthermore, viral suppression was also found to be significantly associated with higher QoL scores, and having a stable sex partner. The analysis result also showed that patients with a stable sex partner, higher educational levels, higher QoL scores, lower eosinophils count, lower monocyte counts, and higher RBC indices were more likely to spend more time in undetectable viral load state. Conclusions: To achieve and maintain the UNAIDS 90% suppression targets, additional interventions are required to optimize antiretroviral therapy outcomes, specifically targeting those with poor clinical characteristics, lower education, younger age, and those with many sex partners. From a methodological perspective, the parametric multistate approach with frailty is a flexible approach for modeling time-varying variables, allowing for dealing with heterogeneity between the sequence of transitions, as well as allowing for a reasonable degree of flexibility with a few additional parameters, which then aids in gaining a better insight into how factors change over time. [ABSTRACT FROM AUTHOR]

In longitudinal studies, it is of interest to investigate how repeatedly measured markers are associated with time to an event. Joint models have received increasing attention on analyzing such complex longitudinal-survival data with multiple data features, but most of them are mean regression-based models. This paper formulates a quantile regression (QR) based joint models in general forms that consider left-censoring due to the limit of detection, covariates with measurement errors and skewness. The joint models consist of three components: (i) QR-based nonlinear mixed-effects Tobit model using asymmetric Laplace distribution for response dynamic process; (ii) nonparametric linear mixed-effects model with skew-normal distribution for mismeasured covariate; and (iii) Cox proportional hazard model for event time. For the purpose of simultaneously estimating model parameters, we propose a Bayesian method to jointly model the three components which are linked through the random effects. We apply the proposed modeling procedure to analyze the Multicenter AIDS Cohort Study data, and assess the performance of the proposed models and method through simulation studies. The findings suggest that our QR-based joint models may provide comprehensive understanding of heterogeneous outcome trajectories at different quantiles, and more reliable and robust results if the data exhibits these features. [ABSTRACT FROM AUTHOR]

In this paper, we assess the effect of tuberculosis pericarditis treatment (prednisolone) on CD4 count changes over time and draw inferences in the presence of missing data. We accounted for the missing data and performed sensitivity analyses to assess robustness of inferences, from a model that assumes that the data are missing at random, to models that assume that the data are not missing at random. Our sensitivity approaches are within the shared-parameter model framework. We implemented the approach by Creemers and colleagues to the CD4 count data and performed simulation studies to evaluate the performance of this approach. We also assessed the influence of potentially influential subjects, on parameter estimates, via the global influence approach. Our results revealed that inferences from missing at random analysis model are robust to not missing at random models and influential subjects did not overturn the study conclusions about prednisolone effect and missing data mechanism. Prednisolone was found to have no significant effect on CD4 count changes over time and also did not interact with anti-retroviral therapy. The simulation studies produced unbiased estimates of prednisolone effect with lower mean square errors and coverage probabilities approximately equal the nominal coverage probability. [ABSTRACT FROM AUTHOR]

Objectives: Despite recent pharmacological progress, memory impairment is still frequently reported in people living with HIV. We aimed to conduct a systematic literature review investigating the presence of impairment of (sub)components of memory function in patients prescribed highly active antiretroviral therapy (ART). Methods: We adopted a cognitive neuropsychological model of memory function as the theoretical framework, distinguishing between a short‐term working memory component and a long‐term component of memory, along with their specific (sub)components. We systematically searched for the presence of impairment of each (sub)component in the selected papers. Careful consideration was given to study design and methods and control of covariates. Results: Only the central executive component of working memory has been consistently reported to be impaired in HIV infection. The other two (sub)components, namely the phonological loop and the visuospatial sketchpad, were unimpaired. Discordant results have been obtained as to verbal and visual episodic memory, as some authors reported an association with HIV infection, whereas others did not. There is little evidence for semantic memory deficit in HIV infection, while there are suggestions that the neural substrate of implicit memory may be damaged by the effects of HIV infection and inflammation. Most studies in this area have been conducted in small samples and with poor control for covariates. Thus, conclusions regarding the association of memory dysfunction with HIV infection are hampered by methodological issues such as selection bias and unmeasured confounding. Conclusions: The task remains for future research to ascertain the impact of HIV infection on memory function. [ABSTRACT FROM AUTHOR]

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Background: Globally, Tuberculosis (TB) is the main cause of morbidity and mortality among infectious disease. TB and Human Immune Virus (HIV) are the two deadly pandemics which interconnected each other tragically, and jeopardize the lives of children; particularly in Sub-Saharan Africa. Therefore, this review was aimed to determine the aggregated national pooled incidence of tuberculosis among HIV- infected children and its predictors in Ethiopia. Methods: An electronic search engine (HINARI, PubMed, Scopus, web of science), Google scholar and free Google databases were searched to find eligible studies. Quality of the studies was checked using the Joanna Briggs Institute (JBI) quality assessment checklists for cohort studies. Heterogeneity between studies was evaluated using Cochrane Q-test and the I2 statistics. Result: This review revealed that the pooled national incidence of tuberculosis among children with HIV after initiation of ART was 3.63% (95% CI: 2.726–4.532) per 100-person-years observations. Being Anemic, poor and fair ART adherence, advanced WHO clinical staging, missing of cotrimoxazole and isoniazid preventing therapy, low CD4 cell count, and undernutrition were significant predictors of tuberculosis incidence. Conclusion: The study result indicated that the incidence of TB among HIV- infected children is still high. Therefore, parents/guardians should strictly follow and adjust nutritional status of their children to boost immunity, prevent undernutrition and opportunistic infections. Cotrimoxazole and isoniazid preventive therapy need to continually provide for HIV- infected children for the sake of enhancing CD4/immune cells, reduce viral load, and prevent from advanced disease stages. Furthermore, clinicians and parents strictly follow ART adherence. [ABSTRACT FROM AUTHOR]

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors, including physical, cultural, structural, and financial barriers, may limit early detection of HIV. This is a first-of-its-kind study on population-level differences in early detection of HIV across time within Tajikistan and any country in the Central Asia region. Utilizing the Tajikistan Ministry of Health's national HIV data (N = 10,700) spanning 2010 to 2023, we developed median regression models with the median CD4 cell count as the outcome and with the following predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old were detected early for HIV, whereas those older than 39 years were detected late. Females were detected earlier compared to their male counterparts regardless of region of residence. Rural populations were detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. There were differences identified among different demographic and geographic groups which warrant further attention. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to investigate the prevalence of self-reported sleep disturbances in people living with HIV considering the effects of age, depression, anxiety, CD4 cell counts, time since HIV diagnosis, study region, and the instruments used to measure sleep disturbances. We searched PubMed, PsycINFO, and EMBASE to include eligible articles. In this meta-analysis of 43 studies, the pooled prevalence of self-reported sleep disturbances was 52.29% (95% confidence interval 47.69–56.87). The subgroup analyses revealed that variations in the sleep measurements and study region significantly contributed to the observed heterogeneity. In the meta-regression analyses, higher proportions of participants with depression or anxiety and longer times since HIV diagnosis were significantly associated with a higher prevalence of self-reported sleep disturbances after adjusting for mean age. Our findings emphasise the substantial burden of sleep disturbances in people living with HIV and identified comorbid depression and anxiety and the time since HIV diagnosis as significant moderators. These results underscore the importance of considering these factors when designing tailored screening programmes for high-risk patients and implementing early interventions to prevent and mitigate sleep disturbances in people living with HIV. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to map place of cancer diagnosis in relation to Human Immunodeficiency Virus (HIV) care centre among people living with HIV (PLHIV) within South Africa (SA) using national laboratory database. Design: We linked HIV and cancer laboratory data from 2004–2014 using supervised machine-learning algorithms. We performed a cross-sectional analysis comparing province where individuals accessed their HIV care versus where they had their cancer diagnosis. Setting: We used laboratory test records related to HIV diagnostics and care, such as CD4 cell counts and percentages, rapid tests, qualitative Polymerase Chain Reaction (PCR), antibody and antigen tests for HIV data that was documented as HIV positive and laboratory diagnosed cancer records from SA. Study population: Our study population consisted of HIV records from the National Health Laboratory Service (NHLS) that linked to cancer record at the National Cancer Registry (NCR) between 2004–2014. Primary and secondary outcomes: We linked HIV records from NHLS to cancer records at NCR in order to study the inherent characteristics of the population with both HIV and cancer. Results: The study population was 68,284 individuals with cancer and documented HIV related laboratory test. The median age at cancer diagnosis was 40 [IQR, 33–48] years for the study population with most cancers in PLHIV diagnosed in females 70.9% [n = 46,313]. Of all the PLHIV and cancer, 25% (n = 16,364 p < 0.001) sought treatment outside their province of residence with 60.7% (n = 10,235) travelling to Gauteng. KZN had 46.6% (n = 4,107) of its PLHIV getting cancer diagnosis in Gauteng. Western Cape had 95% (n = 6,200) of PLHIV getting cancer diagnosis within the province. Conclusions: Our results showed health systems inequalities across provinces in SA with respect to cancer diagnosis. KZN for example had nearly half of the PLHIV getting cancer diagnosis outside the province while Western Cape is able to offer cancer diagnostic services to most of the PLHIV in the province. Gauteng is getting over burdened with referral for cancer diagnosis from other provinces. More effort is required to ensure equitable access to cancer diagnostic services within the country. [ABSTRACT FROM AUTHOR]

Serial limiting dilution (SLD) assays are used in many areas of infectious disease related research. This paper presents SLDAssay, a free and publicly available R software package and web tool for analyzing data from SLD assays. SLDAssay computes the maximum likelihood estimate (MLE) for the concentration of target cells, with corresponding exact and asymptotic confidence intervals. Exact and asymptotic goodness of fit p-values, and a bias-corrected (BC) MLE are also provided. No other publicly available software currently implements the BC MLE or the exact methods. For validation of SLDAssay, results from Myers et al. (1994) are replicated. Simulations demonstrate the BC MLE is less biased than the MLE. Additionally, simulations demonstrate that exact methods tend to give better confidence interval coverage and goodness-of-fit tests with lower type I error than the asymptotic methods. Additional advantages of using exact methods are also discussed., (Copyright © 2017 Elsevier B.V. All rights reserved.)