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Background: HIV has an effect on lowering CD4 cell count, which lowers the ability to resist contamination. For patients on ART in areas with limited resources, the CD4 cell count assessment is crucial for determining treatment responses and therapeutic decisions. The volatility of CD4 counts following the introduction of ART over time is still largely uncharacterized, and there are few fresh datasets on CD4 cell count progressions. The goal of this study was to identify the key factors that change over time in CD4 cells for HIV/AIDS patients receiving ART follow-up in northern Ethiopia., Methods: A total of 216 HIV/AIDS patients who initiated ART in the Mekelle General Hospital between 2013 and 2016 were involved using systematic random selection techniques. An examination of exploratory data was used to describe the individual profiles of HIV patients. A multivariable random intercept and slope linear mixed regression analysis regarded predictor variables to be statistically significant if their p-value was less than 0.05., Results: The random intercept and slope linear mixed model result indicated that there were statistically significant predictors of baseline CD4 cell count (β = 0.0125, P-value = 0.001*) and bedridden functional status (β = -2.459, p = 0.02*) on the change of CD4 cell count over time in HIV/AIDS patients at the 5% significance level., Conclusions: Changes in CD4 counts were influenced by the baseline CD4 cell count and the functional status of being bedridden. Because their CD4 cell counts were lower at baseline and they had a functional status of bedridden, the majority of HIV/AIDS patients on ART had substantial predictors on the change of CD4 cell count over time. So, public health service providers should give exceptional guidance and attention is also necessary for those patients who have lower baseline CD4 cell count and bedridden functional status., (© 2024. The Author(s).)

Background: To date there remains much ambiguity in the literature regarding the immunological interplay between SARS-CoV-2 and HIV and the true risk posed to coinfected individuals. There has been little conclusive data regarding the use of CD4 cell count and HIV viral load stratification as predictors of COVID-19 severity in this cohort., Methods: We performed a retrospective, observational cohort study on people living with HIV (PLWH) who contracted COVID-19 in central and eastern Europe. We enrolled 536 patients from 16 countries using an online survey. We evaluated patient demographics, HIV characteristics and COVID-19 presentation and outcomes. Statistical analysis was performed using SPSS 20.1., Results: The majority of the study cohort were male (76.4%) and 152 (28.3%) had a significant medical comorbidity. Median CD4 cell count at COVID-19 diagnosis was 605 cells/μL [interquartile range (IQR) 409-824]. The majority of patients on antiretroviral therapy (ART) were virally suppressed (92%). In univariate analysis, CD4 cell count <350 cells/μL was associated with higher rates of hospitalization (p < 0.0001) and respiratory failure (p < 0.0001). Univariate and multivariate analyses found that an undetectable HIV VL was associated with a lower rate of hospitalization (p < 0.0001), respiratory failure (p < 0.0001), ICU admission or death (p < 0.0001), and with a higher chance of full recovery (p < 0.0001)., Conclusion: We can conclude that detectable HIV viral load was an independent risk factor for severe COVID-19 illness and can be used as a prognostic indicator in this cohort., (© 2023 British HIV Association.)

Background: Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population., Objective: This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens., Methods: A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks., Results: At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/μL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected., Conclusion: Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: AIDS continues to be a serious global public health issue. It targets CD4 cells and immunological cells, which are in charge of the body's resistance against pathogenic pathogens. In situations with limited resources, CD4 cell measurement is essential for assessing treatment responses and clinical judgments in HIV-infected children receiving Anti-Retroviral Therapy (ART). The volatility of CD4 cells during ART follow-up is still largely uncharacterized, and there are few new datasets on CD4 cell changes over time. Therefore, the purpose of this analysis was to identify the factors that were predictive of CD4 cell count changes over time in children who started ART at Mekelle General Hospital in northern Ethiopia., Methods: A retrospective follow-up study was done. 437 patients in Mekelle general hospital, northern Ethiopia, from 2014-2016 were involved. All patients who have started anti-retrieval treatment (ART) and measured their CD4 cell count at least twice, including the baseline and those who initiated ART treatment, were included in the study population. An exploratory data analysis and linear mixed model analysis were used to explore the predictors of CD4 cell count change in patients and consider variability within and between patients., Results: This study found the correlation variation explained in cells accounted for between patients was 61.3%, and the remaining 38.7% variation existed within. This indicates that there is a substantial change in random slope and intercept between and within patients. WHO clinical stage IV (β = -1.30, 95% CI: -2.37, -0.23), co-infection HIV/TB (β = -1.78, 95% CI: -2.58, -0.98), children aged 2-5 (β = -0.43; 95% CI: -0.82, -0.04), and 6-14 years (β = -1.02; 95% CI: -1.47, -0.56), non-opportunistic infection (β = 1.33, 95% CI: 0.51, 2.14), and bedridden functional status (β = -1.74, 95% CI: -2.81, -0.68) were predictors of cell changes over time., Conclusions: This study found that patients receiving ART experienced a significant change in CD4 cells over time. Because 61.3% of the variation in CD4 cells explained between patients and the remaining 38.7% within patients, such nested data structures are often strong correlation evidence. Co-infection of HIV/TB, functional status, age category of children, WHO clinical stage, and opportunistic infections are potential predictors of CD4 cells count change. Hence, special guidance and attention is also required, especially for those patients who have an opportunistic infections, higher WHO clinical stages, co-infections with HIV and TB, and bedridden functional status., (© 2023. The Author(s).)

Background: HIV/AIDS is the most known powerful risk factor for morbidity and mortality in the world. The greatest biological markers in HIV patients are CD4 cell count and hemoglobin level, as they are independent predictors of survival of HIV patients. The objective of this study was to investigate the common socio-demographic, clinical, and behavioral Predictor's affecting the CD4 cell count, and hemoglobin level with survival time to default from ART treatment among HIV positive adults under ART treatment at university of Gondar comprehensive and specialized hospital, North-west Ethiopia., Method: This study was conducted at University of Gondar comprehensive specialized hospital by using a retrospective cohort follow up study design. The source of data in this study was secondary data obtained from patients chart. Bayesian joint models were employed to get wide-ranging information about HIV/AIDS progression., Result: From a total of 403 HIV positive adults, about 44.2% were defaulted from therapy and the rest were actively followed ART treatment. The estimate of the association parameter for the current true value of CD4 cell count ([Formula: see text]), and hemoglobin level ([Formula: see text]), trend of CD4 cell count ([Formula: see text]) and hemoglobin level ([Formula: see text]) is positive. Positive values indicating that the higher CD4 cell count and hemoglobin level is related with the higher time of defaulting from ART. Predictor's hematocrit, weight, platelet cell count, lymphocyte count, sex, adherence, and WHO clinical stage were joint determinate risk factors affecting CD4 cell count, hemoglobin level and time to default at 5% level of significance., Conclusion: Current study results revealed that hematocrit, weight, BMI, platelet cell count, lymphocyte count, sex (female), and good treatment adherence were significantly associated with higher CD4 cell count, hemoglobin level and time to default while having advanced WHO clinical stage-IV had significantly decreased CD4 cell, hemoglobin level, and time to default from treatment. Patients with HIV should be given special attention based on these important factors to improve their health and prolong their lives., (© 2023. The Author(s).)

Recovery of CD4-positive T lymphocyte count after initiation of antiretroviral therapy (ART) has been thoroughly examined among people with human immunodeficiency virus infection. However, immunological response after restart of ART following care interruption is less well studied. We compared CD4 cell-count trends before disengagement from care and after ART reinitiation. Data were obtained from the East Africa International Epidemiology Databases to Evaluate AIDS (IeDEA) Collaboration (2001-2011; n = 62,534). CD4 cell-count trends before disengagement, during disengagement, and after ART reinitiation were simultaneously estimated through a linear mixed model with 2 subject-specific knots placed at the times of disengagement and treatment reinitiation. We also estimated CD4 trends conditional on the baseline CD4 value. A total of 10,961 patients returned to care after disengagement from care, with the median gap in care being 2.7 (interquartile range, 2.1-5.4) months. Our model showed that CD4 cell-count increases after ART reinitiation were much slower than those before disengagement. Assuming that disengagement from care occurred 12 months after ART initiation and a 3-month treatment gap, CD4 counts measured at 3 years since ART initiation would be lower by 36.5 cells/μL than those obtained under no disengagement. Given that poorer CD4 restoration is associated with increased mortality/morbidity, specific interventions targeted at better retention in care are urgently required., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Objectives: Our objective was to compare the immunological responses to commonly used antiretroviral therapy (ART) regimens among people with advanced HIV in the USA and to assess virological outcomes and regimen persistence., Methods: This study included ART-naïve adults with advanced HIV infection (CD4 cell count <200 cells/μL) initiating ART with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), boosted darunavir (bDRV), dolutegravir (DTG), or elvitegravir (EVG/c)-containing regimens between 1 January 2018 and 31 December 2020 in the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort. Cox proportional hazards models and linear mixed models with random intercept were fit with inverse probability of treatment weighting., Results: Overall, 1349 people with advanced HIV (816 B/F/TAF, 253 DTG, 146 EVG/c, 134 bDRV) were followed for a median of 22 months. Compared with B/F/TAF, a lower likelihood of achieving a CD4 cell count ≥200 cells/μL was observed with bDRV (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.60-0.96), DTG (HR 0.82; 95% CI 0.69-0.98), and EVG/c (HR 0.73; 95% CI 0.57-0.93). All groups had a similar pattern of CD4:CD8 ratio changes: a rapid increase in the first 6 months (ranging from +0.15 to +0.16 units), followed by a slower increase thereafter. Only 40 individuals (4%) achieved CD4:CD8 ratio normalization (≥1). B/F/TAF was associated with a faster time to virological suppression (viral load <200 copies/mL) and a slower time to discontinuation compared with other regimens., Conclusions: Among people with advanced HIV infection, B/F/TAF initiation was associated with faster CD4 cell count recovery and favourable virological outcomes compared with bDRV-, DTG-, and EVG/c-based regimens, although no difference was observed in CD4:CD8 ratio changes over time across regimens., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Few data are available on the impact of COVID-19 vaccination on CD4 counts and HIV-RNA in persons living with HIV (PLWH). We present the data of 235 PLWH who were vaccinated with BNT162b2 in March 2021-February 2022 at the "Cotugno" hospital in Naples. PLWH treated at the "Cotugno" hospital, who were vaccinated at the hospital vaccination center, without prior COVID-19 and for whom immunological/virological data were available in the last 12 months and in the 6 months after vaccination were included. Antispike Ab were available for 187 and 64 PLWH after the second and third doses: PLWH with antispikes >33 binding antibodies units (BAU)/mL increased from 91% to 98%. Antinucleocapsid Ab performed in 147 and 56 patients identified 19 (13%) asymptomatic/paucisymptomatic COVID-19 infections after the second dose and an additional 15 (27%) after the third dose. Immunological/virological data were collected before vaccination (T0), after the second dose (T1), and after the third dose (T2). The absolute number of CD4 increased after the third dose (median 663, 657, and 707 at T0, T1, and T2; p  < 0.000 T0 vs. T2). The proportion of patients with HIV-RNA <50 copies/mL increases significantly after the second dose (73%; 85.7%; 87.7%; p  < 0.000 T0 vs. T2). The presence of COVID-19 asymptomatic/paucisymptomatic infections (demonstrated by the presence of antinucleocapsid Ab) significantly increases SARS-CoV-2 antispike Ab after second dose, but not after third dose. Asymptomatic/paucisymptomatic COVID-19 infections do not have influence on CD4 cell number and HIV-RNA level. Similarly, the presence of not-controlled HIV-RNA (HIV-RNA >50 copies/mL) does not influence antispike Ab response. According to our data, the response to SARS-CoV2 vaccination is effective in people living with HIV. Vaccination against COVID-19 appears to positively affect immunological and virological levels in people living with HIV.

Background: Research on the immune response to inactivated COVID-19 vaccination among people living with HIV (PLWH) is limited, especially among those with low CD4+ T lymphocyte (CD4 cell) count. This prospective cohort study aimed to assess the humoral immune response to inactivated COVID-19 vaccination among PLWH compared to HIV negative controls (HNCs) and to determine the impact of CD4 cell count on vaccine response among PLWH., Methods: The neutralizing antibodies (nAbs) and the specific IgM and IgG-binding antibody responses to the inactivated COVID-19 vaccine at the third month after the second dose of inactivated COVID-19 vaccination were measured among 138 PLWH and 35 HNCs. Multivariable logistic regression and multiple linear regression models were conducted to identify factors associated with the seroconversion rate of antibodies and the magnitude of anti-SARS-CoV-2 antibody titers, respectively., Results: At the end of the third month after two doses of vaccination, the seroconversion rates of IgG were comparable between PLWH (44.9%; 95% CI 36.5-53.3%) and HNCs (60.0%; 95% CI 42.9-77.1%), respectively. The median titers and seroconversion rate of nAbs among PLWH were 0.57 (IQR: 0.30-1.11) log 10 BAU/mL and 29.0% (95% CI 21.3-36.8%), respectively, both lower than those in HNCs (P < 0.05). After adjusting for age, sex, comorbidities, and CD4 cell count, the titers and seroconversion rate of nAbs were comparable between PLWH and HNCs (P > 0.05). Multivariable regression analyses showed that CD4 cell count < 200/μL was independently associated with lower titers and seroconversion rate of nAbs among PLWH (P < 0.05). A positive correlation was observed between the CD4 cell count and nAbs titers in PLWH (Spearman's ρ = 0.25, P = 0.0034)., Conclusion: Our study concluded that the immune response to inactivated COVID-19 vaccination among PLWH was independently associated with CD4 cell count, PLWH with lower CD4 cell count showed a weaker humoral immune response, especially those with CD4 cell count < 200/μL. This finding suggests that expanding COVID-19 vaccination coverage among PLWH is impendency. In addition, aggressive ART should be carried out for PLWH, especially for those with low CD4 cell count, to improve the immune response to vaccines., (© 2023. The Author(s).)

Aims: This study investigated the synergistic and independent effects of adherence to antiretroviral therapy (ART) and viral load on quality of life (QoL) among people with HIV/AIDS., Methods: This was a cross-sectional study of 129 patients with HIV/AIDS. The WHOQOL-BREF and the Morisky Medication Adherence Scale were used to measure QoL and adherence respectively. Information on viral load and CD4 cell count was obtained from patients' records and verified by a physician. An additive interaction method was used to estimate the synergistic effect of the linear regression., Findings: Patients who were adhering to ART and had an undetectable viral load had significantly higher scores on four domains of QoL - environment, physical health, social relationships and psychological - than those who were non-adherent. Moreover, ART adherence and undetectable viral load had a positive synergistic effect on QoL after controlling for covariate variables., Conclusion: Participants were more likely to have a good QoL if they had both undetectable viral loads and good ART adherence.

The CNS manifestation of chronic liver disease can include magnetic resonance (MR) signal hyperintensities in basal ganglia structures. Here, relations between liver (serum-derived fibrosis scores) and brain (regional T1-weighted signal intensities and volumes) integrity were evaluated in a sample of 457 individuals including those with alcohol use disorders (AUD), people living with human immunodeficiency virus (HIV), those comorbid for AUD and HIV, and healthy controls. Liver fibrosis was identified from cutoff scores as follows: aspartate aminotransferase to platelet ratio index (APRI) > 0.7 in 9.4% (n = 43) of the cohort; fibrosis score (FIB4) > 1.5 in 28.0% (n = 128) of the cohort; and non-alcoholic fatty liver disease fibrosis score (NFS) > -1.4 in 30.2% (n = 138) of the cohort. Presence of serum-derived liver fibrosis was associated with high signal intensities selective to basal ganglia (i.e., caudate, putamen, and pallidum) structures. High signal intensities in the pallidum, however, explained a significant portion of the variance in APRI (25.0%) and FIB4 (23.6%) cutoff scores. Further, among the regions evaluated, only the globus pallidus showed a correlation between greater signal intensity and smaller volume (r = -0.44, p <.0001). Finally, higher pallidal signal intensity correlated worse ataxia (eyes open ρ = -0.23, p =.0002; eyes closed ρ = -0.21, p =.0005). This study suggests that clinically relevant serum biomarkers of liver fibrosis such as the APRI may identify individuals vulnerable to globus pallidus pathology and contribute to problems with postural balance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Fever of unknown origin (FUO) is a challenge for clinicians treating patients with HIV/AIDS. CD4 counts can be helpful in the diagnosis and treatment. This study aimed to determine several common etiologies of FUO stratified by CD4 count levels in HIV/AIDS patients., Methods: A cross-sectional retrospective and prospective study was conducted in 195 HIV/AIDS patients with FUO admitted to the National Hospital for Tropical Diseases from January 2016 to June 2019. Clinical parameters, immune status, and etiologies for each patient were recorded. Odds ratios were calculated to compare the distributions of common etiologies in groups with two different CD4 count levels: < 50 cells/mm 3 and ≥ 50 cells/mm 3 ., Results: The proportions of opportunistic infections and noninfectious etiologies were 93.3% and 3.6%, respectively. Tuberculosis was the most common opportunistic infection (46.7%), followed by talaromycosis (29.2%) and Pneumocystis jiroveci (PCP) infection (20.5%). Tuberculosis was predominant in all CD4 level groups. Most patients with talaromycosis had CD4 counts below 50 cells/mm 3 . In total, 53.8% of the patients were infected by one pathogen. The risks of tuberculosis and talaromycosis in FUO-HIV patients were high when their CD4 counts were below 50 cells/mm 3 ., Conclusions: Opportunistic infections, especially tuberculosis, are still the leading cause of FUO in HIV/AIDS patients. Tuberculosis and Talaromyces marneffei (TM) infection should be considered in patients with CD4 cell counts < 50 cells/mm 3 . This study implies that guidelines for appropriate testing to identify the etiology of FUO in HIV/AIDS patient based on the CD4 cell count should be developed, thereby reducing resource waste., (© 2022. The Author(s).)

Background People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear. Methods and Results This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral load were associated with World Health Organization (WHO)-defined SCD risk. Among 144 336 participants (30% people living with HIV), the mean (SD) baseline age was 50.0 years (10.6 years), 97% were men, and 47% were of Black race. During follow-up (median, 9.0 years), 3035 SCDs occurred. HIV infection was associated with increased SCD risk (hazard ratio [HR], 1.14; 95% CI, 1.04-1.25), adjusting for possible confounders. In analyses with time-varying CD4 and HIV viral load, people living with HIV with CD4 counts <200 cells/mm 3 (HR, 1.57; 95% CI, 1.28-1.92) or viral load >500 copies/mL (HR, 1.70; 95% CI, 1.46-1.98) had increased SCD risk versus veterans without HIV. In contrast, people living with HIV who had CD4 cell counts >500 cells/mm 3 (HR, 1.03; 95% CI, 0.90-1.18) or HIV viral load <500 copies/mL (HR, 0.97; 95% CI, 0.87-1.09) were not at increased SCD risk. Conclusions HIV infection is associated with increased risk of WHO-defined SCD among those with elevated HIV viral load or low CD4 cell counts.

Introduction: CD4 count is an important predictor of disease progression, opportunities infection, deaths, and to understand the time interval between initial HIV infection to the first diagnosis. However, baseline CD4 count and the time period between initial infection and the diagnosis amongst PLHIV in Bhutan never been evaluated., Methods: This is a retrospective study of the diagnosed PLHIV from the existing data system from January 10 to 30, 2021. Out of 512 reported HIV cases, 488 of those who were more than or equal to 18 years old and had their CD4 count testing within 6 months before initiating ART were considered for analysis. Descriptive statistical analysis was used to analyze the characteristics of the study population and relationship were established using the χ 2 Test. We have sought ethics approval and waiver for informed consent as it is the retrospective study of the client's record. The client's confidentiality was ensured by removing all the identifiers., Results: The mean CD4 was 345 cells/ml for males and females. Twenty-five percent of the clients had CD4 counts below 200, 30%, between 200 and 349, 25% between 350 and 499, and 20% above 500 cells/ml. A larger number of males showed a CD4 count below 200 cells/ml while more females showed a CD4 count more than 500 cells/ml. The mean time interval between initial infection to the first diagnosis was 4 years in males and females. However, about one-fourth were found to have been infected between 5 and 8 years before diagnosis and less than 10% were diagnosed within less than 1 year of infection., Conclusions: The study revealed a late diagnosis of HIV infection in Bhutan thereby risking the transmission to the community and risk of severe disease and mortality. The upscaling of voluntary counseling and testing, medical screening, and alternative methods like community-based testing including HIV Self Testing for early detection needs to be implemented in the country., (© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

We identify the determinants of the change in CD4 cell count and survival time of children living with HIV taking antiretroviral therapy. In a retrospective study, a cohort of 201 children living with HIV/AIDS aged less than 15 years were followed from October 2013 to March 2017. Separate linear effect models were done for the longitudinal outcome of CD4 cell count. The Cox PH model was conducted for the time-to-event outcome. Joint modeling was performed both for the longitudinal and survival outcomes, results were compared with the separate analysis. However, with the specific interest in identifying the determinants and characterizing the relationship between longitudinal CD4 cell count and time-to-event outcomes, the study focused on joint modeling. The finding from the joint model indicated that the estimated association parameter was -0.10, this shows lower values of CD4 cells associated with higher death. Seemingly; observation time, age, WHO clinical stages, history of Tuberculosis (assuming that Tuberculosis is active), and functional status were determinants for the mean change in the square root of CD4 cell count. Furthermore, WHO clinical stages, functional status, history of TB, and Body Mass Index have a significant negative impact on the survival probabilities of children living with HIV.

Background: HIV is an infectious disease affecting 36.7 million people worldwide. In recent times, Antiretroviral Therapy (ART) has become accessible to the majority of People Living with HIV (PLHIV) and this has transformed the course of infection to one that is chronic, characterized by fewer diseases pathognomonic of AIDS. In view of this, there is a pressing need for better markers, apart from the routine HIV indicators, to detect comorbidities such as Neurocognitive Impairment (NCI). The aim of this study was to find out the association between Veterans Aging Cohort Study (VACS) index and Neurocognitive function in HIV positive patients., Methods: In our study, we included 97 HIV positive patients and their Neurocognitive function was assessed using a combination of Montreal Cognitive Assessment and Grooved Pegboard Test, while VACS index was calculated using the most recent laboratory values. Binomial Logistics Regression analyses, adjusting for potential confounding variables, was performed to determine the association between VACS score and Neurocognitive Impairment., Results: We found that a higher VACS Index was associated with global and domain-wise Neurocognitive impairment (p < 0.01), specifically in the domains of attention (p < 0.01) and fine motor skills (p = 0.01). Our study also showed that among all the VACS components, older age (p = 0.02) and lower hemoglobin (p < 0.01) values were associated with global NCI. After plotting an ROC curve, a VACS cut-off score of 11.00 was identified as it had good sensitivity (87.0%) and specificity (71.4%) in identifying Global NCI., Conclusion: Our findings extend prior research on the use of VACS Index to predict global and domain-wise NCI in HIV-positive patients. However, further research with more comprehensive neurocognitive testing is required in our setting before VACS Index can be used as a tool to screen for neurocognitive dysfunction among PLHIV., (© 2021. The Author(s).)

Background: We analyzed associations between immunodeficiency and cancer incidence in a nationwide cohort of people living with human immunodeficiency virus (HIV; PLWH) in South Africa., Methods: We used data from the South African HIV Cancer Match Study built on HIV-related laboratory measurements from the National Health Laboratory Services and cancer records from the National Cancer Registry. We evaluated associations between time-updated CD4 cell count and cancer incidence rates using Cox proportional hazards models. We reported adjusted hazard ratios (aHRs) over a grid of CD4 values and estimated the aHR per 100 CD4 cells/µL decrease., Results: Of 3 532 266 PLWH, 15 078 developed cancer. The most common cancers were cervical cancer (4150 cases), Kaposi sarcoma (2262 cases), and non-Hodgkin lymphoma (1060 cases). The association between lower CD4 cell count and higher cancer incidence rates was strongest for conjunctival cancer (aHR per 100 CD4 cells/µL decrease: 1.46; 95% confidence interval [CI], 1.38-1.54), Kaposi sarcoma (aHR, 1.23; 95% CI, 1.20-1.26), and non-Hodgkin lymphoma (aHR, 1.18; 95% CI, 1.14-1.22). Among infection-unrelated cancers, lower CD4 cell counts were associated with higher incidence rates of esophageal cancer (aHR, 1.06; 95% CI, 1.00-1.11) but not breast, lung, or prostate cancer., Conclusions: Lower CD4 cell counts were associated with an increased risk of developing various infection-related cancers among PLWH. Reducing HIV-induced immunodeficiency may be a potent cancer-prevention strategy among PLWH in sub-Saharan Africa, a region heavily burdened by cancers attributable to infections., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Despite better access to antiretroviral therapy (ART) over recent years, HIV remains a major global cause of mortality. The present study aimed to identify predictors of in-hospital mortality among HIV-positive patients presenting to an emergency department (ED)., Methods: In this cross-sectional study, HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult ED between 07 July 2017 and 18 October 2018 were prospectively enrolled. Data were compared between participants who survived to hospital discharge and those who died. The data were further subjected to univariate and multivariate logistic regression analyses to determine variables that were associated with in-hospital mortality., Results: Of a total of 1224 participants, the in-hospital mortality was 13.6% (n = 166). On multivariate analysis, respiratory rate > 20 breaths/min [odds ratio (OR) = 1.90, P = 0.012], creatinine > 120 μmol/L (OR = 1.97, P = 0.006), oxygen saturation < 90% (OR = 2.09, P = 0.011), white cell count < 4.0 × 10 9 /L (OR = 2.09, P = 0.008), ART non-adherence or not yet on ART (OR = 2.39, P = 0.012), Glasgow Coma Scale < 15 (OR = 2.53, P = 0.000), albumin < 35 g/L (OR = 2.61, P = 0.002), lactate > 2 mmol/L (OR = 4.83, P = 0.000) and cryptococcal meningitis (OR = 6.78, P = 0.000) were significantly associated with in-hospital mortality., Conclusions: Routine clinical and laboratory parameters are useful predictors of in-hospital mortality in HIV-positive patients presenting to the ED with an acute illness. These parameters may be of value in guiding clinical decision-making, directing the appropriate use of resources and influencing patient disposition, and may also be useful in developing an outcome prediction tool., (© 2021 British HIV Association.)

Background: Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described., Methods: The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics., Results: A total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status., Conclusions: There were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV., Clinical Trials Registration: NCT02344290., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Compared to other countires internationally, South Africa has the largest number of people living with HIV. There are limited data in developing countries on the outcomes of HIV-infected patients in the intensive care unit (ICU). The objectives of this study were to describe the pattern of presentation of these patients and to determine factors that may influence survival to ICU discharge., Methods: The medical charts of 204 consecutive HIV-infected individuals who were admitted to the Charlotte Maxeke Johannesburg Academic Hospital adult general ICU during the calendar year 2017 were retrospectively reviewed. Relevant data were subjected to univariate and multivariate analysis., Results: Two-hundred and four (22.6%) out of a total of 903 patients who were admitted to the ICU were HIV positive. Sepsis-related illnesses were the most common reason for ICU admission (n = 95; 46.6%), followed by post-operative care (n = 69; 33.8%) and non-sepsis-related illnesses (n = 40; 19.6%). The median length of stay in the ICU was 5 (interquartile range 2-9) days. ICU mortality was 33.3% (n = 68). On univariate analysis, age (P = 0.039), length of stay in the ICU (P = 0.040), primary diagnostic category (P < 0.05), sepsis acquired during the ICU stay (P = 0.012), inotrope/vasopressor administration (P < 0.001), mechanical ventilation (P < 0.001), haemodialysis (P = 0.001), CD4 cell count (P = 0.011), Acute Physiology and Chronic Health Assessment (APACHE) II score (P < 0.001) and Sequential Organ Failure Assessment (SOFA) score (P < 0.001) were significantly associated with mortality., Conclusions: Age, diagnostic category, sepsis acquired during the ICU stay, inotrope/vasopressor administration, mechanical ventilation, haemodialysis, CD4 cell count, APACHE II score, SOFA score and length of ICU stay were associated with ICU mortality in HIV-infected patients., (© 2019 British HIV Association.)

Background: CD4 cell count has been identified to be an essential component in monitoring HIV treatment outcome. However, CD4 cell count monitoring sometimes fails to predict virological failure resulting in unnecessary switch of treatment lines which causes drug resistance and limitations of treatment options. This study assesses the use of both viral load (HIV RNA) and CD4 cell count in the monitoring of HIV/AIDS progression., Methods: Time-homogeneous Markov models were fitted, one on CD4 cell count monitoring and the other on HIV RNA monitoring. Effects of covariates; gender, age, CD4 baseline, HIV RNA baseline and adherence to treatment were assessed for each of the fitted models. Assessment of the fitted models was done using prevalence plots and the likelihood ratio tests. The analysis was done using the "msm" package in R., Results: Results from the analysis show that viral load monitoring predicts deaths of HIV/AIDS patients better than CD4 cell count monitoring. Assessment of the fitted models shows that viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count., Conclusion: From this study one can conclude that although patients take more time to achieve a normal CD4 cell count and less time to achieve an undetectable viral load, once the CD4 cell count is normal, mortality risks are reduced. Therefore, both viral load monitoring and CD4 count monitoring can be used to provide useful information which can be used to improve life expectance of patients living with HIV. However, viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count and hence viral load is deemed superior.

To explore reasons for the disproportionate metabolic and cardiovascular disease burdens among older HIV-infected persons, we investigated whether associations of CD4 count and HIV viral load (VL) with non-high-density lipoprotein cholesterol (non-HDL-C) and high-density lipoprotein cholesterol [HDL-C] differed by age. Longitudinal clinical and laboratory data were collected between 2011 and 2016 for HIV-infected outpatients in the DC Cohort study. Using data for patients aged ≥21 years with ≥1 cholesterol result and contemporaneous CD4/VL results, we created multivariable linear regression models with generalized estimating equations. Among 3,912 patients, the median age was 50 years, 78% were male, 76% were non-Hispanic black, 93% were using antiretroviral therapy, 8% had a CD4 count <200 cells/μL, and 18% had an HIV VL ≥200 copies/mL. Overall, CD4 count <200 (vs. >500) cells/μL and VL ≥200 copies/mL were associated with lower non-HDL-C concentrations (p < .01), but associations were more positive with increasing age (CD4-age/VL-age interactions, p < .01). CD4 count <200 cells/μL was associated with lower non-HDL-C among patients aged <50 years [β = -7.8 mg/dL (95% confidence interval, CI: -13.2 to -2.4)] but higher non-HDL-C among patients aged 60-69 years [β = +8.1 mg/dL (95% CI: 0.02-16.2)]. VL ≥200 copies/mL was associated with lower non-HDL-C among patients aged <50 years [β = -3.3 mg/dL (95% CI: -6.7 to 0.1)] but higher non-HDL-C among patients aged ≥70 years [β = +16.0 mg/dL (95% CI: -1.4 to 33.3)], although precision was reduced in age-stratified analyses. Although no age differences were detected for HDL-C, VL ≥200 copies/mL was more strongly associated with lower HDL-C concentrations when CD4 count was <200 cells/μL [β = -7.0 mg/dL (95% CI: -9.7 to -4.3)] versus 200-500 cells/μL [β = -4.2 (95% CI: -5.9 to -2.6)] or >500 cells/μL [β = -2.2 (95% CI: -3.7 to -0.8)] (CD4-VL interaction, p < .01). We detected a novel age-modified relationship between immunosuppression and viremia and atherogenic cholesterol patterns. These findings may contribute to our understanding of the high risk of dyslipidemia observed among persons aging with HIV.

Introduction: Despite increasing focus on test and treat strategies for people living with HIV (PLHIV), many continue to enrol late in care and initiate antiretroviral therapy (ART) when they have advanced HIV disease., Methods: We analyzed PLHIV ≥15 years of age starting ART in Ethiopia, Kenya, Mozambique and Tanzania from 2005 to 2015 based on CD4+ groups at ART initiation (≥200, 100 to 199, 50 to 99 and <50 cells/mm 3 ) to examine attrition (loss to follow-up (LTF) and death) using Kaplan-Meier estimators and Cox proportional hazards models. LTF was defined as no clinic visit >6 months; deaths were ascertained from medical records., Results and Discussion: A total of 305,443 PLHIV were included in the analysis: 118,580 (38.8%) CD4+ ≥200, 91,788 (30.1%) CD4+ 100 to 199, 44,029 (14.4%) CD4+ 50 to 99 and 51,046 (16.7%) CD4+ <50 cells/mm 3 . At 12 months after ART initiation, attrition for those with CD4+ ≥200, 100 to 199, 50 to 99 and <50 cells/mm 3 was 21.3% (95% CI 21.1 to 21.6), 21.8% (95% CI 21.6 to 22.1), 27.3% (95% CI 26.9 to 27.7) and 33.6% (95% CI 33.2 to 34.0) respectively. In multivariable models, compared to PLHIV with CD4+ ≥200 cells/mm 3 , those with CD4+ 50 to 99 cells/mm 3 had 29% increased risk of attrition (adjusted hazard ratio (AHR) 1.29, 95% CI 1.27 to 1.32) and those with <50 cells/mm 3 had 56% increased risk of attrition (AHR 1.56, 95% CI 1.53 to 1.58). Men had higher attrition compared to women across all CD4+ groups and overall were 28% more likely to experience attrition (AHR 1.28, 95% CI 1.26 to 1.29). Even after ART initiation, PLHIV with advanced disease had notably inferior outcomes with substantial gradient within the low CD4+ strata highlighting the need for targeted interventions for these populations., Conclusions: Greater efforts, including the identification of effective differentiated service delivery models, are needed to ensure that all PLHIV starting treatment can garner the benefits from ART and achieve favourable outcomes., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: The CD4 cell count and percent at initiation of combination antiretroviral therapy (cART) are measures of advanced HIV disease and thus are important indicators of programme performance for children living with HIV. In particular, World Health Organization (WHO) 2017 guidelines on advanced HIV disease noted that >80% of children aged <5 years started cART with WHO Stage 3 or 4 disease or severe immune suppression. We compared temporal trends in CD4 measures at cART start in children from low-, middle- and high-income countries, and examined the effect of WHO treatment initiation guidelines on reducing the proportion of children initiating cART with advanced disease., Methods: We included children aged <16 years from the International Epidemiology Databases to Evaluate acquired immunodeficiency syndrome (AIDS) (IeDEA) Collaboration (Caribbean, Central and South America, Asia-Pacific, and West, Central, East and Southern Africa), the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE), the North American Pediatric HIV/AIDS Cohort Study (PHACS) and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 219C study. Severe immunodeficiency was defined using WHO guidelines. We used generalized weighted additive mixed effect models to analyse temporal trends in CD4 measurements and piecewise regression to examine the impact of 2006 and 2010 WHO cART initiation guidelines., Results: We included 52,153 children from fourteen low-, eight lower middle-, five upper middle- and five high-income countries. From 2004 to 2013, the estimated percentage of children starting cART with severe immunodeficiency declined from 70% to 42% (low-income), 67% to 64% (lower middle-income) and 61% to 43% (upper middle-income countries). In high-income countries, severe immunodeficiency at cART initiation declined from 45% (1996) to 14% (2012). There were annual decreases in the percentage of children with severe immunodeficiency at cART initiation after the WHO guidelines revisions in 2006 (low-, lower middle- and upper middle-income countries) and 2010 (all countries)., Conclusions: By 2013, less than half of children initiating cART had severe immunodeficiency worldwide. WHO treatment initiation guidelines have contributed to reducing the proportion of children and adolescents starting cART with advanced disease. However, considerable global inequity remains, in 2013, >40% of children in low- and middle-income countries started cART with severe immunodeficiency compared to <20% in high-income countries., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Unstable housing, including homelessness, is a public policy concern for all populations, and more critically for people with a serious health condition such as HIV. We measure the effect of unstable housing on HIV treatment biomarkers: viral suppression (viral load < 200 HIV RNA copies per ml) and adequate CD4 + T-cell count (CD4>350 cells per μl). We use panel data (1995-2015) from 3082 participants of the Women's Interagency HIV Study (WIHS) sites in Bronx and Brooklyn (NY), Chicago (IL), Los Angeles and San Francisco (CA), and Washington (DC). The instrumental variable (IV) measures allocations for the Housing Opportunities for People with AIDS (HOPWA) per person newly infected with HIV, and it represents actual availability of housing assistance for HIV-positive persons at the metropolitan area level. Using an extended probit model with the IV, we find that unstable housing reduces the likelihood of viral suppression by 51 percentage points, and decreases the probability of having adequate CD4 cell count by 53 percentage points. The endogeneity-corrected results are larger than naïve probits, which show decreases of 8.1 and 7.8 percentage points, respectively. The hypothesized pathways for the effect are: decreased use of mental healthcare/counseling, any healthcare, and less continuity of care. Increasing efforts to improve housing assistance, including HOPWA, and other interventions to make housing more affordable for low-income populations, and HIV-positive populations in particular, may be warranted not only for the benefits of stable housing, but also to improve HIV-related biomarkers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The occurrence of endocrine diseases in people who are infected with HIV is traditionally thought to occur in the setting of AIDS with opportunistic infections and malignancies. However, recent studies find the correlation between hypocortisolism and stage of HIV (CD4 count and WHO clinical stage) inconsistent., Methods: This descriptive cross-sectional study included three hundred and fifty (350) consecutive patients with HIV infection. They were interviewed, and subsequently underwent laboratory evaluation for the detection of hypocortisolism. Blood samples for serum cortisol estimation were taken at baseline and at 30 minutes following the administration of 1µg of tetracosactrin (Synacthen). In addition, the patients had blood samples taken at 0 minutes (baseline) for CD4+ lymphocyte cell counts., Results: At baseline, 108 (30.9%) participants had serum cortisol levels below 100 µg/L with a median value of 55.48 µg/L (11.36-99.96 µg/L), but only 57 (16.3%) study participants had stimulated serum cortisol levels below 180 µg/L with median of 118 µg/L (19.43-179.62). There was no significant difference in the occurrence of clinical features between participants with low and normal serum cortisol, nor WHO clinical stage, CD4 count and ART regimen. The occurrence of hypocortisolism was higher among participants who had been on ART for a longer period of time., Conclusion: There is a high prevalence of hypocortisolism among HIV patients by biochemical testing, especially those who have been on ARVs for a longer duration. Hypocortisolism cannot be predicted based on the participants' WHO clinical stage of disease, CD4 cell count, or the treatment regimen., Funding: Personal Funds., Competing Interests: Conflict of interest: None declared

This systematic review evaluates the association between religion, spirituality and clinical outcomes in HIV-infected individuals. A systematic literature review was conducted for all English language articles published between 1980 and 2016 in relevant databases. Six hundred fourteen studies were evaluated. 15 met inclusion criteria. Ten (67%) studies reported a positive association between religion or spirituality and a clinical HIV outcome. Two (13%) studies failed to detect such an association; and two (13%) demonstrated a negative association. One study (7%) identified features of religiosity and spirituality that had both negative and positive associations with HIV clinical outcomes. Recognizing the religious or spiritual commitments of patients may serve as an important component of patient care. Further longitudinal studies and interventions might be required to further clarify the potential impact of religion and spirituality on HIV clinical outcomes.

Hepatitis E virus (HEV) infection in immunocompromised patients often results in distinct outcome, compared to the infection in general population. This study aimed to investigate the prevalence, potential risk factors, and clinical features of HEV infection among HIV patients treated with antiretroviral therapy (ART) in Yunnan province, China. A total of 770 HIV-infected patients between May 2015 and February 2016 were enrolled in Yunnan, China. All patients received ART. All plasma samples were tested for anti-HEV IgG, anti-HEV IgM antibodies using ELISA kits, and HEV RNA by real-time qRT-PCR. Association between anti-HEV antibody positivity and demographic, clinical and laboratory measures was assessed in univariate and multivariate logistic regression models. Of the 770 HIV-infected patients, 342 patients (44.42%) were anti-HEV IgG antibody positive, and six patients (0.78%) were anti-HEV IgM antibody positive. None of the patients was HEV RNA positive, as tested in our assays. We found that age, gender, CD4 cell count, WHO stage, marital status, and total cholesterol levels were associated with HEV infection. We report a high seroprevalence rate and several potential risk factors of HEV infection in a large HIV cohort from Yunnan province in China. Further research on identification of the circulating HEV strains and the clinical outcome of this patient population is required., (© 2018 Wiley Periodicals, Inc.)

Hispanic and Black adults are disproportionately affected by HIV and experience poorer HIV-related health outcomes relative to non-Hispanic White adults. The current study adopted Sørensen's integrated model to test the hypothesis that lower functional and critical health literacy competencies contribute to poorer HIV-related health and CD4 cell count for Hispanic and Black individuals. Eighty-one non-Hispanic White, Hispanic, and Black HIV seropositive individuals from a large, Southwestern metropolitan area were administered measures of health literacy, including the Expanded Numeracy Scale, Newest Vital Sign, Rapid Estimate of Adult Literacy in Medicine, Test of Functional Health Literacy (TOHFLA)-numeracy, and TOHFLA-reading. Hispanic and Black individuals demonstrated less HIV knowledge than non-Hispanic White individuals. Black participants demonstrated fewer health literacy appraisal skills. Importantly, lower levels of health literacy were linked to poorer CD4 cell count (an index of immune functioning) for Hispanic and Black individuals and not for non-Hispanic White individuals. These findings suggest race group differences for health literacy on current CD4 cell count such as very specific dimensions of low health literacy (e.g. poorer judgment of health-related information), but not other presumed deficits (e.g. motivation, access), play an important role in clinical health outcomes in HIV.

Introduction: Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART)., Methods: We included all HIV-positive adult patients (≥16 years) in care between 2000 and 2014 at three ART programmes in South Africa. Patients with previous TB were excluded. Missing CD4 cell counts and HIV-RNA viral loads at ART start (baseline) and during follow-up were imputed. We used parametric survival models to assess TB incidence (pulmonary and extrapulmonary) by CD4 cell and HIV-RNA levels, and estimated the rate ratios for TB by including age, sex, baseline viral loads, CD4 cell counts, and WHO clinical stage in the model. We also used Poisson general additive regression models with time-updated CD4 and HIV-RNA values, adjusting for age and sex., Results: We included 44,260 patients with a median follow-up time of 2.7 years (interquartile range [IQR] 1.0-5.0); 3,819 incident TB cases were recorded (8.6%). At baseline, the median age was 34 years (IQR 28-41); 30,675 patients (69.3%) were female. The median CD4 cell count was 156 cells/µL (IQR 79-229) and the median HIV-RNA viral load 58,000 copies/mL (IQR 6,000-240,000). Overall TB incidence was 26.2/1,000 person-years (95% confidence interval [CI] 25.3-27.0). Compared to the lowest viral load category (0-999 copies/mL), the adjusted rate ratio for TB was 1.41 (95% CI 1.15-1.75, p  < 0.001) in the highest group (>10,000 copies/mL). Time-updated analyses for CD4/HIV-RNA confirmed the association of viral load with the risk for TB., Conclusions: Our results indicate that ongoing HIV replication is an important risk factor for TB, regardless of CD4 cell counts, and underline the importance of early ART start and retention on ART.

Lues maligna is a rare presentation of an infection with Treponema pallidum. Here we report three lues maligna infections with severe dermatological manifestations in a single HIV-1 infected individual. Despite the start of highly active antiretroviral therapy and a substantial increase in CD4 cell count after the first episode, he developed consecutive episodes. We assume a specific immunological predisposition to react to T. pallidum in this patient.

Background: The incidence of tuberculosis among HIV-infected populations with high CD4 count in high burden countries has not been well studied., Objective: To assess the TB incidence in HIV-infected adults and its associated risk factors., Method: A cohort study with retrospective review of medical records and prospective follow-up of HIV-infected adult participants attending CTC who were 18-55 years old, had CD4 count more than 250 cells/mm 3 in the period of 2008-2010 and were not on ART at enrolment. Cox proportional hazard regression was used to explore the predictors of incident TB., Results: Overall 777 (24%) of 3,279 CTC enrolled HIV-infected adults fulfilled the inclusion criteria of the study. The incidence of TB in the study population ranged from 0.8/100 per person years (PY) at risk (95% CI 0.5-1.3) in the main analysis to 1.7/100 PY at risk (95% CI 1.0-2.6) in sensitivity analyses. Only prior history of TB disease was found to have a significant association with an increased risk of TB, hazard ratio 5.7 (95% CI 2.0-16.4, p value 0.001)., Conclusion: Tuberculosis incidence among HIV-infected adults with medium/high CD4 count in Bagamoyo is lower than in other high TB burden countries. Previously TB treated patients have a much higher risk of getting TB again than those who never had TB before.

Background:  Trends in CD4 + T-cell count at human immunodeficiency virus (HIV) infection diagnosis and antiretroviral therapy (ART) initiation can be characterized using laboratory tests from surveillance., Methods:  We used CD4 + T-cell counts and viral loads from New York City for persons who received a diagnosis of HIV infection during 2006-2012., Results:  From 2006 to 2012, the median CD4 + T-cell count increased from 325 to 379 cells/µL at diagnosis and from 178 to 360 cells/μL at ART initiation. CD4 + T-cell counts were consistently lower in women, blacks, Hispanics, persons who inject drugs, and heterosexuals., Discussion:  Increases in CD4 + T-cell count at diagnosis and ART initiation suggest that the time from HIV infection to ART initiation has been reduced substantially in New York City., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Objectives: Late HIV diagnosis is associated with increased morbidity and mortality, increased risk of transmission, impaired response to antiretroviral therapy and increased health care costs. The aim of this study was to determine the factors associated with late HIV diagnosis in Grampian, North-East Scotland., Study Design: A population based retrospective database analysis., Methods: All newly diagnosed HIV positive individuals in Grampian, North-East Scotland between 2009 and 2014 were included in the study. Participants were classified as having a late diagnosis if the CD4 cell count at presentation was less than 350 cells/mm 3 . Socio-economic and demographic factors were investigated in relation to outcome (late diagnosis) using Chi-squared and Mann-Whitney tests., Results: CD4 cell count results were available for 111 (89.5%) of the 124 newly diagnosed individuals during the study period. The prevalence of late diagnosis was 53.2% (n = 59). Those infected via heterosexual mode of transmission had a 2.83 times higher odds of late diagnosis (OR 2.83 [95% CI: 1.10-7.32]) than men who have sex with men (MSM) and those with no previous HIV testing had a 5.46 increased odds of late diagnosis (OR 5.46 [95% CI: 1.89-15.81]) compared to those who had previously been tested. Missed opportunities for HIV diagnosis were identified in 16.3% (n = 15) of participants., Conclusion: Heterosexual individuals and those with no previous HIV testing were more likely to be diagnosed late. Targeted initiatives to increase perception of HIV risk and uptake of testing in these risk groups are recommended., (Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Tobacco smoking is associated with adverse health effects among people living with HIV (PLWH), including a higher risk of cancer and cardiovascular problems. Further, there is evidence that PLWH are two to three times more likely to smoke than the general population. The aim of this study was to examine the association between tobacco smoking and biomarkers of HIV disease progression, including unsuppressed viral load (viral load >200 copies/mL) and low CD4 cell count (<200 cells/mm(3)). Recent tobacco smoking was reported by 40 % (n = 5942) of 14,713 PLWH enrolled in Ryan White Part A programs in the New York City metropolitan area. In multivariate analyses controlling for sociodemographic and clinical characteristics, recent tobacco smoking was independently associated with unsuppressed viral load (AOR = 1.38, CI 1.26-1.50) and low CD4 cell count (AOR = 1.12, CI 1.01-1.24). Findings suggest the importance of routine assessments of tobacco use in clinical care settings for PLWH.

Background: The principal goal of HAART is sustained viral load (VL) suppression resulting in immune reconstitution and improved HIV outcomes. We studied the factors associated with 10 years of continuous VL suppression on HAART in the US Military HIV Natural History Study., Methods: Participants with continuous VL suppression (CS, n = 149) were compared to those who did not have continuous viral load suppression (NCS, n = 127) for ≥10 years on HAART. Factors associated with >10 years of VL suppression were evaluated by multivariate logistic regression. Additionally, association between CS and CD4 reconstitution was analyzed with a mixed effects model., Results: Compared to NCS participants, a lower proportion of CS participants started HAART in the early HAART era (66 vs 90 %, for years 1996-1999; p < 0.001) and had less antiretroviral use prior to HAART (37 vs 83 %; p < 0.001). At initial HAART, the median CD4 cell count was higher and VL was lower for CS compared to NCS participants (375 cells/uL [256, 499] vs 261 cells/uL [146, 400]; p < 0.001 and 4.4 log10 copies/mL [3.5, 4.9] vs 4.5 log10 copies/mL [3.8, 5.0]; p = 0.048, respectively). New AIDS events were lower during HAART (5 vs 13 %; p = 0.032) and post-HAART CD4 trajectories were greater for the CS compared to NCS group. Factors negatively associated with ≥10 years of VL suppression included log10 VL at first HAART (OR 0.61, 95 % CI 0.4, 0.92; p = 0.020) and antiretroviral use prior to HAART (OR 0.16, 95 % CI 0.06, 0.38; p < .001)., Conclusions: Sustained VL suppression is a key to long-term health in HIV-infected patients, as demonstrated by the lower proportion of AIDS events observed 10 years after HAART initiation. The current use of more potent and well-tolerated regimens may mitigate the negative factors of pre-HAART VL and prior ARV use encountered by treatment initiated in the early HAART era.

Background: Recent studies have suggested that CD4 cell count monitoring has little added value in patients who are virologically suppressed and immunologically stable if viral load (VL) testing is routinely available. These conclusions have not been directly assessed using mortality rate as a study end point in a real-world setting., Methods: This human immunodeficiency virus (HIV) treatment cohort study from 2008 to 2014 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between the frequency of CD4 cell counts and VL testing and death., Results: Compared with monitoring CD4 cell counts ≥3 times during the first year of antiretroviral therapy (ART) initiation, as currently suggested by the Chinese National Free Antiretroviral Treatment Program, monitoring them less than twice during the first year of ART was significantly associated with death; however, monitoring them twice in that year did not significantly increase mortality rates. Compared with testing VL at least once during the first year of ART, as currently suggested by the National Free Antiretroviral Treatment Program, performing no VL tests in the first year after ART initiation was significantly associated with higher mortality rates. Routine CD4 cell count monitoring did not have an impact on mortality rates among HIV-infected patients with VLs <1000 copies/mL or CD4 cell counts ≥350/μL beyond 12 months after ART initiation., Conclusions: Our study suggests that CD4 cell counts can be reduced to twice during the first year of ART and be reduced or stopped for patients who have achieved virologic suppression or immunologic stability after 12 months of treatment., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/μL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression., Methods: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation., Results: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL., Conclusions: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Antiretroviral therapy (ART) policy for people living with human immunodeficiency virus (HIV) has historically been based on clinical indications, such as opportunistic infections and CD4 cell counts. Studies suggest that CD4 counts early in HIV infection do not predict relevant public health outcomes such as disease progression, mortality, and HIV transmission in people living with HIV. CD4 counts also vary widely within individuals and among populations, leading to imprecise measurements and arbitrary ART initiation. To capture the clinical and preventive benefits of treatment, the global HIV response now focuses on increasing HIV diagnosis and ART coverage. CD4 counts for ART initiation were necessary when medications were expensive and had severe side effects, and when the impact of early ART initiation was unclear. However, current evidence suggests that although CD4 counts may still play a role in guiding clinical care to start prophylaxis for opportunistic infections, CD4 counts should cease to be required for ART initiation., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: About 30% of the patients initiated on antiretroviral therapy in Zambia default treatment. Some of these patients later restart treatment; however, the characteristics of these patients have not been well described and documented. The aim of this study was to describe and document the socio-demographic and clinical characteristics of patients who default and restart antiretroviral therapy, and to determine the socio-demographic characteristics associated with CD4 count response at 6 and 24 months of restarting antiretroviral therapy., Methods: A longitudinal retrospective analysis was performed on data from 535 adult patients restarting antiretroviral therapy in 2009 and 2010 at five antiretroviral therapy centres in Copperbelt and Central provinces of Zambia. To determine the association between the socio-demographic characteristics and CD4 cell count, quantile regression models were used., Results: Older age above 45 years was associated with a significantly lower CD4 cell response by 38.1 cells/mm(3) (95% Confidence interval [CI]: -109.4 to -0.2) compared to the younger age (15-29 years). Patients in formal employment (Adjusted Coefficient [AC] 29.5, 95% CI: 22.8 to 81.1) and self-employment (AC 48.1, 95% CI: 18.6 to 77.4) gained significantly higher CD4 cells than those unemployed. In addition, baseline CD4 count, type of treatment, WHO staging, total duration on treatment and duration lost to follow-up were found to be strong predictors of CD4 cell count at 6 and 24 months after restarting antiretroviral therapy treatment., Conclusion: Age and occupation were the only socio-demographic characteristics predicting CD4 count in the patients at 6 months after restarting antiretroviral therapy after adjusting for other confounding clinical variables.

Background: Human papilloma virus (HPV) is a common sexually transmitted virus which infects the cutaneous and mucosal epithelium. HPV Type 16 is one of the viruses that causes cervical cancer and immunocompromised individuals are at high risk of different co-infections. Women living with Human Immunodeficiency Virus (HIV) have greater risk to the virus due to their impaired immunity. This study aimed at determining the seroprevalence of HPV IgM (Type 16) among HIV-infected women in Ogbomoso., Methods: The blood sample of 180 consenting subjects were obtained and their sera subjected to serological assay using Enzyme Linked Immunosorbent Assay. Samples were collected over a period of 6 months (July-December 2014)., Results: The mean age and mean CD4+ count of the subjects was 38.22 ± 0.79 years and 392.80 ± 20.98 cells/μL, respectively. Out of 180 subjects tested, 18 (10%; 95% confidence interval) were positive for HPV Type 16 IgM. HPV Type 16 IgM was highest among the age group 31-45 (61.11%), traders (38.89%), >500 CD4/μL (33.33%). The seroprevalence using logistic regression at P < 0.05 shows there is a significant difference between the age and CD4 (+) cell count., Conclusion: The result provides evidence that HPV Type 16 is present among HIV-infected women in Ogbomoso and they are susceptible to cervical cancer. This seroepidemiological survey is important for the prevention efforts such as availability of vaccine.

Introduction: With more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second-line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second-line treatment and evaluated mortality related to treatment failure among HIV-infected patients in Guinea-Bissau., Methods: In this retrospective cohort study, adult patients infected with HIV-1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time-varying coefficient, were used to estimate the hazard ratio for death and loss to follow-up., Results: We assessed 1,591 HIV-1-infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first- to second-line ART. The overall switching rate was 3.1 per 100 person-years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9-107.8), 7.6 (95% CI: 1.6-35.5) and 3.1 (95% CI: 1.5-6.3) in the first, second and following years, respectively. During the first year of follow-up, patients experiencing treatment failure had a higher risk of being lost to follow-up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7-11.8)., Conclusions: We found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second-line therapy. These factors could lead to an increased risk of resistance development and excess mortality.

Objective: To describe long-term treatment outcomes of a pediatric HIV cohort in Mozambique., Design: Retrospective analysis of routine monitoring data., Setting: Secondary health care facilities in the Chamanculo Health District of Maputo., Subjects: A total of 1,335 antiretroviral treatment (ART) naïve children <15 years of age enrolled in HIV care between 2002 and 2010., Intervention: HIV care, ART (since 2003), task shifting to lower cadre nurses, counseling by lay counselors, active patient tracing, nutritional support, support by a psychologist, targeted viral load testing, and switch to second-line treatment., Main Outcome Measures: Kaplan-Meier estimates for retention in care (RIC), CD4 cell percentage, body mass index for age z-score, and adjusted incidence rate ratios for attrition (death or loss to follow-up) as calculated by Poisson regression., Results: The RIC at 6 years in the pre-ART cohort was 44% (95% confidence interval: 38-49), and the one at 8 years in the ART cohort was 70% (64-75). Risk factors for attrition included young age, low CD4 percentage, underweight, active tuberculosis, and enrollment/treatment initiation after 2006. The mean CD4 percentage increased strongly at 1 year on treatment and remained high thereafter. The body mass index for age z-score sharply increased at 1 year after treatment initiation before stabilizing at pre-ART levels thereafter., Conclusions: Good clinical and immunological treatment outcomes up to 8 years of follow-up on ART can be achieved in a context of shortage of health workers and a high level of task-shifting approach.

Introduction: Since 1996 Brazil has provided universal access to free antiretroviral therapy, and as a consequence, HIV/AIDS patients' survival rate has improved dramatically. However, according to scientific reports, a significant number of patients are still late presenting for HIV treatment, which leads to consequences both for the individual and society. Clinical and immunological characteristics of HIV patients newly diagnosed were accessed and factors associated with late presentation for treatment were evaluated., Methods: A cross-sectional study was carried out in an HIV/AIDS reference center in Belo Horizonte, Minas Gerais, in Southeastern Brazil from 2008 to 2010. Operationally, patients with late presentation (LP) for treatment were those whose first CD4 cell count was less than 350 cells/mm(3) or presented an AIDS defining opportunistic infection. Patients with late presentation with advanced disease (LPAD) were those whose first CD4 cell count was less than 200 cells/mm(3) or presented an AIDS defining opportunistic infection. LP and LPAD associated risk factors were evaluated using logistic regression methods., Results: Five hundred and twenty patients were included in the analysis. The median CD4 cell count was 336 cells/mm(3) (IQR: 130-531). Two hundred and seventy-nine patients (53.7%) were classified as LP and 193 (37.1%) as LPAD. On average, 75% of the patients presented with a viral load (VL) >10,000 copies/ml. In multivariate logistic regression analysis the factors associated with LP and LPAD were age, being symptomatic at first visit and VL. Race was a factor associated with LP but not with LPAD., Conclusion: The proportion of patients who were late attending a clinic for HIV treatment is still high, and effective strategies to improve early HIV detection with a special focus on the vulnerable population are urgently needed., (Copyright © 2015 Elsevier Editora Ltda. All rights reserved.)

Objective: Depression is common in people living with HIV/AIDS and there is some evidence that depressive symptoms may have adverse effects on immune functioning. The purpose of this study was to determine the prevalence of current depressive disorder in patients with HIV/AIDS and its association with CD4 cell count., Methods: A consecutive sample of 310 patients with HIV/AIDS attending Out-patient clinic in Ahmadu Bello University Teaching Hospital (A.B.U.T.H.), Zaria, Nigeria was assessed. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to screen for depressive symptoms, and the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used to confirm the diagnosis of current depressive disorder. The CD4 cell counts of participants with depressive disorder were compared with those of participants without depressive disorder. Multiple regression analysis was conducted to identify socio-demographic and disease-related factors associated with depression., Results: Among the 310 HIV-infected participants assessed for depression, 14.2% had current depressive disorder. Adjusting for age, gender, education, occupation, and marital status, patients with CD4 counts < 150 cells/μl were more likely to be depressed., Conclusion: Depression is common among HIV-infected persons in Nigeria and is associated with low CD4 cell counts. The screening and treatment of mental health problems such as depression should be considered an integral component of HIV care and support., (© 2015, The Author(s).)

The global HIV/AIDS pandemic has resulted in 39 million deaths to date, and there are currently more than 35 million people living with HIV worldwide. Prevention, screening, and treatment strategies have led to major progress in addressing this disease globally. Diagnostics is critical for HIV prevention, screening and disease staging, and monitoring antiretroviral therapy (ART). Currently available diagnostic assays, which include polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and western blot (WB), are complex, expensive, and time consuming. These diagnostic technologies are ill suited for use in low- and middle-income countries, where the challenge of the HIV/AIDS pandemic is most severe. Therefore, innovative, inexpensive, disposable, and rapid diagnostic platform technologies are urgently needed. In this review, we discuss challenges associated with HIV management in resource-constrained settings and review the state-of-the-art HIV diagnostic technologies for CD4(+) T lymphocyte count, viral load measurement, and drug resistance testing.

People from culturally and linguistically diverse backgrounds, including low- and middle-income countries, account for a third of new HIV diagnoses in Australia and are a priority for HIV prevention and treatment programs. We describe the demographic and clinical characteristics of participants in the Australian HIV Observational Database (AHOD) and compare disease outcomes, progression to AIDS and treatment outcomes of those born in low- and middle-income countries, with those born in high-income countries and Australia. All participants enrolled in AHOD sites where country of birth is routinely collected were included in the study. Age, CD4 count, HIV viral load, antiretroviral therapy, hepatitis co-infection, all-cause mortality and AIDS illness were analysed. Of 2403 eligible participants, 77.3% were Australian born, 13.7% born in high-income countries and 9.0% born in middle- or low-income countries. Those born in Australia or high-income countries were more likely to be male (96%) than those from middle- or low-income countries (76%), p < .0001 and more likely to have acquired HIV via male to male sexual contact (77%; 79%) compared with those from middle- or low-income countries (50%), p < .0001. At enrolment, mean CD4 cell count was higher in Australian born (528 cells/µL) than both those born in high-income countries (468 cells/µL) and those born in middle- and low-income countries (451 cells/µL), p < .0001; whereas the mean HIV RNA level (log10 copies/mL) was similar in all three groups (4.44, 4.76 and 4.26, respectively), p = .19.There was no difference in adjusted incidence risk ratios for all-cause mortality and AIDS incidence in all three groups, p = .39. These findings reflect successful outcomes of people born in low- and middle-income countries once engaged in HIV care.

Alcohol and other drugs use seem to be common among people infected with HIV on antiretroviral treatment (ART). Their effects on HIV progression is still in debate. This study aimed to assess the association between alcohol and drug use and an HIV disease progression biomarker (CD4 cell count) among patients on ART. A cross-sectional study was carried out at an HIV treatment center affiliated with Medical School of the University of São Paulo, Brazil. Four hundred and thirty-eight HIV-positive patients on ART were interviewed by trained psychiatrists and psychologists using the following instruments: Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Alcohol Use Disorders Identification Test (AUDIT), 17-item Hamilton Rating Scale for Depression, and the Simplified Medication Adherence Questionnaire (SMAQ). In the previous month, 219 (50%) and 41 (9.3%) patients reported use of alcohol and illicit drugs, respectively. Fifty patients (12.6%) were classified as having harmful alcohol use by AUDIT. According to SCID-I, 80 patients (18.3%) were alcohol abusers, 24 (5.5%) alcohol dependents, and 21 (4.2%) had a current depressive disorder. Almost 73% (n = 319-72.8%) of the patients were adherent to ART. Alcohol dependents were nine times (p < 0.01) more likely to have CD4 cell count ≤200/mm(3), and this association was independent of ART adherence. In conclusion, alcohol dependence seems to be associated with low CD4 cell count in HIV-positive patients. Based on these data, HIV health care workers should always assess alcohol consumption in the treatment setting, and patients should be advised that alcohol dependence may be linked to low CD4.

Studies examining the sex differences in morbidity and mortality among HIV/AIDS patients have yielded inconsistent results. We conducted a meta-analysis of sex differences in disease progression and mortality among HIV/AIDS patients. Medical literature databases from inception to August 2014 were searched for published observational studies assessing sex differences in immunologic and virologic response, disease progression and mortality among HIV-infected patients. Random effects meta-analyses of 115 eligible studies were conducted to obtain pooled estimates of outcomes and heterogeneity was explored in sub-group analyses. Pooled estimates showed an increased risk of progression to AIDS (relative risk [RR]=1.11,95% CI=1.02-1.21) and all-cause mortality (RR=1.23, 95% CI=1.17-1.29) among males compared to females. All-cause mortality differed by sex only in low and middle income countries. The risk of AIDS-related mortality (RR=1.03, 95% CI=0.82-1.30), immunologic failure (RR=1.19,95% CI: 0.97-1.47), virologic suppression (RR=0.98, 95% CI=0.84-1.14), virologic failure (RR=1.26, 95% CI=0.99-1.61) and the change in CD4 cell count (Weighted mean difference [WMD] = -5.15, 95% CI= -13.57 to 3.28) did not differ by sex. These findings were modified by disease severity, adherence and use of highly active antiretroviral therapy. We conclude that HIV-related disease progression and survival outcomes are poorer in males.

Objectives: The extent to which clinical progression of HIV-positive patients leads to an increase in health care utilization, especially prior to their death, is unknown. Thus, we modelled trends in CD4 cell count and emergency department utilization and the likelihood of an emergency department visit leading to a transfer to an acute care-level facility prior to a patient's death from nonaccidental causes., Methods: Eligible patients initiated highly active antiretroviral therapy (HAART) in British Columbia between August 1996 and June 2006 (n = 457). Patients were followed until their death, which occurred on or before 30 June 2007 (period in which the emergency department visit data were available). Trends were modelled using generalized mixed effects., Results: Patients experienced a significantly steep decline in CD4 cell count and a corresponding increase in the number of emergency department visits and transfers to acute-level facilities in the 5 years prior to death. For every 6-month interval prior to death, the CD4 cell count decreased by 13.22 cells/μL, the risk of experiencing an emergency department visit increased by 9%, and among those ever admitted, the odds ratio of being transferred to an acute care-level facility increased by 3%., Conclusions: We showed that patients experienced a steep decline in CD4 cell count, which was associated with an increase in health care utilization prior to their death. These findings highlight the substantial residual avoidable burden that unsuccessfully managed HIV disease poses, even in the HAART era. Further strategies to enhance sustained and successful engagement in care are urgently needed to mitigate high health care utilization., (© 2014 British HIV Association.)