Mortality In HIV-positive Patients Research Articles

Clinical outcomes of ventricular assist device support by HIV infection status: An STS-INTERMACS analysis

Cardiovascular disease remains the leading cause of mortality in human immunodeficiency virus-infected (HIV-positive) patients. Ventricular assist device therapy is rarely offered to these patients and data on outcomes are sparse. We investigated outcomes following ventricular assist device implants for HIV-positive as compared to non-HIV-infected (HIV-negative) patients. We analyzed 22,065 patients from the Interagency Registry for Mechanically Assisted Circulatory Support registry for outcomes by HIV status. A propensity-matched analysis adjusting for 21 preimplant risk factors was also conducted. Compared with 21,980 HIV-negative device recipients, the 85 HIV-positive recipients were younger (median age 58 years vs 59 years, p=0.02), had lower body mass index (26kg/m2 vs 29kg/m2, p=0.001), and had higher rates of prior stroke (8% vs 4%, p=0.02). In the matched HIV-positive and HIV-negative cohorts, there was significantly higher mortality in HIV-positive patients in earlier implant years, however, this association was not seen in later implant years (2018-2020). In both unmatched and matched cohorts, no significant differences in postimplantation stroke, major bleeding, or major infection were noted. With recent advancements in mechanical circulatory support and HIV treatment, ventricular assist device therapy is a viable therapeutic option for HIV-positive patients with end-stage heart failure.

OCCURRENCE OF HEPATITIS B, HEPATITIS C AND TREPONEMAL COINFECTION IN PEOPLE LIVING WITH HIV

Morbidity and mortality of HIV positive patients depends on their response to antiretroviral therapy. Early detection and treatment of co-infection may lead to better outcome as indicated by immune restoration. The present cross- sectional study was undertaken to assess occurrence of coinfections of HBV, HCV and Syphilis and its impact on immune response in HIV positive patients. A total of 200 HIV positive patients receiving ART at the centre of SGH Pune were randomly selected for this study. Blood sample which is routinely collected for CD4 count was taken for our study. No extra sample was taken. This group comprised of 102 male 97 female and one transgender. The age group included in the study was 3years to 76years. A total of 25.5% (51/200) of the patients were tested positive for co-infections. 60.78% (31/51) were positive for Hepatitis B, 3.92% (2/51) for Hepatitis C, 35.29% (18/51) for Syphilis. To study the effect of co-infection on immune response, patient's periodic CD4 count data was analyzed. CD4 count ranged from 15 to 4329 with mean of 392 while in the 51 co-infected patients CD4 count ranged from 3 to 1044 mean 354). A signicant difference in CD4 count was observed between the non-co-infected and co-infected groups. A constantly decrementing trend of CD4 count was the cardinal nding in patients with underlying co-infection.

Machine learning to predict virological failure among HIV patients on antiretroviral therapy in the University of Gondar Comprehensive and Specialized Hospital, in Amhara Region, Ethiopia, 2022

BackgroundTreatment with effective antiretroviral therapy (ART) reduces viral load as well as HIV-related morbidity and mortality in HIV-positive patients. Despite the expanded availability of antiretroviral therapy around the world, virological failure remains a serious problem for HIV-positive patients. Thus, Machine learning predictive algorithms have the potential to improve the quality of care and predict the needs of HIV patients by analyzing huge amounts of data, and enhancing prediction capabilities. This study used different machine learning classification algorithms to predict the features that cause virological failure in HIV-positive patients.MethodAn institution-based secondary data was used to conduct patients who were on antiretroviral therapy at the University of Gondar Comprehensive and Specialized Hospital from January 2020 to May 2022. Patients’ data were extracted from the electronic database using a structured checklist and imported into Python version three software for data pre-processing and analysis. Then, seven supervised classification machine-learning algorithms for model development were trained. The performances of the predictive models were evaluated using accuracy, sensitivity, specificity, precision, f1-score, and AUC. Association rule mining was used to generate the best rule for the association between independent features and the target feature.ResultOut of 5264 study participants, 1893 (35.06%) males and 3371 (64.04%) females were included. The random forest classifier (sensitivity = 1.00, precision = 0.987, f1-score = 0.993, AUC = 0.9989) outperformed in predicting virological failure among all selected classifiers. Random forest feature importance and association rules identified the top eight predictors (Male, younger age, longer duration on ART, not taking CPT, not taking TPT, secondary educational status, TDF-3TC-EFV, and low CD4 counts) of virological failure based on the importance ranking, and the CD-4 count was recognized as the most important predictor feature.ConclusionThe random forest classifier outperformed in predicting and identifying the relevant predictors of virological failure. The results of this study could be very helpful to health professionals in determining the optimal virological outcome.

SARS-CoV-2/COVID-19: Clinical Course Among Subjects HIV-1-Infected in Sao Paulo.

People living with Human Immunodeficiency Virus (HIV) are under risk for co-infection with SARS-CoV-2. This population may be more prone to complications from COVID-19 due to persistent inflammation caused by HIV and higher incidence of metabolic syndromes, cardiovascular diseases, and malignancies, as well as being considered elderly at 50 years of age. The objective of this study was to report SARS-CoV-2 infection frequency, clinical evolution, and mortality in HIV-positive patients on antiretroviral therapy. The period of inquiry ranged from January to September 2020. Due to the social distance and the suspension of in-person medical care during the time of the investigation, we sent electronic questions about demographic, epidemiological, and clinical data to 403 HIV-infected patients. Among 260 patients who answered the questionnaire, thirty-nine patients (15%) had suggestive symptoms and were tested for SARS-CoV-2 infection. Of this, 11 had positive results (32.4%) and no patient died of COVID-19 complications. Nine were male (3.4%), and the mean age of the patients with positive results was 43.2 years (± 9.6). 107 patients (41.1%) were over 50 years of age and their mean T-CD4+ cell count was 768. Eleven patients (4.2%) had a detectable HIV RNA viral load and 127 (48.8%) had comorbidities. These variables were not associated with an increased risk for infection. The frequency of SARS-COV2 infection among HIV-infected is similar to the general population, and the clinical course is associated with the presence of comorbidities and not due to the HIV infection. However, new studies should be done to assess if this vulnerable population could answer the vaccine anti-SARS-Cov2.

Development and internal validation of the HIV In-hospital Mortality Prediction (HIV-IMP) risk score.

Despite advances in availability and access to antiretroviral therapy (ART), HIV still ranks as a major cause of global mortality. Hence, the aim of this study was to develop and internally validate a risk score capable of accurately predicting in-hospital mortality in HIV-positive patients requiring hospital admission. Consecutive HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult emergency department between 7July 2017 and 18 October 2018 were prospectively enrolled. Multivariate logistic regression was used to determine parameters for inclusion in the final risk score. Discrimination and calibration were assessed by means of the area under the receiver operating curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test, respectively. Internal validation was conducted using the regular bootstrap technique. The overall in-hospital mortality rate was 13.6% (n=166). Eight predictors were included in the final risk score: ART non-adherence or not yet on ART, Glasgow Coma Scale <15, respiratory rate >20 breaths/min, oxygen saturation <90%, white cell count <4×109 /L, creatinine >120μmol/L, lactate >2mmol/L and albumin <35g/L. After internal validation, the risk score maintained good discrimination [AUROC 0.83, 95% confidence interval (CI): 0.78-0.88] and calibration (Hosmer-Lemeshow χ2 = 2.26, p=0.895). The HIV In-hospital Mortality Prediction (HIV-IMP) risk score has overall good discrimination and calibration and is relatively easy to use. Further studies should be aimed at externally validating the score in varying clinical settings.

High-sensitivity C-reactive protein in HIV care: Tuberculosis diagnosis and short-term mortality in a cohort of Kenyan HIV patients in the DREAM programme

ObjectiveTuberculosis (TB) is the leading cause of death in HIV-positive people. In Kenya, 140 000 new TB cases occurred in 2019, and 13 000 HIV-positive patients died due to TB. The objective of this study was to investigate the role of high-sensitivity C-reactive protein (HS-CRP) in TB diagnosis and the prediction of mortality in HIV-positive patients. MethodsThe IDEA-TB Study enrolled HIV-positive adult patients attending three DREAM centres in Kenya who were suspected of having TB. A lateral flow urine lipoarabinomannan assay (LF-LAM), serum HS-CRP, and GeneXpert MTB/RIF assay (Xpert MTB/RIF) were performed. Six-month survival was evaluated. ResultsA total of 574 patients were enrolled. The median (interquartile range) age, body mass index, and CD4 count were 45 years (37–54 years), 20.5 kg/m2 (18.5–23.69 kg/m2), and 477 cells/mL (290–700 cells/mL), respectively. TB was confirmed in 87 (15.2%) patients. Concordance between the Xpert MTB/RIF and LF-LAM tests was 87.1%. HS-CRP was higher in TB patients (35.39 mg/l vs 9.21 mg/l). Malnutrition and elevated HS-CRP were associated with TB: odds ratio (OR) 2.5 (95% confidence interval (CI) 1.14–5.72) and OR 6.6 (95% CI 3.87–11.52), respectively. Nine (1.6%) patients died during follow-up. No single factor was associated with mortality. Only the combination of malnutrition and elevated HS-CRP was highly predictive of death (odds ratio (OR) 9.8, 95% CI 1.88–50.95); the association was stronger in TB patients (33.3% vs 1.0%; OR 47.6, 95% CI 7.03–322.23). ConclusionTB diagnosis in HIV-positive patients remains challenging. HS-CRP could play a role in predicting early mortality in symptomatic patients.

Insights Into the Pathophysiology of Liver Disease in HCV/HIV: Does it End With HCV Cure?

HCV-HIV coinfected patients exhibit rapid progression of liver damage relative to HCV monoinfected patients. The availability of new directly acting antiviral agents has dramatically improved outcomes for coinfected patients as sustained virologic response rates now exceed 95% and fibrosis-related parameters are improved. Nevertheless, coinfected patients still have a higher mortality risk and more severe hepatocellular carcinoma compared to HCV monoinfected patients, implying the existence of pathways unique to people living with HIV that continue to promote accelerated liver disease. In this article, we review the pathobiology of liver disease in HCV-HIV coinfected patients in the directly acting antiviral era and explore the mechanisms through which HIV itself induces liver damage. Since liver disease is one of the leading causes of non-AIDS-related mortality in HIV-positive patients, enhancing our understanding of HIV-associated fibrotic pathways will remain important for new diagnostic and therapeutic strategies to slow or reverse liver disease progression, even after HCV cure.

Decreased All-Cause and Liver-Related Mortality Risk in HIV/Hepatitis B Virus Coinfection Coinciding With the Introduction of Tenofovir-Containing Combination Antiretroviral Therapy.

BackgroundThe development of efficacious combination antiretroviral therapy (cART) has led to a dramatic decrease in mortality in HIV-positive patients. Specific data on the impact in HIV/hepatitis B virus (HBV)–coinfected patients are lacking. In this study, all-cause and cause-specific mortality risks stratified per era of diagnosis are investigated.MethodsData were analyzed from HIV/HBV-coinfected patients enrolled in the ATHENA cohort between January 1, 1998, and December 31, 2017. Risk for (cause-specific) mortality was calculated using Cox proportional hazard regression analysis, comparing patients diagnosed before 2003 with those diagnosed ≥2003. Risk factors for all-cause and liver-related mortality were also assessed using Cox proportional hazard regression analysis.ResultsA total of 1301 HIV/HBV-coinfected patients were included (14 882 person-years of follow-up). One-hundred ninety-eight patients (15%) died during follow-up. The adjusted hazard ratio (aHR) for all-cause mortality in patients diagnosed in or after 2003 was 0.50 (95% CI, 0.35–0.72) relative to patients diagnosed before 2003. Similar risk reduction was observed for liver-related (aHR, 0.29; 95% CI, 0.11–0.75) and AIDS-related mortality (aHR, 0.44; 95% CI, 0.22–0.87). Use of a tenofovir-containing regimen was independently associated with a reduced risk of all-cause and liver-related mortality. Prior exposure to didanosine/stavudine was strongly associated with liver-related mortality. Ten percent of the population used only lamivudine as treatment for HBV.ConclusionsAll-cause, liver-related, and AIDS-related mortality risk in HIV/HBV-coinfected patients has markedly decreased over the years, coinciding with the introduction of tenofovir. Tenofovir-containing regimens, in absence of major contraindications, should be strongly encouraged in this population.

Outcomes Among HIV-Positive Patients Hospitalized With COVID-19

SARS-CoV-2 infection continues to cause significant morbidity and mortality worldwide. Preliminary data on SARS-CoV-2 infection suggest that some immunocompromised hosts experience worse outcomes. We performed a retrospective matched cohort study to characterize outcomes in HIV-positive patients with SARS-CoV-2 infection. Leveraging data collected from electronic medical records for all patients hospitalized at NYU Langone Health with COVID-19 between March 2, 2020, and April 23, 2020, we matched 21 HIV-positive patients with 42 non-HIV patients using a greedy nearest-neighbor algorithm. Admission characteristics, laboratory test results, and hospital outcomes were recorded and compared between the 2 groups. Although there was a trend toward increased rates of intensive care unit admission, mechanical ventilation, and mortality in HIV-positive patients, these differences were not statistically significant. Rates for these outcomes in our cohort are similar to those previously published for all patients hospitalized with COVID-19. HIV-positive patients had significantly higher admission and peak C-reactive protein values. Other inflammatory markers did not differ significantly between groups, although HIV-positive patients tended to have higher peak values during their clinical course. Three HIV-positive patients had superimposed bacterial pneumonia with positive sputum cultures, and all 3 patients died during hospitalization. There was no difference in frequency of thrombotic events or myocardial infarction between these groups. This study provides evidence that HIV coinfection does not significantly impact presentation, hospital course, or outcomes of patients infected with SARS-CoV-2, when compared with matched non-HIV patients. A larger study is required to determine whether the trends we observed apply to all HIV-positive patients.

Pathological anatomy of tuberculosis in the presence of human immunodeficiency virus infection

to assess the clinical and morphological characteristics of concurrent TB/HIV infection. An autopsy material obtained from the S.P. Botkin Clinical Infectious Diseases Hospital (CIDH) in 2018 was analyzed. Eight samples stained with hematoxylin and eosin, Ziehl-Neelsen carbol-fuchsin, auramine-rhodamine were thoroughly examined, followed by fluorescent microscopy; an immunohistochemical (IHC) study was performed. 736 autopsies made at the S.P. Botkin CIDH in 2018 revealed 357 deaths from HIV infection; 86 (24%) cases of which were caused by concurrent HIV/TB infection. All the cases showed an extremely diverse and heterogeneous pattern that considerably differed from that of classical granulomatous inflammation in tuberculosis. Ziehl-Neelsen staining could demonstrate single clusters of acid-resistant bacteria with a total of not more than 1000 in the specimen of predominantly rod-shaped bacteria. Auramine-rhodamine staining revealed focal clusters of mycobacteria with a total of 1000 to 2000 in the specimen of predominantly rod-shaped and coccoid bacteria. An IHC study identified clusters of mycobacteria with a total of more than 2000 in the sample, which were characterized by a moderate variety of shapes: rods, cocci, granules, clavate, and branched ones. Mycobacteria were present extracellularly in all the studied cases. Tuberculosis holds the most important place in the pattern of causes of death in HIV infection, accounting for 24%. The lifetime diagnosis of tuberculosis remains not entirely satisfactory. The alterative component of inflammation more often predominates, although without completely losing the ability to form granulomas. The concurrence of different morphological forms of tuberculosis makes it highly desirable to clarify and/or supplement the existing classifications. None of the methods used to detect Mycobacterium tuberculosis in the tissues could reveal the intracellular localization of the pathogen. Most mycobacteria had a typical rod-shaped morphology.

IL-4 polymorphism influences susceptibility to Pneumocystis jirovecii pneumonia in HIV-positive patients.

Objectives:Pneumocystis jirovecii pneumonia (PJP) is an important cause of morbidity and mortality in HIV-positive patients. Polymorphisms in immune genes are increasingly reported to influence susceptibility to fungal infections. We analysed the role of 21 single nucleotide polymorphisms from 19 candidate genes on PJP development in patients from the Swiss HIV Cohort Study.Design and methods:The analysis included patients with a nadir CD4+ T-cell count less than 200 cells/μl, divided into a discovery (N = 1645) and a replication (N = 1861) cohort. The associations were analysed by using cumulative incidence curves as well as competing risk regression over 18 years, starting from the estimated date of HIV infection, considering death a competing risk, with censoring at lost follow-up, and assuming the dominant mode of inheritance.Results:The minor allele of rs2243250 in IL-4 was associated with the risk of PJP in the discovery cohort (cumulative incidence 0.18 versus 0.12, P = 0.002). This association was replicated in the validation cohort (0.16 versus 0.12, P = 0.02). It was still significant in multivariate models, adjusted for HIV transmission mode, viral load, CD4+ T cells slope, age, antiretroviral therapy, tobacco smoking, hepatitis C virus coinfection, year of cohort entry and PJP prophylaxis (global subhazard ratio 1.42, 95% confidence interval 1.17–1.73, P = 0.0004).Conclusion:Our data suggest rs2243250, a single nucleotide polymorphism known to influence IL-4 production, is associated with susceptibility to PJP in HIV-positive patients.

In-hospital mortality of HIV-positive patients with acute kidney injury a decade after the roll-out of anti-retroviral therapy in Cape Town, South Africa

Background: Acute kidney injury (AKI) in HIV-infected patients in sub-Saharan Africa is a common cause of hospitalisation and is associated with high morbidity and mortality. There is a paucity of comparative data regarding the outcomes of AKI in those patients with and without HIV infection from the African continent. Methods: This was a single-centre retrospective study of all consecutive adult patients with AKI referred to the renal unit at Tygerberg Hospital for the period January 2015 to December 2016. The diagnosis of AKI required evidence of the following: a recent normal serum creatinine and/or normal kidney sizes on ultrasound examination and/or granular casts on urine microscopy. Kaplan–Meier curves and logistic regression were used to assess survival and identify factors predicting mortality. Results: We identified a total of 291 patients with AKI of whom 116 (40%) were HIV positive. HIV-positive patients had a mortality rate of 34.5% vs. 29.1% in the HIV-negative patients (P = 0.34). At hospital admission, HIV-positive patients had a higher admission serum creatinine (551 μmol/L vs. 190 μmol/L, P < 0.01). Of those who died, the HIV-positive patients were younger (41 vs. 52 years, P < 0.01), predominantly Black (87.5% vs. 23.5%, P < 0.01) and were mostly admitted to medical wards (92.5% vs. 41.2%, P < 0.01). There was no difference in mortality related to the use of renal replacement therapy (P = 0.50). Logistic regression identified mixed ancestry (OR 2.47, P = 0.02), HIV infection (OR 2.69, P < 0.01) and surgical ward admission (OR 2.05, P = 0.03) as predictors of death. Conclusions: In-hospital mortality of AKI was high, and HIV infection was associated with a greater risk of death. This may be the result of late presentation of both the AKI as well as the HIV infection.

Hospitalization of HIV positive patients in a referral tertiary care hospital in Antananarivo Madagascar, 2010-2016: Trends, causes and outcome.

BackgroundDuring the last few years, significant efforts have been made to improve access to antiretroviral therapy which led to dramatic reduction in AIDS-related events and mortality in HIV positive patients at the global level. However, current data in Africa suggested modest impact of widespread antiretroviral therapy scale-up especially regarding HIV-related hospitalization. In this study, we aimed to describe causes of hospitalization and factors associated with AIDS-defining events and inpatient mortality.Materials and methodsA retrospective study was performed on medical records of HIV positive patients admitted for at least 24 hours in the Infectious Diseases Unit of the University Hospital Joseph Raseta Befelatanana Antananarivo. Cause of hospitalization was considered as the main diagnosis related to the symptoms at admission. Diagnostic criteria were based on criteria described in WHO guidelines. AIDS-defining events were defined as diseases corresponding to WHO stage 4 or category C of CDC classification.ResultsFrom 2010 to 2016, 236 hospital admissions were included. AIDS-defining events were the most frequent cause of hospitalization (61.9%) with an increasing trend during the study period. Tuberculosis (28.4%), pneumocystis pneumonia (11.4%), cerebral toxoplasmosis (7.2%) and cryptococcosis (5.5%) were the most frequent AIDS-defining events. Tuberculosis was also the most frequent cause of overall hospitalization. In multivariate analysis, recent HIV diagnosis (aOR = 2.0, 95% CI: 1.0–3.9), CD4<200 cells/μl (aOR = 4.0, 95%CI: 1.9–8.1), persistent fever (aOR = 4.4, 95%CI: 2.1–9.0), duration of symptoms≥ 6 weeks (aOR = 2.6, 95%CI: 1.2–5.4) were associated with AIDS-defining events. Overall inpatient mortality was 19.5%. Age≥55 years (aOR = 4.9, 95%CI: 1.5–16.6), neurological signs (aOR = 3.2, 95%CI: 1.5–6.9) and AIDS-defining events (aOR = 2.9, 95%CI: 1.2–-7.2) were associated with inpatient mortality.ConclusionsAIDS-defining events were the most frequent cause of hospitalization during the study period. Factors associated with AIDS-defining events mostly reflected delay in HIV diagnosis. Factors associated with mortality were advanced age, neurological signs and AIDS-defining events.

Mental health problem in HIV/AIDS patients

People with HIV positive have risk increased mental health problem than the general population. It associated with psychosocial factors, direct neurological effects of the HIV infection and medication. Overall it can make increased morbidity and mortality in HIV positive patients. The more common mental problem in HIV/AIDS people is dementia, delirium, depression, and mania, suicide, psychotic, sleep problem. Both psychopharmacologic and psychotherapeutic treatment strategies often indicate.

Exploring viral reservoir: The combining approach of cell sorting and droplet digital PCR.

Combined antiretroviral therapy (cART) blocks different steps of HIV replication and maintains plasma viral RNA at undetectable levels. The virus can remain in long-living cells and create a reservoir where HIV can restart replicating after cART discontinuation. A persistent viral production triggers and maintains a persistent immune activation, which is a well-known feature of chronic HIV infection, and contributes either to precocious aging, or to the increased incidence of morbidity and mortality of HIV positive patients. The new frontier of the treatment of HIV infection is nowadays eradication of the virus from all host cells and tissues. For this reason, it is crucial to have a clear and precise idea of where the virus hides, and which are the cells that keep it silent. Important efforts have been made to improve the detection of viral reservoirs, and new techniques are now giving the opportunity to characterize viral reservoirs. Among these techniques, a strategic approach based upon cell sorting and droplet digital PCR (ddPCR) is opening new horizons and opportunities of research. This review provides an overview of the methods that combine cell sorting and ddPCR for the quantification of HIV DNA in different cell types, and for the detection of its maintenance.

A frailty index predicts post-liver transplant morbidity and mortality in HIV-positive patients

BackgroundWe hypothesized that frailty acts as a measure of health outcomes in the context of LT. The aim of this study was to explore frailty index across LT, as a measure of morbidity and mortality. This was a retrospective observational study including all consecutive 47 HIV+patients who received LT in Modena, Italy from 2003 to June 2015.Methodsfrailty index (FI) was constructed from 30 health variables. It was used both as a continuous score and as a categorical variable, defining ‘most frail’ a FI > 0.45. FI change across transplant (deltaFI, ΔFI) was calculated as the difference between year 1 FI (FI–Y1) and pre-transplant FI (FI–t0). The outcomes measures were mortality and “otpimal LT” (defined as being alive without multi-morbidity).ResultsMedian value of FI–t0 was 0.48 (IQR 0.42–0.52), FI–Y1 was 0.31 (IQR 0.26–0.41). At year five mortality rate was 45%, “optimal transplant” rate at year 1 was 38%. All the patients who died in the post-LT were most frail in the pre-LT. ΔFI was a predictor of mortality after correction for age and MELD (HR = 1.10, p = 0.006) and was inversely associated with optimal transplant after correction for age (HR = 1.04, p = 0.01).ConclusionsWe validated FI as a valuable health measure in HIV transplant. In particular, we found a relevant correlation between FI strata at baseline and mortality and a statistically significant correlation between, ΔFI and survival rate.

Dysregulation of mitochondrial bioenergetics and quality control by HIV-1 Tat in cardiomyocytes.

Cardiovascular disease remains a leading cause of morbidity and mortality in HIV-positive patients, even in those whose viral loads are well controlled with antiretroviral therapy. However, the underlying molecular events responsible for the development of cardiac disease in the setting of HIV remain unknown. The HIV-encoded Tat protein plays a critical role in the activation of HIV gene expression and profoundly impacts homeostasis in both HIV-infected cells and uninfected cells that have taken up released Tat via a bystander effect. Since cardiomyocyte function, including excitation-contraction coupling, greatly depends on energy provided by the mitochondria, in this study, we performed a series of experiments to assess the impact of Tat on mitochondrial function and bioenergetics pathways in a primary cell culture model derived from neonatal rat ventricular cardiomyocytes (NRVCs). Our results show that the presence of Tat in cardiomyocytes is accompanied by a decrease in oxidative phosphorylation, a decline in the levels of ATP, and an accumulation of reactive oxygen species (ROS). Tat impairs the uptake of mitochondrial Ca2+ ([Ca2+ ]m ) and the electrophysiological activity of cardiomyocytes. Tat also affects the protein clearance pathway and autophagy in cardiomyocytes under stress due to hypoxia-reoxygenation conditions. A reduction in the level of ubiquitin along with dysregulated degradation of autophagy proteins including SQSTM1/p62 and a reduction of LC3 II were detected in cardiomyocytes harboring Tat. These results suggest that, by targeting mitochondria and protein quality control, Tat significantly impacts bioenergetics and autophagy resulting in dysregulation of cardiomyocyte health and homeostasis.

The effect of HIV status on clinical outcomes of surgical sepsis in KwaZulu-Natal Province, South Africa.

KwaZulu-Natal Province, South Africa (SA), has long been the epicentre of the HIV epidemic, but the impact of HIV co-infection on the clinical outcomes of emergency surgical patients with sepsis remains largely unknown. To review our experience with the management of patients with HIV co-infection and to compare the disease spectrum and outcome with those without HIV infection. A retrospective study was undertaken at the Pietermaritzburg Metropolitan Surgical Service (PMSS), SA over a 5-year period from January 2010 to December 2014. A total of 675 patients with a documented surgical source of sepsis were reviewed. Of these, 332 (49%) were male, and the mean age was 46 (standard deviation 19) years. HIV status was known in 237 (35%) patients, 146 (62%) were HIV-positive and the remaining 91 (38%) were HIV-negative. Other than tuberculosis of the abdomen being significantly more common in HIV-positive than HIV-negative patients (10% v. 2%, p=0.033), there were no differences in the spectrum of diseases between the two groups. There were no significant differences in overall morbidity or mortality. When adjusted for CD4 counts, the mortality in HIV-positive patients with a CD4 count &lt;200 cells/μL was 60% (15/25) and in those with a CD4 count &gt;200 cells/μL it was 2% (2/101) (p&lt;0.001). The clinical presentation and the spectrum of surgical sepsis in patients with HIV co-infection were not markedly different to those in patients who were not HIV-infected. HIV-infected patients with a CD4 count &lt;200 cells/μL had a significantly higher mortality. Management approaches should not differ based solely on the HIV status of patients with surgical sepsis.

Étude comparative de l’insuffisance rénale aiguë communautaire chez le sujet VIH positif et le sujet VIH négatif : expérience d’un service de médecine interne à Abidjan (Côte d’Ivoire)

BackgroundAcute kidney injury (AKI) is commonly associated with HIV infection. ObjectivesTo describe the profile of AKI in HIV infected versus non-infected persons. Patients and methodsThis is a prospective study that was carried out during the study period from January 2010 to December 2015 in the department of nephrology-internal medicine D of Treichville University Hospital (Côte d’Ivoire). ResultsThe prevalence of HIV infection was 35.2% in the population of AKI. The average age of patients was 42±18 years in the HIV positive group against 51±18 years in the HIV negative group (P=0.0001). Etiologies were infections in 65.1% in the HIV positive group against 38.8% in the HIV negative group (P=0.0001) and water loss in 24.7% in the HIV positive group against 7.8% in the HIV negative group (P=0.0001). Factors such as the AIDS stage (P=0.002), severe sepsis (P=0.002) and acute pyelonephritis (P=0.001) were associated with mortality in HIV positive patients against severe anemia (P=0.0001) and severe sepsis (P=0.0001) in the HIV-negative group. ConclusionHIV positive patients are younger with a female predominance. The mortality rate is identical in both groups.

All-cause mortality in HIV-positive adults starting combination antiretroviral therapy: correcting for loss to follow-up.

To estimate mortality in HIV-positive patients starting combination antiretroviral therapy (ART) and to discuss different approaches to calculating correction factors to account for loss to follow-up. A total of 222 096 adult HIV-positive patients who started ART 2009-2014 in clinics participating in the International epidemiology Databases to Evaluate AIDS collaboration in 43 countries in sub-Saharan Africa, Asia Pacific, Latin America, and North America were included. To allow for underascertainment of deaths due to loss to follow-up, two correction factors (one for the period 0-6 months on ART and one for later periods) or 168 correction factors (combinations of two sexes, three time periods after ART initiation, four age groups, and seven CD4 groups) based on tracing patients lost in Kenya and data linkages in South Africa were applied. Corrected mortality rates were compared with a worst case scenario assuming all patients lost to follow-up had died. Loss to follow-up differed between regions; rates were lowest in central Africa and highest in east Africa. Compared with using two correction factors (1.64 for the initial ART period and 2.19 for later), applying 168 correction factors (range 1.03-4.75) more often resulted in implausible mortality rates that exceeded the worst case scenario. Corrected mortality rates varied widely, ranging from 0.2 per 100 person-years to 54 per 100 person-years depending on region and covariates. Implausible rates were less common with the simpler approach based on two correction factors. The corrected mortality rates will be useful to international agencies, national programmes, and modellers.