Mortality In HIV-infected Individuals Research Articles

Incidence of diabetes and influencing factors in HIV-infected individuals after antiretroviral therapy in Dehong Dai and Jingpo Autonomous Prefecture

Objective: To understand the incidence of diabetes and influencing factors, the trend of FPG change and risk for mortality in HIV-infected individuals after antiretroviral therapy (ART) in Dehong Dai and Jingpo Autonomous Prefecture (Dehong). Methods: The HIV/AIDS treatment database was collected from China Information System for Disease Control and Prevention. This retrospective cohort study was conducted in HIV-infected individuals with access to ART in Dehong during 2004-2020.The Cox proportional hazard regression model was used to analyze the incidence density of diabetes, the influencing factors and risk for mortality in HIV-infected individuals with access to ART, mixed linear effects model was used to analyze the trend of FPG change and predict FPG in those with different glucose metabolic status at baseline survey. Statistical analysis was performed using software SAS 9.4. Results: A total of 8 763 HIV-infected individuals were included, in whom 8 432 (96.2%) had no diabetes, 331 had diabetes. The incidence density of diabetes was 2.31/1 000 person years. Multivariate Cox proportional hazard regression analysis revealed that 30- 59 years old, BMI ≥24.0 kg/m2, Efavirenz (EFV) based initial treatment regimen and impaired fasting glucose (IFG) at baseline survey were significantly and positively associated with incidence of diabetes. Mixed effect model revealed that FPG was positively correlated with the duration of ART, age and baseline FPG. Suffering from diabetes was a risk factor for mortality in HIV-infected individuals both at baseline survey and during follow-up. Conclusions: The risk for diabetes increased in HIV-infected individuals who were 30-59 years old, baseline BMI ≥24.0 kg/m2, received EFV based initial treatment, and IFG in HIV-infected individuals after antiretroviral therapy in Dehong, 2004-2020. It is important to pay close attention to their blood glucose, and patients with high blood glucose should receive treatment as early as possible.

SIV Infection Is Associated with Transient Acute-Phase Steatosis in Hepatocytes In Vivo.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a major cause of morbidity and mortality in HIV-infected individuals, even those receiving optimal antiretroviral therapy. Here, we utilized the SIV rhesus macaque model and advanced laparoscopic techniques for longitudinal collection of liver tissue to elucidate the timing of pathologic changes. The livers of both SIV-infected (N = 9) and SIV-naïve uninfected (N = 8) macaques were biopsied and evaluated at four time points (weeks -4, 2, 6, and 16-20 post-infection) and at necropsy (week 32). SIV DNA within the macaques' livers varied by over 4 logs at necropsy, and liver SIV DNA significantly correlated with SIV RNA in the plasma throughout the study. Acute phase liver pathology (2 weeks post-infection) was characterized by evidence for fat accumulation (microvesicular steatosis), a transient elevation in both AST and cholesterol levels within the serum, and increased hepatic expression of the PPARA gene associated with cholesterol metabolism and beta oxidation. By contrast, the chronic phase of the SIV infection (32 weeks post-infection) was associated with sinusoidal dilatation, while steatosis resolved and concentrations of AST and cholesterol remained similar to those in uninfected macaques. These findings suggest differential liver pathologies associated with the acute and chronic phases of infection and the possibility that therapeutic interventions targeting metabolic function may benefit liver health in people newly diagnosed with HIV.

In-hospital mortality of acute HIV-associated pulmonary morbidity among COVID-19 negative medical admissions to Dr. George Mukhari Academic Hospital

Objectives: Human immunodeficiency virus (HIV)-related complications remain a frequent cause of hospital admissions. Pulmonary complications are among the most frequent causes of morbidity and mortality in HIV-infected individuals. We aimed to describe the in-hospital mortality of medical admissions with an acute HIV-associated pulmonary pathology. Materials and Methods: This was an observational study undertaken at a tertiary care center over 12 months. Variables of interest were as follow: Diagnoses, diagnostic work-up, treatment, mortality rate, and impact of comorbidities and HIV-associated factors on mortality. Results: Two-hundred and seventy-two patients were studied. The mean age was 42.0 ± 10.8 years. Males constituted 62.4% of the cases. One hundred and thirty patients (47.8%) were anti-retroviral therapy (ART) naive. The median CD4 count was 76 cells/mm3. The most frequent pulmonary diagnosis was community-acquired pneumonia (CAP) (212; 78%). Gram-negative pathogens were isolated in the majority of patients admitted with infectious complications. Pulmonary tuberculosis (PTB) was confirmed in only 27 (0.9%) of the cases. Significantly more female patients were on ART compared to males (P = 0.0436). Survival rates were not significantly different between the two genders (P = 0.1670). Overall, in-hospital mortality was 25.7%. CD4 counts and comorbidities were not predictive of mortality. Conclusion: HIV-associated acute pulmonary disease is associated with significant mortality. A large number of patients are diagnosed at an advanced stage of HIV. Programs that encourage voluntary testing and treatment are likely to reduce the high number of late presentations and reduce the poor outcomes. Adherence to the South African thoracic society guideline recommended evaluation for PTB in HIV-infected patients diagnosed with CAP cannot be over-emphasized.

Hepatocellular Carcinoma in HIV-Infected Patients: Clinical Presentation and Outcomes in a Racially Diverse Urban Population.

As life expectancy for HIV patients improve, hepatocellular carcinoma (HCC) has become a non-AIDS defining illness with a high impact on morbidity and mortality of HIV-infected individuals. We sought to compare outcomes in HIV- versus non-HIV-infected patients treated for HCC at a multiethnic academic medical health system. A retrospective chart review of patients diagnosed with HCC from 1/1/2005 to 12/31/2016 was performed. Differences in characteristics among HIV and non-HIV subjects were assessed. Associations between HIV status, viral load, CD4 count, and overall survival (OS) were also assessed. We identified 915 subjects (842 non-HIV and 73 with HIV). HIV-infected subjects were younger, predominantly male non-Hispanic Blacks, and more likely to have HBV and HCV co-infection, and alcohol use at diagnosis compared to non-HIV counterparts. Stage, MELD score, Child-Pugh, and ECOG performance status were similar. HIV-positive patients received systemic therapy at significantly higher rates and liver transplantation for HCC at significantly lower rates than those without HIV. The actuarial 3- and 5-year overall survival (OS) for all patients was 48.3% and 39.4%. For HIV-infected subjects, 3- and 5-year OS was significantly worse at 36.8% and 28.3% compared to 49.3% and 40.4%, respectively, for non-HIV subjects (log rank p = 0.033). HIV-infected HCC patients have lower survival rates compared to those without HIV. Despite younger age and similar stage, MELD, and ECOG at diagnosis, HIV portends worse outcomes in patients with HCC.

Machine learning-based in-hospital mortality prediction of HIV/AIDS patients with Talaromyces marneffei infection in Guangxi, China

Talaromycosis is a serious regional disease endemic in Southeast Asia. In China, Talaromyces marneffei (T. marneffei) infections is mainly concentrated in the southern region, especially in Guangxi, and cause considerable in-hospital mortality in HIV-infected individuals. Currently, the factors that influence in-hospital death of HIV/AIDS patients with T. marneffei infection are not completely clear. Existing machine learning techniques can be used to develop a predictive model to identify relevant prognostic factors to predict death and appears to be essential to reducing in-hospital mortality. We prospectively enrolled HIV/AIDS patients with talaromycosis in the Fourth People's Hospital of Nanning, Guangxi, from January 2012 to June 2019. Clinical features were selected and used to train four different machine learning models (logistic regression, XGBoost, KNN, and SVM) to predict the treatment outcome of hospitalized patients, and 30% internal validation was used to evaluate the performance of models. Machine learning model performance was assessed according to a range of learning metrics, including area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanations (SHAP) tool was used to explain the model. A total of 1927 HIV/AIDS patients with T. marneffei infection were included. The average in-hospital mortality rate was 13.3% (256/1927) from 2012 to 2019. The most common complications/coinfections were pneumonia (68.9%), followed by oral candida (47.5%), and tuberculosis (40.6%). Deceased patients showed higher CD4/CD8 ratios, aspartate aminotransferase (AST) levels, creatinine levels, urea levels, uric acid (UA) levels, lactate dehydrogenase (LDH) levels, total bilirubin levels, creatine kinase levels, white blood-cell counts (WBC) counts, neutrophil counts, procaicltonin levels and C-reactive protein (CRP) levels and lower CD3+ T-cell count, CD8+ T-cell count, and lymphocyte counts, platelet (PLT), high-density lipoprotein cholesterol (HDL), hemoglobin (Hb) levels than those of surviving patients. The predictive XGBoost model exhibited 0.71 sensitivity, 0.99 specificity, and 0.97 AUC in the training dataset, and our outcome prediction model provided robust discrimination in the testing dataset, showing an AUC of 0.90 with 0.69 sensitivity and 0.96 specificity. The other three models were ruled out due to poor performance. Septic shock and respiratory failure were the most important predictive features, followed by uric acid, urea, platelets, and the AST/ALT ratios. The XGBoost machine learning model is a good predictor in the hospitalization outcome of HIV/AIDS patients with T. marneffei infection. The model may have potential application in mortality prediction and high-risk factor identification in the talaromycosis population.

Liver Biopsies Reveal Temporal Changes in Pathology and Macrophage Function following SIV Infection of Rhesus Macaques

Abstract Non-alcoholic fatty liver disease (NAFLD) contributes to morbidity and mortality in HIV-infected individuals. To evaluate liver immune changes during SIV infection of macaques, we obtained liver biopsies laparoscopically at 2, 6, and 16 weeks post-infection as well as at necropsy (32 weeks). SIV infection was associated with liver dysfunction that included elevated liver enzymes during acute infection, higher liver weight at necropsy, and histologic changes within the liver lobule (functional unit of the liver) including sinusoidal dilatation near central veins and portal expansion. The type-1 interferon (IFN-1) response (MX1 expression) increased over time post-SIV infection, initially being observed in macrophages (week 2) with a switch to a mixed hepatocyte/monocyte/macrophage response by 16–32 weeks. Over the course of SIV infection, macrophage frequencies also increased – both infiltrating (CD68+CD163+CD206-) and resident (CD68+CD163+CD206+) tissue macrophages – and these macrophages were found more near central veins over time. In contrast, CD68+CD163-CD206− trafficking myeloid cells/monocytes were detected predominantly in the periportal zone of the lobule and associated with elevated MX1 expression in that zone. Our findings identify pathologic changes within the livers of SIV infected macaques as early as 2 weeks post-infection, IFN-1 responses that are initially observed in liver macrophages, and an accumulation of macrophages associated with signs of inflammation by week 32. These studies offer quantitative and spatial insights to inform macrophage-targeted therapeutic approaches that may improve liver function during HIV infection. Supported by grants from NIH (R01AI134630)

Increased Mortality in HIV Infected Individuals with Tuberculosis: A Retrospective Cohort Study, Addis Ababa, Ethiopia.

BackgroundTuberculosis is one of the commonest coinfections and leading causes of death among people living with HIV in resource-limited countries. There is limited evidence on the short- and long-term mortality rate in people receiving antiretroviral therapy and coinfected by tuberculosis in sub-Saharan Africa, where the burden of coinfection is highest.PurposeThis study aimed to compare mortality among HIV positives with and without tuberculosis coinfection receiving antiretroviral therapy in Addis Ababa, Ethiopia.MethodsHIV positives’ medical records were reviewed between 2011 to 2018 and identified 7038 HIV-positive adults enrolled for antiretroviral therapy in Addis Ababa. The outcome of interest for this study was death. A parametric Gompertz regression model was applied to compare mortality between HIV with tuberculosis coinfection versus HIV without tuberculosis.ResultsOverall, 1123 (15.96%, 95% CI: 15.11–16.83%) individuals with HIV had tuberculosis coinfection at antiretroviral therapy enrollment. After adjusting for age, sex, education, marital status, cotrimoxazole therapy, body mass index, baseline CD4 cell count, and year in ART enrollment, HIV positives with tuberculosis coinfection had more than twice a higher overall mortality risk than HIV positives without tuberculosis coinfection (AHR: 2.53; 95% CI 1.63–3.91, p < 0.001).ConclusionThis large retrospective cohort study reveals significantly higher mortality in HIV and tuberculosis coinfected group. This suggests the need for enhanced utility of integrated HIV and tuberculosis health services in sub-Saharan Africa where tuberculosis prevalence is highest.

Liver Bacterial Dysbiosis With Non-Tuberculosis Mycobacteria Occurs in SIV-Infected Macaques and Persists During Antiretroviral Therapy.

Liver disease is a significant contributor to morbidity and mortality in HIV-infected individuals, even during successful viral suppression with combination antiretroviral therapy (cART). Similar to HIV infection, SIV infection of rhesus macaques is associated with gut microbiome dysbiosis and microbial translocation that can be detected systemically in the blood. As microbes leaving the intestines must first pass through the liver via the portal vein, we evaluated the livers of both SIV-infected (SIV+) and SIV-infected cART treated (SIV+cART) rhesus macaques for evidence of microbial changes compared to uninfected macaques. Dysbiosis was observed in both the SIV+ and SIV+cART macaques, encompassing changes in the relative abundance of several genera, including a reduction in the levels of Lactobacillus and Staphylococcus. Most strikingly, we found an increase in the relative abundance and absolute quantity of bacteria within the Mycobacterium genus in both SIV+ and SIV+cART macaques. Multi-gene sequencing identified a species of atypical mycobacteria similar to the opportunistic pathogen M. smegmatis. Phosphatidyl inositol lipoarabinomannan (PILAM) (a glycolipid cell wall component found in atypical mycobacteria) stimulation in primary human hepatocytes resulted in an upregulation of inflammatory transcriptional responses, including an increase in the chemokines associated with neutrophil recruitment (CXCL1, CXCL5, and CXCL6). These studies provide key insights into SIV associated changes in hepatic microbial composition and indicate a link between microbial components and immune cell recruitment in SIV+ and SIV+cART treated macaques.

Study of the severity of depression and quality of life in adults with HIV/Acquired Immunodeficiency Syndrome at antiretroviral therapy center in western Maharashtra

Introduction: The universal access to antiretroviral therapy (ART) has caused a significant reduction in morbidity and mortality in HIV-infected individuals. Depression is one of the most prevalent psychiatric diagnoses seen in HIV-positive individuals, which has a significant impact on health-care utilization, adherence to ART, and quality of life (QOL). Hence, this study was planned to study the depression severity and health-related QOL in HIV-positive individuals. Aim: The aim was to study the severity of depression and QOL in adults with HIV/acquired immunodeficiency syndrome (AIDS). Methods: This was a cross-sectional study conducted at the regional ART center of a tertiary care hospital where 90 adult patients with HIV/AIDS in the age group of 18–60 years fulfilling DSM V criteria for depression were interviewed. A semistructured questionnaire was applied to obtain sociodemographic data. Quick Inventory of Depressive Symptomatology and QOL Scale (WHO QOL-HIV BREF) were used to assess the severity of depression and QOL in patients. Results: Of 90 patients, 40% had severe depression and 60% had mild-to-moderate depression. The severity of depression had a significant correlation with duration of HIV illness, duration of depressive symptoms, and socioeconomic status. The low QOL mean score was observed in all domains of QOL questionnaire. There was a significant correlation between the severity of disease and QOL. No correlation was found between CD4 count and QOL or severity of depression. Conclusions: Early diagnosis and treatment of depression in HIV may help improve the QOL of patients. CD4 cell count alone may be inadequate criteria for the prediction of mental health status and QOL.

Zero Prevalence of HIV and HCV Coinfection in the Highly HIV-infected Population of Rivers State, Nigeria

Background: Hepatitis C affects 5–15% of the 38 million people living with HIV globally. Africa which has the second highest prevalence of HIV/HCV co-infection following Asia. This alarming statistics has made it crucial that studies be done to also ascertain the HIV/HCV co-infection prevalence in the country and host factors which may influence the co-infection.&#x0D; Objective: Therefore, this study was conducted to investigate the seroprevalence of HCV infection amongst the HIV population of Rivers state, Nigeria.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: University of Port Harcourt Teaching Hospital (UPTH), in Rivers State, Nigeria, from February 2017 to September 2019.&#x0D; Methods: In this study, 226 HIV-infected individuals were recruited comprising 105 males and 121 females. These subjects were screened for the presence of HIV and HCV using ELISA and was performed according to the kit manufacturer’s stipulations. The demographic characteristics of the participants were obtained using a questionnaire designed for the study.&#x0D; Results: The presence of antibodies to HIV-1 reconfirmed the HIV status in all the study subject. A seroprevalence rate of 0.0% was observed for HIV/HCV infection. The ratio of females to males was found to be 1.2:1. The ages of the study population ranged from 16 to 70 years with a median age of 42.5 years. A large number (30.5%, n = 69) of the participants were within the age group 40 – 49 years, followed by those within 30 – 39 years (26.1%, n= 59), 50 – 59 years (17.3%, n = 39) and &gt;59 years (13.7%, n = 31). Participants that were within younger age groups had less population; 20 – 29 years (9.7%, n = 22), with those that are &lt;20 years having the least population (2.7%, n = 6). Many (49.1%, n = 111) of the study participants were found to be married. About 46.5% (n = 105) of them were single, while a few (4%, n = 10) were widowed.&#x0D; Conclusion: No coinfection of HIV/HCV was found, in spite of Nigeria being endemic for HCV. However, despite this zero rate of HIV/HCV coinfection, routine screening for HCV markers should be carried out to reduce morbidity and mortality in HIV-infected individuals.

Influence of HLA-B*5701 on 20 year survival rate among patients living with HIV.

BackgroundThe life expectancy of people living with HIV (PLWH) remains shorter than that of the general population, despite significant improvement in the recent years. Mortality in HIV-infected individuals may be associated with a higher viral load at of diagnosis, a lower CD4 count, or clinical variables such as sex or route of transmission. This article investigated the role of the HLA-B*5701 varian on mortality among PLWH.MethodsMaterial for the analysis consist of the data of 2,393 patients for whom the HLA-B*57 variant was known. Those patients were followed under the care of the Infectious Diseases Hospital in Warsaw (n = 1555) and the Clinic of Acquired Immunodeficiency of the Pomeranian Medical University in Szczecin (n = 838). Factors such as age, gender, date of HIV diagnosis, route of transmission, date of death, baseline HIV viral load and baseline CD4 counts, were collected, and end-point cross-sectional analyses were marked at 60, 120, 180 and 240 month of observation.ResultsHLA-B*5701 allele was found in 133 (5.5%) analyzed cases. Median age was notably higher for HLA-B*5701 positive patients [32.7 (28.3–41.3) vs. 31.6 (26.8–38.3)years p = 0.02]. HLA-B*5701 was associated with lower baseline viral load [4.21 (3.5–4.8) vs. 4.79 (4.2–5.3)log copies/ml p<0.001] and higher CD4count [448 (294.5–662) vs. 352 (176–514) cells/μl p<0.001]. There were no association between HLA-B*5701 and survival for any given end-point. Higher mortality was associated to male gender, intravenous drug users, lower CD4 count at baseline and higher baseline viral load.ConclusionsIn our study, the presence of HLA-B*5701 allel was not associated with mortality rate of HIV infected patients, irrespective of being associated with both higher baseline CD4 + cell count and lower baseline HIV viral load.

Assessment of liver disease by non-invasive methods in perinatally infected Brazilian adolescents and young adults living with Human Immunodeficiency Virus (HIV)

IntroductionEffective and long-term combined antiretroviral therapy (cART) has decreased morbidity and mortality in HIV-infected individuals. Despite treatment advances, HIV-infected children continue to develop noninfectious conditions, including liver fibrosis. MethodsCross-sectional study designed to identify liver fibrosis in HIV-infected adolescents and young adults, in an outpatients clinic of Pediatric Infectious Diseases Division at Escola Paulista de Medicina/Universidade Federal de São Paulo (UNIFESP), diagnosed by noninvasive methods (liver elastography–FibroScan®, APRI and FIB4). Variables examined included demographics, clinical, laboratories, HIV treatment. All participants underwent FibroScan® to measure liver parenchyma elasticity. Values equal to above 7.0 kPa were interpreted as the presence of significant liver fibrosis. Two different biomarkers of liver fibrosis were employed: the AST-to-Platelet Ratio Index (APRI) and the Fibrosis-4 score (FIB-4). APRI values above 1.5 have been considered as levels of clinically significant liver fibrosis and FIB-4 values above 3.25 suggested the presence of advanced fibrosis. ResultsBetween August 2014 and March 2017, the study enrolled 97 patients, age 10–27 years old, fourteen of 97 subjects (14.4%) presented liver stiffness (≥7 kPa) detected by the liver elastography. No patient had APRI> 1.5. No patient had FIB4 value > 3.25. The only isolated laboratory parameter that could be significantly associated with high liver stiffness was thrombocytopenia (p = 0.022, Fisher's exact test). ConclusionLiver stiffness was identified in 14.4% (14/97) of this cohort by liver elastography. Liver disease in HIV-infected adolescents and young adults manifests itself silently, so should be routinely investigated.

Interactions of HIV and Antiretroviral Therapy With Neutrophils and Platelets

Neutrophils are important components of the innate immune system that mediate pathogen defense by multiple processes including phagocytosis, release of proteolytic enzymes, production of reactive oxygen species, and neutrophil extracellular trap formation. Abnormalities of neutrophil count and function have been described in the setting of HIV infection, with the majority of antiretroviral agents (ARVs), excluding zidovudine, having been reported to correct neutropenia. Questions still remain, however, about their impact on neutrophil function, particularly the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment. In this context, the effects of protease inhibitors and integrase strand transfer inhibitors, in particular, on neutrophil function remain poorly understood and deserve further study. Besides mediating hemostatic functions, platelets are increasingly recognized as critical role players in the immune response against infection. In the setting of HIV, these cells have been found to harbor the virus, even in the presence of antiretroviral therapy (ART) potentially promoting viral dissemination. While HIV-infected individuals often present with thrombocytopenia, they have also been reported to have increased platelet activation, as measured by an upregulation of expression of CD62P (P-selectin), CD40 ligand, glycoprotein IV, and RANTES. Despite ART-mediated viral suppression, HIV-infected individuals reportedly have sustained platelet activation and dysfunction. This, in turn, contributes to persistent immune activation and an inflammatory vascular environment, seemingly involving neutrophil-platelet-endothelium interactions that increase the risk for development of comorbidities such as cardiovascular disease (CVD) that has become the leading cause of morbidity and mortality in HIV-infected individuals on treatment, clearly underscoring the importance of unraveling the possible etiologic roles of ARVs. In this context, abacavir and ritonavir-boosted lopinavir and darunavir have all been linked to an increased risk of CVD. This narrative review is therefore focused primarily on the role of neutrophils and platelets in HIV transmission and disease, as well as on the effect of HIV and the most common ARVs on the numbers and functions of these cells, including neutrophil-platelet-endothelial interactions.

The impact of HIV on hepatocellular cancer survival in Nigeria.

Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-infected individuals. We compared host and tumour characteristics between HIV-infected and HIV-uninfected Nigerians with HCC and examined the impact of HIV on survival. This prospective observational study was conducted at Jos University Teaching Hospital in Jos, Nigeria, among adults (>18years) with HCC enrolled between September 2015 and September 2017 and followed until April 2019. Demographics, tumour characteristics and survival were compared between HCC subjects with and without HIV. 101 (10 HIV-infected and 91 HIV-uninfected) subjects were enrolled [male 72%; median age 48 (IQR 35-60)]. 60% HIV-infected subjects were receiving ART; 90% had CD4 counts≥200/mm3 at HCC diagnosis, and 20% had HIV RNA levels<20 copies/mL. 57.4% were infected with chronic HBV (HBsAg+). The duration of symptoms was shorter in HIV-infected vs. HIV-uninfected subjects [93 (IQR 54-132) vs. 155 (93-248] days; p=0.02]. At the end of follow-up, 99 of 101 (98.0%) subjects were confirmed to have died: 9 of 10 (90.0%) HIV-infected and 90 of 91 (98.9%) HIV-uninfected. The probability of survival at three months was 22% and 47% in HIV-infected and HIV-uninfected subjects, respectively (P=0.02). Median time to death was significantly shorter in HIV-infected vs. HIV-uninfected subjects [24days (IQR 16-88) vs. 85days (IQR 34-178), respectively (P=0.03)]. High early mortality was observed in this cohort of Nigerian adults with HCC. HIV infection was associated with a faster clinical presentation and shorter survival. More aggressive HCC surveillance may be warranted in HIV-infected subjects, particularly if they are co-infected with chronic HBV.

Changing contextual factors from baseline to 9-months post-HIV diagnosis predict 5-year mortality in Durban, South Africa

ABSTRACT Changes in an individual’s contextual factors following HIV diagnosis may influence long-term outcomes. We evaluated how changes to contextual factors between HIV diagnosis and 9-month follow-up predict 5-year mortality among HIV-infected individuals in Durban, South Africa enrolled in the Sizanani Trial (NCT01188941). We used random survival forests to identify 9-month variables and changes from baseline predictive of time to mortality. We incorporated these into a Cox proportional hazards model including age, sex, and starting ART by 9 months a priori, 9-month social support and competing needs, and changes in mental health between baseline and 9 months. Among 1,154 participants with South African ID numbers, 900 (78%) had baseline and 9-month data available of whom 109 (12%) died after 9-month follow-up. Those who reported less social support at 9 months had a 16% higher risk of mortality. Participants who went without basic needs or healthcare at 9 months had a 2.6 times higher hazard of death compared to participants who did not. Low social support and competing needs at 9-month follow-up substantially increase long-term mortality risk. Reassessing contextual factors during follow-up and targeting interventions to increase social support and affordability of care may reduce long-term mortality for HIV-infected individuals in South Africa.

Baseline Serum C-Reactive Protein Level Predicts Mortality in Cryptococcal Meningitis.

BackgroundC-reactive protein (CRP) is an acute phase protein produced by the liver in response to systemic inflammation. CRP is a helpful surrogate biomarker used for following the progression and resolution of infection. We aimed to determine the association of baseline CRP level and the temporal change in CRP over time with cryptococcal meningitis outcome.MethodsWe reviewed 168 prospectively enrolled HIV-infected Ugandans with confirmed first-episode cryptococcal meningitis. Baseline plasma CRP collected within 5 days of meningitis diagnosis was categorized into quartiles. We compared baseline CRP with 18-week survival using time-to-event analysis.ResultsOf 168 participants, the baseline first quartile of serum CRP was <29.0 mg/L, second quartile 29.0–49.5 mg/L, third quartile 49.6–83.6 mg/L, and fourth quartile >83.6 mg/L. Baseline CD4 count, HIV viral load, and cerebrospinal fluid results did not differ by CRP quartile. Participants with CRP >49.5 mg/L more likely presented with Glasgow Coma Scale (GCS) <15 (P = .03). The 18-week mortality rate was 55% (46/84) in the highest 2 quartile CRP groups (>49.5 mg/L), 41% (17/42) in the mid-range CRP group (29.0–49.5 mg/L), and 14% (6/42) in the low-CRP group (<29.0 mg/L; P < .001). After adjustment for possible confounding factors including GCS <15, CRP remained significantly associated with mortality (adjusted hazard ratio, 1.084 per 10 mg/L; 95% CI, 1.031–1.139; P = .0016).ConclusionsHigher baseline CRP is associated with increased mortality in HIV-infected individuals with first-episode cryptococcal meningitis. CRP could be a surrogate marker for undiagnosed coinfections or may reflect immune dysregulation, leading to worse outcomes in persons with advanced AIDS and concomitant cryptococcal meningitis.

Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up Risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India: A Prospective Cohort Study.

Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy, the incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and preemptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /μL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. A total of 116 patients were analyzed. Asymptomatic cryptococcal antigenemia was detected in 5.17% of patients and is correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. Serum cryptococcal antigen positivity is correlated with an increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/μL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

Cardiovascular risk and D-dimer levels in HIV-infected ART-naïve Africans.

Anti-retroviral therapy (ART) has decreased morbidity and mortality in HIV-infected individuals. With the adoption of the 90-90-90 strategy prevention and control of non-communicable disease, particularly knowledge of the burden and profile of cardiovascular disease, will become increasingly important. Our study assessed cardiovascular risk among recently diagnosed HIV-infected ART-naïve patients in a first referral urban hospital in a low-income country in sub-Saharan Africa. HIV-positive ART-naïve patients were submitted to cardiovascular risk assessment, clinical history, physical examination and laboratory workout, including 12-lead electrocardiography, portable transthoracic echocardiography, glycemia, lipidemia, hemogram and D-dimers. Three years after the diagnosis their vital status and occurrence of major cardiovascular events was assessed. We recruited 70 patients, all of black ethnicity (41 females; mean age 37±10.7). CD4 levels were very low (mean 21.3 cells/mL; SD 10.4). Twenty-one (26.6%) were overweight, 13 (16.7%) were obese, 19 (20.5%) had hyperglycemia and 20 patients (25.6%) had hypercholesterolemia. The median blood pressure was 119.5/79 mmHg (IQR 107-141/67-83); 20 patients (25.6%) had hypertension. Four (5.7%) patients had signs of heart failure, and left ventricular ejection fraction was reduced in 17 (25%). High levels of circulating D-dimers were found in 44 (62.8%) patients; the mean levels were 725.9 (SD 555.1). We found high occurrence of cardiovascular risk factors, left ventricular dysfunction and evidence of a pro-coagulant state in these HIV-infected ART-naïve patients. Active cardiovascular risk screening and stratification, as well as management protocols tailored to low-income settings are needed to sustain the gains obtained with increased availability of ART in Africa.

Early HIV infection is associated with reduced proportions of gamma delta T subsets as well as high creatinine and urea levels.

Renal dysfunctions are major predictors of co-morbidities and mortality in HIV-infected individuals. Unconventional T cells have been shown to regulate kidney functions. However, there is dearth of information on the effect of HIV-associated nephropathies on γδ and DN T cells. It is also not clear whether γδ T cell perturbations observed during the early stages of HIV infection occur before immune activation. In this study, we investigated the relationship between creatinine and urea on the number of unconventional T cells in HIV-infected individuals at the early and chronic stages of infection. Persons in the chronic stage of infection were divided into treatment naïve and exposed groups. Treatment exposed individuals were further subdivided into groups with undetectable and detectable HIV-1RNA in their blood. Creatinine and urea levels were significantly higher among persons in the early HIV infection compared with the other groups. Proportions of γδ T, γδ+CD8, γδ+CD16 cells were also significantly reduced in the early stage of HIV infection (P<.01). Markers of immune activation, CD4+HLA-DR and CD8+HLA-DR, were also significantly reduced during early HIV infection (P<.01). Taken together, our findings suggest that high levels of renal markers as well as reduced proportions of gamma delta T cells are associated with the early stages of HIV infection. This event likely occurs before systemic immune activation reaches peak levels. This study provides evidence for the need for early HIV infection diagnosis and treatment.

Long-Term Fever and Cytomegalovirus Infection in the Field of HIV Immunosuppression in Two Cases and Review of the Literature

Cytomegalovirus (CMV) infection is an infection that most often affects immunocompromised individuals with a seroprevalence of more than 80%. CMV co-infection is associated with increased mortality in HIV-infected individuals despite antiretroviral treatment. It has the potential for hematogenous dissemination to all the organs, but only becomes symptomatic when the viral load is high. This is especially possible when the human immune system is well controlled so that the individual infected with CMV generally remains asymptomatic, and possibly for a long period. Once the immune system fails, CMV infection becomes symptomatic. Diagnosis is not easy and is often done postmortem in developing countries with limited technical facilities. We report here two cases diagnosed at the Internal Medicine Service of the CNHU-HKM in Cotonou. The patients were infected with HIV and had a long term fever. The diagnoses were made on the basis of CMV serology. The first diagnosis was post-mortem, and the second patient died 48 hours after the start of the treatment.