Mortality In HIV-infected Patients Research Articles

Mortality in Perinatally HIV-infected Adolescents After Transition to Adult Care in Spain.

After the introduction of combination antiretroviral treatment, (ART) mortality in HIV-infected patients has dramatically decreased. However, it is still high in patients at risk, as adolescents transitioning to adult care (AC) without virologic control. The aim of this study was to characterize mortality and comorbidities of perinatally infected HIV (PHIV) patients after transition to AC. A multicenter retrospective study from patients included in the CoRISpe-FARO Spanish cohort was conducted. PHIV patients who died after transition to AC between 2009 and 2019 were included. Clinical, immunovirologic characteristics, treatments received, comorbidities and causes of death were described. Among 401 PHIV patients, 14 died (3.5%). All were Spanish, 11/14 (78.6%) women. The median age at diagnosis was 1.5 years (interquartile range [IQR] 0.5-3.9), at transfer to AC was 18 years [16.1-19.9] and at death was 25.8 years [23.6-27.1]. In pediatric units [pediatric care (PC)], CD4+ nadir was 85 cells/μL [IQR 9.7-248.5] and 6/14 patients were classified as C-clinical stage. During AC, all patients were on C-clinical stage and CD4+ nadir dropped to 11.5 cells/μL [4.5-43.3]. cART adherence was extremely poor: in PC, 8/14 patients registered voluntary treatment interruptions; only one had undetectable VL at transition. In AC, 12/14 patients stopped treatment 2 or more periods of time. All deaths were related to advanced HIV disease. Mental health disorders were observed in 7/14 (50%). Main complications described: recurrent bacterial infections (57.1%), wasting syndrome (42.9%), esophageal candidiasis (28.6%) and Pneumocystis jirovecii pneumonia (28.6%). Four women had 11 pregnancies; 5 children were born (none infected). Young adults PHIV infected who transition to AC without virologic suppression or proven ability to adhere to ART are at high risk of mortality. Mortality was noted as a consequence of advanced HIV disease, frequent mental health problems and poor adherence to ART.

Temporal trends of cutaneo-mucous histoplasmosis in persons living with HIV in French Guiana: Early diagnosis defuses South American strain dermotropism.

Histoplasmosis is the most frequent opportunistic infection and the first cause of mortality in HIV-infected patients in French Guiana and presumably in much of Latin America. Mucocutaneous lesions of histoplasmosis are considered as rare and late manifestations of the disease. It has been debated whether the greater proportion of cutaneo-mucous presentations in South America relative to the USA was the reflection of Histoplasma strains with increased dermotropism or simply delayed diagnosis and advanced immunosuppression. The objective of this study was to describe the clinical presentation, frequency, prognosis and temporal trends of cutaneomucous histoplasmosis in French Guiana. A retrospective study of patients with AIDS-related disseminated histoplasmosis followed in the three hospitals of French Guiana was performed between 1981 and 2014. Incident cases of histoplasmosis, proved by pathology and/or mycological examinations, were studied. Mucocutaneous histoplasmosis was confirmed by a positive cutaneous or mucosal biopsy. Mucocutaneous lesions were polymorphic. Ninety percent of patients were profoundly immunocompromised patients (CD4<50/mm3) and over 80% were not on antiretroviral treatment. The frequency of mucocutaneous forms and case fatality of disseminated histoplasmosis within one month of antifungal treatment significantly decreased over time (p<0,001). In this South American territory, diagnostic and therapeutic improvements have led to the quasi disappearance of cutaneous manifestations. There may be South American dermotropism in the laboratory but at the bedside early diagnosis seems to be the main parameter explaining the proportion of cutaneomucous presentations in South America relative to the USA.

Gender difference in all-cause mortality of people living with HIV in Iran: findings from a 20-year cohort study.

Gender differences in the efficacy of treatment and the mortality of HIV-infected patients have not yet been fully elucidated. For the first time, we used data from a 20-year cohort of people living with HIV (PLWH) in four provinces (Fars, Bushehr, Bandar Abbas, and Kohgiluyeh and Boyer-Ahmad) in the southern part of Iran to assess the gender difference in all-cause mortality in PLWH in Iran. We analysed data for 1216 patients aged ≥ 15years who were diagnosed with HIV/AIDS between 1997 and 2017. Three hundred and fourteen (25.8%) were women. The death rate from all causes among women was 13.7% vs. 43.8% among men (P<0.001). All-cause mortality was significantly associated with gender [the adjusted hazard ratio (aHR) for men compared with women was 3.20], not being on antiretroviral therapy (ART) compared with being on ART at the last visit (aHR5.42), older age (aHR1.03), delayed HIV diagnosis compared with early diagnosis (aHR1.72), history of incarceration (aHR1.57), higher log CD4 count at diagnosis (aHR0.54), and prophylaxis for Pneumocystis pneumonia (aHR0.09). The results of this 20-year cohort study suggest that gender is an important predictor of survival among HIV-infected patients. Improving early HIV diagnosis and early ART initiation in men, as well as increased access to hepatitis C virus treatment are needed to increase the survival rate of HIV-infected patients in Iran.

AIDS-duration predictors of HIV/AIDS patients on antiretroviral therapy at Debre Berhan referral hospital, north-central Ethiopia

Background: Receiving ART treatment prolongs the life of HIV/AIDS patients by increasing substantially their CD4 count, even though the level is different from one individual patient to the other. The aim of this study was to identify the potential predictors of death of HIV-infected patients attending ART treatment. Methods: A hospital-based retrospective cohort chart review study design was conducted on 647 HIV-infected patients at a public hospital in North-Central Ethiopia from July 2012-January 2017. Kaplan-Meier plots, Log-rank and Wilcoxon tests, and Cox-proportional hazard model were employed. Data analysis was done with the help of statistical software (R version 3.2.2). 95% confidence interval for hazard ratio (HR) and p-value ≤ 0.05 was used to statistically associate with time till event occurred. Results: Among the total of 647 patients on 192(29.68%) event were occurred; while 455(70.32%) were censored. HIV-infected patients were followed for a total of 54 months, with a mean of 22.13(13.16) and a median of 21.47months. The prevalence of event was about 30 out of 100 HIV patients. According to the present study, the median CD4 count at the initial time of ART was 247 (IQR:120-375)cells/µl, whereas the median CD4 count at the time of event was 362 (IQR:225-532)cells/µl. Patients with higher baselineCD4 count,&gt;200cells/µl were 32.10% lower in risk of death than patients with lower baselineCD4 count, &lt; 200cells/µl (HR:0.679; 95%CI:0.537-0.857; p-value=0.001). Conclusions: ART treatment is effective enough in slowing down the progression of HIV-infection to AIDS and decreasing the mortality rate of patients significantly. Being Widowed/ divorced, bedridden, ambulatory began with lower baseline CD4 count and being on TDF-3TC-EFV regimen were the predictors of mortality in HIV-infected patients on ART. It is recommended that HIV patients start antiretroviral treatment early, track the progression of HIV to AIDS.

What is AIDS in the Amazon and the Guianas in the 90-90-90 era?

IntroductionIn the past decade, new diagnostic methods and strategies have appeared, HIV testing efforts and the generalization of antiretroviral therapy may have influenced the number of opportunistic diagnoses and mortality of HIV-infected patients. To test this hypothesis we compiled data on the top opportunistic infections and causes of early death in the HIV cohort of French Guiana.MethodsHIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals from 2010 to 2019 were studied. Annual incidence of different opportunistic infections and annual deaths are compiled. For patients with opportunistic infections we calculated the proportion of early deaths.ResultsAt the time of analysis, among 2 459 patients, (treated and untreated) 90% had a viral load <400 copies, 91% of the patients in the cohort were on antiretroviral treatment, and 94.2% of patients on treatment for over 6 months had undetectable viral loads. Only 9% of patients had CD4 counts under 200 per mm3. Histoplasmosis clearly remained the most frequent (128 cases) opportunistic infection among HIV-infected persons followed by cerebral toxoplasmosis (63 cases) and esophageal candidiasis (41 cases). Cryptococcal meningitis was ranked 5th most frequent opportunistic infection as was tuberculosis (31 cases). The trend for a sharp decline in early deaths continued (3.9% of patients).ConclusionsDespite the successes of antiretrovirals, patients presenting with advanced HIV are still common and they are still at risk of dying. Improved diagnosis, and notably systematic screening with appropriate tools are still important areas of potential progress.

PD-3 Hepatocellular carcinoma in HIV-infected patients: Clinical presentation and outcomes in a racially diverse urban population

As life expectancy for HIV patients improves in the highly active antiretroviral treatment (HAART) era, hepatocellular carcinoma (HCC) has become a non-AIDS-defining illness with a high impact on morbidity and mortality of HIV-infected patients. We sought to compare outcomes in HIV versus non-HIV patients diagnosed with and treated for HCC at a multiethnic urban academic medical center. A retrospective chart review of patients diagnosed with HCC from 1/1/2005 to 12/31/2016 was performed. Subjects included had at least one-week of follow-up and were censored at last point of contact. Variables collected included HIV status, HIV viral load, CD4 count, Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection, TMN stage, ECOG performance status, MELD score, and AFP level at diagnosis, as well as treatments received. Bivariate associations comparing characteristics between HIV and non-HIV subjects were assessed using t-tests or non-parametric equivalents for continuous variables and chi-square tests for categorical variables. Associations between HIV status, viral load and CD4 count, and overall survival (OS) were assessed using Cox proportional hazards regression as well as the Kaplan-Meier method with log-rank test. We identified 819 non-HIV and 73 HIV-infected subjects. Race was 17.3% white and 26.7% black for non-HIV versus 2.7% white and 43.8% black for HIV subjects (p=0.001). Ethnicity was 34.1% Hispanic in non-HIV versus 26.0% in HIV subjects. Mean age was 64.2 versus 57.2 years in non-HIV versus HIV subjects (p< 0.001). Rates of HBV (6.7 versus 17.8%, p< 0.001), HCV (59.8 versus 75.3%, p=0.022), and alcohol use (17.6 versus 38.4%, p< 0.001) were lower in non-HIV compared to HIV subjects. Of non-HIV subjects, 34.7% had AFP level >100 at diagnosis versus 49.3% of HIV subjects (p=0.015). Stage, MELD, and ECOG score at diagnosis showed no significant associations with HIV status. While rates of resection and regional treatments were similar, transplantation occurred more often in non-HIV compared to HIV subjects (10.4 versus 2.7%, p< 0.022). Median follow-up was 18.2 months. The 3-year actuarial OS for all patients was 49.7%, and significantly worse for those with HIV infection (37.0 vs. 50.9%, p=0.024). Patients with HIV also had worse OS on multivariable analysis (HR=1.90, p=0.001) when adjusting for age, MELD, AFP, stage and performance status. Viral load, but not CD4 count showed a significant association with survival (p=0.017 and p=0.070, respectively by log-rank test). HIV-infected HCC subjects have lower survival rates compared with those without HIV. Despite younger age and similar MELD, ECOG, and stage at diagnosis, HCC subjects with HIV have worse outcomes compared to non-HIV counterparts. In our study, HIV-infected subjects had significantly higher rates of HBV, HCV, alcohol use, and lower rates of transplantation--all factors that could mediate the increased mortality observed in these subjects. While the etiology of survival differences between HIV and non-HIV patients with HCC remains unclear, robust efforts should be made to offer the subset of those with HIV not only transplants but also novel systemic therapies, given the profound potential for benefit.

Analysis of risk factors for mortality among adult HIV infected patients on antiretroviral therapy: A case of hossana queen elleni mohammad memorial hospital, hossana, Ethiopia

ven though the use of ART has brought a significant reduction in the mortality and morbidity of patients living with HIV/AIDS, a number of patients still die after the start of ART. This study was aimed at identifying factors associated with mortality among adult HIV infected patients who are on ART in HQEMM Hospital. The data for the study was obtained from HQEMM Hospital ART clinic. The HIV infected patients 15 years of age and who were under ART from March 2009 up to May 2015 were included in the study. Logistic regression model was employed to analyze the data to identify factors associated with Mortality of HIV infected patients. A total of 400 adult HIV infected patients who were taking ART were included in the study. Out of these patients, 18.75% of them died. The results obtained from logistic regression analysis showed that age, level of education, alcohol, baseline weight, TB status, and baseline CD4 count were significant factors of mortality of HIV infected patients taking ART in HQEMM Hospital. Patients with no education were more likely to die than those who attended at least primary school. Patients who drink alcohol were also more likely to die than those who do not. Health workers need to support those patients with no or little education by continuous awareness creation of taking care of themselves and knowing what factors facilitate death. Patients who drink alcohol need to be given advice to reduce excessive drinking.

Effect of tuberculosis infection on mortality of HIV-infected patients in Northern Tanzania

BackgroundTB and HIV are public health problems, which have a synergistic effect to each other. Despite the decreasing burden of these two diseases they still make a significant contribution to mortality. Tanzania is among the 30 high TB and HIV burden countries.MethodsRoutine data over 6 years from people living with HIV (PLHIV) attending health facilities in three regions of Northern Tanzania were analyzed, showing mortality trends from 2012 to 2017 for HIV and HIV/TB subpopulations. Poisson regression with frailty model adjusting for clustering at health facility level was used to analyze the data to determine mortality rate ratios (RR) and 95% confidence intervals (95%CI).ResultsAmong all PLHIV the overall mortality rate was 28.4 (95% CI 27.6–29.2) deaths per 1000 person-years. For PLHIV with no evidence of TB the mortality rates was 26.2 (95% CI 25.4–27.0) per 1000 person-years, and for those with HIV/TB co-infection 57.8 (95% CI 55.6–62.3) per 1000 person-years. After adjusting for age, sex, residence, WHO stage, and bodyweight, PLHIV with TB co-infection had 40% higher mortality than those without TB (RR 1.4; 95% CI 1.24–1.67).ConclusionsOver the 6-year period mortality rates for HIV/TB patients were consistently higher than for PLHIV who have no TB. More efforts should be directed into improving nutritional status among HIV patients, as it has destructive interaction with TB for mortality. This will improve patients’ body weight and CD4 counts which are protective against mortality. Among PLHIV attention should be given to those who are in WHO HIV stage 3 or 4 and having TB co-infection.

Impact of first-line antiretroviral therapy regimens on the restoration of the CD4/CD8 ratio in the CNICS cohort.

The CD4/CD8 ratio is an indicator of immunosenescence and a predictor of all-cause mortality in HIV-infected patients. The effects of different ART regimens on CD4/CD8 ratio recovery remain unclear. Clinical cohort study of ART-treated patients from the CFAR Network of Integrated Clinical Systems (CNICS). We included ART-naive adults with HIV infection who achieved undetectable HIV RNA during the first 48 weeks of treatment and had additional follow-up 48 weeks after virological suppression (VS). Primary endpoints included increase in CD4/CD8 ratio at both timepoints and secondary endpoints were CD4/CD8 ratio recovery at cut-offs of ≥0.5 or ≥1.0. Of 3971 subjects who met the study criteria, 1876 started ART with an NNRTI, 1804 with a PI and 291 with an integrase strand transfer inhibitor (INSTI). After adjusting for age, sex, race, year of entry, risk group, HCV serostatus, baseline viral load and baseline CD4/CD8 ratio, subjects on an NNRTI showed a significantly greater CD4/CD8 ratio gain compared with those on a PI, either 48 weeks after ART initiation or after 48 weeks of HIV RNA VS. The greater CD4/CD8 ratio improvement in the NNRTI arm was driven by a higher decline in CD8 counts. The INSTI group showed increased rates of CD4/CD8 ratio normalization at the ≥1.0 cut-off compared with the PI group. NNRTI therapy was associated with a greater increase in the CD4/CD8 ratio compared with PIs. NNRTI- and INSTI-based first-line ART were associated with higher rates of CD4/CD8 ratio normalization at a cut-off of 1.0 than a PI-based regimen, which might have clinical implications.

Patterns of presentation and survival of HIV-infected patients admitted to a tertiary-level intensive care unit.

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. 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. 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. 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.

The impact of integrase inhibitor-based regimens on markers of inflammation among HIV naïve patients

The use of combination anti-retroviral therapy (cART) correlates with longer and healthier life and with nearly normal life expectancy in people living with HIV. However, cART does not completely restore health. Chronic immune activation and inflammation persist in treated patients and have been described as predictors for clinical events and mortality in HIV-infected patients. Limited information is available on the impact of the various cART regimens on inflammation/immunoactivation. The aim of this work was to explore the impact of elvitegravir, dolutegravir, raltegravir (integrase strand transfer inhibitors, INSTIs) and atazanavir (protease inhibitor, PI) on several soluble markers of immune activation and inflammation during the first year of effective combination anti-retroviral therapy (cART).We conducted an observational retrospective cohort study in HIV-infected cART-naïve patients who initiated an INSTI or atazanavir regimen between March 2015 and February 2016 and a serum sample was available at baseline, 6 and 12 months after initiation. We compared the trend of D-Dimer, TNF- α, IL-2, IL-6, IL-7, IL-10, CCL4/MIP1-β, CCL5/RANTES, s-CD14, s-CD163, hs-CRP levels among the 4 arms of treatment. Percentage of variation from baseline was also measured for all markers.A total of 36 patients were included. We observed heterogeneous modifications in inflammation markers among arms. In particular, we noted that EVG have significant negative effect on s-CD14, hs-CRP, IL-6 and D-Dimer in respect to other INSTIs and this different effect occurs mainly during the first 6 months of cART. IL-7 values increased in the three arms with INSTIs (significantly only in EGV, 159.8%, p = 0.0003) and decreased significantly in patients on PI (−48.96%; p = 0.04) over the period.In conclusion, our results provide further data on changes of inflammatory marker levels, especially for the new INSTIs. Our data show that among INSTIs, EVG seems to have a worse impact on inflammation.

CD8+ T-Cell Response to HIV Infection in the Era of Antiretroviral Therapy.

Although the combined antiretroviral therapy (cART) has decreased the deaths associated with the immune deficiency acquired syndrome (AIDS), non-AIDS conditions have emerged as an important cause of morbidity and mortality in HIV-infected patients under suppressive cART. Since these conditions are associated with a persistent inflammatory and immune activation state, major efforts are currently made to improve the immune reconstitution. CD8+ T-cells are critical in the natural and cART-induced control of viral replication; however, CD8+ T-cells are highly affected by the persistent immune activation and exhaustion state driven by the increased antigenic and inflammatory burden during HIV infection, inducing phenotypic and functional alterations, and hampering their antiviral response. Several CD8+ T-cell subsets, such as interleukin-17-producing and follicular CXCR5+ CD8+ T-cells, could play a particular role during HIV infection by promoting the gut barrier integrity, and exerting viral control in lymphoid follicles, respectively. Here, we discuss the role of CD8+ T-cells and some of their subpopulations during HIV infection in the context of cART-induced viral suppression, focusing on current challenges and alternatives for reaching complete reconstitution of CD8+ T-cells antiviral function. We also address the potential usefulness of CD8+ T-cell features to identify patients who will reach immune reconstitution or have a higher risk for developing non-AIDS conditions. Finally, we examine the therapeutic potential of CD8+ T-cells for HIV cure strategies.

Statins and aspirin in the prevention of cardiovascular disease among HIV-positive patients between controversies and unmet needs: review of the literature and suggestions for a friendly use

BackgroundAs in non-infected subjects, statins and aspirin have a pivotal preventive role in reducing the cardiovascular related morbidity and mortality in HIV infected patients. The persistence of immune activation in these subjects, could contribute to accelerate atherosclerosis, therefore, these treatments that reduce inflammation could provide additional cardiovascular protection. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. Aim of the present position paper is to provide recommendations aimed to overcome the actual differences and limitations among the current ones and to adapt them to the needs of HIV infected patients.ResultsWe propose to adopt the new ACC/AHA guidelines, simple to use and cost effective, to use the ASCVD score that seems to estimate more accurately the cardiovascular risk among these patients. We suggest to start statin therapy in all patients with a calculated 10-year risk of a cardiovascular event of 10% or greater. Rosuvastatin and atorvastatin should be preferred. LDL-C target may be adopted. Aspirin should be always associated with a statin, in secondary prevention, while in primary prevention it should be reserved only to patients with ≥ 20% 10-year risk particularly adherent to treatments, and with low risk of bleeding. We suggest to start with a dose of 100 mg/day. Finally, management of antiplatelet agents or novel oral anticoagulants may include selecting antiretrovirals with a lower potential for drug interactions or choosing agents least likely to interact with antiretrovirals.ConclusionsAs demonstrated in surveys, HIV physicians are generally highly committed regarding CVD and autonomous in prescribing statins and ASA. Consequently, in the light of the previously discussed discrepancies among the different guidelines and of the incomplete indications regarding HIV-positive persons, the present suggestions could overcome the actual differences and limitations among the current ones.

Clinico-epidemiologic characteristics and patterns of care in Kaposi's sarcoma: Data from a single-institution series.

In the late 20th to early 21st century, most new Kaposi's sarcoma cases were associated with HIV coinfection and low CD4 T-cell counts. After introduction of effective antiretroviral therapy, the clinical and epidemiologic characteristics of Kaposi's sarcoma may have changed. We analyzed and now report on 27 consecutive Kaposi's sarcoma patients treated at our institution from 2007 to 2017. Most patients were HIV-positive Caucasian men on antiretroviral therapy; the average CD4 T-cell count was above the AIDS-defining level of 200 cells/mm3. Seven patients had Kaposi's sarcoma with mucosal involvement, and 20 had skin-only Kaposi's sarcoma. Mucosal Kaposi's sarcoma patients had a mean CD4 T-cell count of 83 cells/mm3 as opposed to 381 cells/mm3 for patients with skin-only involvement (p = 0.005). Survival was significantly compromised in both groups but even more so in Kaposi's sarcoma patients with mucosal involvement (306 vs. 609 days). Along with other reports, our findings suggest that Kaposi's sarcoma may develop in HIV patients in the modern era despite well-controlled HIV disease. This is significant since Kaposi's sarcoma remains an important contributor to morbidity and mortality in HIV-infected patients.

Safety of CD34+ Hematopoietic Stem Cells and CD4+ T Lymphocytes Transduced with LVsh5/C46 in HIV-1 Infected Patients with High-Risk Lymphoma

Although the risk of developing lymphoma has decreased in the highly active antiretroviral therapy era, this cancer remains the major cause of mortality in HIV-infected patients. Autologous hematopoietic stem cell transplantation (ASCT) outcome does not differ for HIV-infected versus HIV-uninfected patients. We propose to develop a new treatment for HIV-associated high-risk lymphoma based on autologous transplantation of two genetically modified products: CD4+ T lymphocytes and CD34+ hematopoietic stem cells (HSPCs). The cells will be transduced ex vivo with the Cal-1 lentiviral vector encoding for both a short hairpin RNA (shRNA) against CCR5 (sh5) and the HIV-1 fusion inhibitor C46. The transduced cells will be resistant to HIV infection by two complementary mechanisms: impaired binding of the virus to the cellular CCR5 co-receptor and decreased fusion of the virus as C46 interacts with gp41 and inhibits HIV infection. This phase I/II pilot study, also entitled GENHIV, will involve two French participating centers: Saint Louis Hospital and Necker Hospital in Paris. We plan to enroll five HIV-1-infected patients presenting with high-risk lymphoma and require a treatment with ASCT. The primary objective of this study is to evaluate the safety, feasibility, and success of engraftment of Cal-1 gene-transduced CD4+ T lymphocytes and CD34+ HSPCs.

B-type natriuretic peptides for the prediction of cardiovascular events and mortality in patients living with HIV: Results from the HIV-HEART study

AimsB-type natriuretic peptide (BNP) has been suggested to improve risk prediction of cardiovascular (CV) events and mortality. We aimed to evaluate the value of BNP to predict the composite primary endpoint of CV events and mortality alongside traditional and HIV specific risk factors in a HIV-infected population. MethodsIn this prospective multicenter HIV-HEART study we followed 808 HIV-positive subjects in the German Ruhr area for a median follow up of 120 (IQR:113–129) months since 2004. Association of BNP with the composite primary endpoint was assessed using Cox regression adjusting for traditional cardiovascular and HIV specific risk factors. ResultsAt baseline, median BNP was 10.3 (IQR 5.4–18.9) pg/ml. The composite endpoint occurred in 158 (19.6%) patients. Subjects with high BNP levels showed significantly increased frequencies of CV events and death (22% for BNP ≤5 pg/ml, 30% for BNP >5 up to ≤20 pg ml, 38% for BNP >20 up to ≤35 pg ml, 59% for BNP >35 up to ≤100 pg ml and 86% for BNP >100 pg/ml, p-value < 0.01). In the fully adjusted model that included traditional CV risks as well as HIV specific factors, after a log2 transformation, doubling of BNP was significantly associated with increased risk for the composite endpoint (HR:1.16 (95%CI 1.01–1.33); p = 0.031). Comparing BNP of <5 pg/ml to BNP > 100 pg/ml, HR in the fully adjusted model was 3.25 (95%CI 1.50–7.08; p < 0.001). ConclusionsIncreased BNP is associated with significant excess of incident CV events and mortality in HIV-infected patients. BNP is a valuable marker to improve the prediction of CV events and mortality.

Liver as a target of human immunodeficiency virus infection.

Liver injury is a characteristic feature of human immunodeficiency virus (HIV) infection, which is the second most common cause of mortality in HIV-infected patients. Now it is recognized that liver plays a key role in HIV infection pathogenesis. Antiretroviral therapy (ART), which suppresses HIV infection in permissive immune cells, is less effective in hepatocytes, thereby making these cells a silent reservoir of HIV infection. In addition to direct hepatotoxic effects of HIV, certain ART treatment modalities provide hepatotoxic effects. The exact mechanisms of HIV-triggered chronic hepatitis progression are not elucidated, but the liver is adversely affected by HIV-infection and liver cells are prominently involved in HIV-elicited injury. These effects are potentiated by second hits like alcohol. Here, we will focus on the incidence of HIV, clinical evidence of HIV-related liver damage, interactions between HIV and liver cells and the role of alcohol and co-infection with hepatotropic viruses in liver inflammation and fibrosis progression.

T cell toxicity of HIV latency reversing agents.

Combination antiretroviral therapy reduces morbidity and mortality in HIV infected patients. However, the cure of HIV infection is hindered by the persistence of the latent HIV reservoir. Latency reversing agents (LRAs) are developed to target the HIV latently infected cells for HIV reactivation. In addition to reversal of HIV latency, the eradication of HIV latently infected cells will require effector HIV-specific CD8+ T cells. Therefore it is imperative we understand how LRAs affect immune cells. We have performed a comparative in depth analysis of the cytotoxicity of several compounds belonging to four LRA classes on T cells, B cells, and NK cells. In addition, the effect of these LRAs on activation and inhibitory receptor expression of CD8+ T cells was examined. We show that the HDAC inhibitors romidepsin and panobinostat are highly cytotoxic for CD4+ and CD8+ T cells, whereas the PKC agonists bryostatin and prostratin and BET inhibitors JQ1 and OXT-015 were less cytotoxic. The BAF inhibitors CAPE and pyrimethamine exhibit no cytotoxicity. Drug-specific cytotoxicity on CD8+ T cells was comparable between healthy controls and cART-treated HIV-infected patients. Bryostatin and both BET inhibitors downregulated the expression of CD279 on CD8+ T cells without affecting their activation. Our comparison of LRAs identified differences in cytotoxicity between LRA classes and members within a class and suggests that some LRAs such as bryostatin and BET inhibitors may also downregulate inhibitory receptors on activated HIV-specific CD8+ T cells. These findings may guide the use of LRAs that have the capacity to preserve or restore CD8+ T cell immunity.

Serum cryptococcal antigen titre as a diagnostic tool and a predictor of mortality in HIV-infected patients with cryptococcal meningitis.

The aim was to determine the effectiveness of the serum cryptococcal antigen (CrAg) test in the diagnosis of concurrent cryptococcal meningitis (CM) and as a predictor of mortality in HIV-infected patients. In this retrospective study, all HIV-infected patients admitted to Shanghai Public Health Clinical Center from 1 January 2014 to 31 August 2016 were screened for serum CrAg using the latex agglutination test. Serum CrAg-positive patients underwent lumbar puncture to confirm CM prior to the initiation of appropriate antifungal therapy and were followed up for at least 6months. One hundred and four (7.1%) of the total of 1474 HIV-infected patients screened were serum CrAg-positive. CM was diagnosed in the majority of serum CrAg-positive patients (71.3%; 67 of 94) and was confirmed in all (46 of 46) of the patients with headache or coma and in 43.8% (21 of 48) of patients without neurological symptoms. CrAg titres ≥1:1024 showed a sensitivity of 82.5% and a specificity of 86.7% for the diagnosis of concurrent CM (P<0.001). The positive predictive value for CM in this population was 94.3%. A total of 13 serum CrAg-positive patients [13.8%; 95% confidence interval (CI) 7.5-22.4%] died (11 as a result of CM and two others as a result of bacterial pneumonia) despite early antifungal treatment initiation. Serum CrAg titres ≥1:1024 predicted all-cause mortality (hazard ratio3.69; P=0.03). Serum CrAg titres ≥1:1024 not only were associated with concurrent CM but also predicted mortality. HIV-infected patients with a positive serum CrAg test during screening should receive lumbar punctures regardless of symptoms to rule out CM and patients with serum CrAg titres ≥1:1024 should be offered immediate care.

Cute kidney injury and other factors associated with mortality in HIV-infected patients

cute kidney injury and other factors associated with mortality in HIV-infected patients