Survival Of HIV-infected Patients Research Articles

Chinese Herbal Medicine Usage Reduces Overall Mortality in HIV-Infected Patients With Osteoporosis or Fractures.

The survival of patients with HIV has greatly improved, due to Anti-Retroviral Therapy (ART). However, long-term HIV survivors often develop serious bone abnormalities, possibly due to the interplay of osteoblasts, osteoclasts, HIV ad ART. We evaluated in a nation-wide study in Taiwan the effect of Chinese herbal medicine (CHM) on overall mortality in HIV patients with osteoporosis or fractures. Enrollment period was between 1998 and 2011. Patients with osteoporosis or fractures before the HIV infection, and those with less than 14 days CHM use, were excluded. This left 498 patients, 160 CHM users, 338 without CHM. Univariate Kaplan-Meier and multivariate Cox regression analysis were used to compare the overall mortality in these 2 groups. Due to the nature of Chinese medicine, CHMs inevitably varied. We therefore also used rule mining and network analysis to determine which major CHM clusters were prescribed to the patients. CHM users had a much Lower mortality (hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.24–0.77, p < 0.005) and higher survival (p = 0.004, log-rank test). Although the CHMs greatly varied, network analysis identified one main cluster of strongly related CHM combinations (Chuan-Xiong-Cha-Tiao-San (CXCTS), Gan-Cao (GC; Glycyrrhiza uralensis Fisch.), Liu-He-Tang (LHT), Huang-Qin-Tang (HQT), Jia-Wei-Ping-Wei-San (JWPWS), and Dang-Gui-Long-Hui-Wan (DGLHuiW)). CHM as an additional treatment strongly improves overall survival in HIV-infected patients with osteoporosis and fractures.

Rational in silico drug design of HIV-RT inhibitors through G-QSAR and molecular docking study of 4-arylthio and 4-aryloxy-3-iodopyridine-2(1-H)-one derivative

BackgroundHuman immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV). Antiretroviral therapy (ART) against HIV infection offers the promise of controlling disease progression and prolonging the survival of HIV-infected patients. Reverse transcriptase (RT) inhibitors remain the cornerstone of the drug regimen to treat AIDS. In this direction, by using group-based QSAR study (G-QSAR), identification of the structural need for the development of lead structure with reverse transcriptase inhibition on 97 reported structures was carried out. Docking analysis was performed further and suggested the structural properties required for binding affinity with the receptor. The molecules in the data set were fragmented into six (R1, R2, R3, R4, R5, and R6) by applying the fragmentation pattern. Three G-QSAR models were selected based on the statistical significance of the model. The molecular docking study was performed to explain the structural properties required for the design of potent HIV-RT inhibitors.ResultsThe statistically validated QSAR models reveal the presence of higher hydrophobic groups containing single-bonded –Br atom, 2 aromatic bonded –NH group with less electronegativity, and entropic interaction fields at R2 essential for better anti-HIV activity. The presence of a lipophilic group at R3, oxygen and sulfur connected with two aromatic bonds at R4, and –CH3 group at R5 was fruitful for reverse transcriptase inhibition. Docking studies of the selected inhibitors with the active site of reverse transcriptase enzyme showed hydrogen bond, Van der Waal’s, charge, aromatic, and π–π interactions with residues present at the active site.ConclusionThe results of the generated models provide significant site-specific insight into the structural requirements for reverse transcriptase inhibition during the design and development of novel anti-HIV compounds. Molecular docking study revealed the binding interaction between the ligand and the receptor which gave insight towards the structure-based design for the discovery of more potent compounds with better activity against HIV infection.

Survival of HIV-infected patients with high-grade non-Hodgkin's lymphomas: A retrospective study of experiences in Zimbabwe.

BackgroundRituximab in combination with chemotherapy is now widely accepted as standard of care for AIDS-related lymphomas (ARLs) of B-cell origin. However, the clinical impact of rituximab in resource limited settings remains unknown. Different settings and patient heterogeneity may affect the effect of any given treatment. The study objectives were to determine if rituximab use was associated with improved 18-month overall survival (OS) of patients with ARLs and to identify correlates of 18-month OS.MethodsA retrospective review of medical records of adult HIV infected patients treated for high-grade large cell non-Hodgkin’s lymphoma with chemotherapy +/- rituximab between 2015–2017 was conducted. Vital status and disease progression/relapse at 18 months were determined. Survival functions were estimated using Kaplan-Meier methodology. Equality of survival functions were assessed using Log-rank tests and Cox regression analysis to identify risk factors for mortality.ResultsOne hundred and twenty-four eligible medical records were identified. This was a cohort of black Africans with a median age of 42 (IQR: 33–47) and a 57% male gender distribution. Overall survival at 6, 12 and 18 months for the population was 75.9%, 44.0% and 30.6% respectively. Over the study period, 72.6% of patients were diagnosed with disease progression/ relapse. There was a higher rate of rituximab use in patients who were treated at a private institution and those with medical insurance. Rituximab use was not associated with a reduction in 18-month mortality [adjusted hazard ratio (aHR)1.28, (95% CI 0.63–2.60)]. Risk factors for 18-month mortality were male gender [aHR 1.89, (95% CI 1.04–3.43)], age 40+ years [aHR 2.49, (1.33–4.67)], receipt of <3 chemotherapy cycles [aHR 2.48, (95% CI 1.33–4.60)] and low socioeconomic status [aHR 2.44, (95% CI 1.28–4.67)].ConclusionsPredictors of mortality were male gender, older age, low socioeconomic status and receipt of a less than half of the recommended number of chemotherapy cycles. Rituximab use was not associated with an improvement in 18-month OS in Zimbabwean patients with ARLs.

IMMUNOSUPPRESSIVE OPTION WITH BELATACEPT IN HIV-POSITIVE KIDNEY TRANSPLANT RECIPIENTS

Kidney allograft survival in HIV-infected patients is lower than in the general population. Belatacept increases long-term patients and allografts survival compare to anticalcineurins (CNI). Its use in HIV-positive recipients is poorly documented. We retrospectively reported a French cohort of HIV-positive kidney allograft recipients treated with belatacept. Patient and allograft survivals, HIV immunovirological and clinical evolution, acute rejection, opportunistic infections (OI), and donor-specific anti-HLA antibodies (DSA) were analyzed and compared to an historical CNI control group. Fourteen patients were treated with belatacept: 2 (16%) de novo and 12 (84%) switches 10 [2-30] months after transplantation. One year after belatacept therapy patients’ and allografts survival were 91% and 92% respectively with two (17%) HIV viral rebound linked to antiretroviral therapy non-compliance while CD4+ and CD8+ T cell count remained over time. Serious adverse events included 2 (17%) acute steroid-resistant T-cell mediated rejections and 2 (17%) OI. Kidney allograft function increased significantly 12-months after switch (P=0.009) whereas proteinuria remained comparable. DSAs remained stable 12 months after treatment. Results were similar in control group. Belatacept can be used safely and could increase long-term kidney allograft survival in HIV+ kidney allograft recipients. These results need to be confirmed in a larger cohort.

P1668SIMULTANEOUS LIVER-KIDNEY TRANSPLANTATION IN PEOPLE LIVING WITH HIV: A CASE-SERIES WITH LONG TERM FOLLOW-UP

Abstract Background and Aims The number of simultaneous liver-kidney transplants (SLKT) has been constantly increasing in the past two decades. In the US, the relative proportion of liver transplants performed as part of SLKT augmented from 2.7% in 2000 to 9.3% in 2016. In this rapidly evolving scenario, people living with HIV (PLWH) have been substantially excluded from SLKT. The poor prognosis of SLKT in people living with HIV (PLWH) has refrained transplant centers to perform this procedure. Method We retrospectively describe indications, clinical characteristics and survival of HIV-infected patients who underwent SLKT at the Transplant Centre of Modena, Italy. Results Since 2001 five SLKTs were performed in HIV-affected subjects. With regards to medical eligibility criteria for SLKT all the patients were on hemodialysis and had liver end-stage disease or HCC at time of transplantation (Table 1A). Mean age at transplantation was 47.8± 5.93 years and all patients were Caucasian males. Mean duration of HIV was 25 years and all patients had undetectable HIV-viral load at SLKT. The causes of end-stage renal disease were different in all recipients and only one had biopsy-proven kidney disease. Dialysis vintage was 15.8±10.2 months. Four patients had HCV-related cirrhosis and one had hepato-carcinoma (HCC). Mean HCV-RNA at SOT was 464,327 copies/ml; in three HCV patients, the sustained virologic response to HCV therapy was obtained after transplant with peg-INF in one case (pre-direct antiviral agent era) and with a combination of sofosbuvir, daclatasvir and rifampicin in the other two. Only one patient had HBV-HDV-related cirrhosis and did not experience HBV or HDV relapse during the follow-up. At the end of a mean follow up of 7.6±4.71 years, four out of five patients are still alive One patient died on post-transplant day 41 for disseminated candidiasis with cerebral involvement (Table1 b). During the follow-up period, HIV-VL remained undetectable over nearly 10 years. Clinical outcome was characterized by the reverse of frailty in all the patients. All of them are conducting an independent living with quality of life exceeding 90% using the EUQoL 5D-5L questionnaire. The liver function was normal and remained stable during theobservation period. Bile duct stricture and bile duct calculi were the main surgical complications. Regarding renal function, mean serum creatinine was 1.7±0.4mg/dl corresponding to a mean estimated GFR of 47.7±5.9 ml/min. Only one patient had proteinuria (0.8 gr/daily) after 10 years of transplantation. Contrary to our expectations, no cases of graft rejections occurred during this long-term follow-up despite mean HLA mismatches of 5.75 and underexposure to the immunosuppressive agents. Withdrawn of steroids occurred after 1.8±2.5 years from SLKT. Thereafter, immunosuppressive therapy continued with monotherapy: calcineurin inhibitor in three recipients and inhibitors of the mammalian target of rapamycin in the other one. Conclusion Contrary to the previously published data, this case series describes a favorable clinical outcome in PLWH who received SLKT. The absence of graft rejection despite the reduced immunosuppressive therapy highlights the concept that the liver is able to induce tolerance in kidney transplantation. These results could lead other transplant programs to consider SLKT as a reliable clinical option in PLWH with liver and kidney failure.

P5337Neutrophil-lymphocyte ratio and peripheral arterial disease in HIV infection

Abstract Background/Introduction While antiretroviral therapy has increased survival in HIV-infected patients, cardiovascular mortality is now their leading cause of death. Together with a high prevalence of traditional cardiovascular risk factors in HIV infection, chronic inflammation may be also responsible of an increased risk of cardiovascular diseases. Purpose To determine the association between a systemic inflammation-based biomarker, the neutrophil-lymphocyte ratio, and the occurrence of peripheral arterial disease in HIV infected patients. Methods In a case-control design, 41 patients with peripheral arterial disease and HIV infection were compared to 119 patients with HIV infection but no peripheral arterial disease. All patients were recruited at a Regional Hospital. The ankle-brachial index was measured in all subjects and peripheral arterial disease was defined as an ankle-brachial index &gt;0.9. The neutrophil-lymphocyte ratio was assessed using neutrophil and lymphocyte levels in the complete blood count measurement, from routine hemograms performed six to twelve months before measurement of the ankle-brachial index. The cut-off of neutrophil-lymphocyte ratio &gt;2 was used to categorize patients into low- and high- neutrophil-lymphocyte ratio groups. Odds ratios (OR) with 95% confidence intervals were used to estimate the strength of association. In order to control for potential confounders, a multiple logistic regression model was used. Results There was a significant association between elevated neutrophil-lymphocyte ratio and the presence of peripheral arterial disease (OR 7.25 [3.32–15.85], after adjustment for age (OR 1.07 [1.04–1.11]), smoking index (OR 1.12 [1.02–1.24]. Other considered variables did not contribute to the model (HDL-cholesterol, LDL-cholesterol, triglycerides, sex, diabetes, obesity and treatment). Conclusions The ankle-brachial index is a simple, cost-effective and validated method to assess peripheral arterial disease, which its presence increases the risk of cardiovascular disease morbidity and mortality. The neutrophil-lymphocyte ratio is a simple, rapid and novel inflammation parameter, that may help to identify HIV-infected patients with a higher risk of peripheral arterial disease.

Effect of alpha-fetoprotein on survival in HIV-infected patients with hepatocellular carcinoma

Effect of alpha-fetoprotein on survival in HIV-infected patients with hepatocellular carcinoma

Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART

Background and aimsAlthough combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies showed that circulating levels of extracellular matrix (ECM) fragments might reflect degree of portal hypertension and fibrosis stage in liver disease. In this study, we analyzed the correlation between liver fibrosis assessed by Fibroscan and levels of the formation and degradation markers of type III and IV collagen in HIV positive patients receiving cART.Methods116 HIV positive patients (82.7% male, median age 47 years) were enrolled into the study. Liver stiffness and liver fat content were determined using a Fibroscan with integrated CAP function. We quantified ECM formation and degradation fragments of collagen III and IV: PRO-C3, PRO-C4, C3M and C4M. These fragments were measured in peripheral serum by using specific ELISAs.ResultsFifteen (12.9%) out of the 116 HIV positive patients had relevant fibrosis with a liver stiffness ≥ 7.1 kPa, and 79 patients had relevant steatosis with a CAP value > 248 dB/m. Circulating PRO-C3 levels significantly correlated with increasing degree of liver fibrosis assessed by Fibroscan (p = 0.0005), as well as with APRI score (p = 0.015). Interestingly, circulating PRO-C3 levels were significantly correlated with bilirubin (p = 0.022), reduced platelet count (p = 0.0008) and low albumin levels (p = 0.001), suggesting the association of type III collagen deposition with impaired liver function. None of the other measured ECM components significantly correlated with fibrosis or steatosis.ConclusionThe formation marker of type III collagen, PRO-C3 not only reflects liver fibrosis, but might also mirror liver dysfunction in HIV positive patients receiving cART. Therefore, the circulating levels of PRO-C3 might be suitable to monitor progression of liver fibrosis and deterioration of liver function in HIV positive patients receiving cART.

Prognostic role of inflammatory biomarkers in HIV-infected patients with a first diagnosis of hepatocellular carcinoma: A single-center study.

To assess hepatocellular carcinoma (HCC) survival and to investigate the prognostic role of immunonutritional biomarkers, as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI), in a cohort of human immunodeficiency virus (HIV)-infected patients. All HIV-positive patients diagnosed with HCC at our Department from January 2000 to December 2013 were included. The outcomes were overall survival (OS), recurrence-free survival (RFS), and liver-related death (LRD). To examine the role of inflammatory biomarkers on the outcomes, univariate and multivariable Cox regression models were used. Receiver operating characteristic (ROC) curves were implemented to evaluate the prediction role of NLR, PLR, and PNI. A total of 40 patients (90% males) with a mean age of 48.3 years (SD = 5.6) were recruited. NLR ≥ 2.9 was associated with all causes mortality, as well as, PLR ≥ 126. NLR and PLR were predictors of OS, RFS, and LRD, while PNI did not emerge as a prognostic marker. According to the multivariate analysis, no HCC treatment was the only risk factor associated with risk of death. The areas under the ROC curves were 68.3 (95% confidence interval [CI], 54.5-82.1) for PLR and 66.3 (95% CI, 54.3-78.2) for NLR at 3 years; similar results were found at 5 years of follow-up. Although, if examined singularly, NLR and PLR are prognostic factors for HCC recurrence and survival in HIV-infected patients, at the multivariate analysis, "no HCC treatment" remains the only independent risk factor associated with fatal outcome.

Survival of HIV infected patients on maintenance hemodialysis in Cameroon: a comparative study

BackgroundThere are conflicting reports on the impact of HIV in the era of combined antiretroviral (c-ART) on survival of patient with ESKD. We aimed to compare the one-year survival of HIV positive patients to that of their HIV negative counterparts with ESKD on maintenance haemodialysis in Cameroon.MethodsThis was a retrospective cohort study conducted in the haemodialysis units of the Douala and Yaoundé General Hospitals. All HIV positive patients treated by maintenance haemodialysis between January 2007 and March 2015 were included. A comparative group of HIV negative patients with ESKD were matched for age, sex, co morbidities, year of dialysis initiation and haemodialysis unit. Relevant data at the time of haemodialysis initiation and during the first year of haemodialysis was noted. Survival was analysed using the Kaplan Meier and Cox regression hazard ratio estimator. A p value < 0.05 was considered statistically significant.ResultsA total of 57 patients with HIV and 57 without HIV were included. Mean age was 46.25 ± 11.41 years, and 52.6% were females in both groups. HIV nephropathy (50.9%) was the main presumed aetiology of ESKD in the HIV group, while chronic glomerulonephritis (33.3%) and diabetes (21.1%) were the main aetiologies in the HIV negative group. At initiation of dialysis, the median CD4 count was 212 cell/mm3 (IQR; 138–455) and 77.2% were receiving c-ART. The proportion of patients who initiated dialysis with a temporary venous catheter was similar in both groups (p = 0.06). After one year on haemodialysis, survival rate was lower in the HIV positive group compared to the HIV negative group (61.4%/78.9%, HR: 2.05; 95% CI: 1.03–4.08; p = 0.042).Kaplan Meier survival curve was in direction of a lower survival in HIV positive group (p = 0.052).ConclusionThe one year survival of HIV positive patients on maintenance haemodialysis in Cameroon seems to be lower compared to their HIV negative counterparts.

Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial.

Background:Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods:We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion:Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.

Survival in HIV-infected patients with lymphoma according to the choice of antiretroviral treatment: an observational multicentre study.

Lymphoproliferative disorders are often observed in HIV-positive patients. Combination antiretroviral treatment (cART) during antineoplastic chemotherapy is beneficial, but little is known about the clinical outcome according to different antiretroviral combinations. The aim of the study was to address this gap in current knowledge. A retrospective study was conducted in five large Italian centres for the period from 1998 to 2015; HIV-positive patients diagnosed with lymphoma were included and demographic, clinical and therapeutic variables were recorded and associated with clinical outcomes. Bivariate and multivariate analyses were performed, including Cox proportional hazard models for survival. A total of 399 patients were included in the study. The most common types of lymphoma were diffuse large B-cell lymphoma (DLCLB; n=164), Hodgkin lymphoma (HL; n=99) and Burkitt lymphoma (BL; n=57), followed by plasmablastic lymphoma (PBL; n=38), T-cell lymphoma (TCL; n=17), indolent lymphoma (n=10) and other less common types (n=14). cART was given to 327 (out of 387 evaluable) patients: in 216 subjects it was protease inhibitor (PI)-based, in 73 it was nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and in 18 it was integrase strand transfer inhibitor (INSTI)-based (the remaining 20 individuals received other regimens). The 5-year overall survival was 57.5% (52.8% for DLCLB, 67.8% for HL, 42.3% for BL, 60.6% for PBL and 64.7% for TCL). PI-based ART compared with other compounds was associated with worse survival in non-Hodgkin lymphoma (NHL) and HL patients combined (P≤0.001) and in NHL patients alone (P<0.001); grade 3-4 haematological toxicities were more commonly observed in PI-treated individuals. Lymphoma diagnosis in recent years, better immunovirological status, lower lymphoma stage and better prognostic indexes were associated with better survival. PI-based cART while on chemotherapy was associated with worse overall survival and more frequent haematological complications in HIV-positive patients with lymphoma.

HIV and Vertebral Fractures: a Systematic Review and Metanalysis

The survival of HIV-infected patients has increased with the advent of antiretroviral therapy with the emergence of new comorbidities. Vertebral fracture is a manifestation of reduced bone strength and osteoporosis. This study aims to assess the frequency of spine fractures in HIV-positive men and women aged over 18 years. We performed a systematic review of randomized controlled trials, cohort studies, cross-sectional studies, and case-control studies. Studies that evaluated morphometric and/or clinical vertebral fracture were included. In total 488 studies were found, of which 53 had their full texts evaluated. A total of 85,411 HIV positive individuals were identified in 26 studies. The meta-analysis of the prevalence of vertebral fractures included 12 studies with 10,593 subjects. The prevalence was 11.1% [95% confidence interval (95% CI) 4.5%, 25.0%, I2 98.2% p < 0.00001]. When we evaluated independently studies of clinical vertebral fracture and morphometric vertebral fracture, the prevalence was 3.9% (95% CI 0.9, 15.8, I2 96.4% p < 0.00001) and 20.2% (95% CI 15.7%, 25.6%, I2 69.9% p = 0.003) respectively. HIV-infected individuals had an odds ratio of vertebral fractures of 2.3 (95% CI 1.37, 3.85, I2 98.2% p < 0.00001) when compared with HIV-uninfected patients (n = 9 studies). In conclusion, HIV-positive subjects had a higher risk of vertebral fractures when compared with HIV-negative subjects.

A retrospective cohort study of body mass index and survival in HIV infected patients with and without TB co-infection

BackgroundHigh early morbidity and mortality following antiretroviral therapy (ART) initiation has been a distinguishing feature of ART programmes in resource limited settings (RLS) compared to high-income countries. This study assessed how well body mass index (BMI: kg/m2) correlated with survival among HIV infected patients with and without TB co-infection.MethodsWe retrospectively evaluated clinical data from 1000 HIV infected patients, among whom 389 were also co-infected with TB, between January 2008 and December 2010, in KwaZulu-Natal, South Africa.ResultsAmong 948 patients eligible for analysis, 15.7% (149/948) were underweight (< 18.50), 55.9% (530/948) had normal BMI (≥18.50–24.90), 18.7% (177/948) were overweight (25.00–29.00) and 9.7% (92/948) were obese (≥30.00). Irrespective of TB status, underweight patients, had significantly higher risk of death compared to those with normal BMI at baseline (aHR = 2.9; 95% CI: 1.5–5.7; P = 0.002).ConclusionsIrrespective of TB co-infection, low BMI correlated with mortality in HIV infected patients.Trial registrationUKZN Biomedical Research Ethics Committee Reference number E 248/05, 23 September 2005.

PROTEIN 24 HIV DAN LIMFOSIT T-CD4+ DI INFEKSI HIV TAHAP I (HIV p24 Protein and CD4+ T-lymphocyte in Stage I HIV infection)

Measuring HIV p24 protein is a test which is more practical than determination of CD4+ T-lymphocyte counts and viral load, asit does not require a very sophisticated instrument and requires a lower cost. Independent predictive value of p24 to the decline ofCD4+ T-lymphocytes, clinical progression and survival in HIV-infected patients have been reported. In this study, HIV-infected patientswere found to have HIV p24 protein levels inversely proportional to CD4+ T-lymphocyte counts by using Spearman test (R2=0.225;p=0.0331). Studies on the correlation between HIV p24 protein levels and CD4+ T-lymphocyte counts in stage I HIV infection have notyet been reported. The aim of this study was to prove the correlation between HIV p24 protein levels and CD4+ T-lymphocytes in stageI HIV infection. Research issue was whether a correlation between HIV p24 protein levels and CD4+ T-lymphocyte counts in stage I HIVinfection existed ? The hypothesis was that a correlation between HIV p24 protein levels and CD4+ T-lymphocyte counts in stage I HIVinfection existed. The study design was cross sectional observational. Subjects consisted of 30 stage I HIV-infected patients treated at theInfectious Disease Intermediate Care Unit, Dr. Soetomo Hospital and VCT Clinic of the Dr. Ramelan Naval Hospital, Surabaya from Mayto July 2014. Stage I HIV infection is an asymptomatic HIV infection or with persistent generalized lymphadenopathy and the patientis able to perform normal activities. Levels of p24 were measured by ELISA method and CD4+ T-lymphocyte counts using flowcytometry(BD FACSCaliburTM). The results were statistically analyzed using Pearson's correlation test. HIV p24 protein levels in stage I of HIVinfection ranged from 1.8 to 10.8 pg/mL, mean of 5.14 pg/mL and a standard deviation of 2.08 pg/mL. CD4+ T-lymphocyte countsdecreased with a range of 49-559 cells /uL for absolute values and 4.42–26.02% for percentage values Correlations between blood p24levels and CD4+ T-lymphocyte counts either absolute (r=–0.392, p=0.032) or percentage (r=–0.363, p=0.049) were found. In stageI HIV-infected patients, a negative correlation was found between p24 levels and CD4+ T-lymphocyte counts, in both CD4+T-lymphocytecounts as absolute and as well as percentage values. This negative correlation showed that the p24 HIV levels were inversely proportionalto the CD4+ T-lymphocyte counts. HIV p24 protein levels have a possibility to be used predicting CD4+ T-lymphocyte counts.

Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion: Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.

Risk factors affecting the mortality of HIV-infected patients with pulmonary tuberculosis in the cART era: a retrospective cohort study in China

BackgroundTuberculosis infection still places a great burden on HIV-infected individuals in China and other developing countries. Knowledge of the survival of HIV-infected patients with pulmonary tuberculosis (PTB) would provide important insights for the clinical management of this population, which remains to be well described in current China.MethodsHIV-infected patients with PTB admitted to Shanghai Public Health Clinical Center from January 2011 to December 2015 were retrospectively enrolled. In this cohort, the survival prognosis was estimated by the Kaplan-Meier method, while univariate and multivariate Cox proportional hazards models were used to determine the risk factors affecting mortality.ResultsAfter reviewing 4914 admitted patients with HIV infection, 359 PTB cases were identified. At the time of PTB diagnosis, the patients’ median CD4+ T cell count was 51 /mm3 (IQR: 23–116), and 27.30% of patients (98/359) were on combination antiretroviral therapy (cART). For the 333 cases included in the survival analysis, the overall mortality was 15.92% (53/333) during a median 27-month follow-up. The risk factors, including age older than 60 years (HR: 3.18; 95% CI: 1.66–6.10), complication with bacterial pneumonia (HR: 2.64; 95% CI: 1.30–5.35), diagnosis delay (HR: 2.60; 95% CI: 1.42–4.78), CD4+ T cell count less than 50/mm3 (HR: 2.38; 95% CI: 1.27–4.43) and pulmonary atelectasis (HR: 2.20; 95% CI: 1.05–4.60), might independently contribute to poor survival. Among patients without cART before anti-TB treatment, the later initiation of cART (more than 8 weeks after starting anti-TB treatment) was found to increase the mortality rate (OR: 4.33; 95% CI: 1.22–15.36), while the initiation of cART within 4–8 weeks after starting anti-TB treatment was associated with the fewest deaths (0/14).ConclusionsThe subjects in this study conducted in the cART era were still characterized by depressed immunological competence and low rates of cART administration, revealing possible intervention targets for preventing TB reactivation in HIV-infected individuals under current circumstances. Furthermore, our study indicated that the timely diagnosis of PTB, prevention of secondary bacterial pneumonia by prophylactic management and optimization of the timing of cART initiation could have significant impacts on decreasing mortality among HIV/PTB co-infected populations. These findings deserve further prospective investigations to optimize the management of HIV/PTB-co-infected patients.Trial registrationNCT01344148, Registered September 14, 2010.

Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial

Background:Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods:We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion:Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.

Novel Antiretroviral Drugs in Patients with Renal Impairment: Clinical and Pharmacokinetic Considerations.

Highly active antiretroviral therapy (HAART) has dramatically increased the survival of HIV-infected patients from Western countries reducing the incidence of opportunistic infections and AIDS-related malignancies, and improving the patients' quality of life compared with the pre-HAART era. HIV is thus now considered in the West as a chronic disease, with the majority of HIV-infected patients successfully reaching an optimal immune and virological outcome a few months after starting HAART. However, this switch from acute to chronic disease has been accompanied by an increased incidence of chronic kidney disease (CKD), reported in up to 60% of HIV-infected patients. Tenofovir disoproxil fumarate (TDF) is considered to play a significant role in the development of CKD in these patients. It has been proposed that tenofovir alafenamide (TAF), a prodrug formulation able to providing lower systemic and renal drug exposure, could potentially contribute to reduce the development of CKD in HAART-treated patients. On the other hand, the pharmacokinetics of some components of HAART can be significantly altered in HIV-infected patients developing CKD. TDF- or TAF-based antiretroviral regimens should be avoided in patients with a creatinine clearance of less than 50 or 30mL/min, respectively. This review focuses on the pharmacokinetic changes of novel antiretroviral drugs in HIV-infected patients with renal impairment or requiring renal replacement therapy, and provides some suggestions on how to change drug doses in these clinical settings.

Epidemiology and Outcomes in Critically Ill Patients with Human Immunodeficiency Virus Infection in the Era of Combination Antiretroviral Therapy.

Purpose. The impact of critical illness on survival of HIV-infected patients in the era of antiretroviral therapy remains uncertain. We describe the epidemiology of critical illness in this population and identify predictors of mortality. Materials and Methods. Retrospective cohort of HIV-infected patients was admitted to intensive care from 2002 to 2014. Patient sociodemographics, comorbidities, case-mix, illness severity, and 30-day mortality were captured. Multivariable Cox regression analyses were performed to identify predictors of mortality. Results. Of 282 patients, mean age was 44 years (SD 10) and 169 (59%) were male. Median (IQR) CD4 count and plasma viral load (PVL) were 125 cells/mm3 (30–300) and 28,000 copies/mL (110–270,000). Fifty-five (20%) patients died within 30 days. Factors independently associated with mortality included APACHE II score (adjusted hazard ratio [aHR] 1.12; 95% CI 1.08–1.16; p < 0.001), cirrhosis (aHR 2.30; 95% CI 1.12–4.73; p = 0.024), coronary artery disease (aHR 6.98; 95% CI 2.20–22.13; p = 0.001), and duration of HIV infection (aHR 1.07 per year; 95% CI 1.02–1.13; p = 0.01). CD4 count and PVL were not associated with mortality. Conclusions. Mortality from an episode of critical illness in HIV-infected patients remains high but appears to be driven by acute illness severity and HIV-unrelated comorbid disease rather than degree of immune suppression.