Contemporary Anti-Retroviral Drugs (ARVDs) Disrupt Follicular Development in Female Wistar Rats.

Introduction: There are genuine concerns that long-term use of anti-retroviral drugs may be associated with reproductive complications in females. This study aimed to ascertain the effect of highly active anti-retroviral drugs on the ovarian reserve and reproductive potential of female Wistar rats and by extension to HIV-positive human females. Methods: A total of 25 female Wistar rats, weighing between 140g and 162g, were randomly allotted into non-intervention and intervention groups, receiving the anti-retroviral drugs, Efavirenz (EFV), Tenofovir Disoproxil Fumarate (TDF), Lamivudine (3TC), and a fixed-dose combination (FDC). The dosage was administered orally at 8 am daily for 4 weeks. Serum concentrations of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinising hormone (LH), and estradiol were measured using standard biochemical techniques (ELISA). Follicular counts were made on fixed ovarian tissue from the sacrificed rats. Results: The mean AMH level for the control group and the EFV, TDF, 3TC, and FDC groups were 11.20, 6.75, 7.30, 8.27, and 6.60 pmol/L, respectively. The EFV and FDC groups had the lowest AMH, compared to the other groups, but there was no statistically significant difference in AMH across the groups. The mean count of antral follicles was significantly lower in the group that received EFV when compared to the other groups. The corpus luteal count was significantly higher in the control group than in the intervention groups. Conclusion: The study demonstrated a disruption in the reproductive hormones of female Wistar rats receiving anti-retroviral regimens containing EFV. Clinical studies are required to determine if these changes are seen in women receiving EFV-based treatment, as this may compromise reproductive function and predispose them to early menopause.

Direct and indirect cardiovascular and cardiometabolic sequelae of the combined anti-retroviral therapy on people living with HIV.

With reports of its emergence as far back as the early 1900s, human immunodeficiency virus (HIV) has become one of the deadliest and most difficult viruses to treat in the era of modern medicine. Although not always effective, HIV treatment has evolved and improved substantially over the past few decades. Despite the major advancements in the efficacy of HIV therapy, there are mounting concerns about the physiological, cardiovascular, and neurological sequelae of current treatments. The objective of this review is to (Blattner et al., Cancer Res., 1985, 45(9 Suppl), 4598s-601s) highlight the different forms of antiretroviral therapy, how they work, and any effects that they may have on the cardiovascular health of patients living with HIV, and to (Mann et al., J Infect Dis, 1992, 165(2), 245-50) explore the new, more common therapeutic combinations currently available and their effects on cardiovascular and neurological health. We executed a computer-based literature search using databases such as PubMed to look for relevant, original articles that were published after 1998 to current year. Articles that had relevance, in any capacity, to the field of HIV therapy and its intersection with cardiovascular and neurological health were included. Amongst currently used classes of HIV therapies, protease inhibitors (PIs) and combined anti-retroviral therapy (cART) were found to have an overall negative effect on the cardiovascular system related to increased cardiac apoptosis, reduced repair mechanisms, block hyperplasia/hypertrophy, decreased ATP production in the heart tissue, increased total cholesterol, low-density lipoproteins, triglycerides, and gross endothelial dysfunction. The review of Integrase Strand Transfer Inhibitors (INSTI), Nucleoside Reverse Transcriptase Inhibitors (NRTI), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) revealed mixed results, in which both positive and negative effects on cardiovascular health were observed. In parallel, studies suggest that autonomic dysfunction caused by these drugs is a frequent and significant occurrence that needs to be closely monitored in all HIV + patients. While still a relatively nascent field, more research on the cardiovascular and neurological implications of HIV therapy is crucial to accurately evaluate patient risk.

Starting effect of highly active antiretroviral therapy on the incidence of anemia in HIV-infected patients / 上海预防医学

ObjectiveTo investigate the risk factors of anemia in HIV-infected patients receiving highly active antiretroviral therapy （HAART） in the Pudong New Area. MethodsA retrospective cohort study was conducted among HIV-infected patients who started HAART from 2005 to 2020 in Pudong New Area. Cox proportional hazards model was used to analyze the risk factors of anemia， moderate or severe anemia， and chronic anemia. The piecewise linear mixed-effect model was used to analyze the association between initial HAART classes and hemoglobin change in the follow-up. ResultsA total of 2 403 HIV-infected patients were included in the analysis. Among them， there were 357 cases of new onset anemia， 86 cases of chronic anemia and 102 cases of moderate or severe anemia， with the incidence density of 4.41/100 person years， 0.89/100 person years and 0.96/100 person years respectively. Multifactorial Cox regression analysis results showed that female， age >45 years， baseline CD4+ T lymphocyte count （CD4） <200 cells‧μL-1， opportunistic infections， glomerular filtration rate （eGFR） <60 mL‧min-1‧（1.73 m2）-1， and zidovudine （AZT） or protease inhibitor （PIs） based regimens were associated factors for the development of anemia. Female， age >45 years， CD4 <200 cells‧μL-1， opportunistic infections， and AZT-based regimens were associated with the development of chronic anemia. Mild anemia at baseline and AZT-based regimens were associated with the development of moderate or severe anemia. Linear mixed-effects model showed that the use of AZT （-7.87 g‧L-1， 95%CI： -9.42 to -6.32） or PIs （-3.43 g‧L-1， 95%CI： -5.57 to -1.30） was associated with lower Hb at follow-up. ConclusionInitial use of AZT and PIs is associated with progression to anemia and a lower follow-up hemoglobin level. Increased hemoglobin monitoring in users of AZT and PIs may be beneficial， especially during the first 6 months after initiation of HAART.

[Adverse cardiovascular effects of antiretrovirals in female mice during gestation].

Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.

Orthostatic hypotension as the initial presentation of disseminated cryptococcosis in a kidney transplant recipient.

Background: Solid organ transplant recipients are immunocompromised and at risk for invasive viral, fungal, and bacterial pathogens. Cryptococcus neoformans is the third most common invasive fungal infection in transplant recipients, and the clinical presentation of Cryptococcus neoformans infection can vary widely. Cryptococcal disease can affect the brain, lungs, skin, or vasculature, and it is frequently disseminated. Meningitis typically presents with fever, headache, and altered mental status. Solid organ transplant recipients with cryptococcosis tend to have poorer outcomes than HIV patients with cryptococcosis. Case presentation: In this case report, we describe the case of a 69 year-old man with a past medical history of a deceased donor kidney transplant who presented with severe orthostatic hypotension and was found to have disseminated cryptococcosis. Conclusions: This case report emphasizes the importance of broadening the differential diagnosis in transplant recipients who present with non-specific chief concerns. Availability of data and materials: No datasets were used in the preparing of this manuscript. All patient information comes from the electronic health record and authors personal care of this patient.

The spectrum of kidney biopsy findings in Chinese HIV-infected patients.

OBJECTIVES: HIV-associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical presentation, laboratory findings and pathological spectrum of different subtypes of HIV-associated kidney disease in China. METHODS: Eighteen HIV patients with renal biopsy indications at the Peking Union Medical College Hospital from January 2002 to October 2021 were retrospectively enrolled. All had CD4 counts and HIV viral load measurements. Renal biopsies were examined with light microscopy, immunofluorescence, and electron microscopy. Shapiro-Wilk test was used to test whether the data was normally distributed. The data is presented as medians (interquartile range), number (%), or means (±SD) according to their distribution. RESULTS: Seventeen patients had glomerular disease, and one patient had interstitial nephritis. Membranous nephropathy was present in eight patients (47.1%), and IgA nephropathy in four patients (23.5%). The difference in urine protein and serum albumin before and after treatment was statistically significant and no deaths or dialysis were observed to the end of follow-up. CONCLUSION: This study found that classic HIV-associated nephropathy (HIVAN) was uncommon in Chinese HIV patients. HIV immune complex kidney (HIVICK) disease, such as membranous or IgA nephropathy, was more common, and associated with better prognosis. Antiretroviral therapy, ACE inhibitors, and angiotensin II receptor blockers were effective in decreasing proteinuria and preserving renal function. The use of corticosteroids and immunosuppressive agents seems safe. However, the nephrotoxic effect of antiretroviral agents and other medications should be carefully monitored.

Prevalence, Predictors, and Outcomes of Esophageal Candidiasis in Cirrhosis: An Observational Study With Systematic Review and Meta-Analysis (CANDID-VIEW).

BACKGROUND: Gastrointestinal candidiasis is often neglected and potentially serious infection in cirrhosis patients. Therefore, we evaluated the prevalence, risk factors, and outcomes of esophageal candidiasis (EC) in cirrhotics and did a systematic review to summarize EC's available evidence in cirrhosis. METHODS: Consecutive patients with cirrhosis posted for esophagogastroduodenoscopy (EGD) at a tertiary care institute were screened for EC (cases) between January 2019 and March 2020. EC was diagnosed on EGD findings and/or brush cytology. Controls (without EC) were recruited randomly, and EC's risk factors and outcomes were compared between cases and controls.Four electronic databases were searched for studies describing EC in cirrhosis. Prevalence estimates of EC were pooled on random-effects meta-analysis, and heterogeneity was assessed by I2. A checklist for prevalence studies was used to evaluate the risk of bias in studies. RESULTS: EC was diagnosed in 100 of 2762 patients with cirrhosis (3.6%). Patients with EC had a higher model for end-stage liver disease (MELD) (12.4 vs. 11.2; P = 0.007), acute-on-chronic liver failure (ACLF) (26% vs. 10%; P = 0.003) and concomitant bacterial infections (24% vs. 7%; P = 0.001), as compared with controls. A multivariable model, including recent alcohol binge, hepatocellular carcinoma (HCC), upper gastrointestinal (UGI) bleed, ACLF, diabetes, and MELD, predicted EC's development in cirrhosis with excellent discrimination (C-index: 0.918). Six percent of cases developed the invasive disease and worsened with multiorgan failures, and four patients with EC died on follow-up.Of 236 articles identified, EC's pooled prevalence from 8 studies (all with low-risk of bias) was 2.1% (95% CI: 0.8-5.8). Risk factors and outcomes of EC in cirrhosis were not reported in the literature. CONCLUSIONS: EC is not a rare infection in cirrhosis patients, and it may predispose to invasive candidiasis and untimely deaths. Alcohol binge, HCC, UGI bleed, ACLF, diabetes, and higher MELD are the independent predictors of EC in cirrhosis. At-risk patients with cirrhosis or those with deglutition symptoms should be rapidly screened and treated for EC.

Effects of a four-week aerobic exercise programme on depression, anxiety and general self-efficacy in people living with HIV on highly active anti-retroviral therapy.

The Human Immunodeficiency Virus (HIV) remains a major public health concern. Depression, anxiety and reduced self-efficacy are common psychological problems experienced by people living with HIV. We investigated the effects of a four-week, supervised aerobic exercise programme on depression, anxiety and self-efficacy of people living with HIV on HAART in Ibadan, Nigeria. A quasi-experimental design was used. Fifty-three eligible participants completed the study and only their data were analysed. The experimental subjects received aerobic exercise training for thirty minutes, three times per week for four weeks, alongside HAART, while control subjects were only on HAART. Depression, anxiety and self-efficacy scores were assessed at baseline and after the fourth week. Descriptive statistics of mean and standard deviation were used to summarise data, and inferential statistics of independent t-test was used to compare data between groups. At the end of the aerobic exercise programme, there was significant improvement in depression (p < 0.001), anxiety (p < 0.001) and self-efficacy scores (p = 0.042) in the experimental group, compared to the control group. More attention should be given to the prevention and management of psychological problems in people living with HIV through the use of aerobic exercise.

Anti-Retroviral Protease Inhibitors Regulate Human Papillomavirus 16 Infection of Primary Oral and Cervical Epithelium.

Epidemiology studies suggest that Human Immunodeficiency Virus (HIV)-infected patients on highly active anti-retroviral therapy (HAART) may be at increased risk of acquiring opportunistic Human Papillomavirus (HPV) infections and developing oral and cervical cancers. Effective HAART usage has improved survival but increased the risk for HPV-associated cancers. In this manuscript, we report that Protease Inhibitors (PI) treatment of three-dimensional tissues derived from primary human gingiva and cervical epithelial cells compromised cell-cell junctions within stratified epithelium and enhanced paracellular permeability of HPV16 to the basal layer for infection, culminating in de novo biosynthesis of progeny HPV16 as determined using 5-Bromo-2'-deoxyuridine (BrdU) labeling of newly synthesized genomes. We propose that HAART/PI represent a novel class of co-factors that modulate HPV infection of the target epithelium. Our in vitro tissue culture model is an important tool to study the mechanistic role of anti-retroviral drugs in promoting HPV infections in HAART-naïve primary epithelium. Changes in subsequent viral load could promote new infections, create HPV reservoirs that increase virus persistence, and increase the risk of oral and cervical cancer development in HIV-positive patients undergoing long-term HAART treatment.

Retrospective Hospital-based Study of Opportunistic Neuroinfections in HIV/AIDS.

BACKGROUND: Patients with retroviral disease are prone to opportunistic infections (OIs) of the central nervous system which cause significant mortality and morbidity. Cryptococcosis, tuberculosis, and toxoplasma are the most commonneuroinfections occurring at all stages of the disease. OBJECTIVE: This study was undertaken to evaluate the clinical pattern of OIs and in-hospital mortality in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: This retrospective analysis was conducted in a teaching hospital from 2001 to2014. Clinical data, laboratory investigations, and outcome of patients with meningoencephalitis were obtainedfrom case records. RESULTS: The total number of patients with human immunodeficiency virus (HIV) and AIDS with neurological manifestations was 277, among whom 167 (60.3%) had meningoencephalitis. There were 131 malesand 36 femaleswith a male-to-female ratio of 3.63:1andage ranging from 16 to 67 years (39.25 ± 8.85 years). Clinical presentation was acute in 58%, subacute in 32%, and chronic in 10%. Symptoms includedheadache (85.8%), fever (65.7%), altered sensorium (37.1%), and seizures (25.1%). Cryptococcal meningitis was the most commoninfection (67) followed by tuberculosis (32), mixed meningitis (24), and toxoplasmosis (10), and 16 patients had progressive multifocal leucoencephalopathy. Pathogenic organism could not be identified in 18 patients. Fifteen patients died during hospital admission. Mortality was the highest in mixed meningitis (16.7%) followed by cryptococcal meningitis (10.4%). Opportunistic neuroinfection occurred as AIDS-defining illness in 59.3%. Prior use of highly active anti-retroviral therapy did not affect the outcome. CONCLUSION: Opportunistic neuroinfections are the most commonneurological manifestation in patients with AIDS, with cryptococcal meningitis being the most commonopportunistic neuroinfection occurring as AIDS-defining illness in one-third of the patients with neuro-AIDS.

Acute paraparesis in HIV-infected patient after initiation of highly active antiretroviral therapy.

Neurological syndromes occur in around 40-70% of HIV-infected people. Direct central nervous system involvement by the virus usually manifests as HIV encephalitis, HIV leucoencephalopathy, vacuolar leucoencephalopathy or vacuolar myelopathy. Indirect involvement is usually associated with neurotropic opportunistic infections which include tuberculosis, toxoplasmosis, cryptococcosis and viral encephalitis such as herpes simplex, varicella-zoster, cytomegalovirus and Human polyomavirus 2. We report a case of transverse myelitis in a recently diagnosed HIV patient who was otherwise asymptomatic initially and developed paraparesis after 1 month of initiation of antiretroviral therapy. After ruling out opportunistic infections and other causes of compressive and non-compressive myelopathy, development of transverse myelitis was attributed to immune reconstitution inflammatory syndrome in view of baseline low CD4 count and their improvement after HAART initiation. Prompt treatment with corticosteroids successfully reversed the symptoms.

Essential trace elements and progression and management of HIV infection.

This review was written to update the review that we published in Nutrition Research in 2007 by examining studies published in the last 11 years which describe the effects of trace mineral deficiencies and micronutrient supplementation on HIV infection and its progression. In addition, we included studies that explore the interactions between Highly Active Anti-Retroviral Therapy (HAART) and micronutrient nutrition, focusing on the essential trace minerals. This review summarizes the results described in relevant articles that were identified by literature searches conducted using the OVID Medline database. Four of the nine essential trace minerals, specifically chromium, iron, selenium, and zinc, can influence HIV progression and/or its treatment. Notably, copper-containing filters may prevent transmission of the HIV virus via breastfeeding. However, there is a lack of good evidence to date that fluoride, iodine, manganese, or molybdenum influence HIV infection. Recent studies reveal that HAART can alter serum trace mineral and vitamin concentrations, but the effects vary based on the medications used. Although they have contributed useful new data, the sample sizes for most of these studies were too small to draw definitive conclusions for introducing changes in the management of HIV infection. Larger studies are needed to better understand and define the roles of trace mineral and vitamin deficiencies and micronutrient supplementation in the management and treatment of HIV-infected patients.

Angiogenesis, Lymphangiogenesis, and the Immune Response in South African Preeclamptic Women Receiving HAART.

Purpose of the review: This review highlights the role of angiogenesis, lymphangiogenesis, and immune markers in human immunodeficiency virus (HIV)-associated preeclamptic (PE) pregnancies in an attempt to unravel the mysteries underlying the duality of both conditions in South Africa. Recent findings: Studies demonstrate that HIV-infected pregnant women develop PE at a lower frequency than uninfected women. In contrast, women receiving highly active anti-retroviral therapy (HAART) are more inclined to develop PE, stemming from an imbalance of angiogenesis, lymphangiogenesis, and immune response. Summary: In view of the paradoxical effect of HIV infection on PE development, this study examines angiogenesis, lymphangiogenesis, and immune markers in the highly HIV endemic area of KwaZulu-Natal. We believe that HAART re-constitutes the immune response in PE, thereby predisposing women to PE development. This susceptibility is due to an imbalance in the angiogenic/lymphangiogenic/immune response as compared to normotensive pregnant women. Further large-scale studies are urgently required to investigate the effect of the duration of HAART on PE development.

Total thyroidectomy in HIV positive patient with buffalo hump and taurine neck.

BACKGROUND: The authors present a case of multinodular goiter in an HIV-positive patient affected by lipodystrophy with particular accumulation of adipose tissue in the region of the neck and trunk. CASE PRESENTATION: The patient, a 53-year-old man, presented with multinodular struma with partial retrosternal engagement, as well as multiple thyroid nodules increasing in size; some of the nodules had suspicious characteristics on ultrasound. Needle aspiration biopsy was difficult to use to determine the presence of lipodystrophy; however, even in the absence of cytology, surgical treatment was necessary due to the presence of dyspnea during exercise, the dimension of the goiter with retrosternal engagement, and the ovalization of the tracheal lumen. The patient underwent total thyroidectomy by anterior cervicotomy with particular attention to patient positioning because of the buffalo hump and taurine neck. Histological examination was positive for adenomatous hyperplasia with outbreaks of papillary microcarcinoma. CONCLUSIONS: The aim of this case report was to highlight the importance of the perioperative teamwork, with particular attention to patient positioning before surgery, as well as professional collaboration and experience among the operators.

[Survival status and influencing factors of HIV/AIDS on highly active anti-retrovial therapy in Shandong province].

Objective: To understand the survival status and influencing factors for HIV/AIDS patients on highly active anti-retroviral therapy (HAART) in Shandong province. Methods: Both Kaplan-Meier (K-M) method and cumulative incidence function (CIF) were used to calculate the cumulative incidence of AIDS-related death respectively, and Fine-Gray model was used to identify the influencing factors related to survival time. Results: Through K-M method, a higher AIDS-related cumulated death rate than the CIF, was estimated. Among all the HIV/AIDS patients who initiated HAART from 2003 to 2015 in Shandong, 5 593 of them met the inclusion criteria. The cumulative incidence rate for AIDS-related death was 3.08% in 1 year, 4.21% in 3 years, 5.37% in 5 years, and 7.59% in 10 years respectively by CIF. Results from the F-G analysis showed that HIV/AIDS patients who were on HAART, the ones who had college degree or above (HR=0.40, 95%CI: 0.24-0.65) were less likely to die of AIDS-associated diseases. However, HIV/AIDS patients who were on HAART and living in the western areas of Shandong (HR=1.33, 95%CI: 1.01-1.89), diagnosed by medical institutions (HR=1.39, 95%CI: 1.06-1.80), started to receive care ≥1 year after diagnosis (HR=2.02, 95%CI: 1.30-3.15), their CD(4) cell count less than 200 cells/µl (HR=3.41, 95%CI: 2.59-4.59) at the time of diagnosis, with NVP in antiviral treatment (ART) regime (HR=1.36, 95%CI: 1.03-1.88), at Ⅲ/Ⅳ clinical stages (HR=2.61, 95%CI: 1.94-3.53) and CD(4) cell count less than 350 cells/µl (HR=5.48,95%CI: 2.32-12.72) at initiation of HAART ect., were more likely to die of AIDS-associated diseases. Conclusions: With the existence of competing risks, the cumulative incidence rate for AIDS-related death was overestimated by K-M, suggesting that competing risk models should be used in the survival analysis. Measures as early diagnoses followed by timely care and early HAART could end up with the reduction of AIDS-related death.

Indinavir-Loaded Nanostructured Lipid Carriers to Brain Drug Delivery: Optimization, Characterization and Neuropharmacokinetic Evaluation.

PURPOSE: As an anti-retroviral Protease Inhibitor (PI), Indinavir (IDV) is part of the regimen known as Highly Active Anti-Retroviral Therapy (HAART) widely used for Human Immunodeficiency Virus (HIV) infection. The drug efficiency in treatment of the brain manifestations of HIV is, however, limited which is mainly due to the efflux by P-glycoprotein (P-gp) expressed at the Blood-Brain Barrier (BBB). METHODS: To overcome the BBB obstacle, NLCs were used in this study as carriers for IDV, which were optimized through two steps: a "one-factor-at-a-time" screening followed by a systematic multiobjective optimization. Spherical smooth-surfaced Nanoparticles (NPs), average particle size of 161.02±4.8 nm, Poly-Dispersity Index (PDI) of 0.293±0.07, zeta potential of -40.62±2.21 mV, entrapment efficiency of 93±1.58%, and loading capacity of 9.15±0.15% were obtained after optimization which were, collectively, appropriate in terms of the objective of this study. RESULT: The surface of the optimized NPs was, then, modified with human Transferrin (TR) to improve the drug delivery. The particle size, zeta potential, and PDI of the TR-modified NLCs were 185.29±6.7nm, -28.68±3.37 mV, and 0.247±0.06, respectively. The in vitro release of IDV molecules from the NPs was best fitted to the Weibull model indicating hybrid diffusion/erosion behavior. CONCLUSION: As the major in vivo findings, compared to the free drug, the NLCs and TR-NLCs displayed significantly higher and augmented concentrations in the brain. In this case, NLC and TR-NLC were 6.5- and 32.75-fold in their values of the brain uptake clearance compared to free drug.

Survival status and influencing factors of HIV/AIDS on highly active anti-retrovial therapy in Shandong province / 中华流行病学杂志

Objective: To understand the survival status and influencing factors for HIV/AIDS patients on highly active anti-retroviral therapy (HAART) in Shandong province. Methods: Both Kaplan-Meier (K-M) method and cumulative incidence function (CIF) were used to calculate the cumulative incidence of AIDS-related death respectively, and Fine-Gray model was used to identify the influencing factors related to survival time. Results: Through K-M method, a higher AIDS-related cumulated death rate than the CIF, was estimated. Among all the HIV/AIDS patients who initiated HAART from 2003 to 2015 in Shandong, 5 593 of them met the inclusion criteria. The cumulative incidence rate for AIDS-related death was 3.08% in 1 year, 4.21% in 3 years, 5.37% in 5 years, and 7.59% in 10 years respectively by CIF. Results from the F-G analysis showed that HIV/AIDS patients who were on HAART, the ones who had college degree or above (HR=0.40, 95%CI: 0.24-0.65) were less likely to die of AIDS-associated diseases. However, HIV/AIDS patients who were on HAART and living in the western areas of Shandong (HR=1.33, 95%CI: 1.01-1.89), diagnosed by medical institutions (HR=1.39, 95%CI: 1.06-1.80), started to receive care ≥1 year after diagnosis (HR=2.02, 95%CI: 1.30-3.15), their CD(4) cell count less than 200 cells/μl (HR=3.41, 95%CI: 2.59-4.59) at the time of diagnosis, with NVP in antiviral treatment (ART) regime (HR=1.36, 95%CI: 1.03-1.88), at Ⅲ/Ⅳ clinical stages (HR=2.61, 95%CI: 1.94-3.53) and CD(4) cell count less than 350 cells/μl (HR=5.48,95%CI: 2.32-12.72) at initiation of HAART ect., were more likely to die of AIDS-associated diseases. Conclusions: With the existence of competing risks, the cumulative incidence rate for AIDS-related death was overestimated by K-M, suggesting that competing risk models should be used in the survival analysis. Measures as early diagnoses followed by timely care and early HAART could end up with the reduction of AIDS-related death.

Survival status and influencing factors of HIV/AIDS on highly active anti-retrovial therapy in Shandong province / 中华流行病学杂志

Objective To understand the survival status and influencing factors for HIV/AIDS patients on highly active anti-retroviral therapy (HAART) in Shandong province.Methods Both Kaplan-Meier (K-M) method and cumulative incidence function (CIF) were used to calculate the cumulative incidence of AIDS-related death respectively,and Fine-Gray model was used to identify the influencing factors related to survival time.Results Through K-M method,a higher AIDS-related cumulated death rate than the CIF,was estimated.Among all the HIV/AIDS patients who initiated HAART from 2003 to 2015 in Shandong,5 593 of them met the inclusion criteria.The cumulative incidence rate for AIDS-related death was 3.08％ in 1 year,4.21％ in 3 years,5.37％ in 5 years,and 7.59％ in 10 years respectively by CIF.Results from the F-G analysis showed that HIV/AIDS patients who were on HAART,the ones who had college degree or above (HR=0.40,95％CI:0.24-0.65) were less likely to die of AIDS-associated diseases.However,HIV/AIDS patients who were on HAART and living in the western areas of Shandong (HR=1.33,95％CI:1.01-1.89),diagnosed by medical institutions (HR=1.39,95％CI:1.06-1.80),started to receive care ≥1 year after diagnosis (HR=2.02,95％CI:1.30-3.15),their CD,cell count less than 200 cells/μl (HR=3.41,95％CI:2.59-4.59) at the time of diagnosis,with NVP in antiviral treatment (ART) regime (HR=1.36,95％CI:1.03-1.88),at Ⅲ/Ⅳ clinical stages (HR=2.61,95％CI:1.94-3.53) and CD4 cell count less than 350 cells/μl (HR=5.48,95％CI:2.32-12.72) at initiation of HAART ect.,were more likely to die of AIDS-associated diseases.Conclusions With the existence of competing risks,the cumulative incidence rate for AIDS-related death was overestimated by K-M,suggesting that competing risk models should be used in the survival analysis.Measures as early diagnoses followed by timely care and early HAART could end up with the reduction of AIDS-related death.

Human Immunodeficiency Virus Infection: Does Highly Active Antiretroviral Therapy Influence Ear Nose Throat Manifestations?

To study the change in trend of ear, nose and throat (ENT) manifestations in patients who were on treatment, before and after availability of highly active antiretroviral therapy (HAART). To find out the prevalence of ENT manifestations in human immunodeficiency virus (HIV) infected people who were on treatment, in the year of 2004 (before the availability of HAART) and in 2014 (after the availability of HAART). Design A combination of a retrospective and prospective study. Setting Anti Retroviral Therapy (ART) Center at Our Hospital. Subjects Patients with HIV infection on ART. Methods Retrospective review of case records of the patients visiting the center in the year 2004 and prospective study of the patients visiting in the year 2014 was conducted. Sample size was calculated as 200 in each group based on 95% confidence and 96% power. Convenience sampling was used in our study. The prevalence of ENT manifestations in HIV patients were found to be 86% in 2004 and 93% in 2014. Among ENT manifestations oropharyngeal manifestations were most common. Lesser the CD4 count more was the prevalence of disorders in oropharynx. Our study showed a high prevalence of ENT manifestations in HIV patients who were on treatment, irrespective of the gap of 10 years and introduction of HAART therapy. Most common ENT manifestation both in 2004 and 2014 was oropharyngeal candidiasis. Lesser the CD4 count more was the prevalence of disorders in oropharynx.