Problem In HIV-infected Patients Research Articles

CME: Dyslipidämie und kardiovaskuläres Risiko bei HIV-infizierten Patienten CME-Fragen

CME: Dyslipidemia and Cardiovascular Risk in HIV Infected Patients Abstract. Dyslipidemia is a common problem in HIV-infected patients and can contribute to an elevated cardiovascular risk among this patient group. An untreated HIV infection as well as certain antiretroviral drugs can lead to an unfavorable change of the lipid profile. This article describes the diagnosis, work up and treatment of dyslipidemia in HIV-infected patients.

Common dermatological conditions in the HIV patient

The introduction of antiretroviral medication has changed the epidemiology, morbidity and mortality of HIV disease. Nevertheless, cutaneous disorders due to HIV infection remain a major problem in HIV-infected patients. These disorders are mainly infections, inflammatory and neoplastic in origin. Some of these disorders occur at normal CD4 cell counts, while others occur typically at low CD4 cell counts. Clinicians should be aware of various presentations of these disorders and their treatment as they can impact negatively on patient’s quality of life

Non-AIDS defining bacterial infections in patients with HIV infection

The use of effective combinated antiretroviral therapy has significantly improved the prognosis of patients with HIV infection. Although current antiretroviral regimens are very effective in inhibiting viral replication, its elimination is not a viable goal of treatment. Despite cART, non–AIDS-defining bacterial infections are still a serious problem. The spectrum of these infections, and in particular the proportion of particular bacterial pathogens, is not sufficiently described in the scientific literature. In the study, HIV-infected patients followed at the HIV Out-Patient Clinic in Warsaw were registered in the clinic from 1 January 2007 to 31 July 2016. Survival analysis included 558 patients who met the study criteria. Among 251 (44.9%) of those with positive culture, the most common bacterial pathogen was Staphylococcus aureus (33%) and Escherichia coli (11.1%). The most common bacteria in the upper respiratory tract was Staphylococcus aureus (26.6%). In urine cultures the most common bacteria was Escherichia coli (9.5%). Staphylococcus aureus (2.3%) and Staphylococcus epidermidis (2.3%) were the most common bacterial cultures in the wound. In skin cultures the most common bacteria was Staphylococcus aureus (3.9%). The highest number of positive cultures was obtained from the upper respiratory tract -166 (66.1%). Non–AIDS-defining bacterial infections are a common clinical problem in HIV-infected patients despite the introduction of antiretroviral therapy and the pathogens that cause these infections are a very diverse group.

A SIV molecular clone that targets the CNS and induces neuroAIDS in rhesus macaques.

Despite effective control of plasma viremia with the use of combination antiretroviral therapies (cART), minor cognitive and motor disorders (MCMD) persist as a significant clinical problem in HIV-infected patients. Non-human primate models are therefore required to study mechanisms of disease progression in the central nervous system (CNS). We isolated a strain of simian immunodeficiency virus (SIV), SIVsm804E, which induces neuroAIDS in a high proportion of rhesus macaques and identified enhanced antagonism of the host innate factor BST-2 as an important factor in the macrophage tropism and initial neuro-invasion of this isolate. In the present study, we further developed this model by deriving a molecular clone SIVsm804E-CL757 (CL757). This clone induced neurological disorders in high frequencies but without rapid disease progression and thus is more reflective of the tempo of neuroAIDS in HIV-infection. NeuroAIDS was also induced in macaques co-inoculated with CL757 and the parental AIDS-inducing, but non-neurovirulent SIVsmE543-3 (E543-3). Molecular analysis of macaques infected with CL757 revealed compartmentalization of virus populations between the CNS and the periphery. CL757 exclusively targeted the CNS whereas E543-3 was restricted to the periphery consistent with a role for viral determinants in the mechanisms of neuroinvasion. CL757 would be a useful model to investigate disease progression in the CNS and as a model to study virus reservoirs in the CNS.

Anal chromoendoscopy using gastroenterological video-endoscopes: A new method to perform high resolution anoscopy for diagnosing intraepithelial neoplasia and analcarcinoma in HIV-infected patients.

Introduction Anal carcinoma represents an increasing problem in HIV-infected patients. Anal intraepithelial neoplasia (AIN), the precursor lesion, is currently diagnosed by high-resolution anoscopy (HRA) using optical magnification derived from gynecological colposcopy. This prospective study evaluates anal chromoendoscopy (ACE) using standard gastroenterological video-endoscopes in diagnosing AIN. Methods After clinical examination, proctoscopy and surface staining with acetic acid followed by Lugol's solution, ACE was performed with a mucosectomy cap on the tip of the endoscope. Biopsy specimens were collected from areas with a pathological staining pattern and from areas with normal appearance; combined results were considered as reference. Results Two hundred eleven HIV-positive patients seen between 2007 and 2013 were evaluated. Of these, 95.7 % were males, and the median age was 45 years. In 86.7 %, the mode of HIV transmission was sex among males. Combination antiretroviral treatment was applied in 75.8 %. The sensitivity of ACE in diagnosing AIN was 0.85, the specificity was 0.55, the positive predictive value was 0.50, and the negative predictive value (NPV) was 0.87. Diagnostic performance increased in individuals with high-grade lesions (NPV: 0.99) and in the second study period from 2011 to 2013. Side effects were rare and of minor clinical relevance. Conclusions Anal chromoendoscopy is safe and effective in diagnosing AIN in a population of HIV-infected patients. It is particularly useful for the exclusion of high-grade lesions that have the strongest risk of progression to anal carcinoma. Therefore, ACE may become a valuable new tool to manage AIN and to prevent anal malignancy in HIV-positive patients.

High prevalence of signs of renal damage despite normal renal function in a cohort of HIV-infected patients: evaluation of associated factors.

Renal disorders are an emerging problem in HIV-infected patients. We performed a cross-sectional study of the first 1000 HIV-infected patients attended at our HIV unit who agreed to participate. We determined the frequency of renal alterations and its related risk factors. Summary statistics and logistic regression were applied. The study sample comprised 970 patients with complete data. Most were white (94%) and men (76%). Median (IQR) age was 48 (42-53) years. Hypertension was diagnosed in 19%, dyslipidemia in 27%, and diabetes mellitus in 3%. According to the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation, 29 patients (3%) had an eGFR<60 ml/min/1.73 m(2); 18 of them (62%) presented altered albumin/creatinine and protein/creatinine (UPC or UAC) ratios. Of the patients with eGFR>60 mL/min, it was present in 293 (30%), 38 of whom (7.1%) had UPC>300 mg/g. Increased risk of renal abnormalities was correlated with hypertension (OR, 1.821 [95%CI, 1.292;2.564]; p=0.001), age (OR, 1.015 [95%CI, 1.001;1.030], per one year; p=0.040), and use of tenofovir disoproxil fumarate (TDF) plus protease inhibitor (PI), (OR, 1.401 [95%CI, 1.078;1.821]; p=0.012). Current CD4 cell count was a protective factor (OR, 0.9995 [95%CI, 0.9991;0.9999], per one cell; p=0.035). A considerable proportion of patients presented altered UPC or UAC ratios, despite having an eGFR>60 mL/min. CD4 cell count was a protective factor; age, hypertension, and use of TDF plus PIs were risk factors for renal abnormalities. Based on our results, screen of renal abnormalities should be considered in all HIV-infected patients to detect these alterations early.

Evidence-based Screening for Low Bone Mineral Density in HIV-infected Men

Low bone mineral density, which leads to osteoporosis and fracture risk, is an emerging clinical problem in HIV-infected patients. Our evidence-based practice project screened a convenience sample of 225 HIV-infected men for low bone mineral density using the Osteoporosis Self-Assessment Tool, and of those men, 173 were also screened by quantitative ultrasound of the calcaneus. One hundred twelve men had low bone mineral density by either or both screening methods. Seventy-one of these 112 men were tested by dual-energy x-ray absorptiometry and 73% had low bone mineral density. The positive protective value of the Osteoporosis Self-Assessment Tool was 73% and for quantitative ultrasound was 88%. These results suggest that routine low bone mineral density screening should be included as standard practice for all HIV-infected patients.

Impact of HIV Infection on Colorectal Tumors

Non-AIDS defining cancer has recently become a major problem in HIV-infected patients. Little has been reported on whether HIV infection is a risk factor for colorectal adenoma, especially in Asians. The study was conducted under a prospective cross-sectional design and included all adults who underwent colonoscopy. Subjects were matched by age and sex to compare the prevalence of colorectal adenoma, adenocarcinoma, polyps, and other tumors. Detailed risk factors were assessed, including lifestyle habits, medications, comorbidities, gastrointestinal symptom rating scale, HIV-associated factors, and human papillomavirus infection. To evaluate the effects of HIV infection on adenoma, the odds ratio (OR) was estimated by multivariate logistic regression. A total of 177 HIV-infected patients and 177 controls were selected for analysis. No significant difference was noted in the prevalence of adenoma (n = 29 vs. 40, P = 0.14). Multivariate analysis adjusted by baseline demographics and risk factors showed that HIV is not associated with increased risk of adenoma (adjusted OR = 0.66, P = 0.16). Kaposi's sarcoma was more common in HIV-infected patients (n = 6 vs. 0, P = 0.03). Among HIV-infected patients, advanced age was an independent and significant risk factor for adenoma (adjusted OR = 2.28, P < 0.01). CD4 count, HIV-RNA, history of antiretroviral treatment, and oncogenic human papillomavirus infection were not risk factors for adenoma. HIV infection was not identified as risk for adenoma in Asian patients. However, advanced age was independently associated with increased risk of adenoma. HIV-infected patients should not miss screening opportunity for colorectal adenoma and other gastrointestinal malignancies.

ST106 Macrophage targeted therapy for AIDS

Background: HIV associated neurocognitive disease (HAND) involves ongoing migration of blood associated monocytes into areas of disease. The migrant CD163 expressing macrophages implicated in HAND have recently been implicated in HIV associated atherosclerosis a growing problem in HIV infected patients including those with HAND. We describe a novel approach to AIDS related macrophage diseases using PA300 (MGBG; methylglyoxal bis(guanylhydrazone) dihydrochloride monohydrate), a formulated oral polyamine biosynthesis regulator (Pathologica, LLC, Burlingame CA). Methods: PA300 was evaluated for dose dependent responses in a) in vitro macrophage culture systems and b) a rhesus model of SIV encephalopathy. Results: PA300 blocked induction of monocyte differentiation into polarized macrophages, blocked HIV infection of macrophages and killed exposed HIV infected macrophages in vitro. (ED80: 0.3-1uM). Eight rhesus macaques were SIV-infected and CD8+ T lymphocyte depleted. At 21 days post-infection, a time when CNS disease would be apparent, animals were given PA300 (3mg/kg; n=2, 10mg/kg; n=2; 30mg/kg; n=2) or vehicle control (n=2). After one month of treatment: No evidence for CNS infection, macrophage infiltration or brain pathology was observed at the highest dose with intermediate efficacy at lower doses. SIV associated myocarditis was also reversed. Blood CD14+ cells showed no detectible SIV DNA at intermediate and high doses of PA300. Summary: PA300 is a novel macrophage differentiation regulator with additional activity against HIV infected macrophages. Treatment of macaques with SIV associated encephalopathy and myocarditis resulted in disease reversal and loss of infected macrophages in the brain and blood.

Incidence, Medical and Socio-Behavioural Predictors of Psychiatric Events in An 11-Year Follow-Up of HIV-Infected Patients on Antiretroviral Therapy

Psychiatric disorders are relatively common among HIV-infected patients. However, there are few studies about their potential risk factors. This analysis aimed to measure the incidence of severe psychiatric events (PE) among patients receiving combination antiretroviral therapy (cART) of the French APROCO-COPILOTE (ANRS CO8) cohort, and to identify the medical and socio-behavioural correlates of their first episode of depression, suicide or suicide attempt (D/S/SA). APROCO-COPILOTE is a cohort of patients started on a protease inhibitor regimen between 1997 and 1999, with prospective medical standardized records and self-administered questionnaires collecting socio-demographic and socio-behavioural data. This analysis included all 11-year follow-up visits for 1,095 patients having completed baseline self-administered questionnaires. A proportional hazard Cox model was used to identify the correlates of a first D/S/SA event. The overall prevalence of severe PE remained low: 50 patients experienced 67 events (incidence rate [95% CI] =1.04 [0.82, 1.32] per 100 person-years). Depression (n=16), suicides (n=5) and suicide attempts (n=14) were the most frequently diagnosed PE (0.54 [0.39, 0.76] per 100 person-years) among 25 patients. Multivariate results showed that unemployment, unstable housing, detectable viral load and smoking more than 20 cigarettes/day were independently associated with D/S/SA. Although the incidence of severe PE remained relatively low among the patients of APROCO-COPILOTE cohort, this study's results underline a clinically important problem in HIV-infected patients receiving cART. Furthermore, our findings not only emphasize the importance of comprehensive care, especially for socially vulnerable patients, but may also help future studies designed to assess the effectiveness of interventions in reducing the risk of PE during cART.

Liver disease, HIV and aging.

The life expectancy of HIV-infected patients has increased due to the efficacy of highly active antiretroviral therapy (HAART) in controlling HIV replication; thus, the population living with HIV infection is steadily aging. Liver-related morbidity and mortality has emerged as a leading problem in HIV-infected patients. Since aging, HIV infection and HAART all affect the liver, understanding the impact of the combination of these factors on liver disease is crucial for optimisation of care in the aging HIV-infected population. This review will focus on the current understanding of liver disease in older (>50 years old) HIV-negative individuals and in HIV-infected individuals. Areas for future research in the area of HIV, liver disease and aging will also be discussed.

Tuberculous meningitis in HIV-infected patients in Brazil: clinical and laboratory characteristics and factors associated with mortality

Tuberculous meningitis (TBM) is a growing problem in HIV-infected patients in developing countries, where there is scarce data about this co-infection. Our objectives were to analyze the main features and outcomes of HIV-infected patients with TBM. This was a retrospective study of HIV-infected Brazilian patients admitted consecutively for TBM. All patients had Mycobacterium tuberculosis isolated from the cerebrospinal fluid (CSF). Presenting clinical and laboratory features were studied. Multivariate analysis was used to identify variables associated with death during hospitalization and at 9 months after diagnosis. Survival was estimated using the Kaplan-Meier method. We included 108 cases (median age 36 years, 72% male). Only 15% had fever, headache, and meningeal signs simultaneously. Forty-eight percent had extrameningeal tuberculosis. The median CD4+ cell count was 65 cells/microl. Among 90 cases, 7% had primary resistance to isoniazid and 9% presented multidrug-resistant strains. The overall mortality during hospitalization was 29% and at 9 months was 41%. Tachycardia and prior highly active antiretroviral therapy (HAART) were associated with 9-month mortality. The 9-month survival rate was 22% (95% confidence interval 12-43%). Clinical and laboratory manifestations were unspecific. Disseminated tuberculosis and severe immunosuppression were common. Mortality was high and the 9-month survival rate was low. Tachycardia and prior HAART were associated with death within 9 months of diagnosis.

Efficacy and safety of darunavir and etravirine in a patient with retroviruses and multiple virologic failure

Drug resistance to antiretroviral regimen is a challenging problem in HIV-infected patients. We describe a case of a 45-year-old Caucasian male that, after failure of several successive antiretroviral regimens, has been successfully treated with a combination of darunavir, a protease inhibitor, and etravirine, a non-nucleoside reverse transcriptase inhibitor. This case report underlines the difficulties of everyday management of HIV-infected patients and the importance of an early identification of resistances and the individualization of the therapy

Age and height predict neuropathy risk in patients with HIV prescribed stavudine

Sensory neuropathy is a common problem in HIV-infected patients and is the dose-limiting toxicity of stavudine. Affordable methods of predicting neuropathy risk are needed to guide prescribing in countries where some use of stavudine remains an economic necessity. We therefore aimed to identify factors predictive of neuropathy risk before antiretroviral use. A total of 294 patients attending clinics in Melbourne, Kuala Lumpur, and Jakarta were enrolled in a cross-sectional neuropathy screening program in 2006. Neuropathy was defined by the presence of symptoms and signs on the AIDS Clinical Trials Group Brief Peripheral Neuropathy Screen. Demographic, laboratory, and treatment details were considered as possible risk factors for neuropathy. The role of patient demographics in predicting stavudine neuropathy were then assessed in 181 patients who reported that they were free of neuropathy symptoms when first prescribed this drug. The prevalence of neuropathy was 42% in Melbourne (n = 100), 19% in Kuala Lumpur (n = 98), and 34% in Jakarta (n = 96). In addition to treatment exposures, increasing age (p = 0.002) and height (p = 0.001) were independently associated with neuropathy. Age and height cutoffs of > or=170 cm or > or =40 years predicted neuropathy. Among 181 patients who were asymptomatic before stavudine exposure, the risk of neuropathy following stavudine was 20% in younger, shorter patients, compared with 66% in older, taller individuals. Stavudine neuropathy risk increases with patient age and height. Prioritizing older and taller patients for alternative agents would be an inexpensive strategy to reduce neuropathy rates in countries where the burden of HIV disease limits treatment options.

Gastroenteropancreatic Neuroendocrine Tumors in Patients With HIV Infection: A Trans-Atlantic Series

BackgroundNon-AIDS–defining cancers are an important problem in HIV-infected patients. The occurrence of neuroendocrine (NE) tumors in sites other than the lung and skin has not been well characterized in the setting of concurrent HIV infection. MethodsHIV-positive patients with biopsy-confirmed NE tumors localized to the gastrointestinal tract were identified based on the personal archives of the authors. A retrospective chart review was performed, and data regarding demographics, HIV status, presenting symptoms and signs, diagnostic work-up, therapeutic interventions, and outcome were extracted. ResultsWe identified 4 adult patients, mean age 42 years (range: 37–47) infected with HIV, who developed NE tumors originating in their gastrointestinal tact. They had only moderate immunosuppression with a median CD4+ count of 497 cells/mm3 (range: 182–1100) and chronic HIV infection (2–15 years duration). Symptoms at presentation were nonspecific, including abdominal pain, diarrhea, weight loss, and rectal bleeding. A specialized diagnostic work-up was required, including serum chromogranin and urinary 5-hydroxyindoleacetic acid levels, colonoscopy, radioactive isotope scans, and the demonstration of NE differentiation in procured pathologic material. The spectrum of tumors ranged from benign (typical carcinoid) to highly aggressive neoplasms (NE carcinoma). Treatment with octreotide, surgical resection, or systemic chemotherapy provided effective symptomatic relief and was associated with a favorable outcome, despite metastases in 2 patients. ConclusionsThese cases serve to broaden the spectrum of neoplasms that may be encountered in the current HIV era, and illustrate the difficulty in establishing the diagnosis of NE tumors in the context of HIV infection.

Factors associated with tuberculosis treatment default among HIV-infected tuberculosis patients in Thailand

Ensuring completion of tuberculosis (TB) treatment remains a major public health problem. In HIV-infected patients, TB is the most common severe opportunistic infection. Few studies have evaluated risk factors for TB treatment default in HIV-infected patients. We conducted a prospective, observational study of HIV-infected TB patients in Thailand. Patients underwent standardised evaluations at the beginning of TB treatment, at the end of the intensive phase and at the end of TB treatment. TB treatment outcomes were assessed according to WHO guidelines. The analysis was limited to patients who defaulted or who had treatment success. Of the 554 patients analysed, 61 (11%) defaulted. In multivariate analysis, factors associated with TB treatment default included incarceration history [adjusted odds ratio (AOR) 2.0, 95% CI 1.1-3.7), smoking (AOR 2.3, 95% CI 1.3-4.1) and having a symptom complaint score >15 (AOR 3.4, 95% CI 1.4-8.0); one marker of wealth, namely owning a refrigerator, was protective (AOR 0.4, 95% CI 0.2-0.8). Default during TB treatment was a significant problem in HIV-infected patients. Reducing default may require enhancing services for patients with a history of incarceration or smoking and designing patient-centred systems to address poverty and patient wellness.

Candida infection in HIV positive patients 1985–2007

Infection with Candida species remains a major problem in HIV infected patients. The analysis of over 15,000 hospitalisations (1985-2007) in the AVK cohort shows an increasing incidence of non-albicans species in candida esophagitis. Although our analysis shows a decreasing incidence of opportunistic infections like PCP, cerebral toxoplasmosis and others since the introduction of highly active antiretroviral therapy the incidence of candida esophagitis remains as high as in the years before the HAART era. This observation might reflect the development of resistance against fluconazole and the selection of non-albicans species as a consequence of a long-term prophylactic treatment of HIV+ patients over years.

Prevalence and Impact of Diarrhea on Health-related Quality of Life in HIV-infected Patients in the Era of Highly Active Antiretroviral Therapy

Before the introduction of highly active antiretroviral therapy (HAART), the majority of HIV-infected patients experienced diarrhea. The aims of this study were to compare the prevalence of diarrhea among HIV-infected and uninfected patients in the HAART era, and to evaluate the impact of diarrhea on health-related quality of life (HRQOL). Diarrheal symptoms experienced by 163 consecutive HIV-infected patients and 253 HIV-seronegative control subjects were ascertained using a validated questionnaire. The HRQOL of these patients was assessed using the Medical Outcomes Study (MOS) SF-36 and MOS-HIV Health surveys. Among the 163 HIV-infected patients, the median CD4 cell count was 370 cells/mm and 150 individuals were taking HAART. Significantly, more HIV-infected subjects reported having 3 or more bowel movements daily within the past 7 days than did HIV-seronegative subjects (28.2% vs. 7.1%, P<0.001), even after adjusting for potential confounding variables (odds ratios=6.65; 95% confidence intervals, 3.36-13.17). In addition, diarrhea was significantly more common in HIV-infected patients than in control subjects when assessed by several other criteria. HIV-infected patients reported significantly worse HRQOL across all domains of the MOS SF-36 as compared with control subjects. Among HIV-infected patients, individuals with diarrhea had significantly worse HRQOL in nearly all domains of the MOS-HIV as compared with those without diarrhea. Diarrhea remains an important clinical problem in HIV-infected patients and is associated with significant impairments in HRQOL. It is important that healthcare providers specifically evaluate their HIV-infected patients for diarrhea so that these symptoms may be optimally managed.

Prevalence of Dilated Cardiomyopathy in HIV-Infected African Patients Not Receiving HAART: A Multicenter, Observational, Prospective, Cohort Study in Rwanda

Several studies performed before the introduction of highly active antiretroviral therapy (HAART) have shown that HIV-1 infection is an important cause of dilated cardiomyopathy. However, factors associated with the development of HIV-associated cardiomyopathy in developing countries are still debated. To assess the prevalence of dilated cardiomyopathy, diagnosed by echocardiography, in HIV-infected Rwandese patients not receiving HAART and the risk factors associated with its development. A sample of 416 HIV-infected african patients, without a previous definite history of cardiovascular disease, attending University hospitals in Rwanda, from January to December 2005, were included in a multicenter, observational, prospective, cohort study, with the collaboration of two European Clinical Centers (in France and in Italy). Clinical and laboratory tests along with echocardiographic examination were performed in all patients included in the study. Out of 416 patients included in the study, dilated cardiomyopathy was documented by echocardiography in 71 (17.7%). By both univariate and multivariate analysis, low socio-economic status, estimated duration of HIV-1 infection, CD4 count, HIV-1 viral load, CDC stage B and C of HIV disease and low plasmatic level of selenium were factors significantly associated with the development of cardiomyopathy. Alcohol consumption and smoking were factors associated with the development of cardiomyopathy only by univariate analysis. HIV-associated cardiomyopathy is a significant clinical problem in HIV-infected patients not receiving HAART in Rwanda. Early tracking of cardiomyopathy in African HIV-infected patients is therefore recommended. Before administering HAART, clinicians should be aware of a possible existing cardiomyopathy to ensure appropriate, comprehensive, and rational patient care.

Dramatic interaction between levothyroxine and lopinavir/ritonavir in a HIV-infected patient

Dramatic interaction between levothyroxine and lopinavir/ritonavir in a HIV-infected patient