Hypophosphatemic Osteomalacia Associated with Tenofovir: a Multidisciplinary Approach is Required.

Tenofovir is widely used as first-line treatment of HIV infection, although its use is sometimes complicated by a reversible proximal renal tubulopathy.We report the case of a 45-year-old woman with chronic HIV infection and personality disorder, who after 12 months of tenofovir, complained of fatigue, diffuse bone pain and gait disturbances. The elevated level of alkaline phosphatase, hypophosphatemia and inappropriate phosphaturia suggested the diagnosis of hypophosphatemic osteomalacia secondary to proximal renal tubulopathy. A dual-energy x-ray absorptiometry showed a bone mineral density below the expected range for age (lumbar spine Z-score -3.3, femoral neck Z-score -2.1). A whole body (99m)Tc-methylene diphosphonate bone scan showed multiple areas of increased focal activity in the lumbar and thoracic spine and in sacroiliac and hip joints consistent with pseudofractures. Two months after tenofovir discontinuation and administration of vitamin D and phosphate, osteomalacia-related symptoms disappeared. Eleven months later, bone and mineral metabolism data were normal and bone scintigraphy did not show any pathological findings.This report highlights the importance of considering the diagnosis of osteomalacia in patients treated with tenofovir and emphasizes the need for monitoring alkaline phosphatase, blood and urinary phosphate and creatinine, especially in patients with risk factors for bone disease.

Negative influence of HIV infection on day-night blood pressure variability.

OBJECTIVE: An attenuation of the physiological day-night blood pressure (BP) reduction is an important predictor of cardiovascular (CV) events and death. We compared circadian BP profile in treatment-naive HIV-infected patients and in healthy control subjects. METHODS: Fifty-two antiretroviral therapy-naive HIV-infected patients (85% men, age 39 ± 11 years, BP 125/78 ± 11/9 mm Hg) and 156 age- and BP-matched HIV-negative controls (85% men, age 39 ± 10 years, BP 125/78 ± 9/7 mm Hg) underwent 24-hour BP monitoring. Subjects with a nocturnal reduction of systolic BP <10% were defined as "nondippers." RESULTS: Nighttime BP was higher in HIV-infected subjects (113/69 ± 11/9 vs 109/67 ± 8/6 mm Hg, P = 0.008/0.005). Nocturnal systolic/diastolic BP reduction was 8.8/13.2% in HIV-positive patients and 11.7/17.2% in HIV negative (P = 0.002/0.001). The prevalence of "nondippers" was 35% and 15%, respectively (P = 0.003). In multivariate analysis, nocturnal systolic BP fall was negatively associated to HIV infection (ß = -0.22, P = 0.001). HIV viral load, low CD4 cell count, and AIDS progression risk were all related with a flattened day-night BP profile (P < 0.01). CONCLUSIONS: HIV infection per se negatively affects circadian BP rhythm. These findings, obtained in subjects without major CV risk factors and antiretroviral naive, suggest that day-night BP changes may play a role in the HIV-related increase in CV risk.

Cardiovascular risk assessment in antiretroviral-naïve HIV patients.

Various studies have been conducted to evaluate the role of antiretroviral therapy in the onset of cardiovascular risk among HIV-1-infected patients, while fewer data are available regarding antiretroviral-naïve patients. Our objective was to evaluate the cardiovascular risk among naïve subjects examining traditional risk factors, immunovirologic parameters, assessing the Framingham risk score (FRS), and detecting the presence of subclinical carotid lesions by means of color Doppler ultrasonography. One hundred seventy-two antiretroviral-naïve patients underwent color Doppler ultrasonography. An intima-media thickness (IMT) greater than 0.9 mm and/or atherosclerotic plaques were considered pathologic findings. Demographic, immunovirologic data, and risk factors for cardiovascular disease were collected. The 10-year probability of acute coronary events was assessed by the FRS. The statistical analysis was performed using t test and chi(2), Fisher's test, and conditional multiple logistic. Thirty-six patients (20.9%) had lesions at ultrasonographic investigation. The presence of lesions was significantly related to male gender (p = 0.005), age (p = 0.003), sedentary life (p = 0.05), Centers for Disease Control and Prevention (CDC) group C or CD4(+) less than 150 cells/mm(3), and viral load (VL) > 100,000 copies per milliliter (p = 0.04). The presence of subclinical carotid lesions showed a highly significant direct association with the estimated FRS (p < 0.002). The presence of subclinical atheromasic lesion results was also high among antiretroviral-naïve patients. FRS is highly predictive of the lesions, but also an advanced stage of disease plays a significant role. Our data support the hypothesis that HIV infection per se is a risk factor for atherosclerosis. We recommend an ultrasonographic assessment both among patients with FRS 6% or more and among those in advanced stage of disease.

Fusobacterium nucleatum endocarditis mimicking polymyalgia rheumatica.

A case of Fusobacterium nucleatum endocarditis in an 80-year-old man is reported. The patient presented with a headache and nonspecific musculoskeletal symptoms and was misdiagnosed as having polymyalgia rheumatica. The diagnosis of bacterial endocarditis was delayed because of an insidious presentation, typical in infections with low virulence micro-organisms. The musculoskeletal symptoms, unresponsive to protracted corticosteroids, completely resolved with intravenous ampicillin treatment. Rheumatologic symptoms may hinder the correct diagnosis of subacute infective endocarditis. An atypical evolution of a common rheumatic disorder such as polymyalgia rheumatica should alert physicians to the possibility of bacterial endocarditis.

Identifying HIV patients with an unfavorable cardiovascular risk profile in the clinical practice: results from the SIMONE study.

OBJECTIVE: To identify and characterize HIV-infected patients at higher cardiovascular risk in ordinary clinical settings. DESIGN: Multicenter, nationwide cross-sectional study. METHODS: Consecutive HIV-patients, attending scheduled visits at facilities involved in the Italian coordination group for the study of allergies and HIV infection (CISAI), were included between February and April, 2005. Their 10-year probability of acute coronary events was calculated using the Framingham Risk Score (FRS) as well as 3 other cardiovascular algorithms ("PROCAM", "PROGETTO CUORE", "SCORE"); Metabolic Syndrome (MS) was diagnosed according to the National Cholesterol Education Program definitions. An estimated 10-year CVD >or=10% and/or MS led to the diagnosis of high CV risk. We compared selected clinical features between high- and low-risk patients. RESULTS: A total of 1230 HIV infected patients (72% males, mean age of 43+/-9 years), 185 of whom treatment-naive, were evaluated. FRS gave the highest estimate of CV risk. The mean 10-year risk for acute coronary events according to FRS was 7.4+/-7.0. MS was present in 22% of the observed patients. Accordingly, 443 patients (36%) were classified at high risk. Twelve percent of the patients (n=142) had both a FRS >or=10% and a diagnosis of MS. The main single predictor of increased cardiovascular risk was smoking (60% of whole sample). A higher prevalence of clinically evident lipodystrophy and a higher CD4 T-cell counts were found both in patients with higher FRS and in patients with high FRS and MS (both p<0.001). CONCLUSIONS: The worst estimation of CV risk was obtained with the FRS algorithm. Clinical evidence of lipodystrophy and higher CD4 T-cell counts were closely associated to a worse cardiovascular risk profile.

Cholesterol levels in HIV-HCV infected patients treated with lopinavir/r: results from the SCOLTA project.

BACKGROUND: It is not known whether antiretroviral therapy (ART) including lopinavir/r has a different effect on the lipid metabolism in HIV patients co-infected with HCV. This study investigated changes in lipid levels, comparing patients with HIV infection alone and those with HCV too, in the lopinavir/r cohort of the SCOLTA project. METHODS: We analyzed the data for the lopinavir/r nationwide cohort from 25 Italian infectious disease departments, which comprises 743 HIV-infected patients followed prospectively, comparing subjects with HIV-HCV co-infection and those with single-infection. RESULTS: At enrolment, co-infected patients had significantly lower mean cholesterol than HCV negative cases (162+/-43mg/dL vs. 185+/-52mg/dL, p=0.0009). Total and non-HDL cholesterol and triglycerides rose significantly from baseline in HIV single-infection patients, but not in those with co-infection. The patients with dual HIV-HCV infection, treated with an ART regimen including lopinavir/r, have only limited increases in total and non-HDL cholesterol and triglycerides. CONCLUSIONS: Changes in serum lipids in co-infected patients differed significantly from those in patients without HCV. It remains to be seen whether this is associated with a lower risk of progression of atherosclerotic disease.

Is estimated cardiovascular risk higher in HIV-infected patients than in the general population?

Cardiovascular disease (CVD) is an increasing concern for human immunodeficiency virus (HIV)-infected patients, and risk assessment is recommended in routine HIV care. The absolute cardiovascular risk in an individual is determined by several factors, and various algorithms may be applied. To date, few comparisons of HIV patients with persons of the same age from the general population have been conducted. We hypothesized that the calculated risk of CVD may be increased in HIV patients. The probability for acute coronary events within 10 y (Framingham Risk Score) and the probability for fatal cardiovascular disease (SCORE algorithm) were assessed in 403 consecutive HIV-positive subjects free from overt cardiovascular disease, as well as in 96 age- and gender-matched control subjects drawn from the general population living in the same geographical area. The average 10-y risk for acute coronary events (Framingham Risk Score) was 7.0%+/-5% in HIV subjects and 6.3%+/-5% in the control group (p =0.32). The 10-y estimated risk for cardiovascular mortality (SCORE algorithm) was 1.23%+/-2.3% and 0.83%+/-0.9%, respectively (p =0.01). The main contributor to the increased CVD risk was the high proportion of smokers, but not an increase in cholesterol level. In conclusion, a limited increase in estimated risk of CVD was found in HIV-infected patients compared to the general population. In HIV-infected individuals other factors of less value in the general population and not included in any cardiovascular algorithm might be important. In our patients intervention to modify traditional risk factors should be addressed primarily towards modifying smoking habits.