Evaluation of NucliSens-AmpliScreen methodology to detect subtypes G of HIV-1 and 4c/4d of HCV in the screening of blood donors.

BACKGROUND AND OBJECTIVES: Albeit, the NucliSens Extractor combined with the Ampliscreen was validated for application in NAT minipool screening, a study to evaluate the reliability of the procedure in relation to subtypes G of human immunodeficiency virus (HIV)-1 RNA and 4c/4d of hepatitis C virus (HCV) RNA should be performed, due to their genetic differences and the high frequency in our country. STUDY DESIGN: Samples from patients infected with subtypes G of HIV-1 RNA and 4c/4d of HCV RNA were diluted with negative plasma and tested eight times for each concentration. For nucleic acid extraction we used an automated silica-based extraction method (NucliSens Extractor) and for amplification and detection the AmpliScreen HIV-1 version 1.5 and AmpliScreen HCV version 2.0 (Roche Diagnostic Systems) were applied. RESULTS: The sensitivity for HIV-1 RNA genotype G using the NucliSens-AmpliScreen method-95% detection limit (95% CI) of 25 (18-50) copies per ml-is comparable with those described for genotypes B and E and to that obtained by the Multiprep procedure. In the case of HCV, the sensitivity of the method was also similar, when we compared the detection limits obtained for genotype 4c/4d-95% detection limit (95% CI) of 34 (24-71) IU/ml-with the genotype 1 published. CONCLUSIONS: The data presented here suggest that these infections will not be missed because of genetic variation, as the platform exhibited similar limits of detection for the subtypes evaluated, meeting the sensitivity requirements set by the regulatory bodies.

Dendritic changes in the hippocampal formation of AIDS patients: a quantitative Golgi study.

We have previously shown that in the hippocampal formation of patients with acquired immunodeficiency syndrome (AIDS) there is neuronal atrophy, without cell loss. Because reductions in neuronal size are suggestive of associated neuritic alterations, we decided to study the dendritic trees of the main neuronal populations in the hippocampal formation. Material was obtained in five male AIDS patients and five male controls. After Golgi impregnation, the dendritic arborizations of dentate granule and hilar basket cells, and of CA3 and CA1 pyramidal cells, were hand traced, and their segments classified, counted and measured. We found an impoverishment of the dendritic trees in all neuronal populations in the AIDS group, which was more striking in the hilus and CA3 field. Specifically, hilar neurons had fewer dendritic segments, and reduced branching density and dendritic extent; in CA3 pyramids there was a decrease in the number of terminal segments in the basal trees, and a reduction in the total number of segments, number of medium order terminals, dendritic branching density and dendritic extent in the apical trees. In CA1 pyramids, the terminals were shorter in the apical trees and the dendritic spine density decreased in the basal trees, whereas in granule cells only the dendritic spine density was reduced in AIDS patients. Subtle signs suggestive of dendritic reorganization were observed. These results point to a regional vulnerability of the hippocampal formation to HIV infection, and might contribute to explaining the occurrence of dementia, as a consequence of overall reduction in the hippocampal neuronal receptive surface.

AIDS does not alter the total number of neurons in the hippocampal formation but induces cell atrophy: a stereological study.

Although cognitive dysfunction is a common finding in patients with acquired immunodeficiency syndrome (AIDS) its pathogenesis remains controversial. Given the involvement of the hippocampal formation in the processing of cognitive information and the scarcity of quantitative studies in this brain region, we have examined, using stereological methods, the hippocampal formations of AIDS patients. The study was performed in ten AIDS patients and ten age-matched controls. All cases were male. The Principle of Cavalieri was applied to estimate the volume of the layers of the dentate gyrus and of the CA3 and CA1 hippocampal fields. The fractionator and the nucleator were used as estimators of the total number, and mean somatic and nuclear volumes of the neurons in the cell-containing layers of all hippocampal subdivisions. No cell death was detected in AIDS patients but the global volume of their hippocampal formations was significantly decreased due to the reduced volume of its layers, mainly the cell-containing layers. Furthermore, the somatic and nuclear volumes of the neurons in the hippocampal formation were significantly decreased in AIDS patients. No correlation was found between the estimates obtained and the presence or absence of neurological involvement. Our results show that neurons in the hippocampal formation of AIDS patients display marked morphological changes, despite the maintenance of their total number. These alterations are likely to lead to dysfunction of the hippocampal circuitries and, thus, might contribute to explaining the dementia features which occur in this condition.

Pericardial involvement in human immunodeficiency virus infection.

STUDY OBJECTIVES: Previous studies have showed that the pericardium is frequently involved in HIV infection. However, the characteristics and etiology of the pericardial abnormalities that have been found remained poorly defined. We analyzed the features of pericardial involvement in these patients and investigated the clinical variables associated with moderate and severe effusions. DESIGN: Prospective, clinical, and echocardiographic study. SETTING: The service of infectious diseases of a university hospital. PATIENTS: 181 consecutive patients at all stages of HIV infection. RESULTS: Only one patient (0.55%) had acute pericarditis. Seventy-five patients (41%) had an asymptomatic pericardial effusion; in 23 patients (13% of all patients), the effusion was either moderate or severe. Ten cases (5.5% of all patients) of moderate or severe effusions resulted in right atrium diastolic compression, and three of these cases (1.6% of all patients) required pericardiocentesis for the management of tamponade. Six patients (3%) presented with echogenic pericardial masses of undetermined etiology. A moderate or severe effusion was present in a greater number of patients with symptomatic HIV infection than was present in asymptomatic HIV-infected patients, respectively: 17 vs 2% (p = 0.015). The following are variables independently associated with moderate or severe pericardial effusions: heart failure (odds ratio, 20.3; p = 0.0001); Kaposi's sarcoma (odds ratio, 8.6; p = 0.01), tuberculosis (TB; odds ratio, 47.2; p = 0.0006); and other pulmonary infections (odds ratio,15.0; p = 0.02). CONCLUSIONS: Most of these moderate or severe effusions are clinically unsuspected, but they can lead to life-threatening tamponade. This fact seems to justify echocardiographic surveillance in HIV-infected patients, especially in those with heart failure, Kaposi's sarcoma, TB, or other pulmonary infections.

Predictors of myocardial dysfunction in human immunodeficiency virus-infected patients.

BACKGROUND: Some of the most frequent manifestations of heart involvement in human immunodeficiency virus (HIV) infection include right and left ventricular dysfunction. The pathogenesis remains obscure. METHODS AND RESULTS: This prospective clinical and echocardiographic study involved 181 patients at all stages of HIV infection. We tested a set of clinical variables using a backward logistic regression model to assess their ability to independently predict the presence of ventricular dysfunction. The presence of pulmonary infections (all etiologies mixed) was the only variable independently associated with isolated right ventricular dysfunction (odds ratio = 4.08; P = .02). Signs suggestive of pulmonary arterial hypertension were present in 71% of the patients with right ventricular dilation. History of previous opportunistic infections (all etiologies mixed) (odds ratio = 10.9; P = .0026) and time since the diagnosis of acquired immunodeficiency syndrome more than 12 months (odds ratio = 6.6; P = .03) were the only two independent predictors of left ventricular dysfunction. CONCLUSIONS: Isolated right ventricular dysfunction may be secondary to pulmonary hypertension caused by repetitive pulmonary infections and not to primary myocardial disease. The aggressive treatment of opportunistic infections may become an important element of heart failure prophylaxis in HIV infection because they may be associated with left ventricular dysfunction.

Left ventricular dysfunction in human immunodeficiency virus (HIV)-infected patients.

We evaluated left ventricular function by echocardiography in a prospective study that included 98 consecutive human immunodeficiency virus (HIV)-infected patients and 40 HIV-seronegative normal controls. When compared with controls, HIV patients showed increased isovolumic relaxation time (101+/-18 ms versus 71+/-10 ms; p<0.0001) and left ventricular diastolic diameters (51+/-6 mm versus 47+/-3 mm; p<0.0005), and decreased fractional shortening (31+/-6% versus 37+/-2%; p<0.0001). Diastolic dysfunction was the most frequent finding (63% of the patients). We found depressed ejection fraction in 31 (32%) patients. Only 8 (8%) patients had symptomatic congestive heart failure. Left ventricular dysfunction was not attributable to intravenous drug abuse or to therapy. It was less severe in earlier stages of the infection (fractional shortening: acquired immunodeficiency syndrome=30%+/-6%, asymptomatic HIV-seropositives 34%+/-5%; p<0.005) and in HIV-2-infected patients. Patients with opportunistic infections (all aetiologies mixed) had more frequent congestive heart failure than those without infections (16% of the patients with versus 4% of the patients without infections; p<0.05). The fact that even asymptomatic HIV-seropositives had signs of left ventricular dysfunction (fractional shortening: asymptomatic HIV-seropositives=34%+/-5%; controls=37%+/-2%; p<0.05) favours the hypothesis of the HIV being one of the causes of these abnormalities.

Inhalatory pentamidine therapy and the duration of the QT interval in HIV-infected patients.

We evaluated the effect of chronic Pneumocystis carinii pneumonia (PCP) prophylaxis, with a once a month dose of 300 mg of inhalatory pentamidine isethionate, on QT interval duration. We included 22 human immunodeficiency virus (HIV)-infected patients: 11 were on this medication and 11 were not. The two groups were matched for age, sex and HIV infection stage. No patient had any clinical condition or was under any medication known to affect the duration of the QT interval. The heart rate-corrected QT (QTc) was obtained by averaging the observations of three independent observers. QTc duration was similar in both groups. The time separating pentamidine administration and the performance of the ECG did not influence the results, neither did the duration of inhalatory pentamidine therapy. Our results suggest that inhalatory pentamidine does not prolong the QT interval duration and so, as opposed to what has been reported concerning intravenous pentamidine therapy, does not seem to induce an increased risk of torsades de pointes.

Zidovudine therapy and left ventricular function and mass in human immunodeficiency virus-infected patients.

Human immunodeficiency virus-infected (HIV) patients frequently present left ventricular dysfunction. Its etiology is not elucidated but zidovudine has been postulated as a possible cause factor. This study is an attempt to clarify this issue by evaluating the effect of zidovudine therapy on left ventricular function in these patients. We prospectively studied by echocardiographic examination 11 consecutive HIV-infected patients who were assigned for zidovudine therapy. We excluded patients that had a history or a physical examination suggestive of ischemic, rheumatic, congenital, or hypertensive heart disease. Patients with diabetes mellitus, excessive ethanol intake and patients on potentially cardiodepressant drugs were also excluded. Echocardiographic examination was performed immediately before the initiation of zidovudine therapy and 1 and 3 months later. Left ventricular diameters, mass and fractional shortening showed no significant difference from baseline, at 1 or 3 months after the initiation of zidovudine therapy. Our results suggest that zidovudine therapy has no effect on left ventricular diameters, mass or fractional shortening during a short term.

HIV-2 infection with a long asymptomatic period.

We give details of a patient infected with HIV-2 which had what we believe to be the longest asymptomatic period so far reported. The infection was probably acquired though a blood transfusion in Africa 27 years ago. At present the patient remains asymptomatic and her cellular defence mechanisms, evaluated by CD+4 lymphocyte counts and hypersensitivity skin tests, are not severely compromised. HIV-2 has come distinct epidemiological, clinical and biological features which are different from the related HIV-1 and deserve investigation in order for its natural history to be better understood.

Dysrhythmic profile of human immunodeficiency virus infected patients.

We prospectively studied, with 24-h Holter monitoring, 21 consecutive human immunodeficiency virus (HIV) infected patients, at all stages of the infection, in order to assess their dysrhythmic profile. Three (14.3%) patients presented one isolated run of supraventricular tachycardia, with < 10 beats, that was considered clinically irrelevant. No patient presented other clinically relevant supraventricular or ventricular tachy or bradydysrhythmias. One (4.8%) patient presented intermittent Mobitz type I second-degree AV block, two (9.5%) patients paroxistic 2:1 AV block and one (4.8%) patient presented a bifascicular block on the 12-lead ECG that persisted during the ambulatory recording. This study suggests that clinically relevant cardiac tachydysrhythmias are rare in our population of HIV infected patients. On the other hand we found an unexpectedly high incidence of cardiac impulse conduction disturbances.