Adverse reactions to thalidomide in patients infected with human immunodeficiency virus

Thalidomide is emerging as a useful agent in the management of several complications of disease due to human immunodeficiency virus (HIV). We conducted three prospective studies of 56 HIV-infected patients who were treated with thalidomide for 14-21 days; 24 (43%) of these patients discontinued therapy owing to adverse reactions. Cutaneous and/or febrile reactions were the most frequent toxicities, arising in 20 (36%) of the patients. These reactions occurred after a mean interval (+/-SD) of 10 +/- 3 days and were associated with significantly lower CD4 T lymphocyte counts in reactors than in nonreactors (median count, 52.5/mm3 vs. 242 cells/mm3, respectively; P = .009). Four of four rechallenged patients experienced accelerated hypersensitivity; hypotension occurred in one case. Although sedation was an almost universal side effect among the patients, it was moderate or severe in only seven (13%); constipation was moderate or severe in five (9%) of the patients. Severe neuropathic symptoms and mood changes were each noted in two (4%) of the 56 patients. We conclude that the increasing use of thalidomide to treat HIV-infected patients must be accompanied by recognition of the drug's increased potential for toxicity in this population.     

Intensive care for patients with the human immunodeficiency virus]

RATIONALE AND OBJECTIVES: The authors evaluate a new flat-panel x-ray detector (FD) with respect to foreign body detection and reduction of radiation dose compared with screen-film radiography. METHODS: Flat-panel x-ray detector is based on amorphous silicon technology and uses a 1 k x 1 k photo-detector matrix with a pixel size of 143 x 143 microns and 12-bit digital output. A thallium-dotted cesium iodide scintillation layer converts x-rays into light. An ex vivo experimental model was used to determine the detectability of foreign bodies. Foreign bodies with varying sizes were examined: glass with and without addition of lead, bone, aluminium, iron, copper, gravel fragments, and graphite. Four hundred observation fields were examined using conventional radiography (speed, 400; system dose: 2.5 microGy) as well as FD with a simulated speed of 400, 800, 1200, and 1600, corresponding to a detector dose of 2.5 microGy, 1.25 microGy, 0.87 microGy, and 0.625 microGy, respectively. Four independent radiologists performed receiver operating characteristic analysis of 8000 observations. RESULTS: Flat-panel x-ray detector with a simulated speed of 400 was significantly superior (P = 0.012) to screen-film radiography (speed, 400). At a simulated speed of 800 and 1200 FD yielded results equivalent to screen-film radiography. Flat-panel x-ray detector was significantly inferior to screen-film radiography at a simulated speed of 1600 (P = 0.012). CONCLUSIONS: Flat-panel x-ray detector technology allows significant reduction in radiation dose compared with screen-film radiography without loss of diagnostic accuracy.     

Pleural effusion in patients infected with the human immunodeficiency virus

In order to analyze the etiology, cytological and biochemical characteristics, and outcome of pleural disease in patients infected with HIV, the medical records of 86 HIV-positive patients with pleural effusion were reviewed. Controls were 106 HIV-negative patients with parapneumonic or tuberculous effusion. Most HIV-positive patients were intravenous drug abusers (95.3%). Pleural effusions in HIV-positive patients were caused by infections in 76 (89.4%) cases. Parapneumonic effusion was diagnosed in 59 patients and tuberculous pleuritis in 15 patients. Staphylococcus aureus was the most frequently isolated bacteria. Parameters for differentiating complicated cases of parapneumonic exudate from uncomplicated cases, such as pleural fluid pH < 7.20 (sensitivity 80% vs. 84.3%), pleural fluid glucose < 35 mg/dl (sensitivity 45% vs. 56.25%) pleural fluid LDH > 1600 UI/l (sensitivity 85% vs. 62.50%), showed similar sensitivity in HIV-positive and HIV-negative patients. Monocytes in pleural fluid were significantly decreased in tuberculous pleuritis in HIV-positive patients (506 +/- 425 vs. 1014 +/- 1196 monocytes/ml, p < 0.05). No significant differences were detected in the outcome of HIV-positive and HIV-negative patients with pleural disease. It can be concluded that the pleural effusion was of predominantly infectious etiology in HIV-positive patients from populations with a high prevalence of intravenous drug abuse. Neither the biochemical parameters in pleural fluid nor the outcome differed significantly between HIV-positive and HIV-negative patients.     

Approach to the diagnosis of pulmonary disease in patients infected with the human immunodeficiency virus

Patients infected with the human immunodeficiency virus are predisposed to develop a variety of common and uncommon infectious and neoplastic pulmonary diseases. Clinical information that can stratify the risk of occurrence of these pulmonary conditions includes: 1) CD4 cell count-the most important determinant; 2) concurrent antimicrobial therapy; 3) prior travel history; 4) known latent infections that may reactivate: and 5) underlying respiratory disease. Specific pulmonary diseases are discussed including: bacterial pneumonia, bronchitis, mycobacterial and fungal infections, pneumocystis carinii pneumonia, toxoplasmosis, cytomegalovirus, Kaposi sarcoma, lymphoma, and lung cancer. A differential diagnosis can be generated based on the chest radiographic pattern. Focal or multifocal areas of consolidation usually represent conventional bacterial pneumonia or, less commonly, tuberculosis. In severely immunocompromised patients, unusual diseases causing consolidation should be considered including: Rhodococcus infection, nocardiosis, cryptococcosis, aspergillosis, and lymphoma. Nodules can be present in tuberculosis, histoplasmosis, cryptococcosis, and Kaposi sarcoma. Interstitial opacities are common in pneumocystis carinii pneumonia, histoplasmosis, and cytomegalovirus pneumonia. Cavitation and cysts are features of pneumocystis carinii pneumonia, tuberculosis, aspergillosis, and lung cancer. Disease of the airways is increasingly recognized in those with acquired immunodeficiency syndrome. Lymphadenopathy is most common in mycobacterial infection, but can be a feature of fungal infection, lymphoma, Kaposi sarcoma, and lung cancer. The combined use of clinical information, knowledge of typical conditions associated with the human immunodeficiency syndrome, and radiographic patterns offers a useful approach to the diagnosis of pulmonary disease in the patient with the human immunodeficiency virus.     

Common themes of antibody maturation to simian immunodeficiency virus, simian-human immunodeficiency virus, and human immunodeficiency virus type 1 infections

Characterization of virus-specific immune responses to human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) is important to understanding the early virus-host interactions that may determine the course of virus infection and disease. Using a comprehensive panel of serological assays, we have previously demonstrated a complex and lengthy maturation of virus-specific antibody responses elicited by attenuated strains of SIV that was closely associated with the development of protective immunity. In the present study, we expand these analyses to address several questions regarding the nature of the virus-specific antibody responses to pathogenic SIV, SIV/HIV-1 (SHIV), and HIV-1 infections. The results demonstrate for the first time a common theme of antibody maturation to SIV, SHIV, and HIV-1 infections that is characterized by ongoing changes in antibody titer, conformational dependence, and antibody avidity during the first 6 to 10 months following virus infection. We demonstrate that this gradual evolution of virus-specific antibody responses is independent of the levels of virus replication and the pathogenicity of the infection viral strain. While the serological assays used in these studies were useful in discriminating between protective and nonprotective antibody responses during evaluation of vaccine efficacy with attenuated SIV, these same assays do not distinguish the clinical outcome of infection in pathogenic SIV, SHIV, or HIV-1 infections. These results likely reflect differences in the immune mechanisms involved in mediating protection from virus challenge compared to those that control an established viral infection, and they suggest that additional characteristics of both humoral and cellular responses evolve during this early immune maturation.     

Incidence of enteropathogens in patients with human immunodeficiency virus infection

BACKGROUND: To establish the incidence of diarrhea and its evolution over time, the causal microorganisms, recurrence and associated mortality in patients with AIDS or severe immunologic alterations (CD4 lymphocytes lower than 0.5 x 10(9)/l). METHODS: A prospective longitudinal study was carried out from 1984 to 1992. The following patients were included in the study: 1) all those patients with diarrhea in whom a pathogenic microorganism was identified in the stools, and 2) patients with fever and positive blood cultures for enteropathogenic bacteria. The patients belonged to a series of 1,456 patients with infection by HIV. RESULTS: Of the 1,456 controlled patients, 253 (17%) had infection by enteropathogenic microorganisms. The incidence was greater in homosexual patients (26%) than in drug addicts (12%). The most frequent germs were Cryptosporidium, in 104 episodes and Salmonella sp. in 78 episodes (31 as isolated bacteria). The mortality in the 15 days following isolation was 2%, the referred microorganisms being the most frequent responsible for the deaths. The mean of CD4 lymphocytes in the patients with enteropathogens was 0.17 x 10(9)/l). SD 0.14 x 10(9)/l). In patients with infection by Cryptosporidium the CD4 lymphocyte count was lower than that observed in the cases of infection by Isospora belli. Prior to 1988, 21% of the patients had infection by enteropathogenic bacteria and 23% by parasites, those percentages being 3% and 6%, respectively in 1991. CONCLUSIONS: Infections by enteropathogenic microorganisms in patients with infection by the human immunodeficiency virus in an advanced stage are frequent, particularly, in homosexuals. The patients with enteritis by Cryptosporidium have a greater grade of immunosuppression (CD4 lymphocytes lower than 0.1 x 10(9)/l) than patients with infection by other enteropathogenic microorganisms. In the last few years, the incidence of enteropathogenic bacteria, especially Salmonella sp. and protozoa has decreased [corrected].     

The epidemiology of human immunodeficiency virus infection.

The epidemiology and natural history of infection with the human immunodeficiency virus (HIV) is reviewed. HIV is associated with a broad spectrum of disease, including AIDS. In presenting the natural history, early and late clinical manifestations, diagnosis of infection, incubation and latency periods, and survival time are discussed. Data from the published literature on the distribution of HIV infection in the adult U.S. population and factors that affect the acquisition and spread of the virus are also reviewed. Understanding of the epidemiology of this infection in certain high-risk groups is substantial and has provided a clear focus for preventive efforts and counseling. Many questions about spread in heterosexuals and about factors that may affect the natural history of the disease await completion of ongoing and planned studies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Infection due to Klebsiella rhinoscleromatis in two patients infected with human immunodeficiency virus

Two cases of rhinoscleroma in patients infected with the human immunodeficiency virus (HIV) who had stayed in an area of endemic Klebsiella rhinoscleromatis are reported. One of the patients presented with oropharyngeal lesions, an unusual clinical picture. Both patients suffered from a major cellular immune deficiency. The importance of Klebsiella rhinoscleromatis infection in AIDS-related oropharyngeal pathology and the possible treatment of such infection in HIV-positive patients are not yet clearly established.     

Cerebral infarction associated with vasculitis due to varicella zoster virus in patients infected with the human immunodeficiency virus

Cases of herpes zoster ophtalmicus (HZO) with delayed contralateral hemiparesis caused by hemispheric stroke secondary to granulomatous angiitis have been reported and are a well-recognized complication of herpes zoster. Similar cases have been reported more recently during infection with human immunodeficiency virus (HIV). We describe two HIV+ patients without any clinical history of zoster dermatitis who developed a sudden hemiparesis followed 2 weeks later for one by an acute retinal necrosis. Computerized tomography (CT) scan, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) were performed and showed a hemispheric stroke with evidence of a segmental arteritis of the carotid syphon. Varicella zoster virus (VZV) was found in the cerebro spinal fluid (CSF) in the two patients and after puncture of the vitreous fluid of the patient with the acute retinal necrosis. These two cases exemplify the difficulty of diagnosis of stroke in HIV+ patients, which seems to be more frequent than in similarly aged non-infected patients and demonstrates that VZV needs to be taken in consideration and identified even without any past history of zoster dermatitis.     

Range of neuromuscular involvement in 47 patients infected with the human immunodeficiency virus

Over a 30 month period, 47 out of 749 patients infected with the human immunodeficiency virus had various neuromuscular symptoms. Based on clinical and electrophysiological data, 47% had distal symmetric polyneuropathy, 11% chronic inflammatory demyelinating polyneuropathy (CIDP), 8.5% toxic neuropathy related to 2-3-dideoxyinosine (DDI), 8.5% cranial neuropathy, 8.5% mononeuropathy multiplex or isolated focal neuropathy, 8.5% progressive lumbosacral polyradiculopathy, and 8.5% myopathy. Half of the patients exhibited previous or concomitant signs of central nervous system involvement and 18 patients died during the study period. CIDP and cranial neuropathies usually appeared early in the course of the disease and consequently showed neurological improvement. Nerve conduction studies of DDI related toxic neuropathies showed distal axono-myelinic sensitivo-motor neuropathy, differing from CIDP by the absence of a conduction block. Distal symmetric polyneuropathies, frequent in the advanced systemic illness, do not systematically require an extended workup, but more unusual peripheral neuropathies which might be treatable necessitate further investigations (electromyography, radiology, serological blood tests; protein chemistry and routine workup of the cerebrospinal fluid). For example, progressive lumbosacral polyradiculopathies responded to early treatment, with a better outcome in one case of herpetic origin than in another case due to cytomegalovirus infection. Our observations suggest that myopathies in HIV infected patients should first be tackled by temporary interruption of virostatic medication, followed by muscle biopsy if the symptoms persist.     

The clinical characteristics of pleural tuberculosis in patients with and without human immunodeficiency virus infection

OBJECTIVE: To determine whether or not there are differences in the characteristics of pleural tuberculosis (PT) related to whether patients are or are not infected by human immunodeficiency virus (HIV). METHODS: We conducted a retrospective study of the medical histories of patients diagnosed of PT in our hospital between 1986 and 1993. RESULTS: We found no significant differences in the proportions of tuberculosis patients with or without HIV infection (8% versus 11%) who were diagnosed of PT. Of the 119 patients diagnosed of PT, 10% were also HIV positive. The HIV patients had more serious forms of PT, and among them there was a higher incidence of pleural discharge, more isolations of Mycobacterium tuberculosis in sputum and pleural fluid (42% and 45% versus 13% and 15%, p < 0.05), and more deaths before end of treatment (17% versus 1%, p < 0.05). The HIV patients had a lower rate of positive results in Mantoux's intradermal reaction test (17% versus 67%, p < 0.01), however, and fewer positive results for pleural biopsy (36% versus 84% positivity for granulomas, p < 0.01). CONCLUSIONS: The frequency of PT was similar for subjects with and without HIV infection in our study. In patients with both HIV and PT pleural fluid and sputum cultures are more useful diagnostic tools than pleural biopsy, and the former tests should therefore be stressed.     

Which are the vaccines that human immunodeficiency virus infected patients must receive?

Patients with aids are at increased risk of opportunistic and non opportunistic infections. It is now known that the incidence can be reduced by prophylactic measures and/or the use of vaccines. HIV infection produces an elevated frequency of severe pneumococcal disease with a rate of bacteriemia caused by Streptococcus pneumoniae 150-300 fold greater than rates reported in non-HIV infected people. For this reason, pneumococcal vaccine should be administered as early as possible in the course of the infection. Besides, the antibody response may be significantly higher for asymptomatic persons. Acute hepatitis caused by hepatitis B virus is milder than in non HIV infected patients but chronic disease is more frequent. The prognosis is worse and there is higher risk for infecting another persons. Hepatitis B vaccine is indicated for all the patients with HIV and negative serology for hepatitis B virus. Influenza vaccine is of limited effectiveness due to the high variability of the virus. Besides, influenza incidence is low among approximately young adults, HIV related immunodeficiency increased influenza risk only minimally, the vaccine is administered yearly and HIV-replication can increase in temporal association with vaccination. For all these reasons, fewer hospitalizations and deaths are prevented making it a far less cost-effective prevention strategy than pneumococcal vaccination. The risk of Haemophilus influenzae infections is elevated, but the vaccine is not routinely recommended because the more frequent serotype in HIV infected patients is b. For these subjects, passive immunization with immunoglobulin may also be necessary to provide protection. In conclusion, pneumococcal and hepatitis B vaccination is a reasonable prevention strategy for HIV infected patients at all stages of immunodeficiency. Influenza and H. influenzae vaccination are not recommended and alternative prevention strategies may be done.     

The inhibition of human immunodeficiency virus proteases by 'interface peptides'

The active human immunodeficiency virus type 1 (HIV-1) protease has a homodimeric structure, the subunits are connected by an 'interface' beta-sheet formed by the NH2- and COOH-terminal amino acid segments. Short peptides derived from these segments are able to inhibit the protease activity in the range of micromolar IC50 values. We have further improved the inhibitory power of such peptides by computer modelling. The best inhibitor, the palmitoyl-blocked peptide Pam-Thr-Val-Ser-Tyr-Glu-Leu, has an IC50 value of less than 1 microM. Some of the peptides also showed very good inhibition of the HIV-2 protease. The C-terminal segment of the HIV-1 matrix protein, Acetyl-Gln-Val-Ser-Gln-Asn-Tyr, also inhibits HIV-1 protease. Kinetic studies confirmed the 'dissociative' mechanism of inhibition by the peptides. Depending on the peptide structure and ionic strength, both dimerization inhibition and competitive inhibition were observed, as well as synergistic effects between competitive inhibitors and interface peptides.     

Characteristics of chronic hepatitis C in patients infected by human immunodeficiency virus

BACKGROUND: After recently published own investigations on subjective and objective cyclorotatory changes following inferior oblique recession for inferior oblique overaction, it was our aim to determine and to compare subjective and objective cyclorotatory changes following a modified Harada-Ito procedure for acquired trochlear palsy. PATIENTS AND METHODS: Eight patients suffering from acquired uni-(n = 3) or bilateral (n = 5) trochlear palsy were investigated before surgery and 1 day, 3 days and 4 months after surgery. Subjective cyclodeviation was assessed by Harms' tangent scale. Objective cycloposition was measured by means of fundus cyclometry using an infrared Scanning Laser Ophthalmoscope. RESULTS: The immediate postoperative incyclorotatory effect was 12 degrees in the unilateral group and 18 degrees in the bilateral group. Subjective and objective changes were nearly equal in both groups, with a subjective over-effect of 1 degree. After two days of binocular stimulation a marked regression of the surgical effect was found which still increased after four months. The long term incyclorotatory effect was subjectively and objectively nearly equal in the unilateral group which showed a relaps of subjective excyclodeviation of 5 degrees: in the bilateral group, the subjective effect was more pronounced than the objective effect, the immediate postoperative over-effect being disappeared. CONCLUSIONS: In contrast to our results concerning inferior oblique muscle recession for strabismus sursoadductorius, subjective and objective cyclorotatory changes did not differ grossly following a modified Harada-Ito procedure. Subjective and objective short and long term regression was confirmed which objectively exceeded the amount of over-correction. As the underlying cause mechanical and sensory mechanisms are discussed.