Management of relapsing cytomegalovirus disease in transplant recipients: diagnostic and therapeutic dilemmas.
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Administration, Oral↗
Biomedical subjects
R Manfredi
Publications and source records attributed to R Manfredi.
Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: frequency, relationship with administered drugs, and role of hypolipidaemic therapy with bezafibrate.
OBJECTIVES: To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a lipid-lowering agent. METHODS: We retrospectively compared serum lipid levels of five groups of 40 patients, each of them treated with either saquinavir hard gel, indinavir, or ritonavir (associated with two nucleoside analogues), or dual nucleoside reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovirals, randomly selected from nearly 1000 HIV-infected patients followed-up for >or= 12 months, while on the relevant therapy. Hypertriglyceridaemia was defined by triglyceride levels >or= 172 mg/dl, and hypercholesterolaemia by cholesterol levels >or= 200 mg/dl. All patients with triglyceridaemia > 300 mg/dl and cholesterolaemia > 220 mg/dl for at least 6 months, and unresponsive to a >or= 3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at a <or= 3-month interval, evaluating both efficacy and tolerability of the hypolipidaemic treatment, provided that they did not change their protease inhibitor treatment for reasons other than metabolic abnormalities. RESULTS: Hypertrygliceridaemia occurred in 75 patients out of 200 (37.5%), but was significantly more frequent and severe with ritonavir vs. indinavir (P<0.001), and in subjects given indinavir vs. all remaining patients (either treated or not) (P<0.001), while isolated saquinavir use was associated with higher tri glyceride levels than NRTI-NNRTI treatment alone, or no antiretroviral therapy (P<0.03). Hypercholesterolaemia was found in 27 subjects (13.5%), and a significantly higher frequency and severity was shown in patients treated with indinavir and ritonavir vs. saquinavir, NRTI-NNRTI, and no anti-HIV therapy (P<0.05 to P<0.001). No appreciable difference was found between patients undergoing NRTI-NNRTI and untreated controls, for all evaluated variables. Bezafibrate was administered once daily for 6-18 months to 49 patients with elevated and diet-resistant hyperlipidaemia due to ritonavir or indinavir (27 and 22 subjects, respectively), and reduced triglyceride and cholesterol levels by 35% and 25%, respectively over 6 months, without differences between the underlying protease inhibitor regimen. Thirty-three patients (67.3%) reached a normal triglyceridaemia after 6-9 months, and normal cholesterol levels were obtained in all subjects. Bezafibrate proved safe and well tolerated. CONCLUSIONS: Careful monitoring of the serum lipid profile is needed during antiretroviral therapy, including protease inhibitors, to identify the need for a diet and/or an hypolipidaemic treatment, and to prevent clinical sequelae related to long-term dyslipidaemia. Specific guidelines for the management of disorders of lipid metabolism in HIV-infected patients are needed.
Bezafibrate↗
Osteonecrosis and highly active antiretroviral therapy during HIV infection: report of a series and literature review.
Osteonecrosis has shown an increased incidence in HIV-infected patients during the last few years, and has been looked as a side effect of highly active antiretroviral therapy, possibly related to hyperlipidemia. Five cases of osteonecrosis were observed among over 1300 patients with HIV disease. According to our experience, novel antiretroviral regimens do not represent a constant risk factor for avascular necrosis of bone during HIV infection.
Adult↗
Dual nucleoside analogue treatment in the era of highly active antiretroviral therapy (HAART): a single-centre cross-sectional survey.
Since limited literature exists regarding the outcomes of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) treatment in the highly active antiretroviral therapy (HAART) era, a cross-sectional survey was carried out in a population of around 1000 HIV-infected patients in a single northern Italian university hospital, to assess the frequency, background and long-term evolution of anti-HIV treatment conducted with two NRTIs. An appreciable proportion (20.4%) of the 798 HIV-infected patients currently treated with antiretrovirals at our centre still take a dual NRTI combination, and the great majority of them (68.7%) have a stable disease course (characterized by a viral load <3.7 log(10) HIV RNA copies/mL, a maintained CD4(+) lymphocyte count and absence of HIV disease progression after at least 24 months of follow-up), regardless of the selected regimen, prior antiretroviral therapy use, and baseline virological and immunological situation. Further studies are warranted to establish whether dual NRTI regimens may have residual indications in the HAART era, and whether the shift to a triple antiretroviral combination is expected to lead to long-term advantages in patients with a low risk of disease progression while on dual NRTI treatment.
Anti-HIV Agents↗
Enterobacter spp. infections complicating the course of HIV disease.
Through a retrospective review of clinical and laboratory data of 2517 consecutive patients with HIV disease hospitalized since 1991, 13 patients were identified (0.52%), who suffered from a confirmed Enterobacter spp. infection (urinary tract disease in 7 cases, sepsis in 4 patients, and pneumonia in 2 cases). A severe immunodeficiency was recognized in all cases, as expressed by a mean CD4+ lymphocyte count <60 cells/microL, and frequently, a prior diagnosis of AIDS. Bloodstream infection proved linked to a lower mean CD4+ cell count, a more frequent occurrence of leukopenia-neutropenia, and nosocomial origin of the infecting pathogen. Hospital-acquired Enterobacter spp. disease was more frequent than community-acquired, and was significantly associated with leukopenia-neutropenia, and a diagnosis of AIDS. Antibiotic susceptibility assays showed a resistance rate to ampicillin and cephalothin involving >90% of tested strains, and a higher (but varied) sensitivity to other beta-lactams, aminoglycosides, fluoroquinolones, and cotrimoxazole. Adequate chemotherapy provided clinical and bacteriological success in all evaluated patients, in the absence of mortality or relapses. Only 34 episodes of HIV-associated Enterobacter spp. infection have been reported to date in 11 different literature studies. Our data point out that also Enterobacter spp. organisms may have an appreciable pathogenic potential in patients with HIV disease, especially in those with a low CD4+ lymphocyte count, leukopenia-neutropenia, who are hospitalized. Despite the unpredictable antibiotic susceptibility profile of these organisms, HIV-related Enterobacter spp. disease may be properly managed through rapid identification and timely and appropriate antimicrobial treatment.
Adult↗
Role of gancyclovir and HAART administration in the treatment of a rare complication of HIV disease: cytomegalovirus-associated Guillain-Barré syndrome.
Peripheral nerve disorders are very common in patients with HIV infection, including inflammatory demyelinating polyneuropathies, such as Guillain-Barré syndrome. Causes of these neuropathies are probably multiple, and often dictated by the stage of the underlying HIV disease. Acute demyelinating polyneuropathy is usually preceded by infections, generally sustained by cytomegalovirus or Campylobacter jejuni, and a co-infection with HIV may represent the initial etiopathogenetic event leading to the neurological disorder. An extraordinary case report of a cytomegalovirus-associated Guillain-Barré syndrome occurred in one of our patients with advanced HIV infection, who was cured by gancyclovir and HAART administration, and gives us the opportunity to briefly discuss the intriguing pathogenetic and clinical correlations among HIV disease, cytomegalovirus infection, this neurological syndrome, and its specific treatment.
Adult↗
Pentamidine isethionate as treatment and secondary prophylaxis for disseminated cutaneous leishmaniasis during HIV infection: case report.
Leishmaniasis is emerging as a common and serious opportunistic infection in HIV-infected patients in endemic areas (such as Mediterranean countries), and may occur with various clinical presentations, ranging from typical visceral forms to atypical cases, including cutaneous disease. Although pentavalent antimony compounds have been the mainstay of antileishmanial treatment for half a century, new drugs seem today reliable, including liposomal amphotericin B and pentamidine isethionate. However, the most effective therapy is still unknown. An HIV-infected i.v. drug abuser patient with a very uncommon disseminated cutaneous leishmaniasis, following an initial visceral disease, is described. Primary and recurrent visceral forms of protozoan infection have been treated with liposomal amphotericin B, while pentamidine isethionate was successfully employed as treatment for subsequent cutaneous relapse and as secondary prophylaxis.
AIDS-Related Opportunistic Infections↗
Switch of protease inhibitor-containing HAART in routine clinical practice: a four-year prospective observational study.
An evaluation was made of the frequency of outcomes, the features, and one-year outcomes of the substitution, carried out because of failure or toxicity, of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART). Nine hundred and seventy-two HIV-infected patients were prospectively followed up since 1996, with the condition that they had a minimum 80% adherence to prescribed regimens. Four hundred and fifty-two changes occurred in 397 of the 876 evaluable patients (45.3%). Virological and/or immunological failure was of concern in 245 cases (54.2%). Interest in saquinavir had the greatest incidence and earliest occurrence (although the subsequent switch had a significantly better outcome than that of patients failing with other PIs); nelfinavir benefited from a shorter time to change and a worse long-term outcome (probably attributable to its predominant use in indinavir- and ritonavir-experienced patients); while indinavir showed the lowest overall frequency of substitution. Intolerance occurred in the remaining 207 cases (45.8%); with saquinavir being better tolerated than other PIs. A favourable outcome was obtained more frequently when poor tolerability was of concern, compared with therapeutic failure (P<0.008), while no significant differences were found according to prior antiretroviral experience and the subsequently selected HAART regimen. The overall one-year outcome per single substituted compound proved significantly better for patients who stopped using saquinavir and ritonavir, by contrast with those who stopped using indinavir and nelfinavir (P<0.0008). A significantly shorter mean time to substitution was recognized for nelfinavir and saquinavir than with ritonavir and indinavir (P<0.0001). When analysing the subset of patients experiencing HAART failure, a highly significant reverse relationship was demonstrated between mean time to failure, and rate of subsequent response to a modified antiretroviral regimen (P<0.0001). When considering the different patterns of efficacy, durability, resistance induction, expected adherence, and safety of each antiretroviral drug, initial and subsequent therapeutic choices should be carefully balanced against expected benefits and risks.
Antiretroviral Therapy, Highly Active↗
Gynecomastia associated with highly active antiretroviral therapy.
OBJECTIVE: To report four cases of HIV-associated gynecomastia diagnosed during treatment with nucleoside analogs with or without protease inhibitors. CASE SUMMARY: Four HIV-infected patients developed gynecomastia while taking two nucleoside analogs (stavudine combined with lamivudine in 3 patients, stavudine with didanosine in 1 patient) and protease inhibitors (indinavir, nelfinavir, ritonavir-saquinavir in 3 patients) all patients had received prior treatment with single or associated nucleoside analogs for > or = 21 months. Gynecomastia occurred three to seven months after the start of a triple regimen in the first three patients, and 17 months after initiating the last dual nucleoside analog therapy in the remaining patient. Liver, kidney, and thyroid function were normal; a routine endocrinologic workup showed slight follicle-stimulating hormone and luteinizing hormone abnormalities in one patient only. Other possible causes of drug- or disease-induced gynecomastia were excluded. A concurrent fat redistribution syndrome was present in three patients (including the patient who received nucleoside analogs only), while serum lipid and/or glucose concentration abnormalities were present in all patients. Gynecomastia remained unchanged during the subsequent seven- to 16-month follow-up, even after modification of antiretroviral therapy. DISCUSSION: Gynecomastia has been recently associated with antiretroviral therapy, and all reported cases but one occurred two to 17 months after the start of a protease inhibitor-based regimen. Our experience underlines the possible occurrence of gynecomastia in the absence of protease inhibitor administration, its persistence despite changes of antiretroviral regimen (thus resembling some signs related to lipodystrophy syndrome), and the apparently constant association with prolonged nucleoside analog administration (especially stavudine). CONCLUSIONS: Gynecomastia should be included among emerging adverse effects of antiretroviral therapy, although its etiopathogenesis deserves further investigation.
Adipose Tissue↗
Renocaval arteriovenous fistula as a complication of laparoscopic cholecystectomy.
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Adult↗
[Epidemics of bovine spongiform encephalopathy and new variant of Creutzfeldt-Jakob disease in humans. Most recent findings on prion disease].
Prion diseases have been popularized by extensive media coverage of bovine spongiform encephalopathy (BSE) or "mad cow disease" epidemic, observed in Great Britain since 1986, and new variant Creutzfeldt-Jakob disease (nvCJD), reported for the first time in 1996. In contrast to the classical form of the disease, nvCJD affects younger patients, presents a relatively longer duration of illness and is caused by the same agent as BSE. Evidence from laboratory studies now strongly supports the hypothesis that new variant represents human form of animal disease, linked to exposure, probably through food, to bovine prions. Number of BSE reports in the United Kingdom began to decline in 1993, and has continuously decreased year by year since then, but a great worry spread in European countries in association with new BSE reported cases outside of the Great Britain, and increasing incidence of nvCJD. New epidemiological, clinical, histopathological and experimental data on prion diseases are reviewed, focusing our attention on the possible transmission of prion proteins from animals to humans.
Animals↗
[Cytomegalovirus chorioretinitis in a patient with orthotopic liver transplant. Role of virologic diagnosis and of antiviral chemoprophylaxis].
A case report of cytomegalovirus retinitis in a patient who underwent orthotopic liver transplantation, and suffered from a prior episode of systemic cytomegalovirus disease, is described. Although the diagnosis was obtained only when clinical symptoms prompted ophthalmoscopic evaluation, a successful outcome was attained after ganciclovir treatment. The role of clinical and virologic monitoring of organ transplant recipients, and that of primary and secondary chemoprophylaxis against cytomegalovirus infection are discussed, according to personal observations and to an updated literature review.
Chorioretinitis↗
[Economic burden and clinical course of HIV infection and AIDS today: how the variation of natural history, available treatments, and strictly related costs play a role in needs of health care].
In order to provide an updated balance of the evolution of the natural history of HIV infection, the major clinical end-points of disease morbidity and mortality were compared with the progressively increasing use of highly active antiretroviral therapy (HAART), in a cohort of patients followed by our tertiary care centre in an eight-year period including both the pre-HAART and the HAART era. Although direct expenditures for antiretroviral agents reached even 99.8% of overall costs related to drugs and blood derivatives at our entire unit in the year 2000, a clear shift towards outpatient assistance of HIV infection was realized during recent years, leading to an increased and greatly varied spectrum of infectious diseases hospitalized at our inpatient and Day-Hospital units. Due to the significant reduction of inpatient expenditures, even the elevated costs of management of HIV disease based on HAART and periodic virological and immunological monitoring are expected to remain cost-effective, at least during the next few years.
Acquired Immunodeficiency Syndrome↗
[Anthrax].
Anthrax is a serious bacterial infection sustained by Bacillus anthracis and occurring in most mammals, especially grazing herbivors, but it can also involve humans when bacterial endospores enter the body through abrasions in the skin or by inhalation or ingestion. Human disease results from contact with infected animals or contaminated animal products, while there are no known cases of human-to-human transmission. The most common form of human anthrax is the cutaneous infection, usually curable with antimicrobial therapy and rarely leading to systemic and fatal disease; on the other hand, gastrointestinal and inhalatory forms (resulting from inhalation or ingestion of endospores) are very uncommon, but they show a mortality rate approaching 100 percent, usually related to septic and toxic shock. For centuries, anthrax has caused disease in animals and only a few cases in humans, with some outbreaks in developing countries. Today, after the new events in the United States, at least 17 nations are believed to have offensive biological weapon programs, and this old bacterial infection became a modern menace to world safety.
Adult↗
[Pathogenic role of Acinetobacter spp during HIV infection].
In order to assess the clinical role of bacterial complications due to Acinetobacter spp. during HIV disease, a retrospective survey of clinical and microbiological data of 2221 HIV-infected patients hospitalised during the past 10 years was carried out, evaluating all episodes of Acinetobacter spp. infection according to several epidemiological, clinical and therapeutic variables. Eleven patients of 2221 (0.5%) suffered from Acinetobacter spp. disease: sepsis in 5 cases, and urinary, respiratory tract disease and bacteremic pneumonia in three, two, and one patient respectively. A. calcoaceticus was responsible in 4 cases, A. lwoffii in three, and Acinetobacter spp. in the 4 remaining cases; 4 patients experienced a polymicrobial infection, and 7 had a prior diagnosis of full-blown AIDS. All patients had a severe HIV-related immunodeficiency (mean CD4+ lymphocyte count 118.2 +/- 45.3 cells/microl). Compared with other localizations, sepsis was related to a lower mean CD4+ cell count (p<.001), and a more frequent occurrence of leucopenia-neutropenia (p<.005). Disease episodes diagnosed after the first 72 hours of hospitalisation (deemed no- socomial in origin), proved more frequent than community-acquired ones (9 cases versus 2), affected predominantly patients with AIDS and neutropenia, and were frequent1y associated with bacteremia (p<.04) The use of broad spectrum antibiotics, corticosteroids and cotrimoxazole, was recognized during the month preceding the diagnosis of Acinetobacter spp. disease, in 6, 4, and 8 cases, respectively. One patient only had an indwelling intravascular catheter, while no recent history of surgery, intensive care, or other invasive procedures was found. At in vitro susceptibility studies, bacterial isolates showed complete resistance to ampicillin and cephalothin, and low sensitivity to second-generation cephalosporins, while a higher susceptibility rate was revealed towards ceftazidime, netilmicin, amikacin, and quinolones, followed by cotrimoxazole and piperacillin. A prompt and appropriate antimicrobial therapy (mostly carried out with cephalosporins and aminoglycosides), led all patients to a clinical and microbiological cure within 6-1.3 days, in the absence of mortality or relapses. As opportunist pathogens with a predominant nosocomial origin, Acinetobacter spp. organisms may be responsible for an appreciable morbidity in patients with HIV disease, especially when additional risk factors (immunodeficiency, underlying diseases, and hospitalisation) are present. Notwithstanding the high drug resistance profile of the majority of isolated organisms, a timely diagnosis and a treatment based on in vitro assays, contribute to avoid recurrences and potentially life-threatening complications.
AIDS-Related Opportunistic Infections↗
[Sexually transmitted diseases (STD) and their relationship with sexual behaviour and condom use, in a cohort of teenagers referring to a STD centre. A nine-year, prospective study].
In order to assess the relationship between a diagnosis of sexually-transmitted disease (STD), sexual behaviour, condom use, and other social, demographic, and epidemiological variables in a cohort of young adults who referred to a STD centre during a 9-year period, all patients aged 13-20 years were prospectively evaluated, with special attention paid to sexual behaviour, and use of condom or other contraceptive techniques. The 284 assessed young adults represented 6.1% of all patients with a diagnosis of STD: an increasing temporal trend was noticed (from 3. % in 1991, up to 10.4% nel 1999: p<.0001). On the whole, 70.1% of subjects aged 20 years or less never used a condom during the 6 months preceding the diagnosis of STD: only 21.8% of patients reported regular condom use, and 4.9% more subjects referred occasional use, while in the remaining 3.2% of cases other contraceptive methods were employed. Among under age patients (10.6% of study population), the rate of condom use was 3.3% only, while male homosexuals always denied the use of barrier methods. Although a progressive increase in condom use was observed through the study time (from 0% encountered in 1991-1994, to 57.6% of 1999: p<.0001), this phenomenon proved linked only to the massive increase of immigrant sex workers, which occurred since 1997. When excluding from analysis any probable female prostitutes, lack of condom use tested related to the male gender (p<.05), and a low education (p<.04). Over 50% of patients reported 0-1 partners during the last 6 months, even though an increase in sexual promiscuity was observed during the last three years, compared with 1991-1996 (p<.02). Among the 297 different STD episodes (mostly nongonococcal cervicitis-vaginitis and urethritis, and HPV infection), an increasing incidence of nongonococcal STD and syphilis was found, but no correlation was observed between the spectrum of diagnosed STD, sexual behaviour, and condom use. In particular, in 69.9% of the 103 episodes nongonococcal disease occurred despite regular (65 cases), or occasional (7 episodes) condom use. Moreover, no significant relationship was disclosed between STD occurrence, condom use, and other analyzed social, demographic, epidemiological, and clinical variables. According to our survey, an increased risk of STD seems to involve young adults, and to be related to the variation of multiple demographic, epidemiological, and behavioral features. While immigration and prostitution had the major impact during the last three years, sexual promiscuity and infrequent condom use represent persistent; risk factors in this age population. Besides their diagnostic and therapeutic role, STD centres are able to carry out permanent monitoring of STD, as a starting point to plan adequate information campaigns and specific prevention strategies.
Adolescent↗
[Cellulitis and soft tissue infection in patients with HIV disease: epidemiological and microbiological features].
In order to assess the epidemiological, microbiological, and clinical features of cellulitis and soft tissue infection occurring during the course of HIV disease, clinical and laboratory data of 2221 hospitalizations carried out since 1991 were retrospectively examined, and 67 bacteriologically-proven episodes of cellulitis-soft tissue infection were identified (3.02% of overall admissions). Among the 92 cultured pathogens, Staphylococcus aureus was the most frequent (46 cases), followed by Pseudomonas spp., Escherichia coli, and Streptococcus pyogenes; 38.1% of patients had a polymicrobial infection. i.v. drug use (p<.02) and the male gender (p<.05), were significantly associated with the occurrence of these complications, while a great variation in the severity of underlying immunodeficiency was shown. An elevated rate (83.6%) of episodes of cellulitis or soft tissue infection were community-acquired in origin; the comprehensive frequency of these episodes significantly dropped during the highly active antiretroviral therapy (HAART) era (p<.01). Limbs were involved in over 80% of episodes, and an hematogenous dissemination of bacterial infection (which occurred in 25.4% of cases), proved significantly related to a CD4+ lymphocyte count <100 cells/microL (p<.03), and an absolute neutrophil count <1000 cells/microL (p<.05). S. aureus strains showed an elevated in vitro resistance rate to penicillin, ampicillin, and rifampin, and a 21.7% rate of methicillin-resistance, while among the 29 gram-negative microorganisms, resistance to ampicillin and first-generation cephalosporins, and that to amoxycillin-clavulanate and second-generation cephalosporin, occurred in over 90% and 60% of tested strains, respectively. All episodes of HIV-associated cellulitis and soft tissue infection were favorably treated in 5-16 days, in over 60% of cases with associated beta-lactam and aminoglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in 4 patients only, 6-17 months after the initial episode. Cellulitis and soft tissue infection are underestimated complications of HIV disease, but they have a broad etiological and clinical spectrum, are predominantly community-acquired, and are responsible for an appreciable morbidity, due to the supporting role of i.v. drug addiction, and the frequent hematogenous dissemination (which proved to be significantly related to the progression of immunodeficiency and underlying disease). The frequent polymicrobial etiology requires a combination antimicrobial therapy (to be guided by in vitro susceptibility studies), which may avoid a complicated and recurrent disease course in the great majority of cases.
Adult↗
A case-control study of virological and immunological effects of highly active antiretroviral therapy in HIV-infected patients with advanced age.
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Adult↗