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Biomedical subjects

Roberto Manfredi

Publications and source records attributed to Roberto Manfredi.

At least 91 records · Page 5Linked to original sources
PubMed2003

Multiple opportunistic AIDS-associated disorders strictly related to immunodeficiency levels, in a girl with congenital HIV infection.

A 16-year-old girl with vertical HIV disease treated since birth suffered from six different AIDS-defining disorders until now. Even during the highly active antiretroviral therapy, multiple AIDS-related opportunistic infections may complicate the course of long-term congenital HIV disease, showing a strict relationship with immunological deterioration, which occurs shortly after virologic failure, due to an extensive genotypic resistance to all available antiretroviral compounds.

AIDS-Related Opportunistic Infections↗
PubMed2003

[HIV disease, antiretroviral treatment and the liver--emerging problems].

Both HIV disease and chronic HBV and HCV hepatitis recently benefited by significantly improved combination antiviral treatments, which, led to a remarkably increased life expectancy, and reduced morbidity and mortality rates of these potentially life-threatening disorders. However, many problems still wait definite solutions. Among them, the liver toxicity expected from administration of complex antiviral regimens (especially when co-infection is of concern), potential drug-drug interactions, the still unknown pathogenetic connections with the broad spectrum of metabolic abnormalities complicating long-term antiretroviral treatment, and the expected outcome of these issues on clinical management, therapeutic monitoring, and disease prognosis.

Anti-HIV Agents↗
PubMed2003

Concurrent infectious mononucleosis and measles: a potentially life-threatening association sharing underlying immunodeficiency.

We report lethal interstitial pneumonia in an 18-year-old young man with measles infection following recent infectious mononucleosis. We speculate that the documented T cell immune impairment caused by the concurrent Epstein-Barr and measles viral infections (as expressed by a proportionately low CD4+ lymphocyte count) was responsible for the complicated clinical course and unfavorable outcome.

Adolescent↗
PubMed2003

[Problems in the management of HIV infection in clinical practice. Patients still on dual therapy 8 years after the introduction of HAART].

Eight years after the introduction of HAART as the standard therapy of HIV disease, around one fifth of treated patients of our cohort still rely on isolated dual nucleoside analogue administration, mostly due to an apparently effective treatment initiated with these last drugs before the HAART era, or severe intolerance to triple regimens based on protease inhibitors or non-nucleoside reverse transcriptase inhibitors, or patient's refusal of HAART. Three representative case reports are described, and their implications discussed on the ground of current guidelines of antiretroviral therapy and common clinical practice.

Adult↗
PubMed2003

Multiple AIDS-related malignancies just in the era of potent antiretroviral therapy. A rare but intriguing finding.

Two exceedingly rare cases of dual AIDS-associated neoplasms (Kaposi's sarcoma and non-Hodgkin's lymphoma), occurring in a short time as AIDS-defining diseases of two HIV-infected patients treated with highly active antiretroviral therapy (HAART) are reported and discussed in light of evidence from the available literature. A slowly progressive increase in neoplastic complications following the introduction of HAART and the consequent decline of opportunistic infections such as the main AIDS-related disorders has been observed, and combined cancer diseases may be expected in the next few years, due to the persistent dysregulation of the immune system, or a possible involvement of oncoviruses and HIV itself in the pathogenesis of HIV-associated cancer.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Risk factors for cognitive impairment in HIV-1-infected persons with different risk behaviors.

CONTEXT: Although it is well established that acquired immunodeficiency syndrome dementia complex mainly develops in patients with advanced human immunodeficiency virus 1 (HIV-1) infection and severe immunosuppression, other factors that might increase the risk of early neuropsychological abnormalities are controversial. OBJECTIVE: To identify risk factors for HIV-1-related cognitive impairment. DESIGN: Case-control study. SETTING: Division of Infectious Diseases, University of Bologna. PARTICIPANTS: We studied 272 consecutive individuals: 90 HIV-1-seronegative, 88 asymptomatic HIV-1-seropositive, and 94 symptomatic HIV-1-seropositive persons. MAIN OUTCOME MEASURES: Cognitive impairment was defined as poor performance on at least 2 of the 7 neuropsychological tests included in the battery. Cutoff scores for poor performance on a test were established as 2 or more SDs lower than the mean of the seronegative group in the corresponding risk behavior strata: injecting drug users, hemophiliacs, and other risk behaviors. The following risk factors were studied: age, sex, education, risk behaviors, HIV-1 stage, lymphocyte count, and antiretroviral therapy. RESULTS: Compared with individuals with higher levels of education, those with less than 6 years of schooling had an odds ratio (OR) of 17.2 (95% confidence interval [CI], 3.6-83.3) for cognitive impairment, independent of age, sex, disease stage, antiretroviral therapy, and risk behavior. Compared with injecting drug users, homosexual/bisexual and heterosexual participants had ORs of 9.6 (95% CI, 2.2-42.7) and 6.3 (95% CI, 2.2-18.3), respectively, for cognitive impairment. Use of antiretroviral treatment (any vs none) was associated with lower prevalence of cognitive impairment (OR, 0.1; 95% CI, 0.0-0.3). Compared with persons with high CD4+ cell counts (> or =500/microL), those with low (<200/microL) and moderate (200-499/microL) CD4+ cell counts had adjusted ORs of 8.6 (95% CI, 1.0-71.0) and 6.9 (95% CI, 1.0-48.4), respectively. The presence of prominent depressive symptoms did not change the results. CONCLUSIONS: Low educational level, low CD4+ cell count, and homosexual/bisexual and heterosexual risk behaviors are risk factors for cognitive impairment in HIV-1-seropositive persons. Antiretroviral therapy exerts a beneficial effect against cognitive impairment in symptomatic individuals. Homosexual/bisexual and heterosexual persons who survive longer are expected to be the group at highest risk for cognitive impairment. However, the protective effect of antiretroviral therapy may balance this increased risk.

AIDS Dementia Complex↗
PubMed2002

Epidemiology and microbiology of cellulitis and bacterial soft tissue infection during HIV disease: a 10-year survey.

BACKGROUND: Cellulitis and soft tissue infection are underestimated complications of HIV disease. PATIENTS AND METHODS: Sixty-seven bacteriologically proven consecutive episodes were identified among 2221 HIV-infected patients hospitalized in a 10-year period, and assessed according to several epidemiological, microbiological and clinical variables. RESULTS: Staphylococcus aureus was the most frequently cultured pathogen (50% of 92 isolates), followed by Pseudomonas spp., Escherichia coli and Streptococcus pyogenes; a polymicrobial infection was present in 38.1% of episodes. Drug addiction (p < 0.003) and male gender (p < 0.04) were significantly associated with the occurrence of these complications, which were community-acquired in 83.6% of cases. While a remarkable variation in the severity of underlying immunodeficiency was shown, hematogenous dissemination occurred in 25.4% of episodes, and proved significantly related to a low CD4+ lymphocyte count, and neutropenia. A 21.7% methicillin-resistance rate was shown among S. aureus isolates. All episodes were favorably treated in 5-16 days, in over 60% of cases with associated beta-lactam-aminglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in four patients only. CONCLUSION: Skin and soft tissue infections are continuing causes of morbidity in HIV-infected patients, even in the highly active antiretroviral therapy era.

AIDS-Related Opportunistic Infections↗
PubMed2002

A prospective comparison of the two main indications of efavirenz in 2001 highly active antiretroviral therapy (HAART) regimens: first-line versus salvage use.

OBJECTIVE: To determine the efficacy of efavirenz introduction in first-line HAART compared with salvage multidrug regimens. PATIENTS AND METHODS: Prospective 15 month comparison of 107 consecutive HIV-infected patients starting efavirenz, according to laboratory and clinical outcome of first-line versus rescue drug use, therapeutic history and association of selected antimicrobial agents: naive patients were compared with nucleoside reverse transcriptase inhibitor (NRTI)-experienced patients in the first group, and patients in the second group who had one or more NRTI changed when starting a rescue treatment containing one or more novel protease inhibitors (PIs) were compared with those who did not. RESULTS: Efavirenz was administered with one or more novel NRTIs to 55 patients (27 antiretroviral-naive and 28 patients experienced with NRTIs only), compared with 52 patients who needed a multidrug salvage regimen after two or more failures of a 15-40 month PI-containing regimen. In an intention-to-treat analysis, con-sidering early interruption or an unsatisfactory virological course as a failure, only one patient on salvage therapy completed a favourable 15 month follow-up, compared with 31 patients experiencing first-line efavirenz-based HAART (P < 0.0001). The immunological response was less affected in both intensity and duration in patients undergoing rescue therapy. While no significant outcome difference was detected in the first group between naive and NRTI-experienced patients, among the salvage subjects the change of one or more NRTIs seemed to significantly improve virological and immunological outcome. Viral genotyping detected at least the K103N mutation in 41% of the 78 evaluable patients, despite lack of exposure to efavirenz and related compounds. Salvage patients had a significantly greater frequency of non-nucleoside RTI (NNRTI) resistance compared with the first-line group (P < 0.0001), in proportion to the extent of mutations affecting other drug classes (P < 0.0001). CONCLUSION: An efavirenz-based initial triple drug HAART proved significantly more effective than efavirenz adjunct to a rescue treatment performed after repeated failures of PI-based regimens. The unsatisfactory response of the salvage group was probably due to diffuse cross-resistance descending from previous therapy, even when NNRTIs were never administered.

Alkynes↗
PubMed2002

Dual Candida albicans and Cryptococcus neoformans fungaemia in an AIDS presenter: a unique disease association in the highly active antiretroviral therapy (HAART) era.

A case report of a patient who discovered his HIV infection concurrently with an advanced immunodeficiency and a dual Candida albicans and Cryptococcus neoformans fungaemia is discussed with reference to the changing epidemiology and clinical features of HIV infection and AIDS in the highly active antiretroviral therapy (HAART) era. The tendency to develop multiple concomitant AIDS-defining illnesses at the time of first hospitalisation seems to be an increasing feature in patients who remain unaware of or neglect their HIV disease and who are still at risk of opportunist infections even with the availability of HAART.

AIDS-Related Opportunistic Infections↗
PubMed2002

A life-long antiretroviral treatment of congenital HIV disease, associated with a mixed fat redistribution syndrome and osteopenia already occurred during pre-pubertal age.

An extraordinarily rare case report of mixed fat redistribution syndrome associated with osteopenia but not with relevant metabolic abnormalities is documented in a prepubertal child with congenital HIV infection treated with antiretroviral therapy since the age of six months, up to the present age of 12 years and two months. The possible relationship with prior and present antiretroviral treatment, and with the most recent literature evidences published in both adults and children with HIV disease are discussed, in order to focus these emerging adverse effects of long-term antiretroviral therapy in the paediatric population, and stimulate further investigation in this field.

Adolescent↗
PubMed2002

HIV disease and advanced age: an increasing therapeutic challenge.

The mean age of patients at both first HIV detection and AIDS diagnosis is progressively rising over time. However, reliable epidemiological estimates, clinical data or controlled therapeutic and outcome figures are lacking for elderly patients, especially with regard to laboratory and clinical response to antiretroviral therapy, treatment tolerability, drug-drug interactions, short- and long-term toxicity, and interactions with underlying illnesses and concurrent pharmacological treatment. In fact, the large majority of randomised, controlled trials evaluating and comparing new antiretroviral drugs or anti-HIV therapeutic strategies, as well as antimicrobial treatment or chemoprophylaxis of HIV-related complications, either excluded patients with advanced age and/or concurrent disorders or did not offer substudies or detailed data analysis focusing on older patients compared with younger ones. The life expectancy of HIV-infected persons receiving highly active antiretroviral therapy (HAART) is now extended (approaching that of the general population), so that the definition of AIDS has lost its epidemiological and clinical significance thanks to the immune reconstitution resulting from potent antiretroviral therapy. However, an ever-increasing number of individuals aged > or =50 years with HIV infection is expected in the coming years, as a result of both increased survival of patients with treated disease and delayed recognition of individuals with occult HIV disease. The limited data available about combined antiretroviral therapy in the elderly seem to show an overlapping virological success rate but a slower and blunted immune recovery compared with younger patients. Thymic output, however, seems somewhat preserved even in adulthood and may contribute to the reconstitution of most of the quantitative and functional T cell abnormalities caused by HIV disease. More attention must be paid to underlying end-organ disorders, as well as expected pharmacological interactions and combined drug toxicity that may interfere with HAART efficacy and patients' compliance with recommended regimens and could lead to increased adverse effects. The available guidelines for antiretroviral treatment and therapy and prophylaxis of AIDS-related illnesses should be regularly updated and should include problems related to HIV disease in an aging population. Specific trials or substudies focusing on older people are warranted to obtain controlled data on all issues of antiretroviral therapy in the elderly, including time and mode of initiation, and modification and salvage HAART regimens. Antiretroviral drug dosage adjustment to take into account underlying pathological conditions or other pharmacological treatments is another emerging issue.

Acquired Immunodeficiency Syndrome↗