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Biomedical subjects

G Ippolito

Publications and source records attributed to G Ippolito.

At least 55 records · Page 3Linked to original sources

Changes in neurocognitive performance in a cohort of patients treated with HAART for 3 years.

OBJECTIVES: To describe changes in HIV-associated neurocognitive impairment in patients treated with highly active antiretroviral therapy (HAART) for at least 3 years. METHODS: Prospective, observational study of comprehensive neuropsychologic (NP) testing, neurologic examination, and laboratory measures before HAART and after 6, 15 and 45 months of HAART, on 28 consecutive patients seen in our department since April 1996. RESULTS: At baseline, 16 patients were neurocognitively impaired and 12 were not. Among the 16 impaired patients, 5 patients failed to meet the criteria for impairment after 6 months and 9 patients after both 15 and 45 months of HAART, respectively. Statistically significant improvements ( p < or =.01) were seen in two of six measures exploring the concentration and speed of mental processing, two of three measures exploring mental flexibility, in one of five measures exploring memory, and in two of two measures exploring fine motor functions. Unimpaired study subjects performed better than impaired ones in 10 of 17 measures at baseline, in eight of 17 after 6 months, in six of 17 after 15 months, and in seven of 17 after 45 months of HAART. CONCLUSIONS: During the course of HAART, patients experienced a positive and sustained improvement in their neurocognitive performance. However, the presence of 7 of 16 (43.7%) patients with neurocognitive impairment, and the persistence of statistically significant differences in the neurocognitive performance between impaired and unimpaired patients after more than 3 years of HAART, suggests that ongoing HIV-related neurologic damage can occur even during potent antiretroviral treatment.

AIDS Dementia Complex↗

Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy.

The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor-containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P= .04, chi(2) test). Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30-3.75; P= .004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy.

Acute Disease↗

Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy.

OBJECTIVES: To evaluate the impact of response to highly active antiretroviral therapy (HAART) on the natural history of AIDS non-Hodgkin's lymphoma (NHL) and to analyse the feasibility, efficacy and toxicity of HAART in combination with chemotherapy. DESIGN: Prospective observational study in two AIDS clinical centres in Italy. METHODS: All consecutive HIV-infected patients with NHL were included (n = 44; 48% high-risk group) and prospectively followed for 27 months. HAART was administered concomitantly with chemotherapy. The association between response to HAART and clinical presentation, response to chemotherapy and toxicity was analysed by univariate and multivariate models. Survival analysis was performed by Kaplan-Meier estimates and the Cox proportional hazards regression model. RESULTS: A complete response (CR) to chemotherapy was achieved in 71% of HAART responders and 30% of non-responders. Virological response to HAART was the only variable associated with tumour response on multivariate analysis. A higher relative dose intensity (RDI) of chemotherapy was administered in patients with virological response compared with those without. The probability of 1 year survival was higher in patients with virological or immunological response. At Cox regression analysis, immunological response, a higher RDI and a CR to chemotherapy were all associated with a reduced risk of death. CONCLUSION: In HIV-infected patients with NHL, response to HAART was strongly associated with a better response to chemotherapy and prolonged survival. Concurrent treatments were well tolerated, and HAART-responder patients could receive a higher RDI of chemotherapy. In patients with AIDS lymphomas, combining HAART with chemotherapy could be a feasible and effective approach.

Adult↗

Female sex and the use of anti-allergic agents increase the risk of developing cutaneous rash associated with nevirapine therapy.

To identify factors associated with cutaneous rash, we performed a retrospective multicentre analysis of HIV outpatients starting a highly active antiretroviral therapy regimen containing nevirapine. A total of 62 cutaneous adverse events were observed in 429 patients. Rash hazard was increased in women, by the prophylactic use of glucocorticoids or antihistaminics, and was reduced by escalating the initial dose of nevirapine. Women receiving glucocorticoids had a 3 month cumulative probability of rash of 0.41.

Adult↗

Increasing prevalence of non-clade B HIV-1 strains in heterosexual men and women, as monitored by analysis of reverse transcriptase and protease sequences.

OBJECTIVE: We evaluated the prevalence of HIV-1 non-clade B over time in a formerly clade B-restricted area. Protease and reverse transcriptase regions of the pol gene were used for phylogenetic and recombination analysis and for clade assignment to HIV-1 A-D, F-H, J, and K strains of the M group. METHODS: The pol gene of 349 HIV-1 patients belonging to the Italian Cohort Naive for Antiretrovirals (ICONA) were genotypically analyzed to study the prevalence of antiretroviral-associated resistance mutations. All HIV-1 pol sequences and 32 HIV reference strains were analyzed, including the reference strains for the major HIV-1 subtypes. The non-clade B sequences according to the HIV-1 Subtyping Tool program were further studied by a bootscan analysis (SimPlot) to investigate the likelihood of recombination between subtypes. RESULTS: Phylogenetic analysis detected 19 of 349 (5.4%) non-clade B subtypes. The proportions of patients carrying non-clade B virus before and after 1997 were 1.9% and 8.4%, respectively (p =.008). Among whites, heterosexual infection and female gender were significantly associated with the presence of non-clade B subtypes (p =.001 and.005, respectively). Non-clade B HIV-1 was harbored by 14.5% of the heterosexuals who were found to be HIV-1 positive after 1997, 60% of whom were women. Bootscan analysis identified four strains as F, two as A, one as C, one as G, and 11 (57.9 %) as non-clade B recombinant subtypes. CONCLUSION: Detection of HIV-1 subtypes and intersubtype recombinants in a previously clade B-homogeneous area indicates that the HIV-1 epidemic is evolving in Italy and that heterosexuals and women are at increased risk of infection with non-clade B HIV-1 subtypes. Sequences inferred from the pol gene yield to establish the subtype of circulating HIV-1 strains. As a consequence, genotyping of pol gene for testing resistance to antiretrovirals warrants concomitant surveillance of non-clade B subtypes.

Adult↗

Changing clinical presentation and survival in HIV-associated tuberculosis after highly active antiretroviral therapy.

OBJECTIVE: To assess changes in clinical presentation and outcome of HIV-associated tuberculosis (TB) before and after widespread implementation of highly active antiretroviral therapy (HAART). METHODS: We reviewed clinical charts of HIV-infected patients with culture-confirmed pulmonary TB in two referral clinical centers in Rome, Italy. The 67 patients diagnosed in 1995 to 1996 were compared with 51 patients diagnosed in 1997 to 1998. To analyze factors associated with survival we used a Cox model including antiretroviral therapy as a time-dependent covariate. RESULTS: Patients diagnosed in 1997 to 1998 were more likely to have TB as the first AIDS-defining illness (78% versus 58%, p <.05), to have HIV diagnosed <2 months before TB (33% vs. 7%, p <.005) and to have typical chest radiograph pattern (45% vs. 25%, p <.05), and had a higher CD4(+) count (median 105 vs. 43, p <.005). Survival at 1 year was 80% for patients diagnosed in 1997 to 1998 vs. 65% for those diagnosed in 1995 to 1996 (p by log-rank =.02). After adjusting at multivariate analysis, time period of diagnosis was not confirmed as associated with survival (hazard ratio, 1.05; 95% confidence interval, 0.39--2.81). Age, CD4+ cell count <25/mm(3), and AIDS-defining illnesses before TB diagnosis were all associated with an higher risk of death, whereas a decreased risk of death was observed in patients starting a triple combination antiretroviral therapy after TB diagnosis (hazard ratio, 0.14; 95% confidence interval, 0.03--0.57). CONCLUSIONS: Cases of HIV-associated TB occurring in patients with advanced immunosuppression and presenting with atypical radiologic appearance tend to be relatively less common in the HAART era. HAART is a major factor in prolonging survival in these patients.

Adult↗

Prevalence of infected patients and understaffing have a role in hepatitis C virus transmission in dialysis.

To assess hepatitis C virus (HCV) incidence rates and identify determinants of infection among hemodialysis patients, a multicenter study was conducted in 58 units in ITALY: An initial seroprevalence survey was conducted among 3,492 patients already on hemodialysis therapy as of January 1997 and among an additional 434 patients who began dialysis up to January 1998. HCV antibodies were assessed by third-generation enzyme immunoassays. Patients testing seronegative at baseline were enrolled into a 1-year incidence study with serological follow-up at 6 and 12 months. For patients who seroconverted, an HCV RNA assay was performed on stored baseline samples to confirm new infection. A nested case-control study was subsequently performed to investigate potential risk factors. For each incident case, three controls negative for both HCV antibodies and HCV RNA were randomly selected. At enrollment, HCV seroprevalence was 30.0%. During follow-up, 23 new HCV cases were documented, with a cumulative incidence of 9.5 cases/1,000 patient-years. By logistic regression analysis, an increased risk for HCV infection emerged for patients attending the dialysis units with a high prevalence of HCV-infected patients at baseline (odds ratio [OR], 4.6) and for those attending units with a low personnel-patient ratio (OR, 5.4). Among extradialysis factors, a history of surgical intervention in the previous 6 months (OR, 16.7) significantly increased HCV risk. These findings suggest that the combination of understaffing and a high level of infected patients in the dialysis setting increases the risk for HCV nosocomial transmission. This is likely related to an increased likelihood for breaks in infection control measures.

Aged↗

Risk management of HBsAg or anti-HCV positive healthcare workers in hospital.

Recommendations are made for controlling the transmission of the hepatitis B and hepatitis C viruses from healthcare workers to patients. These recommendations were based both on the literature and on experts' opinions, obtained during a Consensus Conference. The quality of the published information and of the experts' opinions was classified into 6 levels, based on the source of the information. The recommendations can be summarised as follows: all healthcare workers must undergo hepatitis B virus vaccination and adopt the standard measures for infection control in hospitals; healthcare workers who directly perform invasive procedures must undergo serological testing and the evaluation of markers of viral infection. Those found to be positive for: 1) HBsAg and HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and hepatitis C virus RNA must abstain from directly performing invasive procedures; no other limitations in their activities are necessary. Infected healthcare workers are urged to inform their patients of their infectious status, although this is left to the discretion of the healthcare worker; whose privacy is guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker must undergo prophylaxis with specific immunoglobulins, in addition to vaccination.

Algorithms↗

Epidemiology and prognosis of AIDS-associated progressive multifocal leukoencephalopathy in the HAART era.

Whereas most AIDS-related neurologic disorders have reduced incidence since HAART therapy was introduced, we find that the incidence of progressive multifocal leukoencephalopathy (PML) did not significantly differ between the pre-HAART and the HAART period (OR 0.78; 95% CI 0.41-1.50). These findings were confirmed by the preliminary results of the Italian Register Investigative Neuro AIDS (IRINA) Study, a prospective multicenter study started in January 2000, which showed that PML was the second most frequently diagnosed neurologic disorder after TE. A similar proportion of cases were found in HAART-naïve and HAART-experienced patients in our experience. PML was more common in the presence of HIV RNA > 500 copies/ml. Most of the cases occurring in HAART-exposed patients developed within the first 6 months of therapy. As others have reported, we find a prolonged survival in PML subjects prescribed HAART (245 days in the group treated with HAART versus 66 days in the group not treated with HAART; P at log rank = 0.001). However despite the survival benefit, AIDS-associated PML still has a serious prognosis. In fact, PML had the lowest 1-year survival probability of any cerebral disorder in our study (P = 0.0005). Our findings also confirm that CSF JCV DNA burden at baseline is a useful prognostic indicator with a threshold of 4.7 log(10) JCV copies/ml (P at log rank = 0.01) in our experience. CSF JCV DNA load at 4 weeks of follow-up and clearance of JCV-DNA from CSF are associated with a better neurologic outcome and a longer survival.

AIDS-Related Opportunistic Infections↗

Potent anti-retroviral therapy with or without cidofovir for AIDS-associated progressive multifocal leukoencephalopathy: extended follow-up of an observational study.

To analyze the clinical efficacy of cidofovir combined with highly active anti-retroviral therapy (HAART) in AIDS-related progressive multifocal leukoencepalopathy (PML), a multicenter observational study was performed. Consecutive HIV-positive patients with histologically or virologically proven PML and at least 4 weeks of treatment after diagnosis were examined: 27 patients were treated with HAART, whereas 16 patients were treated with HAART plus cidofovir 5 mg/kg intravenously per week for the first 2 weeks and every other week thereafter. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR. Baseline virologic, immunologic, and clinical characteristics as well as HIV RNA and CD4 responses to HAART were homogeneous between the groups. The median follow-up was 132 weeks. In one case (6%), cidofovir was permanently discontinued because of severe proteinuria. One-year cumulative probability of survival was 0.61 with cidofovir and 0.29 without (log rank test P = 0.02). After adjusting for baseline CD4 counts, JC viral load in CSF, Karnofsky, and use of HAART prior to the onset of PML, the use of cidofovir was independently associated with a reduced risk of death (hazard ratio, 0.21, 95% confidence interval, 0.07-0.65; P = 0.005). A randomized study will definitively establish whether cidofovir confers significant advantage over HAART alone in AIDS-related PML.

AIDS-Related Opportunistic Infections↗

Risk of exposure to bloodborne infection for Italian healthcare workers, by job category and work area. Studio Italiano Rischio Occupazionale da HIV Group.

OBJECTIVE: To analyze the rate of occupational exposure to blood and body fluids from all sources and specifically from human immunodeficiency virus (HIV)-infected sources among hospital workers, by job category and work area. DESIGN: Multicenter prospective study. Occupational exposure data (numerator) and full-time equivalents ([FTEs] denominator) were collected over a 5-year period (1994-1998) and analyzed. SETTING: 18 Italian urban acute-care hospitals with infectious disease units. RESULTS: A total of 10,988 percutaneous and 3,361 mucocutaneous exposures were reported. The highest rate of percutaneous exposure per 100 FTEs was observed among general surgery (11%) and general medicine (10.6%) nurses, the lowest among infectious diseases (1.1%) and laboratory (1%) physicians. The highest rates of mucocutaneous exposure were observed among midwives (5.3%) and dialysis nurses (4.7%), the lowest among pathologists (0%). Inadequate sharps disposal and the prevalence of sharps in the working unit influence the risk to housekeepers. The highest combined HIV exposure rates were observed among nurses (7.8%) and physicians (1.9%) working in infectious disease units. The highest rates of high-risk percutaneous exposures per 100 FTE were again observed in nurses regardless of work area, but this risk was higher in medical areas than in surgery (odds ratio, 2.1; 95% confidence interval, 1.9-2.5; P<.0001). CONCLUSION: Exposure risk is related to job tasks, as well as to the type and complexity of care provided in different areas, whereas HIV exposure risk mainly relates to the prevalence of HIV-infected patients in a specific area. The number of accident-prone procedures, especially those involving the use of hollow-bore needles, performed by job category influence the rate of exposure with high risk of infection. Job- and area-specific exposure rates permit monitoring of the effectiveness of targeted interventions and control measures over time.

Blood-Borne Pathogens↗

Changing patterns of "hospital-at-home" care use by persons with AIDS in the era of combination antiretroviral therapy.

This study describes how hospital-at-home care (HHC) use by persons with acquired immune deficiency syndrome (PWA) has changed since the introduction of combination antiretroviral therapy (ART). For this study, all adult PWA (877) admitted for the first time to the HHC program, established for PWAs in the metropolitan area of Rome, between January 1994 and December 1998, were enrolled. Temporal changes in sociodemographic and clinical characteristics were evaluated. For subjects who concluded their first HHC cycle (851/877), the reasons for ending the service were assessed over time. From 1994 to 1998, the proportion of patients admitted to HHC of those living with AIDS in the Rome area decreased significantly (from 15.1% to 7.5%), while the median CD4+ cell count at HHC entry increased significantly. The proportion of patients referred to outpatient services at the end of their cycle of HHC increased sevenfold from 1994 to 1998, with a steep increase between 1996 and 1997. In multivariate analysis, only the use of triple-combination ART was significantly associated with referral to outpatient care (odds ratio [OR] = 4.26; 95%, confidence interval [CI] = 1.94-9.34). The results suggest that HHC use by PWAs in the ART era has diminished, while the HHC use pattern has also changed: there is a growing tendency to provide care to patients with less advanced human immunodeficiency virus (HIV) disease, prior to the beneficial effects of drugs, and the consequent referral to outpatient care.

Acquired Immunodeficiency Syndrome↗

HIV infection among foreign transsexual sex workers in Rome: prevalence, behavior patterns, and seroconversion rates.

BACKGROUND: The Azienda Sanitaria Locale Roma E (ASL-RME) outpatient clinic is the main reference center in Rome for HIV testing of foreign people. GOAL: To define the prevalence and incidence of HIV infection among foreign transsexual sex workers attending the center. STUDY DESIGN: A cross-sectional, follow-up study was conducted. RESULTS: Between 1993 and 1999, 353 transsexuals attended the ASL-RME. They were from Colombia (n = 208), Brazil (n = 122), and other countries (n = 23). Most of these transsexuals reported having 5 to 10 partners per day. The overall HIV prevalence was 38.2%, which multivariate analysis found to be associated with origin from Brazil and a higher number of sex partners. The observed HIV seroconversion rate was 4.1 per 100 person-years, and non-regular condom use was the only factor related to seroconversion. CONCLUSIONS: The data from this study suggest that promotion of safer sex practices and regular condom use still is the main priority among marginalized population subgroups, such as foreign prostitutes, involved in sex activities that put them at risk for HIV infection.

Adult↗

The changing picture of the HIV/AIDS epidemic.

Twenty years after it was first recognized, the HIV/AIDS epidemic continues to expand, but its impact varies greatly in different parts of the World. The worst of the epidemic is now centered in developing countries, especially sub-Saharan Africa, and areas such as Eastern Europe, which was only marginally involved a few years ago but has recently experienced the largest growth in the epidemic. In industrialized countries Highly Active Antiretroviral Therapy (HAART) has changed the natural history of HIV/AIDS, causing a reduction in mortality and morbidity due to HIV/AIDS and related diseases. Many interlocking factors determine the impact of HAART at the population level, including reduction of morbidity and mortality, changes in the natural history of HIV/AIDS and associated illnesses, and the effects of HAART on HIV transmission. To fully appreciate the potential benefits of HAART, the epidemic should continue to be monitored in the future, and the effects of HAART on reducing HIV transmission should also be evaluated. Interventions addressed to encourage the adoption of safer sex practices are badly needed, since a "rebound" in risky sexual behaviors was recently reported among high risk groups, which is, at least in part, attributable to the optimism about new treatments.

Acquired Immunodeficiency Syndrome↗