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Biomedical subjects

E Vaccher

Publications and source records attributed to E Vaccher.

At least 55 records · Page 3Linked to original sources

Human immunodeficiency virus seroprevalence and condom use among female sex workers in Italy.

BACKGROUND AND OBJECTIVES: In two different studies, we evaluated the human immunodeficiency virus (HIV) seroprevalence rate and the condom use in a group of female sex workers working in Italy. STUDY DESIGN: In the first study we collected data on HIV serologic testing of female sex workers; in the second study, we evaluated the use of condoms and high-risk sexual practices by sex workers with their clients and nonpaying partners. RESULTS: Overall, 131 of 802 (16%) were HIV positive: 36 of 558 (6%) professional sex workers and 95 of 244 (39%) sex workers who used intravenous drugs. There was a significant increase of seroprevalence among professional sex workers between 1988 to 1990 and 1991 to 1995 (2% versus 11%, P < or = 0.001), whereas among the sex workers who used intravenous drugs, the increase was not significant (37% versus 40%, P = 0.70). Similarly, the HIV seroprevalence in the Italian professional sex workers is constant in the two periods of time (2% versus 1%). In the second study, 97 of 102 (95%) sex workers reported regular condom use with clients, whereas 63% of sex workers reported they never used them with nonpaying partners. Fourteen sex workers reported having nonpaying partners who used intravenous drugs and 6 reported having nonpaying bisexual partners; 8 of these 20 partners were HIV positive. CONCLUSION: The results of the first study showed a significant increase of seroprevalence among professional sex workers, whereas the high seroprevalence among sex workers who used intravenous drugs was constant. The results of the second study showed that sex workers may be at higher risk for HIV infection through noncommercial sexual intercourses.

Adult↗

Dynamics of HIV-1 mRNA expression in patients with long-term nonprogressive HIV-1 infection.

A large number of evidences indicate that progression of HIV disease is driven by an increase in viral burden. It is still unclear, however, to what extent this is contributed by the dysregulation of the molecular mechanisms governing virus gene expression at the transcriptional or posttranscriptional levels. To address this issue, several quantitative virologic parameters (including provirus transcriptional activity and splicing pattern) were analyzed in individuals with nonprogressive HIV infection and compared with those of a matched group of progressor patients. Exact quantification was achieved by a competitive PCR procedure using a multicompetitor template. Nonprogressors were characterized by striking differences in the levels of viremia, provirus copy number, and overall levels of all viral mRNA classes in peripheral blood mononuclear cells. Additionally, the transcriptional activity of the proviral DNA in these patients was mainly engaged in the production of multiprocessed transcripts, with a pattern resembling the early phases of the experimental infection. Taken together, these results show that both viral load and provirus transcription pattern are remarkably different in infected individuals nonprogressing toward overt disease, and further support the notion that disease progression is accompanied by a change in the kinetics of HIV gene expression.

Adult↗

Malignant tumors and AIDS.

One in six patients with acquired immunodeficiency syndrome (AIDS) both in the USA and Europe develop malignancies, in particular Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL). After an initial rapid increase, the proportion of AIDS patients with KS steadily declined in the USA and in Europe, while the proportion of AIDS-NHL has been stable during the last decade in the USA and Europe. Human immunodeficiency virus (HIV) infected patients are living longer due to advances in antiretroviral therapy and treatment of prophylaxis against opportunistic infections, yet because of their immunodeficiency they are at high risk for cancers, especially NHL. The natural history of cancers in patients with HIV infection differs from that of the general population. Unusual aspects of tumor localization, growth behavior and therapeutical response distinguish tumors in patients with HIV infection from those without. The pathologic and virological aspects of HIV-related tumors are peculiar and a pathological classification of HIV-associated systemic lymphomas based on the morphological features of the two main types, ie, blastic and anaplastic cell lymphomas, has been formulated. The treatment of HIV-related neoplasms is controversial as it is not clear whether conventional therapy, particularly chemotherapy, is able to modify the natural history of these malignancies in the HIV setting. Moreover the treatment of HIV-related tumors presents several problems due to the aggressive behaviors of tumors and because of immunosuppressive chemotherapy employed in patients with immunodeficiency. This paper reviews the most relevant data on the epidemiology, pathology and treatment of malignant tumors in patients with HIV infection.

AIDS-Related Opportunistic Infections↗

Solitary meningeal recurrence in a patient with transitional cell carcinoma of the bladder with locally bulky disease at presentation.

Patients with locally advanced transitional cell carcinoma (TCC) of the bladder are at high risk for systemic relapse, with liver, bone and lung being the commonest sites of metastases. We report the case of a 52-year-old woman with a solitary meningeal relapse, a rare site of recurrence, after 8 months of complete remission obtained with M-VEC for locally advanced TCC of the bladder. We speculate on the likely risk factors related to this unusual site of recurrence.

Carcinoma, Transitional Cell↗

HIV-associated human herpesvirus 8-positive primary lymphomatous effusions: radiologic findings in six patients.

PURPOSE: To define the imaging features of body cavity-based lymphoma (BCBL) related to the acquired immunodeficiency syndrome. This is a peculiar type of non-Hodgkin lymphoma harboring infection by human herpesvirus 8 (HHV-8) and displaying a peculiar tropism for the serous body cavities. MATERIALS AND METHODS: At diagnosis of BCBL, six consecutive patients were investigated with radiography of the chest and conventional computed tomography (CT) of the chest and abdomen. For all patients, clinical features and results of biologic characterization of the lymphoma were also available. RESULTS: In all patients, chest radiographs displayed bilateral or unilateral pleural effusion in the absence of parenchymal opacities or mediastinal enlargement. CT scans confirmed chest radiographic findings and revealed a slight thickening of the parietal pleura in all patients and a pericardial thickening in four patients. CT also depicted pericardial and abdominal effusions in five and two patients, respectively, in the absence of solid tumor masses or parenchymal abnormalities. CONCLUSION: BCBL must be included among the differential diagnoses of serous effusions detected radiologically in individuals infected with the human immunodeficiency virus (HIV). Since the combination of serous effusion, slight serosal thickening, and absence of solid masses is compatible with, though not specific for, BCBL in the context of HIV infection, radiologic findings need to be complemented by a detailed biologic and virologic characterization of tumor cells.

Adult↗

Human herpesvirus type-8 (HHV-8) in haematopoietic neoplasia.

Human herpesvirus type-8 (HHV-8) is a lymphotropic herpesvirus originally identified in Kaposi's sarcoma. Among lymphoproliferative disorders, HHV-8 infection is restricted to body-cavity-based lymphoma (BCBL) and multicentric Castleman's disease (MCD). BCBL are B-cell lymphomas growing in liquid phase in the body cavities and most frequently associated with AIDS. BCBL express indeterminate phenotypes, in all cases are associated with HHV-8 infection, and frequently carry Epstein-Barr virus genomes in the absence of c-MYC rearrangements or other genetic lesions characteristic of B-cell lymphomas. The clinical outcome of BCBL is poor with a median survival of only few months. MCD is an atypical lymphoproliferative disorder which displays marked vascular hyperplasia and is commonly associated with Kaposi's sarcoma. HHV-8 infection occurs in 100% of AIDS-related MCD and in approximately 40% of AIDS-unrelated cases. Overall, the consistency of HHV-8 infection in BCBL and MCD, its selectivity throughout the spectrum of lymphoproliferative disorders and the high copy number of HHV-8 DNA sequences in infected cells suggest that the virus plays a pathogenetic role in these disorders.

Acquired Immunodeficiency Syndrome↗

The effects of antineoplastic chemotherapy on HIV disease.

Six patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma receiving chemotherapy (CT) with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus granulocyte colony-stimulating factor were sequentially monitored to study the effects of these treatments on their immunologic status (CD4 and CD8 cell counts) and on HIV plasma viremia. We show that mean CD4 cell counts declined significantly after the third cycle of CT (187 +/- 117/microliters before CT versus 92.4 +/- 60/microliters; p = 0.04) and remained significantly reduced 4 months after completion of CT. Modifications of CD8 cell counts were not statistically significant. The effects of CT on plasma viremia, as measured by a competitive polymerase chain reaction technique, were delayed until the fourth cycle, when an increase of viral load ranging from 0.6 to 2 logs (p = 0.027) was observed. After this point, viremia returned to baseline levels, with the exception of two patients who later developed opportunistic infections and one who underwent disease progression. These results suggest that, contrary to CD4 cell counts, plasma viremia could be a faithful surrogate marker for monitoring of HIV disease progression in patients undergoing CT.

Antineoplastic Agents↗

Combination chemotherapy with doxorubicin, bleomycin, and vindesine for AIDS-related Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma is the most common neoplasm in patients with human immunodeficiency virus (HIV) infection. Although the best therapeutic approach is still unclear, patients with advanced KS are usually treated with systemic chemotherapy. METHODS: A prospective multiinstitutional Italian study evaluated the efficacy and toxicity of combination chemotherapy with doxorubicin, bleomycin, and vindesine (ABVi) in patients with progressive and extensive HIV-related KS. Patients were given doxorubicin, 20 mg/m2 on Day 1; bleomycin, 15 mg on Day 1, and vindesine, 4 mg on Day 1 biweekly +/- granulocyte-colony stimulating factor. RESULTS: Overall, 21 of 38 evaluable patients (55%) achieved an objective response (OR): there was 1 complete response and 20 partial responses. The most important bone marrow toxicity was granulocytopenia in 61% of the evaluable patients; 34% had Grades 3-4 toxicity, according to the World Health Organization Classification. The majority of patients (64%) developed some type of opportunistic infection (OI) during chemotherapy or the follow-up, with cytomegalovirus infection being the most frequent OI observed. The median duration of survival from KS diagnosis and from the start of ABVi therapy was 19 months (range, 3.4-88.5 months) and 9.9 months (range, 0.1-42.4 months), respectively. CONCLUSIONS: The high rate of OI during ABVi chemotherapy and the follow-up is of concern, although these infections possibly could be due to our patients' low CD4+ lymphocyte counts. However, no toxic death was observed in our patients, suggesting that ABVi could be used in patients with aggressive disease, especially those who were previously untreated.

Acquired Immunodeficiency Syndrome↗

Second-line chemotherapy in human immunodeficiency virus-related non-Hodgkin's lymphoma: evidence of activity of a combination of etoposide, mitoxantrone, and prednimustine in relapsed patients.

BACKGROUND: There is very little experience reported in the literature on the treatment of patients with relapsed or resistant human immunodeficiency virus-related non-Hodgkin's lymphoma (HIV-NHL). We performed a prospective study to evaluate the feasibility and activity of a second-line chemotherapy regimen consisting of etoposide, mitoxantrone, and prednimustine (VMP) in this setting. METHODS: Twenty-one patients were consecutively treated. Thirteen patients were resistant to primary chemotherapy and 8 patients had relapsed after their first complete remission (CR). Etoposide and prednimustine were both given orally at doses of 80 mg/m2 daily for 5 days, and mitoxantrone was given intravenously at a dose of 10 mg/m2 on Day 1; the cycles were repeated every 3 weeks. RESULTS: Nineteen of 21 patients were evaluable for response. The median number of cycles administered was 2 (range, 1-5). A CR occurred in 5 of 19 patients (26%; exact 95% confidence interval; 9-51%). Four of these CRs were observed in the 7 evaluable relapsed patients. Of 45 cycles evaluable for toxicity, severe neutropenia (< 500/microL) occurred in 19 (42%) cycles and severe thrombocytopenia (< 25,000/microL) in 6 (13%) cycles. One toxic death occurred due to sepsis during neutropenia. The overall median survival was 2 months (range, < 1-13 months); the median survival time for the 5 patients with CR (13 months; range, 6-13 months) was statistically significantly longer than that observed in patients without CR (2 months; range, < 1-7 months). CONCLUSIONS: Although the overall prognosis of patients with resistant or relapsed HIV-NHL is very poor, palliative therapy with VMP can be effective and relatively safe in the latter group. Prolonged survival has been observed in some patients who had relapsed after initial chemotherapy.

Adult↗

Human herpesvirus 6 in human immunodeficiency virus-infected individuals: association with early histologic phases of lymphadenopathy syndrome but not with malignant lymphoproliferative disorders.

Preliminary evidence suggested that human herpesvirus-6 (HHV-6) may act as a cofactor in acquired immunodeficiency syndrome (AIDS) and may contribute to the pathogenesis of lymphoproliferative disorders occurring in individuals infected with the human immunodeficiency virus (HIV). To understand better the biological and clinical significance of HHV-6 infection in the context of HIV-related immunosuppression, the polymerase chain reaction was used to study the frequency and variant distribution of HHV-6 in peripheral blood mononucleated cells (PBMCs) from HIV-seropositive individuals, either asymptomatic or with lymphadenopathy syndrome (LAS) or with overt AIDS. Non-neoplastic and malignant lymphoproliferative disorders from both HIV-infected and HIV-seronegative patients were also investigated using the same series of samples for the presence of Epstein-Barr virus (EBV). When compared with healthy blood donors (12/42, 29%), HHV-6 prevalence in PBMCs showed a progressive decline in HIV-seropositive individuals with asymptomatic HIV infection (3/26, 11%) and in patients with LAS (1/13, 8%) and a significant reduction in patients with overt AIDS (1/20, 20%; P = 0.02). The decrease correlated with the number of CD4+ cells at the time of examination. In addition, HHV-6 DNA sequences were significantly more prevalent in LAS biopsies (13/20, 65%) than in HIV-unrelated reactive lymphadenopathies (2/10, 20%; P = 0.02) and the presence of HHV-6 sequences correlated closely with a histologic pattern of follicular hyperplasia (13/16, 81%; P = 0.003). Strikingly, HHV-6 prevalence decreased in PBMCs of LAS patients, suggesting that the likelihood of interactions between HHV-6 and HIV varies in different body districts. In particular, the demonstration that all HHV-6-carrying LAS samples were also positive for HIV infection suggests that LAS lymph nodes constitute one of the sites where biologically relevant interactions between the two viruses might occur. Also, the prevalence of EBV was higher in LAS (14/20, 70%) than in non-neoplastic lymph nodes from HIV-seronegative individuals (4/10, 40%), although the difference was not statistically significant. EBV was associated strongly with HIV-related malignant lymphoproliferative disorders, being detected in 100% of patients with Hodgkin's disease (HD) and 53% of B-cell non-Hodgkin's lymphomas (NHL). In contrast, the prevalence of HHV-6 DNA in HD and B-cell NHL arisen in HIV-infected patients (30% and 6% respectively) was remarkably lower and similar to that observed in lymphoproliferative disorders from HIV-seronegative patients. Finally, as observed in healthy individuals, HHV-6 variant B was more prevalent than variant A in benign and malignant lymphoproliferative disorders from bot HIV-infected and HIV-seronegative patients. These results suggest that the interactions between HHV-6 and HIV could be different in the various phases of HIV disease and in different districts; HHV-6 has probably no direct role in the pathogenesis of HIV-associated B-cell NHL and HD cases, and behave differently from EBV; and HIV-related immunosuppression does not alter the distribution of HHV-6 variants in these tissues, as observed in the case of EBV.

AIDS-Related Complex↗

Long-term survival of patients with HIV-related systemic non-Hodgkin's lymphomas.

BACKGROUND: the overall outcome of patients with HIV-related non-Hodgkin's lymphomas (HIV-NHL) is poor because of the adverse clinico-pathological features of HIV-NHL and the underlying HIV infection. However, the experience of physicians in the management of HIV-NHL has increased, in particular in the use of intensive chemotherapy regimens, leading to an improvement in the prognosis of some of these neoplasms. Because some patients with AIDS may survive up to 5 years, it is possible to evaluate the long-term efficacy of the treatment of patients with HIV-NHL. In the general population, aggressive NHL, that are those occurring in HIV patients, may be considered cured after 2 years of lasting complete remission (CR) after chemotherapy. PATIENTS AND METHODS: we reviewed our monoinstitutional case-series of 73 HIV-infected patients with systemic NHL, observed between April 1985 and February 1993. Two groups of patients were arbitrarily identified, the first one (group A) including patients with a CR lasting for at least 2 years (N = 13) and the other including all remaining patients (group B) (N = 60). RESULTS: the 13 patients of group A differed significantly from the other patients in terms of higher CD4+ cell count and performance status (PS) at the time of diagnosis of NHL. There was no significant difference in the histological subtypes of the HIV-NHLs. The overall survival of the 73 patients was 8 months. In a separate analysis on all patients, age less than 30 years, PS less or equal to 1, a CD4+ cell count equal to or higher than 100/mm3 and the absence of B symptoms were significantly associated with a longer survival. The median survival in patients of group A was 42 months, however none of these patients relapsed during a median observation time of 42 months (range, 24-90). CONCLUSIONS: long-term survival and possibly cure can be obtained in some patients with HIV-NHL, in particular in those with a better PS and a less advanced immune dysfunction. In fact some of these patients are alive without evidence of disease 4 to 7 years after therapy, and others died of causes related to underlying HIV infection, in particular opportunistic infections, rather than relapse of NHL.

Adult↗

Immunophenotypic and molecular analyses of acquired immune deficiency syndrome-related and Epstein-Barr virus-associated lymphomas: a comparative study.

Limited information is current available on the molecular and immunophenogenotypic characteristics of CD30-positive anaplastic large cell (ALC) lymphomas occurring in human immunodeficiency virus (HIV)-infected individuals. To address this issue, the authors have undertaken a combined analysis of these lymphomas in a comparison with other Epstein-Barr virus (EBV)-associated tumors in the setting of HIV infection. Twenty-one AIDS-related lymphomas, including five CD30-positive ALC and 11 small noncleaved cell (SNCC) lymphomas, and five Hodgkin's disease (HD) specimens were characterized regarding the immunophenogenotypic features, the frequency and subtype distribution of EBV (as defined by in situ hybridization [ISH], Southern blot, and a polymerase chain reaction [PCR] amplification of the EBV nuclear antigen-2 [EBNA-2] region) antigen expression (latent membrane protein-1 [LMP-1], EBNA-2, and for alterations of the tumor suppressor gene p53. Combined immunophenotypic and immunogenotypic analyses showed a derivation from anomalously matured B cells in four of five CD30-positive ALC lymphomas, whereas SNCC showed features of mature B cells; no evidence of immunoglobulin or TCR gene rearrangement could be obtained in HD cases. Combined ISH and Southern blot analyses revealed that EBV was more strictly associated with HD (five of five) and CD30-positive ALC lymphomas (four of five) than with SNCC lymphomas (four of 11). EBV-positive samples from CD30-positive ALC lymphomas carried type 1 EBV (two of two specimens tested), whereas both EBV subtypes were observed in SNCC lymphomas and HD samples. All three forms of viral latent gene expression were found in the EBV positive CD30-positive ALC lymphomas. SNCC specimens did not express LMP-1 or EBNA-2, whereas HD specimens expressed LMP-1 (four of five tested) but no EBNA-2. Immunostaining for ZEBRA was consistently negative. HHV-6 DNA sequences were detected by PCR in one SNCC of the 19 specimens analyzed. Three out of five CD30-positive ALC lymphoma specimens and six of 10 SNCC showed nuclear staining for p53. No mutation was detected in any of the three CD30-positive Alc lymphoma analyzed, whereas an aberrant SSCP pattern was found in all the four SNCC samples tested. At variance with SNCC lymphomas, AIDS-related B-cell CD30- positive ALC lymphomas are strictly associated with EBV infection and may also express the broad lymphoblastoid cell line-like (LMP-1-positive, EBNA-2-positive) pattern, and lack p53 genetic lesions. Unlike EBV, HHV-6 probably does not represent a relevant factor involved in the pathogenesis of CD30-positive ALC and other HIV related lymphomas.

Adult↗