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Biomedical subjects

Fabio Soldani

Publications and source records attributed to Fabio Soldani.

7 recordsLinked to original sources
PubMed2006

Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir.

The mutation RT-K65R confers resistance to tenofovir (TDF). Although its prevalence is increasing with the use of this drug, clinical and genotypic correlates of K65R occurrence have yet to be fully identified. Clinical, virological and immunological and genotypic data of patients naïve for TDF who failed HAART regimens and underwent genotypic resistance test (GRT) during 1999-2003 were collected in a database and analyzed retrospectively. Out of 1392 GRT performed for 771 patients, 12 TDF-naïve patients had the K65R mutation with an overall prevalence of 1.6%. Previous AIDS, the use of abacavir, and treatment with efavirenz at GRT were independently associated with a greater risk of expressing K65R, while patients with longer exposure to lamivudine were less likely to present the mutation. Among genotypic correlates, the presence of M184V and NAMs seems to be protective for the emergence of K65R, while a strong positive correlation was found with the Q151M complex mutation. Moreover, the L100I mutation was independently associated with a higher probability of presenting K65R. The selection of mutation K65R in patients failing without TDF is rare. However, exposure to abacavir and/or efavirenz, presence of Q151M and/or L100I, and prior AIDS may favor the selection of this mutation. Conversely, long 3TC exposure, and the presence of M184V or NAMs seem to be protective.

Adenine↗
PubMed2004

Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy.

Among 470 patients with acquired immune deficiency syndrome and/or human immunodeficiency virus infection (HIV/AIDS) who underwent genotype resistance testing (GRT) after the failure of therapy, 17 (3.6%) harbored the Q151M mutation. The Q151M mutation was associated with younger age, lower CD4(+) lymphocyte count, higher HIV RNA level, and treatment with >2 pre-GRT regimens. By contrast, the Q151M mutation was inversely associated with lamivudine administration. A full reversion of the Q151M mutation was observed in 5 of 5 patients who underwent treatment interruption after GRT. The reversion was followed by a response to salvage therapy in 4 (80%) of 5 patients.

Adult↗
PubMed2004

Post-exposure prophylaxis of HIV infection in healthcare workers: recommendations for the European setting.

The European Commission funded a project for the standardisation of the management of occupational exposures to HIV/blood-borne infections and antiretroviral post-exposure prophylaxis (PEP) in Europe. Within this project, the following recommendations and rationale were formulated by experts representative of participating countries. Based on assessment of the exposure, material, and source characteristics, PEP should be started as soon as possible with any triple combination of antiretrovirals approved for the treatment of HIV-infected patients; initiation is discouraged after 72 hours Rapid HIV testing of the source could reduce inappropriate PEP. HIV testing should be performed at baseline, 4, 12, and 24 weeks, with additional clinical and laboratory monitoring of adverse reactions and potential toxicity at week 1 and 2. HIV resistance tests in the source and direct virus assays in the exposed HCW are not recommended routinely. These easy-to-use recommendations seek to maximise PEP effect while minimising its toxicity and inappropriate use.

Anti-HIV Agents↗
PubMed2003

Drug-induced aminotransferase alterations during antiretroviral HIV post-exposure prophylaxis.

In 655 individuals receiving HIV postexposure prophylaxis (PEP), drug-induced aminotransferase alterations were frequent and severe in the nevirapine-including regimen, rare and mild-to-moderate in other combinations, and always reversible. Grade 3-4 incidence in protease inhibitor or nevirapine PEP was 0.5 and 25.0 per 100 person-months, respectively. Apart from nevirapine, continuing PEP appears to be safe even in the case of aminotransferase alterations. The usefulness of routine monitoring of liver function during PEP could be re-considered.

Adolescent↗
PubMed2003

HIV Type 1 replication in cerebrospinal fluid of patients with AIDS-related non-Hodgkin's lymphoma receiving chemotherapy and antiretroviral therapy.

Chemotherapy for cancer could have negative effects on HIV-1 dynamic in addition to the effects on immunological status. At the moment few data are available about the effects of chemotherapy on systemic HIV-1 replication, but the effects on the central nervous system, considered an independent compartment for viral replication, has never been investigated. We studied 19 HIV-1-infected patients with non-Hodgkin lymphoma (NHL) treated concomitantly with chemotherapy and highly active antiretroviral therapy (HAART) to evaluate HIV-1 replication and assess virological response to HAART in cerebrospinal fluid during chemotherapy. No patients were diagnosed with lymphoma involvement of the central nervous system. In 18 of 19 patients an HIV-1 load below 200 copies/ml was obtained in cerebrospinal fluid (CSF) during treatment. A correlation between plasma and CSF HIV-1 RNA levels was present at baseline, and was confirmed at the fourth cycle of chemotherapy. A significant decline in the mean difference between plasma and CSF HIV-1 RNA load was observed when comparing the value at the first cycle of chemotherapy with subsequent cycles. HAART even during chemotherapy allows us to obtain an effective control of HIV-1 infection in CSF in patients affected by NHL. In HIV-infected patients with NHL, the contemporaneous administration of HAART and chemotherapy is advisable to obtain a suppression of HIV-1 replication in CNS compartment during the potentially immunosuppressing effect of cancer treatment.

Adult↗
PubMed2002

Factors influencing virological response to antiretroviral drugs in cerebrospinal fluid of advanced HIV-1-infected patients.

OBJECTIVE: To determine the effectiveness of antiretroviral therapy in controlling cerebrospinal fluid (CSF) HIV-1 replication and to assess factors related to virological response in advanced patients. DESIGN: A cross-sectional and longitudinal study. METHODS: Consecutive paired CSF and plasma samples from HIV-1-infected patients were collected before starting or changing highly active antiretroviral therapy (HAART). RESULTS: In the cross-sectional analysis 75 patients were included, 55 (73%) with neurological disease, 28 (37%) naive for antiretroviral agents. A significant correlation between plasma and CSF levels at baseline was observed only in antiretroviral-experienced patients. The absence of neurological disease, lower plasma HIV-1 load and a previous exposure to indinavir were all associated with a baseline CSF HIV-1-RNA level less than 80 copies/ml at multivariate analysis. In 29 patients included in the longitudinal study a significant reduction in CSF HIV-1 RNA was observed. Plasma HIV-1-RNA change, CSF HIV-1-RNA level at baseline, overall months of antiretroviral treatment and the magnitude of difference between plasma and CSF HIV-1-RNA levels were all correlated to CSF HIV-1-RNA change during treatment. A significant difference in the magnitude of CSF HIV-1-RNA reduction was observed according to naive status and to the use of three or more drugs penetrating the blood-brain barrier. CONCLUSION: HAART effectively reduces HIV-1 replication in CSF. A variable response to antiretroviral therapy was observed in CSF, reflecting a different compartmentalization of infection during treatment. Naive status and the use of CNS-penetrating drugs substantially enhance antiviral response. A negative interaction between virological response and the duration of antiretroviral treatment suggests long-term selection of drug-resistant CSF HIV-1 strains.

Adult↗