Aims: To define the relationship between morphological injury of the intestinal mucosa and infect... more Aims: To define the relationship between morphological injury of the intestinal mucosa and infections in AIDS patients. Methods: Forty-nine AIDS patients were examined by upper gastrointestinal (GI) endoscopy and 8 of them also by lower GI endoscopy. Biopsy specimens, taken from the lower duodenum, esophagus and rectum, were studied by light (L.M.) and transmission electron microscopy (T.E.M.). Stool examination for microorganisms was routinely performed in all patients. Results: Microorganisms were detected in 37 of the 49 patients (75.5%) by combined tissue and stool examination. The histological study revealed villous atrophy, inter- and intra-enterocyte oedema and epithelial degenerative changes in most of the patients whether or not they had detectable microorganisms. Conclusions: Combined methods (endoscopy, L.M. and T.E.M., studies of tissue samples, microbiological study of stool samples) may be used to improve the documentation of infections and morphological injury of the intestinal mucosa in AIDS patients.
Aims: To define the relationship between morphological injury of the intestinal mucosa and infect... more Aims: To define the relationship between morphological injury of the intestinal mucosa and infections in AIDS patients. Methods: Forty-nine AIDS patients were examined by upper gastrointestinal (GI) endoscopy and 8 of them also by lower GI endoscopy. Biopsy specimens, taken from the lower duodenum, esophagus and rectum, were studied by light (L.M.) and transmission electron microscopy (T.E.M.). Stool examination for microorganisms was routinely performed in all patients. Results: Microorganisms were detected in 37 of the 49 patients (75.5%) by combined tissue and stool examination. The histological study revealed villous atrophy, inter- and intra-enterocyte oedema and epithelial degenerative changes in most of the patients whether or not they had detectable microorganisms. Conclusions: Combined methods (endoscopy, L.M. and T.E.M., studies of tissue samples, microbiological study of stool samples) may be used to improve the documentation of infections and morphological injury of the intestinal mucosa in AIDS patients.
Antiretrovirals related lipodystrophy may have a negative impact on quality of life due to disfig... more Antiretrovirals related lipodystrophy may have a negative impact on quality of life due to disfiguring body changes
The role of lipodystrophy as a factor affecting adherence has been suggested by several authors, ... more The role of lipodystrophy as a factor affecting adherence has been suggested by several authors, but up to now no clinical trials have been conducted to investigate this relation
Digestive apparatus is a common target of atypical mycobacteriosis in AIDS patients (at least 50%... more Digestive apparatus is a common target of atypical mycobacteriosis in AIDS patients (at least 50% of patients with CD4+ lymphocytes < 50/mm3). We describe the clinical-histological features of two cases of Whipple-like syndrome likely caused by Mycobacterium avium (MAI) (study performed by light and electron microscopy), of one case of infection caused by two morphological variants of a MAI strain with a different sensitivity to antibiotics, of one case of M. kansasii infection and of two cases of M. genavense infection accompanied by sensitivity tests to antibiotics (as far as we know, these are the first described quantitative sensitivity tests of M. genavense to antibiotics). In conclusion, we discuss the present therapeutical outlines for M. kansasii and avium, together with the teramporary pharmacological options for M. genavense as suggested by antibiotic sensitivity tests performed on the strains isolated from the studied patients.
International Journal of Antimicrobial Agents, Oct 1, 2019
OBJECTIVES This study aims to compare the tolerability and viro-immunologic efficacy of dolutegra... more OBJECTIVES This study aims to compare the tolerability and viro-immunologic efficacy of dolutegravir-based regimens (DTG group) with regimens based on EVG, RAL, PI, NNRTI (NODTG group) in patients with acute HIV-1 infections (AHI). METHODS All patients diagnosed with AHI between 2015 and 2017, who started ART in 5 different centers in Italy, were included and followed-up to 30th April 2018. AHI was defined by the presence of the positive p24 antigen with negative or indeterminate western blot. RESULTS Forty-three patients were enrolled: 20 on DTG, 23 in NODTG. Nine patients (20.9%), 4 in DTG and 5 in NODTG group, were prescribed a four-drug regimen. In the cohort, 81.4% were Italian and 83.7% males with a median age of 41 years (IQR 31-48). The median time elapsed between HIV diagnosis and ART initiation was 12 days [IQR 5-28]. Seven patients harbored a virus with transmitted mutations at baseline (16.2%), all in DTG group (p=0.005). All patients achieved HIV-RNA undetectable at the end of follow up except two subjects, of whom one had 57 copies and one was lost to follow-up. In Kaplan-Meier analysis, time to virologic suppression was not different between the two groups (log rank: p= 0.7155). After achieving virologic suppression, four patients stopped first ART due to toxicity: 2 on DTG, 2 on EVG for neurological and gastrointestinal toxicity, respectively. CONCLUSION In our setting, ART in AHI is started very early. DTG showed a good viro-immunologic efficacy even when NRTI transmitted mutations were present. DTG interruption rarely occurred.
In a multicentre, open-label, clinical trial, 43 patients virologically suppressed while receivin... more In a multicentre, open-label, clinical trial, 43 patients virologically suppressed while receiving a standard triple antiretroviral therapy were randomized (1:1:1) to switch to monotherapy with darunavir/ritonavir (DRV/r-MT arm), monotherapy with lopinavir/ritonavir (LPV/r-MT arm) or to continue on the ongoing regimen (cART arm). The proportion (95% CI) of patients with virological success (Snapshot analysis) at week 48 was 73% (48%-90%) in the DRV/r-MT arm, 69% (42%-88%) in the LPV/r-MT arm and 87% (61%-98%) in the cART arm. Virological failure was detected in only one patient receiving LPV/r-MT. The LPV/r-MT arm showed a modest worsening in lipid profile.
Journal of Antimicrobial Chemotherapy, Oct 22, 2022
Objectives We aimed to investigate and compare the efficacy and safety of two dolutegravir-based ... more Objectives We aimed to investigate and compare the efficacy and safety of two dolutegravir-based two-drug regimens: dolutegravir + lamivudine versus dolutegravir + rilpivirine. Methods We analysed a cohort of people living with HIV (PLWHIV) switching to dolutegravir + lamivudine or dolutegravir + rilpivirine. We excluded from the analysis PLWHIV with no available pre-switch genotypic test or with a known resistance mutation to one of the study drugs. We evaluated incidence of virological failure (VF) and treatment discontinuation (TD), as well as changes in immunological and metabolic parameters. Results We enrolled 592 PLWHIV: 306 in the lamivudine group and 286 in the rilpivirine group. We observed nine VFs in the lamivudine group [1.4 VF per 100 patient-years of follow-up (PYFU)] and four VFs in the rilpivirine group (0.6 VF per 100 PYFU). Subsequent genotypic analysis showed no acquired resistance-associated mutations in those experiencing VF. Estimated probability of maintaining virological suppression at 144 and 240 weeks were 96.6% and 92.7%, respectively, in the lamivudine group and 98.7% and 98.7%, respectively, in the rilpivirine group (log-rank P = 0.172). The estimated probability of maintaining study regimen at Week 240 was 82.3% in the lamivudine group and 85.9% in the rilpivirine group (log-rank P = 0.018). We observed a significant improvement in CD4+ cell count at Week 240 in the lamivudine group (P = 0.012); in the rilpivirine group we registered a significant increase in CD4/CD8 ratio (P = 0.014). Conclusions Both analysed strategies are effective and safe as switch strategies in clinical practice, with a low incidence of VF and a favourable immunological recovery, even in the long term.
International Journal of Antimicrobial Agents, 2022
BACKGROUND The impact of drug resistance mutational load and APOBEC editing in heavily treatment-... more BACKGROUND The impact of drug resistance mutational load and APOBEC editing in heavily treatment-experienced (HTE) people living with multidrug-resistant HIV has not been investigated. MATERIAL AND METHODS We explored the HIV-DNA and HIV-RNA mutational load of drug resistance and APOBEC-related mutations through next-generation sequencing (NGS, Illumina MiSeq) in 20 failing HTE persons enrolled in the PRESTIGIO registry. RESULTS Patients showed high levels of both HIV-DNA (4.5 [4.0-5.2] log10 copies/106 T-CD4+ cell) and HIV-RNA (4.5 [4.1-5.0] log10 copies/mL) with complex resistance patterns in both compartments. Among the 255 drug resistance mutations found, 66.3% were concordantly detected in both HIV-DNA and HIV-RNA; 71.3% of mutations were already present in historical Sanger genotypes. At intra-patient frequency >5%, a considerable proportion of mutations detected through DNA-NGS were found in historical genotypes but not through RNA-NGS, and few patients had APOBEC-related mutations. Of 14 individuals who switched therapy, those five who failed treatment had DNA resistance with higher intra-patient frequency, higher DNA/RNA mutational load in a context of tendentially less pronounced APOBEC editing compared to those who responded. CONCLUSIONS Using NGS in HIV-DNA and HIV-RNA together with APOBEC editing evaluation might help to identify HTE individuals with MDR who are more prone to experience virological failure.
Aims: To define the relationship between morphological injury of the intestinal mucosa and infect... more Aims: To define the relationship between morphological injury of the intestinal mucosa and infections in AIDS patients. Methods: Forty-nine AIDS patients were examined by upper gastrointestinal (GI) endoscopy and 8 of them also by lower GI endoscopy. Biopsy specimens, taken from the lower duodenum, esophagus and rectum, were studied by light (L.M.) and transmission electron microscopy (T.E.M.). Stool examination for microorganisms was routinely performed in all patients. Results: Microorganisms were detected in 37 of the 49 patients (75.5%) by combined tissue and stool examination. The histological study revealed villous atrophy, inter- and intra-enterocyte oedema and epithelial degenerative changes in most of the patients whether or not they had detectable microorganisms. Conclusions: Combined methods (endoscopy, L.M. and T.E.M., studies of tissue samples, microbiological study of stool samples) may be used to improve the documentation of infections and morphological injury of the intestinal mucosa in AIDS patients.
Aims: To define the relationship between morphological injury of the intestinal mucosa and infect... more Aims: To define the relationship between morphological injury of the intestinal mucosa and infections in AIDS patients. Methods: Forty-nine AIDS patients were examined by upper gastrointestinal (GI) endoscopy and 8 of them also by lower GI endoscopy. Biopsy specimens, taken from the lower duodenum, esophagus and rectum, were studied by light (L.M.) and transmission electron microscopy (T.E.M.). Stool examination for microorganisms was routinely performed in all patients. Results: Microorganisms were detected in 37 of the 49 patients (75.5%) by combined tissue and stool examination. The histological study revealed villous atrophy, inter- and intra-enterocyte oedema and epithelial degenerative changes in most of the patients whether or not they had detectable microorganisms. Conclusions: Combined methods (endoscopy, L.M. and T.E.M., studies of tissue samples, microbiological study of stool samples) may be used to improve the documentation of infections and morphological injury of the intestinal mucosa in AIDS patients.
Antiretrovirals related lipodystrophy may have a negative impact on quality of life due to disfig... more Antiretrovirals related lipodystrophy may have a negative impact on quality of life due to disfiguring body changes
The role of lipodystrophy as a factor affecting adherence has been suggested by several authors, ... more The role of lipodystrophy as a factor affecting adherence has been suggested by several authors, but up to now no clinical trials have been conducted to investigate this relation
Digestive apparatus is a common target of atypical mycobacteriosis in AIDS patients (at least 50%... more Digestive apparatus is a common target of atypical mycobacteriosis in AIDS patients (at least 50% of patients with CD4+ lymphocytes < 50/mm3). We describe the clinical-histological features of two cases of Whipple-like syndrome likely caused by Mycobacterium avium (MAI) (study performed by light and electron microscopy), of one case of infection caused by two morphological variants of a MAI strain with a different sensitivity to antibiotics, of one case of M. kansasii infection and of two cases of M. genavense infection accompanied by sensitivity tests to antibiotics (as far as we know, these are the first described quantitative sensitivity tests of M. genavense to antibiotics). In conclusion, we discuss the present therapeutical outlines for M. kansasii and avium, together with the teramporary pharmacological options for M. genavense as suggested by antibiotic sensitivity tests performed on the strains isolated from the studied patients.
International Journal of Antimicrobial Agents, Oct 1, 2019
OBJECTIVES This study aims to compare the tolerability and viro-immunologic efficacy of dolutegra... more OBJECTIVES This study aims to compare the tolerability and viro-immunologic efficacy of dolutegravir-based regimens (DTG group) with regimens based on EVG, RAL, PI, NNRTI (NODTG group) in patients with acute HIV-1 infections (AHI). METHODS All patients diagnosed with AHI between 2015 and 2017, who started ART in 5 different centers in Italy, were included and followed-up to 30th April 2018. AHI was defined by the presence of the positive p24 antigen with negative or indeterminate western blot. RESULTS Forty-three patients were enrolled: 20 on DTG, 23 in NODTG. Nine patients (20.9%), 4 in DTG and 5 in NODTG group, were prescribed a four-drug regimen. In the cohort, 81.4% were Italian and 83.7% males with a median age of 41 years (IQR 31-48). The median time elapsed between HIV diagnosis and ART initiation was 12 days [IQR 5-28]. Seven patients harbored a virus with transmitted mutations at baseline (16.2%), all in DTG group (p=0.005). All patients achieved HIV-RNA undetectable at the end of follow up except two subjects, of whom one had 57 copies and one was lost to follow-up. In Kaplan-Meier analysis, time to virologic suppression was not different between the two groups (log rank: p= 0.7155). After achieving virologic suppression, four patients stopped first ART due to toxicity: 2 on DTG, 2 on EVG for neurological and gastrointestinal toxicity, respectively. CONCLUSION In our setting, ART in AHI is started very early. DTG showed a good viro-immunologic efficacy even when NRTI transmitted mutations were present. DTG interruption rarely occurred.
In a multicentre, open-label, clinical trial, 43 patients virologically suppressed while receivin... more In a multicentre, open-label, clinical trial, 43 patients virologically suppressed while receiving a standard triple antiretroviral therapy were randomized (1:1:1) to switch to monotherapy with darunavir/ritonavir (DRV/r-MT arm), monotherapy with lopinavir/ritonavir (LPV/r-MT arm) or to continue on the ongoing regimen (cART arm). The proportion (95% CI) of patients with virological success (Snapshot analysis) at week 48 was 73% (48%-90%) in the DRV/r-MT arm, 69% (42%-88%) in the LPV/r-MT arm and 87% (61%-98%) in the cART arm. Virological failure was detected in only one patient receiving LPV/r-MT. The LPV/r-MT arm showed a modest worsening in lipid profile.
Journal of Antimicrobial Chemotherapy, Oct 22, 2022
Objectives We aimed to investigate and compare the efficacy and safety of two dolutegravir-based ... more Objectives We aimed to investigate and compare the efficacy and safety of two dolutegravir-based two-drug regimens: dolutegravir + lamivudine versus dolutegravir + rilpivirine. Methods We analysed a cohort of people living with HIV (PLWHIV) switching to dolutegravir + lamivudine or dolutegravir + rilpivirine. We excluded from the analysis PLWHIV with no available pre-switch genotypic test or with a known resistance mutation to one of the study drugs. We evaluated incidence of virological failure (VF) and treatment discontinuation (TD), as well as changes in immunological and metabolic parameters. Results We enrolled 592 PLWHIV: 306 in the lamivudine group and 286 in the rilpivirine group. We observed nine VFs in the lamivudine group [1.4 VF per 100 patient-years of follow-up (PYFU)] and four VFs in the rilpivirine group (0.6 VF per 100 PYFU). Subsequent genotypic analysis showed no acquired resistance-associated mutations in those experiencing VF. Estimated probability of maintaining virological suppression at 144 and 240 weeks were 96.6% and 92.7%, respectively, in the lamivudine group and 98.7% and 98.7%, respectively, in the rilpivirine group (log-rank P = 0.172). The estimated probability of maintaining study regimen at Week 240 was 82.3% in the lamivudine group and 85.9% in the rilpivirine group (log-rank P = 0.018). We observed a significant improvement in CD4+ cell count at Week 240 in the lamivudine group (P = 0.012); in the rilpivirine group we registered a significant increase in CD4/CD8 ratio (P = 0.014). Conclusions Both analysed strategies are effective and safe as switch strategies in clinical practice, with a low incidence of VF and a favourable immunological recovery, even in the long term.
International Journal of Antimicrobial Agents, 2022
BACKGROUND The impact of drug resistance mutational load and APOBEC editing in heavily treatment-... more BACKGROUND The impact of drug resistance mutational load and APOBEC editing in heavily treatment-experienced (HTE) people living with multidrug-resistant HIV has not been investigated. MATERIAL AND METHODS We explored the HIV-DNA and HIV-RNA mutational load of drug resistance and APOBEC-related mutations through next-generation sequencing (NGS, Illumina MiSeq) in 20 failing HTE persons enrolled in the PRESTIGIO registry. RESULTS Patients showed high levels of both HIV-DNA (4.5 [4.0-5.2] log10 copies/106 T-CD4+ cell) and HIV-RNA (4.5 [4.1-5.0] log10 copies/mL) with complex resistance patterns in both compartments. Among the 255 drug resistance mutations found, 66.3% were concordantly detected in both HIV-DNA and HIV-RNA; 71.3% of mutations were already present in historical Sanger genotypes. At intra-patient frequency >5%, a considerable proportion of mutations detected through DNA-NGS were found in historical genotypes but not through RNA-NGS, and few patients had APOBEC-related mutations. Of 14 individuals who switched therapy, those five who failed treatment had DNA resistance with higher intra-patient frequency, higher DNA/RNA mutational load in a context of tendentially less pronounced APOBEC editing compared to those who responded. CONCLUSIONS Using NGS in HIV-DNA and HIV-RNA together with APOBEC editing evaluation might help to identify HTE individuals with MDR who are more prone to experience virological failure.
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Papers by Gaetana Sterrantino