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1.
J Low Genit Tract Dis ; 27(3): 236-241, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37052458

RESUMEN

BACKGROUND: Lichen sclerosus (LS) is an inflammatory disease mostly arising at the genital level. It is unclear whether human papillomaviruses (HPVs) have an etiological significance in LS, and data on their prevalence in patients with LS are controversial. OBJECTIVES: The authors assessed alpha, beta, and gamma HPV prevalence in patients with genital LS. The association of HPV positivity with demographic and clinical factors was also investigated. METHODS: One hundred thirty-two formalin-fixed, paraffin-embedded LS samples (2016-2020) were retrieved from the archives of a pathology department. Alpha HPVs were genotyped with the INNO-LiPA HPV Genotyping Extra II kit. Beta and gamma HPVs were searched by multiplex Polymerase Chain Reaction. Immunostaining for p16 INK4a was performed on high-risk HPV-positive samples. RESULTS: Patients had a median age of 61 years, were mostly women ( n = 73, 55.3%), and with an early disease stage ( n = 79, 59.8%). Alpha HPVs were detected in 12/132 cases (9.1%). Among the 5 high-risk HPV-positive cases, only 2 displayed a strong and diffuse p16 INK4a staining. Beta genus was the most prevalent (35/132, 26.5%) and HPV5 was the most frequent beta genotype (25/132, 18.9%). There were 3 gamma HPV-positive cases among those with a valid result (3/131, 2.3%). Multiple infections with genotypes belonging to different genera were infrequent (3/131, 2.3%). No significant differences in the prevalence of the individual genera were observed according to sex and disease stage. CONCLUSIONS: Of the 3 HPV genera, beta genus showed the highest prevalence. Further research is needed to clarify whether the presence of beta HPVs in genital LS has a clinical significance.


Asunto(s)
Liquen Escleroso y Atrófico , Infecciones por Papillomavirus , Humanos , Femenino , Persona de Mediana Edad , Masculino , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Virus del Papiloma Humano , Liquen Escleroso y Atrófico/epidemiología , Liquen Escleroso y Atrófico/complicaciones , Estudios Retrospectivos , Estudios Transversales , Papillomaviridae/genética , Genotipo , Genitales , ADN Viral
2.
Sex Transm Infect ; 98(6): 420-426, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34789510

RESUMEN

OBJECTIVES: To evaluate and characterise meningococcal carriage among healthy men who have sex with men (MSM) within a screening programme for Neisseria gonorrhoeae infection at the San Gallicano Dermatological Institute, Italy. METHODS: A total of 441 MSM attending the STI/HIV Centre of the San Gallicano Institute, Rome, Italy, in 2016 were routinely screened for N. gonorrhoeae infection by pharyngeal and rectal swabs. N. meningitidis isolates were evaluated for antibiotic susceptibility and characterised by whole genome sequencing. Genetic relationships among the meningococcal carriage isolates were determined using core genome multilocus sequence typing analysis. The soluble domain of AniA (sAniA) protein expression by western blotting was also evaluated. RESULTS: A total of 62 (14.1%, 95% CI 11.1 to 17.6) carriage meningococci were found among 441 MSM. Forty-three viable N. meningitidis isolates were cultivated (42 from pharyngeal and 1 from rectal swabs). All the viable isolates were susceptible to cefotaxime, ceftriaxone, ciprofloxacin and rifampicin. Four isolates were penicillin G-resistant and 73% of those penicillin G-susceptible showed a minimum inhibitory concentration from 0.064 µg/mL to 0.25 µg/mL. Serogroup B was the most frequent (44.2%), followed by Z (16.3%), E (9.3%), and Y and W (2.3%), respectively. Multilocus sequence typing analysis identified 29 sequence types belonging to 12 clonal complexes. The sAniA protein was expressed in 8 out of 28 (29%) screened meningococcal carriage isolates. CONCLUSIONS: Serogroup B meningococcal carriage identified from oral and anal specimens among healthy MSM was the most frequent serogroup identified in this study. Molecular evaluation revealed a degree of similarity among strains belonging to the same clonal complex.


Asunto(s)
Infecciones Meningocócicas , Neisseria meningitidis , Minorías Sexuales y de Género , Antibacterianos/farmacología , Portador Sano/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Infecciones Meningocócicas/diagnóstico , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/prevención & control , Neisseria meningitidis/genética
3.
J Antimicrob Chemother ; 76(12): 3272-3279, 2021 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-34529797

RESUMEN

OBJECTIVES: To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options. METHODS: HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm. RESULTS: Overall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33-211) and 312 (155-517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%-10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count <200 cells/mm3, who were perinatally infected and with a long treatment history significantly increased as FPR levels decreased. Regarding resistance, 933 (67.5%) individuals accumulated at least one class resistance, with 52.7%, 48.2%, 23.5% and 13.2% of individuals showing resistance to NRTIs, NNRTIs, PIs and INIs; while 23.2%, 27.2%, 14.3% and 2.8% harboured resistance to 1, 2, 3 and 4 classes, respectively. Individuals with FPR ≤5% showed a significantly higher level of resistance to PIs, NRTIs and INIs compared with others. The proportion of individuals harbouring strains susceptible to ≤2 active drugs was only about 2%; nonetheless, this proportion doubled (4.6%) in patients infected with FPR ≤5%. CONCLUSIONS: Our findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.


Asunto(s)
Infecciones por VIH , VIH-1 , Recuento de Linfocito CD4 , Genotipo , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Tropismo , Carga Viral , Tropismo Viral
4.
Sex Transm Infect ; 96(7): 528-536, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32001661

RESUMEN

OBJECTIVE: We aimed to assess incidence and clearance of oral human papillomavirus (HPV) infection and the respective risk factors in HIV-infected and uninfected men who have sex with men (MSM). METHODS: Oral rinse and gargles were collected semiannually from 244 MSM (103, 42.2% HIV-infected). HPV-DNA testing was performed with the Linear Array HPV Genotyping test. A Markov model was used for estimation of incidence, clearance and risk factor analysis. RESULTS: Incidence rates for any HPV were 21.2 and 15.0×1000 person-months in HIV-infected and uninfected MSM, respectively. The respective figures for high-risk HPVs were 10.7 and 6.5×1000 person-months. The clearance rate was 4-12 times higher than the respective incidence rate. HIV-infected MSM with >95 lifetime oral sex partners showed increased incidence of any HPV (adjusted HR, aHR: 8.46, 95% CI 1.89 to 37.92). Condomless oral sex appeared the strongest predictor for incident infection by high-risk HPVs in this group (aHR: 13.40, 95% CI 2.55 to 70.53). Those aged >46 years (aHR: 0.30, 95% CI 0.12 to 0.74) and those with nadir CD4+ T count of <200 cells/mm3 (aHR: 0.14, 95% CI 0.03 to 0.75) displayed a significantly reduced clearance of any and high-risk HPVs, respectively. HIV-uninfected MSM aged >46 years had increased risk of acquiring any HPV (aHR: 3.70, 95% CI 1.30 to 10.52) and high-risk HPV (aHR: 5.33, 95% CI 1.06 to 26.68). Any HPV clearance declined in those with more than six recent oral sex partners (aHR: 0.18, 95% CI 0.05 to 0.65). CONCLUSIONS: Acquisition of oral HPV infection in MSM seems to occur rarely, whereas clearance seems to be a frequent event. Oral HPV natural history in these at-risk subjects is differently influenced by age and sex behaviour, depending on HIV status.


Asunto(s)
Infecciones por VIH/epidemiología , Boca/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Adulto , Genotipo , Homosexualidad Masculina , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Estudios Prospectivos , Factores de Riesgo , Minorías Sexuales y de Género
5.
Dermatol Ther ; 33(6): e14277, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32888384

RESUMEN

Lichen sclerosus (LS) is a chronic relapsing, inflammatory skin disorder usually involving the anogenital region of both sexes lacking a resolutive therapy. This study compared adipose tissue derived-stromal vascular fraction (AD-SVF) and AD-SVF-enriched platelet-rich plasma (PRP) therapy in the management of genital LS patients. Additionally, in vitro evaluation of cells and growth factors contained in the injected SVF has been evaluated as possible predictive factors for treatment outcome. The study population was 40 patients diagnosed with LS who were symptomatic despite medical treatment. Patients (age 43-78 years) randomized into two groups using a 1:1 allocation ratio, were evaluated clinically and assessing dermatology life quality index (DLQI) before and 6 months after treatment. Both procedures demonstrated a strong safety profile with no complications linked to the therapy. After 6 months, both treatments allowed for a significant improvement respect to baseline. Combinatory therapy demonstrated decreased efficacy in late stage patients. No correlations have been found between clinical and biological findings. AD-SVF and AD-SVF plus PRP are safe and effective regenerative approaches for genital LS patients. Clinical results support the preferential use of combinatory therapy for early stage patients confirming a synergic effect of AD-SVF and PRP. In contrast, AD-SVF plus PRP is discouraged for late stage patients.


Asunto(s)
Liquen Escleroso y Atrófico , Tejido Adiposo , Adulto , Anciano , Femenino , Genitales , Humanos , Liquen Escleroso y Atrófico/diagnóstico , Liquen Escleroso y Atrófico/terapia , Masculino , Persona de Mediana Edad , Plasma Rico en Plaquetas , Piel
6.
Cancer ; 125(15): 2587-2593, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31034590

RESUMEN

BACKGROUND: Testing for oral high-risk human papillomavirus (HPV) DNA may be useful for identifying individuals at increased risk for HPV-driven oropharyngeal cancer (OPC). However, positivity for HPV DNA provides no information on the transforming potential of the infection. In contrast, the detection of high-risk HPV E6/E7 messenger RNA (mRNA) may help to identify clinically significant infections because of the indispensable role of E6/E7 viral oncoproteins in the carcinogenic process. METHODS: Oral rinses were collected with a mouthwash from cancer-free individuals at increased risk for oral HPV infection. High-risk HPV DNA and mRNA were evaluated via the testing of the oral rinses with the Linear Array HPV genotyping test and the Aptima HPV assay, respectively. RESULTS: Overall, 310 subjects with no clinical evidence of lesions of the oral cavity and oropharynx were included in the study. Thirty-three (10.6%) harbored high-risk HPV DNA in their oral rinse. These cases, together with 10 random samples negative for high-risk HPV DNA, were tested with the Aptima assay. A valid result was obtained for 41 of the 43 specimens (95.3%). Among the 31 cases that were positive for high-risk HPV DNA and had a valid Aptima result, 4 (12.9%) were positive for HPV mRNA. HPV mRNA was not detected in any of the samples negative for high-risk HPV DNA. CONCLUSIONS: HPV mRNA is detectable in oral rinses of cancer-free subjects. Oral HPV mRNA testing may be useful in the screening and/or early detection of HPV-driven OPC by possibly identifying active and transforming oral infections. The testing of individuals at increased risk for HPV-related OPC via simply and noninvasively collected oral specimens is an attractive option for future screening strategies.


Asunto(s)
ADN Viral/genética , Neoplasias Orofaríngeas/genética , Infecciones por Papillomavirus/complicaciones , ARN Mensajero/genética , Adulto , Femenino , Técnicas de Genotipaje , Humanos , Persona de Mediana Edad , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/virología , Factores de Riesgo
7.
Sex Transm Infect ; 95(8): 588-593, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31101722

RESUMEN

BACKGROUND: An observational study was conducted to assess recreational drug use in association with recent STIs among clients of an STI/HIV reference centre in Rome, Italy. METHODS: Attendees self-compiled a questionnaire concerning sexual behaviours and drug use, including the nine drugs used for sex (amphetamines, poppers, cocaine, ketamine, erectile dysfunction agent (EDA), steroids and the three chemsex drugs, ie, chems: γ-hydroxybutyric acid/γ-butyrolactone, crystal and Mcat). RESULTS: Overall, 703 patients participated, with men who have sex with men (MSM) accounting for 50.4% of the total and 73.2% of HIV-positive patients. Apart from condylomatosis, whose prevalence was higher among females (38.8%) and non-MSM (45.8%) than MSM (14.4%), STIs were more frequent among MSM, particularly syphilis (14.1%), gonorrhoea (4.8%), urethritis (3.4%) and hepatitis A (6.5%). Recreational drug use was significantly more frequent among MSM (39.8% vs 17.6% in females and 22.7% in non-MSM). A total of 26.3% of MSM used at least one of the nine drugs and 5.1% at least one of the three chems. Cocaine (13.3%) and poppers (13.0%) were the most used sex drugs in MSM.The use of any of the nine drugs was associated with being MSM (adjusted OR (AOR): 1.94, 95% CI 1.05 to 3.58), sex with partner contacted online (1.99, 95% CI 1.14 to 3.45), group sex (4.08, 95% CI 2.40 to 6.93) and STI in the last year (1.65, 95% CI 1.05 to 2.61). Use of any of the nine chems among MSM was associated with condomless sex (2.24, 95% CI 1.21 to 4.14), group sex (2.08, 95% CI 1.01 to 4.31) and STI diagnosis in the last year (4.08, 95% CI 2.32 to 7.19). CONCLUSIONS: Our data suggest that recreational drug use is quite common among MSM in Italy. No evidence of association with STI was found among non-MSM and females, where only cannabis and cocaine use was reported. The use of chems is still limited, but cocaine, poppers and EDA are widely used among MSM. Recreational drug use appears associated with high-risk sexual behaviours and a higher risk of STI.


Asunto(s)
Utilización de Medicamentos/estadística & datos numéricos , Drogas Ilícitas , Enfermedades de Transmisión Sexual/epidemiología , Trastornos Relacionados con Sustancias/complicaciones , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Ciudad de Roma/epidemiología , Conducta Sexual/estadística & datos numéricos , Encuestas y Cuestionarios
9.
J Antimicrob Chemother ; 73(7): 1949-1954, 2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29788156

RESUMEN

Background: Biomarkers of systemic inflammation predict non-AIDS events and overall mortality in virologically suppressed HIV-1-infected patients. Objectives: To determine whether switching to a dual antiretroviral maintenance therapy was associated with modification of biomarkers of systemic inflammation as compared with continuation of successful standard triple therapy. Methods: In this substudy of the randomized ATLAS-M trial, we compared in virologically suppressed patients the impact at 1 year of simplification to a dual therapy with atazanavir/ritonavir plus lamivudine versus maintaining atazanavir/ritonavir plus two NRTI triple therapy on markers of systemic inflammation. Plasma levels of interleukin-6, C-reactive protein (CRP), soluble CD14 (sCD14) and D-dimer were quantified by ELISA at baseline and at 48 weeks. Results: A subset of 139 of 266 randomized patients with available samples was analysed: 69 in the triple therapy arm and 70 in the dual therapy arm. The baseline biomarker levels were comparable between randomization arms. No significant differences in changes from baseline to week 48 were observed between arms (dual therapy versus triple therapy): IL-6, -0.030 versus -0.016 log10 pg/L; CRP, +0.022 versus +0.027 log10 pg/mL; sCD14, -0.016 versus +0.019 log10 pg/mL; and D-dimer, -0.031 versus +0.004 log10 pg/mL. A history of cancer was associated with higher baseline levels of IL-6 (P = 0.002) and CRP (P = 0.049). No relationship was observed between baseline biomarker level and persistent residual viraemia, HIV-1 DNA load, plasma lipids and other potential explanatory variables. Conclusions: Simplification with atazanavir/ritonavir plus lamivudine does not affect plasma markers of systemic inflammation in virologically suppressed patients. The association between these findings and clinical outcomes requires further evaluation.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Sulfato de Atazanavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inflamación/sangre , Lamivudine/uso terapéutico , Ritonavir/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa , Biomarcadores/sangre , Quimioterapia Combinada , Femenino , Infecciones por VIH/mortalidad , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga Viral/efectos de los fármacos
10.
J Antimicrob Chemother ; 73(7): 1955-1964, 2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29668978

RESUMEN

Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Sulfato de Atazanavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lamivudine/uso terapéutico , Ritonavir/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Sulfato de Atazanavir/efectos adversos , Quimioterapia Combinada , Femenino , VIH-1/efectos de los fármacos , Humanos , Lamivudine/efectos adversos , Masculino , Persona de Mediana Edad , ARN Viral , Ritonavir/efectos adversos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Carga Viral/efectos de los fármacos
11.
Postepy Dermatol Alergol ; 35(5): 447-453, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30429700

RESUMEN

INTRODUCTION: Lichen sclerosus (LS) is a chronic inflammatory disease affecting mainly the genital mucous membranes in both sexes. In the past, different terms were used to describe the disease, rendering a unique and specific clinical classification impossible. AIM: New therapeutic approaches are being defined, which may contribute to a proper clinical management, however, a stage classification is essential to better define appropriate treatment for every stage of the disease. MATERIAL AND METHODS: One hundred and fifteen patients (50 women and 65 men) with a diagnosis of LS were enrolled between January 2014 and September 2016. All patients underwent cutaneous biopsy to confirm the clinical diagnosis of LS. Clinical and symptomatological parameters were used in order to put the patients into the correct stage of LS. The Dermatology Life Quality Index (DLQI) was used to classify patients based on subjective symptoms. Different cutaneous alterations and structural modifications of the genital mucosa were also taken into consideration in order to assign every patient to a specific stage. CONCLUSIONS: Lichen sclerosus is clinically described differently in females and in males and every form of LS is put into one of two stages according to the degree of severity: early and late stages. Within the clinical practice, it is useful to screen patients for groups of early or late forms of the disease in order to obtain a uniform subdivision of patients: those who may benefit from localized treatments, require a systemic drug and must undergo physical treatments (surgical, stem cells infiltrations).

12.
J Clin Microbiol ; 55(9): 2827-2837, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28701420

RESUMEN

HIV-1 non-B subtypes/circulating recombinant forms (CRFs) are increasing worldwide. Since subtype identification can be clinically relevant, we assessed the added value in HIV-1 subtyping using updated molecular phylogeny (Mphy) and the performance of routinely used automated tools. Updated Mphy (2015 updated reference sequences), used as a gold standard, was performed to subtype 13,116 HIV-1 protease/reverse transcriptase sequences and then compared with previous Mphy (reference sequences until 2014) and with COMET, REGA, SCUEAL, and Stanford subtyping tools. Updated Mphy classified subtype B as the most prevalent (73.4%), followed by CRF02_AG (7.9%), C (4.6%), F1 (3.4%), A1 (2.2%), G (1.6%), CRF12_BF (1.2%), and other subtypes (5.7%). A 2.3% proportion of sequences were reassigned as different subtypes or CRFs because of misclassification by previous Mphy. Overall, the tool most concordant with updated Mphy was Stanford-v8.1 (95.4%), followed by COMET (93.8%), REGA-v3 (92.5%), Stanford-old (91.1%), and SCUEAL (85.9%). All the tools had a high sensitivity (≥98.0%) and specificity (≥95.7%) for subtype B. Regarding non-B subtypes, Stanford-v8.1 was the best tool for C, D, and F subtypes and for CRFs 01, 02, 06, 11, and 36 (sensitivity, ≥92.6%; specificity, ≥99.1%). A1 and G subtypes were better classified by COMET (92.3%) and REGA-v3 (98.6%), respectively. Our findings confirm Mphy as the gold standard for accurate HIV-1 subtyping, although Stanford-v8.1, occasionally combined with COMET or REGA-v3, represents an effective subtyping approach in clinical settings. Periodic updating of HIV-1 reference sequences is fundamental to improving subtype characterization in the context of an effective epidemiological surveillance of non-B strains.


Asunto(s)
Proteasa del VIH/genética , Transcriptasa Inversa del VIH/genética , VIH-1/clasificación , VIH-1/genética , Tipificación Molecular/métodos , Automatización de Laboratorios , Secuencia de Bases , Bases de Datos Genéticas , Infecciones por VIH/diagnóstico , Infecciones por VIH/virología , Humanos , Filogenia , Sensibilidad y Especificidad , Análisis de Secuencia de ARN
13.
J Antimicrob Chemother ; 72(7): 2055-2059, 2017 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-28333353

RESUMEN

Objectives: The AtLaS-M randomized trial showed that in patients with HIV-1 RNA <50 copies/mL on atazanavir/ritonavir + two NRTIs, switching to a dual therapy with atazanavir/ritonavir+lamivudine had superior efficacy as compared with continuing the previous triple therapy. This substudy was designed to evaluate at 48 weeks the impact of the dual therapy versus the three-drug atazanavir/ritonavir-based therapy on the HIV-1 cellular reservoir as reflected by the quantification of blood-associated HIV-1 DNA levels. Methods: In a representative subset of 201 of 266 randomized patients (104 in the dual-therapy arm and 97 in the triple-therapy arm) total HIV-1 DNA levels in whole blood at baseline and after 48 weeks and factors associated with the HIV-1 DNA levels were evaluated. Results: The mean baseline HIV-1 DNA levels (2.47 log 10 copies/10 6 leucocytes) were comparable between arms. A significant mean decrease between baseline and week 48 was observed: -0.069 log 10 copies/10 6 leucocytes in the dual-therapy arm ( P = 0.046) and -0.078 in the triple-therapy arm ( P = 0.011); the mean difference between arms was -0.009 ( P = 0.842). Nadir CD4 count was inversely correlated with baseline HIV-1 DNA ( P = 0.009); longer duration of ART and lower nadir CD4 correlated with a less prominent HIV-1 DNA decrease (both P < 0.005). Higher baseline HIV-1 DNA was associated with residual viraemia at week 48 ( P = 0.031). Conclusions: When compared with continuing three-drug therapy, atazanavir/ritonavir+lamivudine dual therapy resulted in a similar decline in HIV-1 DNA levels in patients with sustained virological suppression. These data support the safety of this simplified treatment strategy in terms of its effect on the cellular HIV-1 reservoir.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Sulfato de Atazanavir/uso terapéutico , ADN Viral/sangre , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Lamivudine/uso terapéutico , Ritonavir/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa , Sulfato de Atazanavir/administración & dosificación , Recuento de Linfocito CD4 , ADN Viral/efectos de los fármacos , Quimioterapia Combinada , Femenino , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/genética , Humanos , Lamivudine/administración & dosificación , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Ritonavir/administración & dosificación , Carga Viral/efectos de los fármacos
14.
J Antimicrob Chemother ; 72(4): 1163-1171, 2017 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-28093483

RESUMEN

Background: Combination ART (cART)-related toxicities and costs have prompted the need for treatment simplification. The ATLAS-M trial explored 48 week non-inferior efficacy of simplification to atazanavir/ritonavir  +  lamivudine versus maintaining three-drug atazanavir/ritonavir-based cART in virologically suppressed patients. Methods: We performed an open-label, multicentre, randomized, non-inferiority study, enrolling HIV-infected adults on atazanavir/ritonavir + two NRTIs, with stable HIV-RNA <50 copies/mL and CD4 + >200 cells/mm 3 . Main exclusion criteria were hepatitis B virus coinfection, past virological failure on or resistance to study drugs, recent AIDS and pregnancy. Patients were randomly assigned 1:1 to either switch to 300 mg of atazanavir/100 mg of ritonavir once daily and 300 mg of lamivudine once daily (atazanavir/ritonavir + lamivudine arm) or to continue the previous regimen (atazanavir/ritonavir + two NRTIs arm). The primary study outcome was the maintenance of HIV-RNA <50 copies/mL at week 48 of the ITT-exposed (ITT-e) analysis with switch = failure. The non-inferiority margin was 12%. This study is registered at ClinicalTrials.gov, number NCT01599364. Results: Between July 2011 and June 2014, 266 patients were randomized (133 to each arm). After 48 weeks, the primary study outcome was met by 119 of 133 patients (89.5%) in the atazanavir/ritonavir + lamivudine arm and 106 of 133 patients (79.7%) in the atazanavir/ritonavir + two NRTIs arm [difference atazanavir/ritonavir + lamivudine versus atazanavir/ritonavir + two NRTIs arm: +9.8% (95% CI + 1.2 to + 18.4)], demonstrating non-inferiority and superior efficacy of the atazanavir/ritonavir + lamivudine arm. Virological failure occurred in two (1.5%) patients in the atazanavir/ritonavir + lamivudine arm and six (4.5%) patients in the atazanavir/ritonavir + two NRTIs arm, without resistance selection. A similar proportion of adverse events occurred in both arms. Conclusions: Treatment simplification to atazanavir/ritonavir + lamivudine showed non-inferior efficacy (superiority on post-hoc analysis) and a comparable safety profile over continuing atazanavir/ritonavir + two NRTIs in virologically suppressed patients.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Sulfato de Atazanavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Lamivudine/uso terapéutico , Ritonavir/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Sulfato de Atazanavir/administración & dosificación , Coinfección , Quimioterapia Combinada , Femenino , Infecciones por VIH/virología , Humanos , Lamivudine/administración & dosificación , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Ritonavir/administración & dosificación , Carga Viral , Adulto Joven
15.
J Neurovirol ; 23(1): 147-151, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27431677

RESUMEN

In this retrospective case-control study, we compared the number of circulating lymphocyte subsets among 31 healthy controls, 18 naïve and 40 antiretroviral-treated HIV patients, 28 untreated and 18 treated relapsing-remitting multiple sclerosis (MS) patients. Lymphocyte subsets were no different between untreated MS patients and controls. Untreated and treated MS had a lower CD8+ count and a higher CD4+ number compared to untreated and treated HIV patients except similar CD4+ number between treated MS and HIV patients. CD4/CD8 ratio was lower in female HIV non-responders and in relapsing MS women compared, respectively, to female HIV responders and remitting MS women, and there were no differences in men.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/diagnóstico , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Adulto , Terapia Antirretroviral Altamente Activa , Biomarcadores/análisis , Recuento de Linfocito CD4 , Relación CD4-CD8 , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/virología , Estudios de Casos y Controles , Femenino , Acetato de Glatiramer/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Inmunofenotipificación , Interferón beta/uso terapéutico , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple Recurrente-Remitente/virología , Pronóstico , Estudios Retrospectivos , Factores Sexuales , Carga Viral/efectos de los fármacos
17.
BMC Infect Dis ; 17(1): 386, 2017 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-28577539

RESUMEN

BACKGROUND: Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by L1, L2, L3 serovars of C. trachomatis (CT). Since 2003, LGV cases have been increasing in Europe. Aim of this report is to describe the LGV cases diagnosed in the largest STI center in Rome, Italy, from 2000 to 2016. This report shows that two clinically and epidemiologically different series of cases exist, and that, at present, the ano-rectal LGV represents the clinical variant occurring more frequently among men having sex with men (MSM), particularly those HIV-infected. CASE PRESENTATION: Ten cases of LGV were observed. Three were diagnosed in 2009 in HIV-negative heterosexuals patients that presented the classical genito-ulcerative form with lymphadenopathy. Seven cases were observed in 2015-2016 in HIV-infected MSM, that presented the rectal variant and L2b serovar infection; 4 of these had been misclassified as a chronic bowel disease. Chlamydia infection was confirmed by CT-specific PCR (ompA gene nested PCR), followed by sequence analysis to identify the serovar. All the patients were treated with doxycycline for 3 weeks, obtaining a complete response with healing of both clinical symptoms and dermatological lesions. CONCLUSIONS: Our findings suggest that, in case of persistent rectal symptoms in HIV-infected MSM, LGV should be taken into account and investigated through molecular analyses, in order to achieve a correct diagnosis and management of the patients.


Asunto(s)
Linfogranuloma Venéreo/etiología , Infecciones Oportunistas Relacionadas con el SIDA , Adulto , Chlamydia trachomatis/genética , Chlamydia trachomatis/patogenicidad , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/microbiología , Homosexualidad Masculina , Humanos , Linfogranuloma Venéreo/tratamiento farmacológico , Linfogranuloma Venéreo/microbiología , Masculino , Persona de Mediana Edad , Ciudad de Roma
20.
BMC Infect Dis ; 16(1): 401, 2016 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-27515949

RESUMEN

BACKGROUND: Aim of the study was to assess predictors of discontinuation/toxicity of boosted PI-based (PI/r) dual therapy (DT). METHODS: Observational, retrospective switch study in patients successfully treated with triple drugs regimen. Patients switched to PI/r based DT [darunavir (DRV/r), lopinavir (LPV/r) or atazanavir (ATV/r)] plus a second drug: [raltegravir (RAL), maraviroc (MVC) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF)] between 2009 and 2014 were included. The effect of each drug as well as other clinical and virological cofactors over treatment discontinuation (TD) was assessed using survival analysis. RESULTS: Overall, 376 patients were included with mean follow-up of 73 weeks. The most commonly used drugs in DT were DRV/r (63.0 %) and RAL (53.7 %). TD was observed in 77 (20,4 %) patients: 38 (10,1 %) virological failure, 35 (9,3 %) toxicity/intolerance (4 deaths) and 4 (1 %) interruptions for patients decision. At Cox Model, adjusted by demographic and laboratory variables, DRV/r and ATV/r significantly reduced the likelihood of TD and longer treatment was associated with lower risk, while low CD4 count at baseline and number of previous regimens with a higher risk. Moreover, RAL and 3TC use were significantly associated with lower TD by toxicity. CONCLUSIONS: In our clinical practice experience, switching virologically suppressed patients to PI/r based DT showed adequate safety and efficacy, so that it may be used in selected patients with specific medical needs.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Darunavir/uso terapéutico , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lamivudine/uso terapéutico , Lopinavir/uso terapéutico , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Raltegravir Potásico/uso terapéutico , Estudios Retrospectivos , Riesgo , Tenofovir/uso terapéutico
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