Diego Cecchini

Nocardiosis en pacientes infectados por el VIH

Antecedentes. La nocardiosis es una enfermedad bacteriana asociada con estados de inmunodeficiencia, incluyendo la infeccion por el virus de la inmunodeficiencia humana (VIH). Metodos. Se analizaron en forma retrospectiva las historias clinicas de 27 pacientes con nocardiosis e infeccion por VIH asistidos entre los anos 1993 y 2004. Se evaluaron las caracteristicas epidemiologicas, clinicas, inmunologicas, microbiologicas y terapeuticas. Resultados. Eran hombres el 81% con una mediana de edad de 30 anos. Un elevado porcentaje de pacientes (89%) tenian antecedentes de enolismo, tabaquismo (80%) y uso de drogas intravenosas (82%). El 85% tenia diagnostico previo de infeccion por el VIH. La mediana de linfocitos T CD4+ (n = 17) al momento del diagnostico de nocardiosis fue de 15 cel./µl. Predominaron las formas clinicas pulmonar (70%), cutanea (11%) y diseminada (11%). Los materiales mas frecuentes para el diagnostico incluyeron muestras de esputo (52%), puncion-aspiracion de piel y partes blandas (22%) y lavado broncoalveolar (19%). El patron radiologico pulmonar predominante fue alveolar: 74%, seguido de cavidades pulmonares en el 32%. La especie se pudo identificar en 13 pacientes (48%); la mas frecuente fue el complejo Nocardia asteroides en el 84% (n = 11). Los antimicrobianos mas utilizados fueron cotrimoxazol (78%), amikacina (59%) y ciprofloxacino (33%). En el 78% de los casos el tratamiento fue combinado y la asociacion mas frecuente fue cotrimoxazol-amikacina. La mortalidad global fue del 37%. Conclusiones. La nocardiosis es una enfermedad poco frecuente en pacientes infectados por el VIH. Su diagnostico deberia considerarse en sujetos con inmunodepresion grave (linfocitos T CD4+ < 50 cel./µl) y compromiso pulmonar o pericardico.

Tuberculous meningitis in HIV-infected patients: drug susceptibility and clinical outcome.

The objective of this study was to identify prognostic factors of death in patients with tuberculous meningitis (TM) and show the impact of infection by multidrug-resistant strains on the outcome of this disease. We retrospectively analysed clinical charts of HIV-infected patients with culture-confirmed TM attending our institution during 1996–2004. The following variables were associated with death during hospitalization: neurological signs at admission, a CD4 T-cell count less than 50 cells/μl and infection by multidrug-resistant strains.

Potential drug–drug interactions in HIV-perinatally infected adolescents on antiretroviral therapy in Buenos Aires, Argentina

An increasing number of treatment‐experienced perinatally HIV‐infected adolescents (PHA) are being transitioned from paediatric centres to adult HIV‐care [ 1 ]. Most of them had been heavily exposed to antiretroviral drugs (ARVs), harbour drug‐resistant viruses and require non‐antiretroviral medication due to comorbidities [ 2 ]. This may predispose for clinically significant drug–drug interactions (CSDDIs) [ 3 ]. There are no studies concerning CSDDIs in PHA. We aimed to evaluate the prevalence of concomitant medications and CSDDIs in PHA who were transitioned for adult HIV‐care to the Infectious Diseases Unit, Cosme Argerich Hospital, Buenos Aires City, Argentina.

Transmitted drug resistance in women with intrapartum HIV-1 diagnosis: a pilot epidemiological survey in Buenos Aires, Argentina

Surveillance of primary resistance to antiretroviral drugs is particularly important in pregnant population, in which infection by drug‐resistant HIV has not only implications for maternal treatment, but could also jeopardize the efficacy of neonatal prophylaxis. We aim to describe the prevalence of resistance associated mutations (RAMs) in pregnant women with intrapartum HIV diagnosis in a public hospital of Buenos Aires, Argentina.

Etravirine resistance mutations in HIV‐infected pregnant women

Etravirine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) that provides an important treatment option for patients who have resistance to other NNRTIs [1]. Reproductive toxicology studies in animals found that etravirine did not affect fertility, early embryonic development or teratogenicity at exposures equivalent to those in humans at the recommended 200 mg twice-daily dose. The drug is classified as belonging to Pregnancy Category B (animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and wellcontrolled studies in pregnant women) [1,2]. Preliminary data showed that etravirine pharmacokinetic parameters in HIV-infected pregnant women (HPW) were comparable to those in nonpregnant adults, suggesting that no dose adjustment is needed during the third trimester [3]. In view of this favourable pharmacokinetic profile, etravirine may constitute a promising therapeutic option for those pregnant women with resistance to first-generation NNRTIs and other antiretroviral agents. In such patients, the benefits in preventing mother-to-child transmission outweigh potential risks, as clinical experience in human pregnancy with the drug is limited. However, the presence of etravirine resistance mutations (ERMs) may reduce its antiviral activity despite adequate concentrations being achieved during pregnancy. No data regarding the prevalence of such mutations in HPW have been published to date. The objective of the present study was to describe the prevalence of ERMs and the impact on the predicted susceptibility to this drug in a population of HPW receiving care at the Cosme Argerich Hospital, Buenos Aires, Argentina. During the period March 2008 to February 2011, baseline plasma samples from 78 HPW were analysed for viral load using the Versant HIV-1 RNA 3.0 Assay (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA) and sequenced using the Trugene HIV-1 Genotyping Kit (Siemens Healthcare Diagnostics Inc.). ERMs were identified according to the Tibotec Weighted Genotype Score [4] and Monogram Enhanced Score [5] and analysed according to each weighted mutation score to predict susceptibility. HPW with a weighted score 2.5 for the Tibotec Weighted Genotype Score and 4 for the Monogram Enhanced Score were considered to have possible resistance or reduced susceptibility, respectively. Considering the Tibotec Weighted Genotype Score, patients were substratified as follows: 0–2, highest response; 2.5–3.5, intermediate response; 4, reduced response. The HIV-1 viral subtype was determined using REGA Subtyping Tool 2.0 (REGA Institute, Catholic University of Leuven, Leuven, Belgium). The predominant HIV-1 subtype was B/F, which was found in 70.5% of patients, followed by B/B (24.4%), F/F (2.6%), B/C (1.3%) and B/K (1.3%). Of 78 HPW, 39 (50%) were experienced in antiretroviral therapy: 27 (69%) had prior exposure to NNRTIs (57% to nevirapine, 31% to efavirenz and 12% to both). None of them had received etravirine in the past. At least one ERM was found in 13 of 78 HPW (17%) according to the Tibotec Weighted Genotype Score and in 15 of 78 HPW (19%) according to the Monogram Enhanced Score. Considering all patients with ERMs, the median (interquartile range) age, gestational age, viral load and CD4 T-cell count were 25 (19–34) years, 12 (7–24) weeks, 13851 (2549–50970) HIV-1 RNA copies/mL and 274 (85– 483) cells/mL, respectively. The HIV-1 subtype was B/F in 11 patients (73.3%) and B in four patients (26.7%). No association between the presence of ERMs and any specific HIV-1 subtype was found (data not shown). Eight of 15 patients harbouring ERMs were experienced in antiretroviral therapy, with a median (interquartile range) prior NNRTI exposure of 63 (6-119) months. The prevalence of ERMs in the experienced group was 15% (six of 39) according to the Tibotec Weighted Genotype Score and 20% (eight of 39) according to the Monogram Enhanced Score. All experienced patients harbouring ERMs had prior NNRTI exposure. The prevalence of ERMs in the naïve group was 18% (seven of 39) according to both scores. Correspondence: Diego Martin Cecchini, Infectious Diseases Unit, Hospital Cosme Argerich, Almirante Brown 240, Buenos Aires 1155ADP, Argentina. Tel: +54 11 4121-0828; fax: +54 11 4307-5952; e-mail: diegocec@gmail.com

Variables that influence HIV-1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis

BackgroundThe central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF) viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1) CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer); (2) CSF HIV-1 viral load and HIV-1 plasma viral load; and (3) CSF leukocyte count and the peripheral blood CD4+ T lymphocyte count.MethodsOur approach was to use a prospective collection and analysis of pre-treatment, paired CSF and plasma samples from antiretroviral-naive HIV-positive patients with cryptococcal meningitis and assisted at the Francisco J Muñiz Hospital, Buenos Aires, Argentina (period: 2004 to 2006). We measured HIV CSF and plasma levels by polymerase chain reaction using the Cobas Amplicor HIV-1 Monitor Test version 1.5 (Roche). Data were processed with Statistix 7.0 software (linear regression analysis).ResultsSamples from 34 patients were analyzed. CSF leukocyte count showed statistically significant correlation with CSF HIV-1 viral load (r = 0.4, 95% CI = 0.13-0.63, p = 0.01). No correlation was found with the plasma viral load, CSF protein concentration and cryptococcal antigen titer. A positive correlation was found between peripheral blood CD4+ T lymphocyte count and the CSF leukocyte count (r = 0.44, 95% CI = 0.125-0.674, p = 0.0123).ConclusionOur study suggests that CSF leukocyte count influences CSF HIV-1 viral load in patients with meningitis caused by Cryptococcus neoformans.

Rilpivirine resistance associated mutations in HIV-1 infected pregnant women☆

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Kinetics of HIV-1 in cerebrospinal fluid and plasma in cryptococcal meningitis.

In order to determine HIV-1 kinetics in cerebrospinal fluid (CSF) and plasma in patients with cryptococcal meningitis (CM), we undertook a prospective collection of paired CSF/plasma samples from antiretroviral therapy-free HIV-infected patients with CM. Samples were obtained at baseline (S1) and at the second (S2) and third (S3) weeks of antifungal therapy. HIV-1 CSF concentrations were significantly lower in both S2 and S3 with respect to S1. Plasma concentrations remained stable. HIV-1 concentrations were higher in plasma than CSF in all cases. Patients who survived the episode of CM (but not those who died) showed a decrease in CSF viral load, what suggests different viral kinetics of HIV-1 in the CSF according to the clinical course of this opportunistic disease.

Suicidality among nonadherent patients living with HIV in Buenos Aires, Argentina: prevalence and correlates

ABSTRACT Of those in the general population hospitalized for suicidal ideation and suicide attempts in Argentina, many reattempt suicide and are readmitted. However, few studies in Argentina have examined suicidal ideation and suicide-related behaviors among people living with HIV (PLHIV) and none have examined these factors among nonadherent PLHIV, though the prevalence of suicidal ideation in this group may be higher than in the general population and also than in other groups of PLHIV. This study of PLHIV in Buenos Aires, Argentina, examined the correlates of suicidal ideation in nonadherent PLHIV. Nonadherent patients with HIV (N = 118) were recruited from two clinics providing outpatient healthcare services to PLHIV in Buenos Aires, Argentina. Participants completed assessments on demographic characteristics, depression and suicidality, stigma, and self-efficacy. Participants were HIV-infected men (51%) and women (49%) with a median age of 40 years (IQR = 11). About half had completed high school or more, two-thirds were employed, and had a mean monthly income of 4196.79 (SD = 3179.64) Argentine pesos (USD

Antiretroviral therapy containing raltegravir to prevent mother-to-child transmission of HIV in infected pregnant women

221). Thirty-three (28% [95% CI 20.3, 37.3]) participants reported suicidal ideation in the past two weeks, and one-third (35.6% [27.1, 44.9]) reported lifetime suicidal ideation. In bivariate analyses, attending a public clinic, being female, younger, unemployed, and experiencing greater stigma and depression were associated with suicidal ideation. In multivariable logistic regression, stigma interacted with the number of years since HIV diagnosis to predict suicidal ideation. The impact of stigma on suicidal ideation decreased with time since HIV diagnosis, suggesting that suicidal ideation may arise following HIV diagnosis due to perception of HIV-related stigma. Interventions to reduce perceived stigma during the period following HIV diagnosis may reduce suicidal ideation in this population. Organizational initiatives that explore HIV stigma microagressions in the healthcare setting may be needed to optimize health outcomes.