Viruela símica: descripción de dos casos en seguimiento en Buenos Aires / Monkeypox: description of two cases under follow-up in Buenos Aires

Resumen La viruela símica es una enfermedad endémica en varios países de África. En mayo de 2022 varios países donde la viruela símica no es endémica notificaron casos, incluyendo algunos países de las Américas. El 23 de julio de 2022, el Director General de la OMS declaró que este brote multinacional constituye una emergencia de salud pública de importancia internacional. Comunicamos dos casos de pacientes en segui miento en la Ciudad de Buenos Aires, Argentina, entre junio y julio de 2022. Ambos eran hombres que tienen sexo con hombres, con aparición de lesiones en zona genital sin período prodrómico. En los dos casos se realizó tratamiento en primera instancia con sospecha de infecciones de transmisión sexual. Señalamos la importancia de considerar esta enfermedad como diagnóstico diferencial teniendo en cuenta el contexto epidemiológico actual.

Abstract Monkeypox is an endemic disease in several African countries. In May 2022, an outbreak was repor ted in dozens of non-endemic countries. On July 23, 2022, the WHO Director-General declared this multinational outbreak a public health emergency of international concern. We report two cases of patients under follow-up in Buenos Aires, Argentina, between June and July 2022. Both were men who have sex with men, with the appea rance of lesions in the genital area without a prodromal period. In both cases, treatment was carried out in the first instance with suspicion of sexually transmitted infections. We highlight the importance of considering this pathology as a differential diagnosis, taking into account the current epidemiological context.

Antiretroviral therapy and arterial elasticity in HIV-infected patients.

Cardiovascular risk is increased in HIV-infected patients and has become a leading cause of morbi-mortality in this population. The purpose of this study is to compare HIV-infected patients on antiretroviral therapy (ART) and ART-naïve HIV-infected patients regarding arterial elasticity. From September 2010 to September 2015, 105 HIV-infected subjects were enrolled, 41 ART-naïve and 64 on ART with stable viral suppression. Elasticity of large and small arteries (LAE and SAE) was assessed by analysis of radial pulse waveforms using a calibrated device. A single set of measurements was performed. Multivariate linear regression models were constructed to estimate independent correlates of arterial elasticity. On-ART and ART-naïve patients were similar with respect to gender, age, body mass index, Framingham cardiovascular risk score, smoking habits, and CD4+ counts. Median time on treatment was 60 months and 79% of patients were on regimens based on non-nucleoside reverse-transcriptase inhibitors. No significant differences in LAE and SAE assessments were found between groups. However, time on ART and cholesterol levels were independently associated with LAE impairment. No association between arterial elasticity and CD4+ counts was found. We conclude that cumulative exposure to ART may play a role on LAE impairment and deserves further investigation.

Antiretroviral therapy and arterial elasticity in HIV-infected patients

Cardiovascular risk is increased in HIV-infected patients and has become a leading cause of morbimortality in this population. The purpose of this study is to compare HIV-infected patients on antiretroviral therapy (ART) and ART-naïve HIV-infected patients regarding arterial elasticity. From September 2010 to September 2015, 105 HIV-infected subjects were enrolled, 41 ART-naïve and 64 on ART with stable viral suppression. Elasticity of large and small arteries (LAE and SAE) was assessed by analysis of radial pulse waveforms using a calibrated device. A single set of measurements was performed. Multivariate linear regression models were constructed to estimate independent correlates of arterial elasticity. On-ART and ART-naïve patients were similar with respect to gender, age, body mass index, Framingham cardiovascular risk score, smoking habits, and CD4+ counts. Median time on treatment was 60 months and 79% of patients were on regimens based on non-nucleoside reverse-transcriptase inhibitors. No significant differences in LAE and SAE assessments were found between groups. However, time on ART and cholesterol levels were independently associated with LAE impairment. No association between arterial elasticity and CD4+ counts was found. We conclude that cumulative exposure to ART may play a role on LAE impairment and deserves further investigation.

El riesgo cardiovascular está incrementado en los pacientes HIV seropositivos y se ha convertido en una de las principales causas de morbimortalidad en esta población. El objetivo de este estudio fue comparar la elasticidad de grandes y pequeñas arterias (LAE y SAE) en pacientes infectados por HIV con y sin terapia antirretroviral. De septiembre de 2010 a septiembre de 2015 se enrolaron 105 pacientes con infección por HIV, 41 vírgenes de antirretrovirales y 64 con tratamiento estable en supresión viral. LAE y SAE fueron evaluados mediante análisis de la onda de pulso radial. Se construyeron modelos de regresión lineal múltiple para evaluar los predictores independientes de la elasticidad arterial. Los grupos en tratamiento y naïve fueron similares con respecto al sexo, edad, índice de masa corporal, índice de Framingham, tabaquismo y recuento de CD4+. La mediana de tiempo en tratamiento antirretroviral fue 60 meses y el 79% de los pacientes recibieron inhibidores no nucleosídicos. No hubo diferencias significativas entre los grupos en los valores de LAE y SAE. Sin embargo, el tiempo en tratamiento y el nivel de colesterol plasmático se asociaron independientemente con deterioro de LAE. No observamos asociaciones entre la elasticidad arterial y los recuentos de CD4+. Concluimos que la exposición acumulada al tratamiento antirretroviral podría contribuir al deterioro de la LAE. Este hallazgo merece ulterior investigación.

Late diagnosis of HIV infection in asymptomatic patients

Recent findings from the START Trial provided evidence that early initiation of antiretroviral treatment should be implemented as the global standard of care. However, a large proportion of patients are still being diagnosed in late stages. Our objective was to evaluate the temporal trend in the CD4+ cell count at diagnosis during a 13 year period and the factors associated with late HIV diagnosis in asymptomatic individuals tested in the Centre for Prevention, Counselling and Diagnosis of our hospital. It was a retrospective study including all asymptomatic patients with new diagnosis of HIV infection. Very late presenters (VLP) were defined as those with CD4+ counts < 200 and late presenters (LP) with CD4+ < 350 cell/mm³. We also evaluated the proportion of patients diagnosed with CD4+ cell counts below 500 cell/mm3. Between January 2002 and December 2014, 20 263 patients were tested for HIV, 1104 with a positive result of whom 995 asymptomatic individuals were included. Overall, median CD4+ count was 372 cells/mm3 and HIV-RNA 31 145 copies/ml. There was no evidence that the CD4+ count at diagnosis progressively increased over time, nor that the proportion of VLP and LP decreased. In a multivariate model older age, heterosexual transmission and intravenous drug use remained as independent factors associated with LP. In conclusion, late diagnosis of HIV infection remains prevalent among asymptomatic patients, highlighting the need to continue implementing strategies towards early diagnosis.

Los resultados del estudio START han evidenciado que la iniciación temprana del tratamiento antirretroviral debe ser un estándar global. No obstante, una gran proporción de pacientes aún se diagnostican en etapas tardías. Nuestro objetivo fue evaluar la tendencia en el recuento de CD4+ al diagnóstico de infección por HIV, la proporción de presentadores tardíos entre 2002 y 2014, y los factores asociados con el diagnóstico tardío en pacientes asintomáticos en el Centro de Prevención, Asesoramiento y Diagnóstico de nuestro hospital. Se incluyeron en un estudio retrospectivo todos los sujetos asintomáticos con un diagnóstico de HIV. Se consideraron presentadores muy tardíos (PMT) a aquellos pacientes con CD4+ < 200 y presentadores tardíos (PT) con cifras de CD4+ < 350 células/mm³. Adicionalmente evaluamos la proporción de pacientes diagnosticados con recuentos de CD4+ inferiores a 500 células/mm³. Desde enero 2002 a diciembre de 2014 se testearon para HIV 20 263 pacientes, 1104 con resultado positivo, de los cuales 995 eran asintomáticos. Globalmente, la mediana de CD4+ fue 372 células/mm3 y la de HIV-ARN de 31 145 copias/ml. No hubo evidencia de que el recuento de CD4+ al diagnóstico haya aumentado en el tiempo, ni de disminución de la proporción de PT o PMT. En un modelo multivariado, la mayor edad, la transmisión heterosexual y el uso de drogas intravenosas se asociaron independientemente con PT. En conclusión, el diagnóstico tardío de infección por HIV se mantiene prevalente en pacientes asintomáticos, resaltando la necesidad de continuar implementando estrategias orientadas a favorecer el diagnóstico temprano.

Factors associated with D-dimer levels in HIV-infected individuals.

BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. METHODS: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. RESULTS: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. CONCLUSIONS: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels.

Mother-to-Child Transmission of Hepatitis C Virus (HCV) Among HIV/HCV-Coinfected Women.

BACKGROUND: Maternal human immunodeficiency virus (HIV) coinfection has been associated with increased hepatitis C virus (HCV) mother-to-child transmission (MTCT). We hypothesized that HCV/HIV-coinfected women with well-controlled HIV disease would not have increased HCV MTCT. METHODS: The NISDI Perinatal and LILAC cohorts enrolled HIV-infected pregnant women and their infants in Latin America and the Caribbean. This substudy evaluated the HCV infection status of mothers at participating sites and their live born, singleton infants who had a 6-month postnatal visit by December 31, 2008. Mothers who were anti-HCV-positive, or who had CD4 counts (cells/mm(3)) <200 with detectable HCV RNA, were considered HCV-infected. All HCV-infected women were tested for HCV RNA. Infants with HCV RNA were considered HCV-infected. RESULTS: Of 1042 enrolled women, 739 (71%) mother-infant pairs met the inclusion criteria. Of the 739 women, 67 (9%) were anti-HCV-positive and 672 anti-HCV-negative [68 (10%) with CD4 counts <200; of these, 3 (4.4%) were HCV RNA-positive]. Therefore, our study population comprised 70 HCV-infected (47 with HCV RNA) and 669 HCV-uninfected women (and their infants). Factors associated with maternal HCV infection included unemployment (odds ratio [OR] = 2.58); tobacco (OR = 1.73) or marijuana (OR = 3.88) use during pregnancy; enrollment HIV viral load ([VL] copies/mL) ≥10 000 (OR = 2.27); HIV clinical disease stage C (OR = 2.12); and abnormal alanine aminotransferase (OR = 4.24) or aspartate aminotransferase (OR = 11.98). Four of 47 infants (8.5%) born to HCV-viremic women were HCV-infected, and all 4 mothers had HIV VL <1000 at hospital discharge after delivery. CONCLUSIONS: HCV MTCT among HIV/HCV-coinfected women with well-controlled HIV disease may be lower than reported in other coinfected populations. Studies with longer infant follow-up are needed.

TB meningitis in HIV-positive patients in Europe and Argentina: clinical outcome and factors associated with mortality.

OBJECTIVES: The study aimed at describing characteristics and outcome of tuberculous meningitis (TBM) in HIV-positive patients and comparing these parameters with those of extrapulmonary TB (TBEP) and pulmonary TB (TBP). METHODS: Kaplan-Meier estimation and Poisson regression models were used to assess the mortality following TB diagnosis and to evaluate potential prognostic factors for the 3 groups of TB patients separately. RESULTS: A total of 100 patients with TBM, 601 with TBEP, and 371 TBP were included. Patients with TBM had lower CD4 cell counts and only 17.0% received antiretroviral therapy (ART) at TB diagnosis. The cumulative probability of death at 12 months following TB was 51.2% for TBM (95% CI 41.4-61.6%), 12.3% for TBP (8.9-15.7%), and 19.4% for TBEP (16.1-22.6) (P<0.0001; log-rank test). For TBM, factors associated with a poorer prognosis were not being on ART (adjusted incidence rate ratio (aIRR) 4.00 (1.72-9.09), a prior AIDS diagnosis (aIRR=4.82 (2.61-8.92)), and receiving care in Eastern Europe (aIRR=5.41 (2.58-11.34))). CONCLUSIONS: TBM among HIV-positive patients was associated with a high mortality rate, especially for patients from Eastern Europe and patients with advanced HIV-infection, which urgently calls for public health interventions to improve both TB and HIV aspects of patient management.

Infecciones de transmisión sexual en personas transgénero y otras identidades sexuales / Sexually transmitted infections among transgender individuals and other sexual identities

Existen pocos datos disponibles acerca del comportamiento de riesgo y la prevalencia de infecciones de transmisión sexual (ITS), incluyendo HIV-1, en personas transgénero. El objetivo del estudio fue comparar las características demográficas, factores de riesgo, prevalencia de HIV-1 e ITS en personas transgénero versus personas no transgénero que consultan al Centro de Prevención, Asesoramiento y Diagnóstico del Hospital General de Agudos J.M. Ramos Mejía. Se utilizó el diseño de estudio de corte transversal y se incluyeron pacientes asistidos en nuestro centro que firmaron consentimiento informado entre noviembre de 2002 y abril de 2006. Se obtuvieron datos sociodemográficos, uso de drogas, utilización de preservativos, nivel de educación alcanzado, diagnóstico de ITS y estado actual de la pareja. Se utilizó estadística descriptiva y chi² para comparar proporciones. En la población estudiada (n: 4118) se identificaron a 105 personas transgénero. La prevalencia de infección por HIV-1 fue del 27.6% (29/105), mientras que en personas no transgénero (n: 4013) fue de 6.2% (247/4013); p:0.0000. El bajo nivel educativo, el consumo de alcohol, el abuso de drogas, los antecedentes de ITS y el trabajo sexual (100% en transgénero y 2.3% en no transgénero) fueron más frecuentes en personas transgénero. La prevalencia de sífilis fue del 42% en personas transgénero y del 18% en personas no transgénero. Estos datos demuestran que las personas transgénero que consultan en nuestro centro tienen alta prevalencia de infección por HIV-1 e ITS. Esta información podría contribuir al diseño de estrategias de prevención necesarias en esta población.

Few data are available regarding the prevalence of sexually transmitted infections (STI), including HIV-1 infection, and risk behaviors of transgender individuals. Previous reports indicate that this community has a high prevalence of HIV and STIs. Our objective was to compare the prevalence of HIV-1 infection, STI and risk behaviors of transgender people versus non transgender people. We used a cross sectional design study. Patients who received services at our testing site between November 2002 and April 2006, and provided written informed consent, were included in the analysis. Socio-demographic data, sexual behaviour, recreational drug use, condom use, concurrent or previous STI and HIV-1 infection diagnosis and partner serologic status, were collected. We used descriptive statistics and chi² for comparisons of proportions. In the period of the study, 105 transgender individuals were identified in a population of 4118 patients tested. The prevalence of HIV infection in the transgender group was 27.6% (29/105), while in the non transgender group was 6.2% (247/4013) p:0.0000. Low level of formal instruction, alcohol consumption, drug abuse, previous history of STI and sex work (100% transgenders and 2.3% of non-transgenders) were significantly more frequent in the transgender. The referred correct use of condom was similar in both groups. The prevalence of syphilis was 42.3% in transgender group and 18.1% in non-transgender individuals. These data show that this population has a very high prevalence of HIV-1 and STI. This information could be instrumental to design targets for intensive HIV prevention strategies in this particular high risk population.

Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study.

BACKGROUND: The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group, participants started ART when the CD4+ cell count was <250 cells/microL. Clinical outcomes in participants not receiving ART at entry inform the early use of ART. METHODS: Patients who were either ART naive (n=249) or who had not been receiving ART for >or= 6 months (n=228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death); (ii) OD (fatal or nonfatal); (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths; and (iv) the composite of outcomes (ii) and (iii). RESULTS: A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for >or= 6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for 6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95% confidence interval [CI], 1.26-9.56; p=.02); outcome (ii), 3.26 (95% CI, 1.04-10.25; p=.04); outcome (iii), 7.02 (95% CI, 1.57-31.38; p=.01); and outcome (iv), 4.19 (95% CI, 1.69-10.39; p=.002 ). CONCLUSIONS: Initiation of ART at CD4+ cell counts >350 cells/microL compared with <250 cells/microL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial.

Infectious disease morbidity among young HIV-1-exposed but uninfected infants in Latin American and Caribbean countries: the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study.

OBJECTIVE: The goal was to describe the frequency, characteristics, and correlates of infectious disease morbidity during the first 6 months of life among HIV-1-exposed but uninfected infants. METHODS: The study population consisted of infants enrolled in the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study who were HIV-1 uninfected and had follow-up data through the 6-month study visit. Definitive and presumed infections were recorded at study visits (birth, 6-12 weeks, and 6 months). RESULTS: Of 462 HIV-1-uninfected infants with 11,644 child-weeks of observation, 283 experienced > or = 1 infection. These 283 infants experienced 522 infections (1.8 infections per infant). The overall incidence rate of infections was 4.5 cases per 100 child-weeks of observation. Overall, the most common infections were skin or mucous membrane infections (1.9 cases per 100 child-weeks) and respiratory tract infections (1.7 cases per 100 child-weeks). Thirty-six percent of infants had > 1 respiratory tract infection (1.8 cases per 100 child-weeks). Incidence rates of upper and lower respiratory tract infections were similar (0.89 cases per 100 child-weeks and 0.9 cases per 100 child-weeks, respectively). Cutaneous and/or oral candidiasis occurred in 48 neonates (10.3%) and 92 older infants (19.3%). Early neonatal sepsis was diagnosed in 12 infants (26.0 cases per 1000 infants). Overall, 81 of 462 (17.5%) infants were hospitalized with an infection. Infants with lower respiratory tract infections were hospitalized frequently (40.7%). The occurrence of > or = 1 neonatal infection was associated with more-advanced maternal HIV-1 disease, tobacco use during pregnancy, infant anemia, and crowding. Lower maternal CD4+ cell counts, receipt of intrapartum antibiotic treatment, and country of residence were associated with postneonatal infections. CONCLUSIONS: Close monitoring of HIV-1-exposed infants, especially those who are anemic at birth or whose mothers have more-advanced HIV-1 disease or who smoked during pregnancy, remains important.

Prevention of mother to child hiv transmission

En este estudio se describe el impacto de las estrategias implementadas para reducir la trasmisión vertical de HIV en una cohorte de mujeres embarazadas. Se evaluó, también, la toxicidad relacionada a la terapia antirretroviral y la prevalencia de malformaciones congénitas. Se revisaron, retrospectivamente, las historias clínicas y la base de datos de 351 mujeres embarazadas, con infección por HIV, admitidas en un hospital público de la Ciudad de Buenos Aires, entre abril de 1994 y agosto de 2003. Se obtuvieron datos completos de 351 pacientes. El 80% de las mujeres adquirieron la infección por HIV por vía sexual. El diagnóstico de infección por HIV fue previo al de embarazo en el 38.5% de los casos. Un total de 241 pacientes recibieron algún tipo de terapia antirretroviral durante el embarazo y 123, recibieron terapia antirretroviral combinada. El índice de transmisión global fue de 9.6%, y el uso de terapia antirretroviral fue el factor más significativo asociado al índice de transmisión. El odds ratio (OR) para la transmisión vertical del HIV fue de 0.04 para cualquier tipo de tratamiento antirretroviral versus la ausencia de tratamiento. No se detectaron casos de transmisión entre las mujeres que recibieron terapia combinada. Los efectos secundarios más frecuentes asociados a la terapia fueron: anemia, hipercolesterolemia, aumento en los niveles de fosfatasa alcalina e hipertrigliceridemia. En conclusión, la terapia antirretroviral, especialmente la terapia combinada, se asoció con reducción en el riesgo de transmisión vertical del VIH, independientemente del tipo de parto. No se detectó mayor toxicidad o incidencia de malformaciones congénitas, en el corto plazo.

Avances en el tratamiento antirretroviral / Advances in antiretroviral treatment

Descubrimientos recientes nos han permitido un mejor conocimiento de la cinética del VIH y el diseño de nuevas estrategias de tratamiento. Este artículo revisa los métodos más difundidos para medir la carga viral y su uso en la toma de decisiones; las características de los inhibidores de la proteasa disponibles en la Argentina y los resultados preliminares de varios ensayos clínicos de tratamientos combinados que han modificado el tratamiento. La determinación de carga viral representa un marcador sustituto con valor predictivo independiente del recuento de CD4. La combinación de drogas es la elección siempre que se decida iniciar tratamiento.