Assessing endocrine and immune parameters in human immunodeficiency virus-infected patients before and after the immune reconstitution inflammatory syndrome

ABSTRACT Objective The present study compares immune and endocrine parameters between HIV-infected patients who underwent the Immune Reconstitution Inflammatory Syndrome (IRIS-P) during antiretroviral therapy (ART) and HIV-patients who did not undergo the syndrome (non-IRIS-P). Materials and methods Blood samples were obtained from 31 HIV-infected patients (15 IRIS-P and 16 non-IRIS-P) before ART (BT) and 48 ± 2 weeks after treatment initiation (AT). Plasma Interleukin-6 (IL-6) and Interleukin-18 (IL-18) were determined by ELISA. Cortisol, dehydroepiandrosterone sulfate (DHEA-S) and thyroxin concentrations were measured using chemiluminescence immune methods. Results Concentrations of IL-6 (7.9 ± 1.9 pg/mL) and IL-18 (951.5 ± 233.0 pg/mL) were significantly higher (p < 0.05) in IRIS-P than in non-IRIS-P (3.9 ± 1.0 pg/mL and 461.0 ± 84.4 pg/mL, respectively) BT. Mean T4 plasma level significantly decreased in both groups of patients after treatment (p < 0.05). In both groups cortisol levels were similar before and after ART (p > 0.05). Levels of DHEA-S in IRIS-P decreased AT (1080.5 ± 124.2 vs. 782.5 ± 123.8 ng/mL, p < 0.05) and they were significantly lower than in non-IRIS-P (782.5 ± 123.8 vs. 1203.7 ± 144.0 ng/mL, p < 0.05). IRIS-P showed higher values of IL-6 and IL-18 BT and lower levels of DHEA-S AT than in non-IRIS-P. Conclusion These parameters could contribute to differentiate IRIS-P from non-IRIS-P. The significant decrease in DHEA-S levels in IRIS-P after ART might suggest a different adrenal response in these patients, which may reflect the severity of the disease.

Cutaneous tuberculosis and HIV infection at a referral centre in Rio de Janeiro, Brazil

BACKGROUND Cutaneous tuberculosis (CTB) is a rare extrapulmonary form of tuberculosis (TB). Despite the increase in the number of cases of TB and HIV, few cases of CTB have been reported. OBJECTIVE To describe CTB cases among patients with HIV infection from a cohort with tuberculosis. METHODS We describe a series of 15 CTB and HIV cases, based on secondary data from 2000 to 2016. Diagnosis was based on isolation of Mycobacterium tuberculosis in culture or clinical response to anti-tuberculous treatment associated with positive smear or histopathologic findings from affected skin or an adjacent lymph node. FINDINGS Scrofuloderma was present in 12 (80%) patients and solitary gumma in three (20%) patients. One case of scrofuloderma was associated with papulonecrotic tuberculid. Seven (46.6%) patients had pulmonary TB. Diagnosis was based on culture in nine patients (60%). The median CD4 cell count was 262 cells/µL. All patients were cured at the end of treatment (median time 6 months). Three patients presented with immune reconstitution inflammatory syndrome. CONCLUSIONS In this study, CTB associated with HIV infection presented as localised forms or in association with pulmonary TB. In patients with HIV who have subacute and chronic skin lesions, CTB should be considered in differential diagnosis, which may represent a good opportunity for early diagnosis of active TB.

Síndrome inflamatorio de reconstitución inmune (SIRI) en pacientes pediátricos que acuden a la consulta de VIH/SIDA del servicio de pediatría médica infecciosa del Hospital Universitario de Caracas / Immune reconstitution inflammatory syndrome (IRIS) in pediatric patients attending consultation HIV / AIDS medical service pediatric infectious Hospital Universitario de Caracas

La Organización Mundial de la Salud define al síndrome inflamatorio de reconstitución inmune (SIRI) como un grupo de signos y síntomas que resultan de la recuperación inmunológica del paciente VIH/SIDA después del inicio de la terapia retroviral de gran actividad (TARGA) cuya incidencia es del 10% al 25%. Estudiar los pacientes con diagnóstico de infección por VIH controlados en el Servicio de Pediatría Médica Infecciosa del Hospital Universitario de Caracas que desarrollaron SIRI. Se realizó estudio retrospectivo con revisión de datos de pacientes pediátricos con diagnóstico de VIH que presentaron SIRI. Los mismos fueron recabados de la base de datos de la consulta VIH/SIDA diseñada en Access 2010 y analizados con EPIINFO 3.5.4. El 15% de los pacientes con diagnóstico de VIH presentaron SIRI, siendo del sexo masculino 80%; 60% fueron clasificados inicialmente en estadio C3. La edad media fue de 5,26 años, (SD: ± 4,34). La carga viral de inicio de TARGA 320.318 copias/mL (SD: ± 260 727), contaje de linfocitos T CD4+: 127 células/mm³ (SD:±148) relación CD4/CD8: 0,17 (SD: ± 0,11); TARGA inicial: 90% utilizaron 3TC, 60% AZT, 40% ABC y 80% inhibidores de proteasa. Las manifestaciones clínicas más frecuentemente observadas fueron BCGitis (30%), tuberculosis (30%) y neumocistosis (20%). En un 90% las manifestaciones de SIRI ocurrieron en los primeros 3 meses de iniciado TARGA. Al momento del SIRI se observó en promedio un aumento del contaje de linfocitos T CD4+ en 411 células/mL y disminución de CV en 2 log. El SIRI es frecuente en pacientes pediátricos con VIH/SIDA y debe ser tomado en cuenta cuando se inicia tratamiento en estados severos de inmunodepresión

The World Health Organization defines the Immune Reconstitution Inflammatory Syndrome (IRIS) as a group of signs and symptoms as a result of the HIV/AIDS patients’ immune recovery after initiation of highly active antiretroviral therapy (HAART), being the incidence 10% to 25%. To study patients with HIV infection in control at the Pediatric Infectious Service of University Hospital of Caracas who developed IRIS. Retrospective data review of pediatric patients diagnosed with HIV who presented SIRI was performed. It was collected from 2010 Access - designed HIV/AIDS consultation database and analyzed with EPIINFO 3.5.4. 15% of patients diagnosed with HIV had IRIS, being 80% male, 60% were initially classified C3 stage. The average age was 5.26 years (SD: +4.34). Viral load (VL) starting HAART: 320 318 copies/mL (SD: ± 260,727), CD4 ± count: 127 cells/mm³ (SD: +148), CD4/CD8: 0.17 (SD: +0.11); initial HAART used: 90% 3TC,60% AZT, 40% ABC and 80% protease inhibitors. The most frequently clinical features observed were: BCGitis (30%), tuberculosis (30%) and pneumocystosis (20%). SIRI manifestations occurred, in 90% of cases, in the first 3 months after initiation of HAART. At the moment of IRIS diagnosis, an average CD4 + T count at 411 cells/ml increase and 2 log VL decreases were recorded. SIRI is common in HIV pediatric patients and should be considered when treatment is started in severe immunosuppression state

Immune reconstitution inflammatory syndrome in HIV and sporotrichosis coinfection: report of two cases and review of the literature

We report 2 cases of patients with immune reconstitution inflammatory syndrome (IRIS) associated with cutaneous disseminated sporotrichosis and human immunodeficiency virus (HIV) coinfection. The patients received specific treatment for sporotrichosis. However, after 4 and 5 weeks from the beginning of antiretroviral therapy, both patients experienced clinical exacerbation of skin lesions despite increased T CD4+ cells (T cells cluster of differentiation 4 positive) count and decreased viral load. Despite this exacerbation, subsequent mycological examination after systemic corticosteroid administration did not reveal fungal growth. Accordingly, they were diagnosed with IRIS. However, the sudden withdrawal of the corticosteroids resulted in the recurrence of IRIS symptoms. No serious adverse effects could be attributed to prednisone. We recommend corticosteroid treatment for mild-to-moderate cases of IRIS in sporotrichosis and HIV coinfection with close follow-up.

Síndrome de restauração imune associada à histoplasmose / Histoplasmosis-associated immune reconstitution inflammatory syndrome

Paciente masculino, 27 anos, portador de HIV, com quadro de histoplasmose cutânea disseminada. Terapia antirretroviral oral e anfotericina B por via EV (dose total acumulada 0,5g) foram introduzidas, verificando-se rápida cicatrização das lesões após duas semanas. A anfotericina B foi substituída por itraconazol (200mg/dia). O paciente interrompeu voluntariamente os tratamentos. A terapia antirretroviral foi reintroduzida, havendo aumento da contagem de células T CD4-positivas (No restante do texto, a autora usa o símbolo "+" (T CD4+) ao invés da palavra "positiva". O que fazer neste caso? Seguimos o padrão do restante do texto ou acatamos essa opção da autora no resumo?!). Neste momento, diagnosticou-se histoplasmose ganglionar. O aumento da contagem de células T CD4-positivas (de novo aqui), associado à redução da carga viral a níveis inferiores ao limite de detecção após a reintrodução da terapia antirretroviral, sugere que essa piora clínica paradoxal seja uma síndrome de restauração imune.

A 27-year-old HIV-positive male patient with disseminated cutaneous histoplasmosis was treated with both HAART and amphotericin B (total accumulated dose of 0.5g). Amphotericin B was later replaced with itraconazole (200mg/day). Two months after therapy had been started and the cutaneous lesions had healed, the patient interrupted both treatments voluntarily and his health deteriorated. HAART was then re-introduced and CD4+ cell count increased sharply at the same time as lymph node histoplasmosis was diagnosed. This paradoxical response? the relapse of histoplasmosis and concomitant increase in CD4+ cell count and undetectable viral load after resumption of HAART ? suggests that this was a case of immune reconstitution inflammatory syndrome (IRIS).

A study of TB-associated immune reconstitution inflammatory syndrome using the consensus case-definition.

Background & objectives: A considerable proportion of patients with HIV associated tuberculosis (TB) started on highly active antiretroviral therapy (HAART) develop immune reconstitution inflammatory syndrome (IRIS), which is difficult to diagnose in a resource-limited setting. In view of the recently proposed consensus case-definitions for TB-IRIS for use in resource-limited settings we undertook this study to describe the incidence and risk factors of TB associated IRIS in a tertiary care hospital and research centre in north India. Methods: Retrospective analysis of antiretroviral treatment (ART) naïve adults started on highly active ART (HAART) from June 2006 to September 2008 was done. Results: Of the 627 patients studied, 237 (38%) had TB at the initiation of HAART. In total, 18 (7.5%) of 237 patients with TB at baseline had paradoxical TB-associated IRIS, and 12 (3%) of 390 patients without TB at baseline developed ART-associated TB. Most IRIS events occurred during the initial 30 days of HAART. Two patients developed TB-associated IRIS after 90 days of HAART. Using univariate analysis, low CD4+ cell count at baseline [64 (28-89) vs. 95 (52-150); P=0.009] and early initiation of HAART [33 (24-41) vs. 48 (35-61) days; P<0.001] were significantly associated with paradoxical TB-associated IRIS. No identifiable risk factors were associated with the development of ART-associated TB. Interpretation & conclusions: A considerable proportion of patients on HAART develop TB-associated IRIS. The consensus case-definition is a useful tool in resource-limited settings for the diagnosis of TB-associated IRIS.

Immune reconstitution syndrome in patients treated for HIV and tuberculosis in Rio de Janeiro

We made a retrospective longitudinal study from January 2000 to January 2003 to examine cases of immune reconstitution syndrome (IRS) and its incidence rate in tuberculosis (TB)-human immunodeficiency virus (HIV) co-infected patients. The incidence rate (IR) was calculated using a Poisson regression. The confidence interval (CI) that was stipulated was 95 percent. IRS occurred in 10/84 HIV and TB-positive patients; nine of them were on highly active anti-retroviral therapy (HAART) during a mean of 61.7 (±59) days following the introduction of antiretrovirals. Lymph-node enlargement was the sole clinical manifestation. CD4 counts were <100 cells/mm³in 50 percent of the patients, at the time of TB diagnosis. All but two patients were treated with prednisone, and recovered from TB within a mean of 91 days (±30 days). One relapse of TB was observed, but there were no IRS-related deaths. The incidence rate was higher (IR=11.18; CI, 1.41-88.76) in patients that had superficial lymph node enlargement at the moment of TB diagnosis (not associated with TB), extrapulmonary TB (IR=1.97; CI, 0.44-8.79), were antiretroviral naive (IR=1.85; CI, 0.48-7.16), and CD4 counts <100 cells/mm³ (IR=1.50; CI, 0.40-5.59), although with a wide CI. IRS was frequent in our sample, occurred more frequently in HIV-naive patients with lymph-node enlargement and extrapulmonary TB. No cases of new pulmonary lesions or worsening of pulmonary infiltrates were observed.

Síndrome de restauración inmune asociado a tratamiento antirretroviral y criptococosis meníngea: Caso clínico / Inflammatory reconstitution immune syndrome associated to antiretroviral therapy and meningeal cryptococcosis

The objective of high activity antiretroviral therapy (HAART) in patients with AIDS, is to obtain immune restoration. This means a reduction of the viral load and restitution of the CD4 cell count. A decreased rate of HIV replication improves both the number and function of CD4 cells. Nevertheless, this treatment sometimes results in the reappearance of previous symptoms from treated conditions due to opportunistic infections (ie: tuberculosis, criptococcosis, hepatitis, Pneumocystis jirovesi, toxoplasmosis, etc) or non infectious condition such as sarcoidosis, Graves disease or Kaposi sarcoma. This is known as Inflammatory Reconstitution Immune Syndrome (IRIS). We report a 37 year-old woman in stage C3-AIDS with a previous criptococcal meningitis. She was treated, achieving a marked improvement with treatment and subsequent suppressive therapy with fluconazole 200 mg/day. IRIS appeared after 8 months of ongoing antiretroviral therapy with immune restoration with the development of aseptic meningitis and intracranial hypertension. The opportunistic agent could not be identified by cultures. Additional laboratory tests excluded toxoplasmosis, tuberculosis, bacterial cerebral abscesses, syphilitic cerebral gummas, and lymphoma. Brain CT and magnetic resonance studies were compatible with brain vasculitis and leptomeningitis. The patient condition improved with general measures, such as a repeated lumbar punctures and non steroidal anti-inflammatory drugs. We conclude that this patient had an IRIS due to a Cryptococcus neoformans antigen.