Branko Brmbolic

The Prognosis of Late Presenters in the Era of Highly Active Antiretroviral Therapy in Serbia

To examine the prognosis of patients who present with very advanced HIV-induced immunodeficiency, and their response to highly active antiretroviral therapy (HAART), a series of 101 treatment naïve patients from the Serbian cohort of HIV infected patients, who presented with a CD4 count of ≤ 50/µL before commencing HAART, was retrospectively analyzed and factors influencing response to HAART and survival investigated. After a mean of three years (range 1-9) of treatment with PI-based and/or NNRTI-based regimens, a favorable response was achieved in 54.5% of the patients, treatment failure occurred in 13.9%, while 31.7% had a dissociative immunological/virological response. The overall estimated survival was eight years. Achievement of undetectable viremia during treatment appeared life saving (OR = 42.5, 95% CI 7.1 – 251.9, P = 0.000, as was a rise in CD4 cell count to over 200/μL (OR = 6.4, 95% CI 1.2-31.8, P = 0.023). However, undetectable viremia was the single predictor of longer survival (OR = 42.5, 95% CI 7.1 – 251.9, P = 0.000), regardless of the level of immune reconstitution (log rank, P = 0.31). Late presenters had a high probability of developing the metabolic syndrome while on HAART, with a median time to hyperlipidemia and lypodystrophy of 5 and 6 years, respectively. We conclude that late presenters on HAART may have a good prognosis, a prerequisite for which is sustained undetectable viremia regardless of the immune recovery.

Intravenous drug use – an independent predictor for HCV genotypes 3 and 4 infection among HIV/HCV co-infected patients

Introduction About one quarter of human immunodeficiency virus (HIV) infected persons in Serbia have also been found to be hepatitis C virus (HCV) co-infected. In the general population, HCV genotype 1 has been shown to be the most prevalent one. Here, we present the first study on the distribution of HCV genotypes among HIV/HCV co-infected patients in Serbia, in relation to epidemiological and clinical features. Material and methods The study included HIV/HCV co-infected and a group of HCV mono-infected patients in the period 1998–2012, with collection of epidemiological, clinical, and behavioral data using a standardized questionnaire. The HCV genotyping to the level of pure genotype was performed by reverse hybridization. Results Intravenous drug use (IDU) was found to be significantly more prevalent among the co-infected patients (p < 0.01). HCV genotype 1 was detected in 87% of patients with mono-infection, compared to 46.3% of patients with co-infection (p < 0.01); genotypes 3 and 4 were significantly more common among co-infected patients (6% and 5%, vs. 27% and 25%, respectively). Multivariate logistic regression confirmed IDU, infection with non-1 HCV genotype and HCV viral load over 5 log to be predictors of HIV co-infection. Conclusions The HCV genotypes 3 and 4 were found to be significantly more prevalent among HIV/HCV co-infected patients in Serbia, compared to HCV mono-infected patients, but also more prevalent compared to the European HIV/HCV co-infected cohort. History of IDU represents an independent predictor of HCV genotypes 3 and 4 infection, with important implications for treatment.

Human case of fasciolosis in Serbia treated with triclabendazole

INTRODUCTION The number of humans infected by Fasciola hepatica is increasing worldwide. Humans can become accidental hosts by ingesting drinking water or plants contaminated with metacercariae. CASE REPORT We reported a case of a 68-year-old Serbian woman, in which the diagnosis of acute fasciolosis had been established after serious diagnostic concerns. Based on clinical picture (episodic right upper quadrant abdominal pain, febrility and generalized body pain) and biochemical analyses (high eosinophilia and high activity of alkaline phosphatase), she was appointed as suspected to the acute fasciolosis. Stool and duodenal aspirate exams were negative for Fasciola ova. In the absence of adequate serologic diagnostic for fasciolosis in Serbia, the diagnosis was confirmed using enzyme immunoassays and immunoblot at the Institute for Tropical Diseases in Hamburg, Germany. Soon after triclabendazole was administered, the symptoms disappeared and biochemical values returned to normal. CONCLUSION The diagnosis of human fasciolosis may be problematic and delayed, especially in non endemic areas, because physicians rarely encounter this disease and a long list of other diseases must be considered in the differential diagnosis. The syndrome of eosinophilia, fever, and right upper quadrant abdominal pain suggest acute fasciolosis. Unclear source does not rule out fasciolosis.

The Prognosis of Pediatric AIDS in Serbia

To determine the outcome of HIV infection in children in a resource-limited setting, a retrospective analysis of a series of 51 pediatric cases from the Serbian cohort of HIV infected patients was performed. Twenty seven patients died in the pre-HAART era, but mono/dual antiretroviral treatment had significantly (p=0.046) prolonged survival. Of the total of 24 HAART-treated patients, 10 had clinical AIDS before HAART initiation. The mean baseline CD4 cell count was 193.9 +/- 170.0/mm(3). After a mean follow-up of 72.6 +/- 44 months, a favorable response was recorded in 62.5%, treatment failure (defined as non-achievement of undetectable viremia) in 20.8%, and a discrepant virological and immunological response (achievement of undetectable viremia but without a rise in CD4 cell counts adequate for age) in 16.7% patients. No patients died, and there were only three hospital admissions after commencing HAART. Five immune restoration inflammatory syndrome episodes were recorded, of which four were due to BCG-osis. Lipodystrophy and hyperlipidemia occurred in 18.2% and 26.3% patients, respectively. We conclude that even in suboptimal facilities, the prognosis of HIV disease among children on HAART may be rather good. The metabolic syndrome seems to emerge as an important issue among long-term surviving children on HAART.

Successful treatment of chronic hepatitis C in a hemodialysis

We present the first case of successful direct acting antiviral therapy of chronic hepatitis C in a hemodialysis patient in Serbia. The patient infected with genotype 1a has been successfully treated with Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ribavirin. There are only a few real world reports regarding this therapeutic option in hemodialysis patients.

The increasing prevalence of HIV/Helicobacter pylori co-infection over time, along with the evolution of antiretroviral therapy (ART)

Helicobacter pylori (H. pylori) is one of the most common human bacterial infections with prevalence rates between 10–80% depending upon geographical location, age and socioeconomic status. H. pylori is commonly found in patients complaining of dyspepsia and is a common cause of gastritis. During the course of their infection, people living with HIV (PLHIV) often have a variety of gastrointestinal symptoms including dyspepsia and while previous studies have reported HIV and H. pylori co-infection, there has been little data clarifying the factors influencing this. The aim of this case-control study was to document the prevalence of H. pylori co-infection within the HIV community as well as to describe endoscopic findings, gastritis topography and histology, along with patient demographic characteristics across three different periods of time during which antiretroviral therapy (ART) has evolved, from pre- highly active antiretroviral therapy (HAART) to early and modern HAART eras. These data were compared to well-matched HIV negative controls. Two hundred and twelve PLHIV were compared with 1,617 controls who underwent their first esophagogastroduodenoscopy (EGD) to investigate dyspepsia. The prevalence of H. pylori co-infection among PLHIV was significantly higher in the early (30.2%) and modern HAART period (34.4%) compared with those with coinfection from the pre-HAART period (18.2%). The higher rates seen in patients from the HAART eras were similar to those observed among HIV negative controls (38.5%). This prevalence increase among co-infected patients was in contrast to the fall in prevalence observed among controls, from 60.7% in the early period to 52.9% in the second observed period. The three PLHIV co-infected subgroups differed regarding gastritis topography, morphology and pathology. This study suggests that ART has an important impact on the endoscopic and histological features of gastritis among HIV/H. pylori co-infected individuals, raising the possibility that H. pylori-induced gastritis could be an immune restoration disease.

Dijagnostika fokalnih promjena u jetri

Uvod. Patoloski procesi u jetri mogu biti difuznog karaktera (zapaljenski,metabolicke bolesti, hematoloske bolesti, toksicne bolesti) i fokalne (zapaljenske,parazitarne i tumorske). Cilj rada je prikaz fokalnih promjena u jetrinomparenhimu nakon ultrazvucne, laparaskopske i patohistoloske dijagnostike.Metode. Retrospektivno-prospektivnim ispitivanjem je obuhvaceno 147punoljetnih pacijenata oba pola. Fokalne promjene jetrinog tkiva su sagledaneultrazvucnom, laparoskopskom i patohistoloskom dijagnostikom.Rezultati. Osnovne karakteristike ispitanika: muskaraca 71 i žena 76 sanajvecim brojem pacijenata (102 - 70%) životne dobi između 40 i 70 godina,sa ravnomjernom distribucijom za svakih deset godina starosti. Međutim,neobicno je veliki broj pacijenata ženskog pola registrovan u cetvrtoj decenijiživota, cak 14 (9,5%) od ukupnog broja ispitanika, odnosno 18% odispitanika ženskog pola. Metastaze cine 104 (71%) svih fokalnih lezija jetre.U vecini slucajeva radilo se o metastazama karcinoma dojke. Iako najcesceimaju tipicnu ultrazvucnu prezentaciju, metastaze u jetri mogu da daju sirokspektar razlicitih ultrazvucnih slikaZakljucak. Najcesce fokalne promjene u jetri su metastaze adenokarcinoma.Samo 3 (2%) fokalne promjene dijagnostikovane ultrazvukom nisu potvrđenekao fokalne laparoskopskom tehnikom i patohistoloskom analizom tkiva jetre.