Raluca Jipa

Characteristics of late presenters in Bucharest

Late presentation is associated with increased healthcare costs, rates of HIV transmission and poor outcome. In Romania, in 2012, one third of individuals with new HIV diagnosis were late presenters (LP).

Toxoplasmosis: a rare cause of IRIS in HIV infected patients. Case series

Results Three patients, one male and 2 women, aged 55 years old, respectively 41 and 42 year-old, all 3 diagnosed concomitantly with HIV infection (as very late presenters) and cerebral toxoplasmosis, with a CD4 count of 6, 6 and 7/cmm respectively, viral loads (VL) of 254,000, 57,000 and 156,000 copies/mL respectively, and CSF viral load below the plasmatic VL in all 3 cases. We recorded minimal abnormalities of CSF analysis regarding the number of cells and biochemical exams; all had positive PCR for Toxoplasma gondii in the CSF and positive serology (IgG). All 3 had intracerebral lesions (abscesses) and all were biopsied at the neurosurgery department for diagnostic purpose before knowing their HIV-positive status. They received high doses of oral trimethoprim/sulfamethoxazole (T/S) for toxoplasmosis and antiretroviral therapy in the first 2 weeks after the diagnosis. They repeated cerebral imagery (MRI) after 3 weeks of T/S and had no regression of the size of lesions (although with the decreasing of perilesional edema) and new lesions, in two cases without having corresponding symptoms; in all 3 cases the CD4 count increased in the first month more than 100%. The search for another cause for the augmentation of their brain lesions was negative. Maintaining the same medication, the next imagery exams showed improvement in 2 out of 3 cases, in which the outcome was favorable with almost complete neurological recovery. In the remaining case the evolution was unfavorable (death).

Molecular determinants of resistance in Escherichia coli-ST131 isolated blood stream infections

Background During the past years an E coli clonal lineage ST131 has emerged explosively, causing predominantly communityonset antimicrobial resistant infections. E coli ST131 has been shown to harbor a number of virulence and resistance genes and is now recognized for its ability to cause potentially severe infections in many parts of the developing world, implying public health measures in attempt to control infection.

Co-infections and co-morbidities among injecting drug users versus sexually infected patients in Bucharest

After the 2008 introduction of new psychoactive substances (NPS) in Romania, the number of newly diagnosed HIV infections showed significant increase among injecting drug users (IDUs). Our objective was to analyze the differences between co‐infections related to the HIV infection, based on the way of transmission (IDUs versus sexually infected).

Rapid clinical score for the diagnosis of tuberculous meningitis: A retrospective cohort study

Objective: The aim of our study was to retrospectively validate a previously described rapid clinical score (RCS) in distinguishing tuberculous meningitis (TBM) from viral meningitis (VM) in people who are at increased risk of tuberculosis, as well as from cryptococcal meningitis (CM) in HIV-infected patients. Methods: We performed a retrospective study of patients admitted with a diagnosis of aseptic meningitis between January 2012 and December 2015, to a referral hospital for infectious diseases. The variables included in RCS were duration of symptoms before admission, neurological stage, cerebrospinal fluid (CSF) to blood glucose ratio, and CSF protein. We included in this retrospective study 31 patients with definite or probable TBM including 14 HIV-infected patients, 62 HIV-noninfected patients with VM, and 18 HIV-infected patients with CM. Results: The sensitivity of RCS to distinguish TBM from VM was 96.7%, with a specificity of 81.1% and the area under the receiver operating characteristic (ROC) curve was 0.949 (0.90–0.99). When all four criteria from the RCS were present, the specificity increased at 100%. In HIV-infected patients, the sensitivity and specificity of RCS in differentiating TBM from CM were 86.6% and 27.7%, respectively, and the area under the ROC curve was 0.669 (0.48–0.85). Conclusion: This easy-to-use RCS was found to be helpful in differentiating TBM from VM, with a better sensitivity than molecular amplification techniques and a relatively good specificity. However, the RCS was not useful to differentiate between TBM and CM in HIV-infected patients.

Comparison of Kaposi disease outlines in patients with and without HIV infection in two tertiary care hospitals in Bucharest, Romania

Methods A retrospective study on KD was performed in two academic centers, tertiary-care hospitals with national addressability in Romania. Two groups were comparatively studied: HIV-infected patients diagnosed in the National Institute for Infectious Diseases “Prof.Dr. Matei Bals” (HIV-positive group), and non-HIV patients diagnosed in the first Clinic of Dermatology, Colentina Clinical Hospital (HIV-negative group). The statistical analysis was performed using IBM SPSS Statistics v.22 (Chicago, USA).

Kaposi Sarcoma in HIV Infected Patients

Abstract Objective: The aim of the study was to describe clinical and laboratory characteristics in HIV-infected patients with Kaposi sarcoma (KS). Methods: We retrospectively studied data on HIV-infected patients hospitalized in one tertiary care hospital in Bucharest, Romania, in whom Kaposi Sarcoma was diagnosed, between January 2008 and November 2013. Results: We identified 27 HIV-infected patients diagnosed with KS within 6 years. They had a median age of 42 years old and a median CD4 cell count of 101 cells per mm3 at the time of KS diagnosis. All patients received antiretroviral therapy (ART), with 18 patients (66%) already on ART at the time of KS diagnosis. Most patients (59%) were classified as ACTG poor-risk and 56% as Mitsuyasu stage I. The overall prognosis was poor, with 41% mortality, in a median time span of 6 months, significantly correlated with gastrointestinal involvement (p=0.019), poor-risk KS in ACTG classification (p<0.001) and stage IV Mitsuyasu (p=0.006). Conclusion: KS remains an important cause of morbidity and mortality in patients with HIV infection, especially in late presenters.

Variation in CD4 cell count among IDUs versus sexually-infected HIV-positive naïve patients in Romania

Since 2011 Romania is experiencing a dramatic increase of newly diagnosed HIV infections among injecting drug users (IDUs), mainly linked to the introduction of new psychoactive substances (NPS) on the Romanian market, their use being related to higher levels of risk behavior compared to opioid abuse. There is no sufficient data showing the natural course of HIV in subjects infected through IDU – the majority are ART-naive due to recently acquired infection (many are asymptomatic and have a CD4 cell count over 350 cells/cmm) and poor adherence. Our objective was to determine if IDUs have a faster decline in CD4 cells than sexually-infected patients. We performed a retrospective study, including ART-naive HIV-positive patients diagnosed between January 2011 and June 2013 at the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, who had 2 subsequent CD4 cell count determinations over a timespan of 6-24 months and a baseline CD4 count higher than 350 cells/cmm. Among 1,248 newly diagnosed patients, 234 met these inclusion criteria. The data were statistically analyzed using SPSS version 17 (independent sample t-test, Mann-Whitney test, linear regression; the significance level was set at 0.05). The majority (80%, 187/234) were men and the median age was 29 years (15-76). More than half of the patients (138; 59%) were former or active IDUs, with low socioeconomic status, most of them injecting both opioids and NPS and 55 (40%) of them were in detention at the moment of HIV diagnosis. Among them, 98% were coinfected with HCV, as opposed to only 21% of the sexually-infected patients. Subtype analysis was performed for 64 patients and revealed the following subtypes and circulating recombinant forms (CRF): 50 F1, 3 B, 10 CRF14_BG and 1 CRF14_F. There was no significant difference of CD4 cell count between the two groups at baseline (p=0.55). The median variation of CD4 cells in IDUs was 150 and 42 in the non IDUs group. IDUs had a statistically significant CD4 cell decline (p=0.01). HCV coinfection was also correlated with a faster decline in CD4 cells (p <0.001). The more rapid decline of CD4 cells among IDUs could be explained by direct effect of drugs, differences in the virulence of the HIV strains circulating among IDUs and HCV coinfection. These data highlight the importance of carefully monitoring IDUs with HIV infection and of initiating ART earlier in this risk group.

Antiretroviral therapy adherence monitoring and its impact on immuno-virological outcome

One of the most important factors in achieving a good outcome is treatment adherence. Poor adherence to antiretroviral therapy (ART) leads to less viral suppression, permanent treatment resistance and increased costs. There are multiple causes of poor adherence: regimen complexity, side effects etc. Aim: to analyze ART adherence, risk factors for poor adherence and their impact on the outcome. We performed a one year survey (from January to December 2013) of HIV infected patients monitored in the Third Department of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”. The data (number of days covered by ART) was collected from patients’ files. We correlated the adherence with gender, regimen rank and complexity. Statistical analysis was made using EPI INFO 6. We retrospectively analyzed 111 patients who came in to our clinic monthly to pick-up their ART, 52 women (46.84%) and 59 men (53.16%) with a mean age of 43.5 years old. The adherence to ART was: 23 (20.62%) – 100% adherence, 36 (32.43%) – more than 96.7% adherence (less than 12 days without medication), 38 (34.23%) – 91.8% to 96.7% adherence (13-30 days without medication), 10 (9%) – 83.6% to 91.8% adherence (30-60 days without medication) and 4 (3.6%) with less than 83.6% adherence (more than 60 days without medication). The level of adherence was correlated with therapeutic failure: for 100% adherence – two failures (8.69%), for more than 96.7% adherence – no failure, for more than 91.8% adherence – 4 failures (11.1%), for more than 83.6% adherence – 2 failures (20%) and for less than 80% adherence – 3 failures (75%). Adherence below 91.8% was correlated with treatment failure: RR 5.65 (CI95% 1.99; 16.09, p=0.0007). We analyzed some possible risk factors for poor adherence: gender, regimen rank and complexity. Although 51.95% from the non-adherence group were women, the adherence wasn’t correlated with gender: RR 1.23 (CI95% 0.93; 1.62, p=0.16). A regimen rank higher than 1 was correlated with low adherence – 45.76% vs. 28.84% in the adherence vs. non-adherence group: RR 1.5 (CI95% 0.95; 2.38, p=0.07). The regimen containing protease inhibitors wasn’t correlated with low adherence: 33.9% vs. 30.8%, RR 1.08 (CI95% 0.71; 1.67, p=0.73). We emphasize the impact of therapy adherence on the outcome. A level of adherence below 91% was correlated with therapeutic failure. ART adherence wasn’t correlated with gender, PI regimen and rank regimen.

Characteristics of Kaposi sarcoma in HIV-infected patients

Objective: to describe clinical and laboratory characteristics; to assess predictors for death in HIV-infected patients with Kaposi sarcoma (KS). We performed a retrospective study of HIV-infected patients diagnosed with KS in one infectious diseases hospital in Romania, between January 2008-November 2013. KS diagnosis was established on physical examination, skin biopsy, and for visceral involvement upper gastrointestinal endoscopy, bronchoscopy and computed tomography. KS was staged according to the AIDS Clinical Trials Group (ACTG) [1] and the Mitsuyasu classification system [2]. We identified 27 HIV-infected patients with KS. The median age was 42 years (IQR 34-52) and 18 (67%) were male. The median CD4 count at HIV diagnosis was 195 cells/cmm (IQR 55-313), while at KS diagnosis the median CD4 count was 101 cells/cmm (IQR 41-270). Eighteen (67%) patients had a CD4 count <200 cells/cmm. The median HIV viral load at the time of KS diagnosis was 120,000 copies/mL (IQR 316-328,522). HIV infection was diagnosed before KS in 19 patients (70%), with a median time between HIV and KS diagnosis of 7 months (IQR 0-58). The most frequent KS localization was the lower limb in 16 (59%) patients and 7 (26%) patients had disseminated KS. Oral, gastrointestinal and pulmonary involvements were seen in 10 (37%), 4 (15%) and 3 (11%) patients respectively. Concomitant opportunistic infections were diagnosed in 20 (74%), while other malignancies in 3 (12%) patients. According to the ACTG classification 16 (59%) patients had poor risk KS. Fifteen (56%), 6 (22%), 1 (4%) and 5 (18%) were in stage 1, 2, 3 and 4, respectively according to the Mitsuyasu classification. Six (22%) patients received specific KS treatment: three local radiotherapy and three systemic therapy (two with interferon; one with liposomal doxorubicin). The overall mortality was 41% with a median duration between KS diagnosis and death of 6 months (IQR 2-15). Gastrointestinal involvement (p=0.019), poor-risk KS in ACTG classification (p<0.001) and stage IV Mitsuyasu (p=0.006) were associated with death in univariate analysis. The mortality rate in this study was high, due to poor immunological status, extended KS and high incidence of opportunistic infections, but also due to the lack of specific systemic treatment.