HIV-1 subtype B spread through cross-border clusters in the Balkans: a molecular analysis in view of incidence trends.

OBJECTIVES: To analyze phylogenetic relations and assess the role of cross-border clusters in the spread of HIV-1 subtype B across the Balkans, given the general trends of new HIV diagnoses in seven Balkan countries. DESIGN: Retrospective phylogenetic and trend analysis. METHODS: In-depth phylogenetic, phylodynamic and phylogeographic analysis performed on 2415 HIV-1 subtype B sequences from 1999 to 2019 using maximal likelihood and Bayesian methods. The joinpoint regression analysis of new HIV diagnoses by country and modes of transmission using 2004-2019 ECDC data. RESULTS: Ninety-three HIV-1 Subtype B transmission clusters (68% of studied sequences) were detected of which four cross-border clusters (11% of studied sequences). Phylodynamic analysis showed activity of cross-border clusters up until the mid-2000s, with a subsequent stationary growth phase. Phylogeography analyses revealed reciprocal spread patterns between Serbia, Slovenia and Montenegro and several introductions to Romania from these countries and Croatia. The joinpoint analysis revealed a reduction in new HIV diagnoses in Romania, Greece and Slovenia, whereas an increase in Serbia, Bulgaria, Croatia and Montenegro, predominantly among MSM. CONCLUSION: Differing trends of new HIV diagnoses in the Balkans mirror differences in preventive policies implemented in participating countries. Regional spread of HIV within the countries of former Yugoslavia has continued to play an important role even after country break-up, whereas the spread of subtype B through multiple introductions to Romania suggested the changing pattern of travel and migration linked to European integration of Balkan countries in the early 2000s.

Helicobacter pylori infection rates in dyspeptic Serbian HIV-infected patients compared to HIV-negative controls.

Helicobacter pylori infection does not belong to the spectrum of opportunistic infections in people living with HIV (PLHIV). To evaluate the Helicobacter pylori infection prevalence rate trends in HIV co-infected individuals in comparison to the HIV-negative population, we compared histopathological findings of H. pylori positive gastritis (gastritis topography and histopathology) between 303 PLHIV and 2642 HIV-negative patients who underwent esophagogastroduodenoscopy (EGD) between 1993 and 2014 due to dyspeptic symptoms. The prevalence of H. pylori infection was significantly higher in HIV-negative controls than in PLHIV (50.2% vs. 28.1%). A significantly positive linear trend of H. pylori co-infection in PLHIV was revealed in the observed period (b = 0.030, SE = 0.011, p = 0.013), while this trend was significantly negative in HIV-negative patients (b = - 0.027, SE = 0.003, p < 0.001). Patients with HIV/H. pylori co-infection had significantly higher CD4+ T cell counts and more often had undetectable HIV viremia, due to successful anti-retroviral therapy (ART). Stomach histopathological findings differed between HIV co-infected and H. pylori mono-infected patients. Our findings confirm that the ART has changed the progression of HIV infection, leading to a significant increase in the prevalence of H. pylori infection in dyspeptic PLHIV over time. Our data also suggests that a functional immune system may be needed for H. pylori-induced human gastric mucosa inflammation.

Severe hepatotoxicity induced by efavirenz in a treatment-naïve, low body mass index HIV-infected, female patient with no hepatitis and other virus co-infections.

Combined antiretroviral therapy (cART) consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI), such as efavirenz, is still the first-line treatment in resource-limited settings. However, efavirenz has shown strong prominence of disadvantages with variance in plasma concentration and central nervous side effects. Our study presents HIV infected, drug naïve, female patient with relatively low BMI, CYP2B6 516G>T (rs3745274) genotype with high efavirenz plasma concentration. In this case report, the patient was admitted at the hospital 6 months after cART initiation with drug-induced severe hepatotoxicity. Furthermore, pathophysiological findings proved confluent parenchymal necrosis after aspiration liver biopsy, with mild to moderate inflammation in portal tracts with focal interface hepatitis. All other possible causes were excluded. Thus, we conclude that efavirenz has a potential harmful effect in patients with low BMI, specific genotyping and interindividual pharmacokinetics affecting high plasma concentration.

Exploring Evolutionary and Transmission Dynamics of HIV Epidemic in Serbia: Bridging Socio-Demographic With Phylogenetic Approach.

Previous molecular studies of Serbian HIV epidemic identified the dominance of subtype B and presence of clusters related HIV-1 transmission, in particular among men who have sex with men (MSM). In order to get a deeper understanding of the complexities of HIV sub-epidemics in Serbia, epidemic trends, temporal origin and phylodynamic characteristics in general population and subpopulations were analyzed by means of mathematical modeling, phylogenetic analysis and latent class analysis (LCA). Fitting of the logistic curve of trends for a cumulative annual number of new HIV cases in 1984-2016, in general population and MSM transmission group, was performed. Both datasets fitted the logistic growth model, showing the early exponential phase of the growth curve. According to the suggested model, in the year 2030, the number of newly diagnosed HIV cases in Serbia will continue to grow, in particular in the MSM transmission group. Further, a detailed phylogenetic analysis was performed on 385 sequences from the period 1997-2015. Identification of transmission clusters, estimation of population growth (Ne), of the effective reproductive number (Re) and time of the most recent common ancestor (tMRCA) were estimated employing Bayesian and maximum likelihood methods. A substantial proportion of 53% of subtype B sequences was found within transmission clusters/network. Phylodynamic analysis revealed Re over one during the whole period investigated, with the steepest slopes and a recent tMRCA for MSM transmission group subtype B clades, in line with a growing trend in the number of transmissions in years approaching the end of the study period. Contrary, heterosexual clades in both studied subtypes - B and C - showed modest growth and stagnation. LCA analysis identified five latent classes, with transmission clusters dominantly present in 2/5 classes, linked to MSM transmission living in the capital city and with the high prevalence of co-infection with HBV and/or other STIs.Presented findings imply that HIV epidemic in Serbia is still in the exponential growth phase, in particular, related to the MSM transmission, with estimated steep growth curve until 2030. The obtained results imply that an average new HIV patient in Serbia is a young man with concomitant sexually transmitted infection.

High Frequency of Human Leukocyte Antigen-B*57:01 Allele Carriers among HIV-Infected Patients in Serbia.

Abacavir is an effective antiretroviral drug and one of the most commonly used nucleoside reverse transcriptase inhibitors in Serbia. А percentage of the treated patients experience a potentially life-threatening hypersensitivity reaction, which was shown to be associated with the presence of the class I MHC allele, HLA-B*57:01; hence genotyping for HLA-B*57:01 prior to starting abacavir is nowadays recommended in international HIV treatment guidelines. In Serbia, this testing became available in 2013. This study was designed to estimate the prevalence of the HLA-B*57:01 allele in Serbian HIV-1-infected patients. The presence of the HLA-B*57:01 allele was analyzed in 273 HIV-1-infected patients aged 18 years or more, who were abacavir naïve. Buccal swab samples were obtained from all participants and assayed for the presence of HLA-B*57:01 using a commercially available HLA-B*57:01 real-time PCR kit. The presence of the HLA-B*57:01 allele was found in 22 of 273 tested individuals (8%; 95% CI 5.4-11.9%). This is the first study that estimated the HLA-B*57:01 prevalence among HIV-infected patients in Serbia. The very high prevalence of HLA-B*57:01 found in our study strongly supports HLA-B*57:01 genotyping, which should be implemented prior to the initiation of an abacavir-containing therapy to reduce the risk of potentially life-threatening hypersensitivity reactions.

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.

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.

Forensic application of phylogenetic analyses - Exploration of suspected HIV-1 transmission case.

Transmission of human immunodeficiency virus (HIV) between individuals may have important legal implications and therefore may come to require forensic investigation based upon phylogenetic analysis. In criminal trials results of phylogenetic analyses have been used as evidence of responsibility for HIV transmission. In Serbia, as in many countries worldwide, exposure and deliberate transmission of HIV are criminalized. We present the results of applying state of the art phylogenetic analyses, based on pol and env genetic sequences, in exploration of suspected HIV transmission among three subjects: a man and two women, with presumed assumption of transmission direction from one woman to a man. Phylogenetic methods included relevant neighbor-joining (NJ), maximum likelihood (ML) and Bayesian methods of phylogenetic trees reconstruction and hypothesis testing, that has been shown to be the most sensitive for the reconstruction of epidemiological links mostly from sexually infected individuals. End-point limiting-dilution PCR (EPLD-PCR) assay, generating the minimum of 10 sequences per genetic region per subject, was performed to assess HIV quasispecies distribution and to explore the direction of HIV transmission between three subjects. Phylogenetic analysis revealed that the viral sequences from the three subjects were more genetically related to each other than to other strains circulating in the same area with the similar epidemiological profile, forming strongly supported transmission chain, which could be in favour of a priori hypothesis of one of the women infecting the man. However, in the EPLD based phylogenetic trees for both pol and env genetic region, viral sequences of one subject (man) were paraphyletic to those of two other subjects (women), implying the direction of transmission opposite to the a priori assumption. The dated tree in our analysis confirmed the clustering pattern of query sequences. Still, in the context of unsampled sequences and inherent limitations of the applied methods, we cannot unambiguously prove that HIV-1 transmission occurred directly between two individuals. Further exploration of the known and suspected transmission cases is needed in order to define methodologies and establish their reliability.

Human papillomavirus and anal carcinoma knowledge in men who have sex with men in Belgrade, Serbia.

BACKGROUND: To evaluate the level of knowledge among men who have sex with men regarding human papillomavirus (HPV), anal cancer screening, and HPV vaccine. METHODS: A cross-sectional study was conducted in 2013 in Belgrade, Serbia, comprising 142 HIV-positive and 128 HIV-negative persons. RESULTS: Of all participants, 34.8% had never heard of HPV infection; 43.3% of participants were informed that HPV infection might be asymptomatic, while 30.4% knew that HPV is not transmitted by towels/cloth. Furthermore, 45.9% answered that HPV is a cause of genital warts, while 28.9%, 14.4%, and 17.4%, respectively, answered that it can cause anal, penile, and oral cancers. Only one-fourth of participants knew that anal cancer is more frequent in homosexual men. More than 50% had not heard of anal Papanicolaou (Pap) smears, and less than 3% had ever had it. Almost 90% of participants did not know which physicians provide anal Pap smears. Less than one-third knew that regular anal Pap smears might prevent consequences of anal HPV infection. The majority of participants did not know that there is a vaccine against HPV and anal cancer. Less than 50% reported willingness to receive HPV vaccine. Knowledge was slightly better in HIV-positive men in comparison with HIV-negative ones. CONCLUSIONS: Results point out the need for community efforts to promote knowledge about HPV, anal carcinoma, and anal Pap screening among men who have sex with men and their healthcare providers, and to increase the acceptance of HPV vaccine by the population.

HIV/AIDS mortality in a south east European country versus a west European country.

INTRODUCTION: Antiretroviral (ARV) treatment available in low-middle income countries differs as suggested in international HIV-treatment guidelines. Thus, we compared ARV regimens introduced as a first-line therapy, time of initiation, frequency of making combination antiretroviral therapy (cART) switches, frequency of viral and immunological monitoring and treatment outcome in south east European (SEE) country (i.e. HIV Centre in Belgrade, Serbia, (HCB)) and west European country (i.e. Royal Free Centre for HIV Medicine at the Royal Free Hospital London, UK (RFH)). MATERIALS AND METHODS: ARV naïve patients starting cART from 2003 to 2012 were included. Comparisons of the two cohorts were made using a chi-square test or Fisher's exact test for categorical variables and a Mann-Witney U test for continuous variables. Kaplan Meier survival curves were compared using the log rank test. RESULTS: Of 597 patients from HCB, 361 (61%) initiated cART with prior AIDS diagnosed, while 337 (19%) of 1763 patients from RFH. Average baseline CD4+ T cell counts were significantly lower in Serbia than in UK (177 cells/mm(3) vs 238 cells/mm(3)). The total (mediana, IQR) CD4+ T cell count measurements in the first year of cART was 2 (1, 2) at the HCB, while it was statistically significant higher at the RFH 5 (3, 7), respectively (p<0.0001). At the RFH, it appeared that the cART switching is due to patient's preference or toxicity (46%), while the lack of supply and toxicity (37%) were the most important reasons for treatment change in HCB, within the same period of time (p<0.05). Mortality rates were higher at the HCB versus RFH (p<0.0001). After 12, 24 and 36 months of cART, 3%, 5% and 8% of patients died in HCB, whereas 2%, 3% and 4% of patients died in RFH, respectively (Figure 1). CONCLUSIONS: In south European countries, as a consequence of low testing rate, ARV treatment is introduced at an advanced stage of disease, having a high mortality rate as a consequence. Switching within ARV drugs appears often due to lack of drug supplies and frequently drug-related toxicity in south east Europe, while in the east European country due to patient's preferences and rarely due to drug-related toxicity.

Ten years survey of primary HIV-1 resistance in Serbia: the occurrence of multiclass resistance.

In Serbia, the first cases of HIV infection were reported in 1985, whereas antiretroviral (ARV) therapy has been in use since 1987. With this study we aimed to assess the occurrence and pattern of HIV resistance mutations among newly diagnosed patients in the period 2002-2011. The study prospectively included 181 adult patients. Genotypic HIV-1 drug resistance testing was performed and drug resistance was scored according to the 2009 WHO list for surveillance of drug resistance mutations (SDRMs). A bioinformatic approach was used to estimate the duration of infection by calculating the percentage of ambiguous basecalls per sequence, with a cutoff of 0.47% as the delimiter for recent infection. The overall prevalence of transmitted drug resistance (TDR) found in the study was 8.8% (16/181, 95% CI=5.5-13.8). Thirty-one percent of resistant samples contained multiple SDRMs. In particular, 5/16 patients with resistance carried viral strains with SDRMs to multiple ARV classes, hence one-third of resistant strains were multiclass resistant, including non-B strains. A total of 51.9% of samples (94/181) were classified as recent infection, with a significant increase in the second part of the study period. However, the prevalence of TDR in recent infection was 6.4% (6/94, 95% CI=2.9-13.2), not statistically different from that found in nonrecent infection. We showed a changing pattern of TDR mutations over the study period, with a substantial occurrence of multiclass resistance, across different HIV subtypes. Our results highlight the need for continued surveillance of primary resistance.

Clinical and immunologic outcomes of HAART-treated HIV-infected women in resource constrain settings: the Belgrade Study.

We performed a study to identify factors related to favorable response to highly active-antiretroviral therapy (HAART) in HIV-infected women. A retrospective study was performed on 216 women who had initiated HAART from January 1, 1998 to December 31, 2012, at the HIV/AIDS Center, Belgrade, Serbia. Participants were followed-up for 8.2 ± 3.4 years. The mean age was 37 ± 9.7 years. During follow-up, it was found that 26 patients had died. Clinical AIDS at initiation of HAART was observed in 43.9% patients, while 64.8% had a CD4+ T-cell count below 200 cells/µL. Multivariate analyses revealed that the single factor independently related to a favorable response to HAART was good compliance (odds [OR] ratio for survival = 2.9, 95% confidence intervals [CI] = 1.0-8.6, p = 0.03), while a baseline CD4+ T-cell count below 100 cells/µL, hepatitis C virus coinfection, and aged 40 years and older were all associated with an unfavorable response to HAART (OR = 0.28, 95% CI = 0.15-0.52, p < 0.001; OR = 0.49, 95% CI = 0.22-0.8, p = 0.008; OR = 0.41, 95% CI = 0.21-0.79, p = 0.008, respectively). The estimated 14-year-survival was 100% in patients with sustained viral suppression, regardless of the CD4+ counts achieved (p = 0.6, log-rank). If women with advanced HIV-related immunodeficiency reach and maintain optimal viral suppression during HAART, regardless of the level of immune recovery, and if they continue to maintain this suppression for up to a mean 8 years of treatment, their prognosis may be fairly good, even in resource-limited settings.

Treatment outcome of HAART-treated patients in a resource-limited setting: the Belgrade Cohort Study.

INTRODUCTION: We evaluated the effects of highly-active-antiretroviral-therapy (HAART) in a resource-limited settings. METHODS: A cross-sectional study was performed in patients who had initiated HAART at the HIV/AIDS-Center, Belgrade, Serbia. Treatment response was considered favorable in case of the achievement of undetectable HIVRNA plasma-viral-load (pVL<50 copies/µL), and with the CD4+ T-cell counts increased above 350cells/µL. The treatment failure was defined as pVL over 1.7 log10 copies/mL, regardless of immunological improvement. RESULTS: Eight hundred and forty HIV infected patients were followed-up for 8.2±3.4years. Out of 697 patients available for follow-up, 113 (16.2%) patients died, 44 (6.3%) experienced treatment failure, while 540 (77.5%) had sustained undetectable viremia. In 419 (60.1%) favorable treatment response was achieved, while the dissociation between immunological and virological responses to HAART occurred in 121 (14.4%). A baseline CD4+ T-cell counts above 200 cells/µL was the single independent predictor of a favorable treatment response (HR=2, 95%CI=1.69-2.61, P=0.001), while pre-treatment with ART, HCV co-infection and AIDS at the time of treatment initiation, were all factors preventing a favorable response (HR=0.27, 95%CI=0.19-0.36, P=0.001; HR=0.75, 95%CI=0.56-0.95, P=0.02; HR=0.73, 95%CI=0.17-0.95, P=0.018, respectively). A sustained viral suppression was an independent predictor of survival (HR=0.2, 95% CI 0.07-0.61, P=0.004). HAART treated HIV-infected patients who reach and maintain undetectable viremia, have an 80% probability of a 14-years survival (P=0.08, log-rank). CONCLUSION: If patient with advanced HIV-related immunodeficiency reach and maintain optimal viral suppression during HAART, regardless of the level of immune recovery, and if they continue to maintain this, their prognosis may be fairly good even in the resource-limited settings.

Molecular typing of the local HIV-1 epidemic in Serbia.

Worldwide HIV-1 pandemic is becoming increasingly complex, with growing heterogeneity of subtypes and recombinant viruses. Previous studies have documented HIV-1 subtype B as the predominant one in Serbia, with limited presence and genetic diversity of non B subtypes. In recent years, MSM transmission has become the most frequently reported risk for HIV infection among newly diagnosed patients in Serbia, but very little is known of the network structure and dynamics of viral transmission in this and other risk groups. To gain insight about the HIV-1 subtypes distribution pattern as well as characteristics of HIV-1 transmission clusters in Serbia, we analyzed the genetic diversity of the pol gene segment in 221 HIV-1-infected patients sampled during 2002-2011. Subtype B was found to still be the most prevalent one in Serbia, accounting for over 90% of samples, while greater diversity of other subtypes was found than previously reported, including subtypes G, C, A, F, CRF01 and CRF02. In total, 41.3% of analyzed subtype B sequences were found associated in transmission clusters/network, that are highly related with MSM transmission route.

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

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.

Diagnostic esophago-gastro-duodenoscopy (EGD) in patients with AIDS-related upper gastrointestinal abnormalities.

BACKGROUND/AIMS: Gastrointestinal (GI) diseases are common among patients infected with human immunodeficiency virus (HIV), and may involve the entire GI tract. The aim of the article is to investigate the prevalence of various upper gastrointestinal abnormalities in patients with AIDS. METHODOLOGY: Diagnostic esophago-gastro-duodenoscopy (EGD) was performed in cohort of AIDS patients (total 186) including non-ART, mono and/or dual ART and HAART treated subgroups. Clinical presentation, level of immunosupression and presence of H. pylori infection was also considered. RESULTS: Endoscopic findings included normal (29), esophageal candidiasis (22), esophageal erosions (16), gastritis/duodenitis (135), gastric/duodenal ulcers (7), erosions (6) and infiltration/tumor in the stomach (5). Thirty-nine patients (20.4%) had opportunistic infections/tumors including candida esophagitis, CMV esophagitis, CMV gastritis, gastric non-Hodgkin's lymphoma (NHL) and gastric cryptosporidiosis. H. pylori infection was present in 25.8% of patients, and majority (89.6%) had chronic non-atrophic gastritis. These patients had a higher mean CD4 count compared with H. pylori negative patients (403.5 vs. 226.9 CD4+ cells/microL, p = 0.001). Patients who received HAART had significantly higher frequency of H. pylori infection then non-ART treated patients (p = 0.048). CONCLUSION: Candidiasis was the marker of advanced immunodeficiency, and H. pylori was more common in patients with higher CD4 cell counts on ART, which may suggest that this infection could be an unusual presentation of immune restoration inflammatory syndrome.

Serbian lymphoma study group (SLG): the prognosis of AIDS-related non-Hodgkin's lymphoma.

BACKGROUND: The majority of patients with AIDS-related non-Hodgkin's lymphoma (ARL) present with advanced disease, aggressive histological type, B-symptoms, and often with an extranodal localization. The prognosis is generally poor. The use of highly active antiretroviral therapy (HAART), in combination with chemotherapy, has improved the outcome of ARL. AIMS: The aims of this study were to detect prognostic factors for patients with ARL and estimate efficacy of concomitant chemotherapy and HAART on overall survival (OS) of these patients. Also, two different chemotherapy regimens have been tested: low dose (ld) mBACOD and CHOP. METHODS: The study series involved 28 patients with ARL treated at the Clinical Center of Serbia in Belgrade during the period 1996-2006. Twenty-six patients had an aggressive type of lymphoma while 2 had an indolent type. Nineteen patients were treated with chemotherapy, 10 with ld mBACOD and 9 with CHOP. Concomitant HAART and chemotherapy were used in 14 patients. RESULTS: This study demonstrated that significant factors for OS in patients with ARL were the high International Prognostic Index (P=0.019), previous AIDS event (P=0.04), aggressive histological type of NHL (P=0.007) and extranodal disease (P=0.04). The usage of concomitant HAART and chemotherapy had significant effect on median survival (90 months), compared with chemotherapy alone (10 months) (P=0.0002). The patients treated with CHOP had a better response than patients treated with ld mBACOD, but this difference was not significant. CONCLUSIONS: Our data suggest that aggressive presentation of ARL implicates the need not only for more intensive chemotherapy regimens, but the concomitant usage of HAART, which should result in higher rates of OS in ARL patients.