Where are we with pre-exposure prophylaxis use in Central and Eastern Europe? Data from the Euroguidelines in Central and Eastern Europe (ECEE) Network Group.

OBJECTIVES: Pre-exposure prophylaxis (PrEP) for HIV infection is an important intervention for control of the HIV epidemic. The incidence of HIV infection is increasing in the countries of Central and Eastern Europe (CEE). Therefore, we investigated the change in PrEP use in CEE over time. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was initiated in February 2016 to compare standards of care for HIV and viral hepatitis infections in CEE. Data on access to PrEP were collected from 23 countries through online surveys in May-June 2017 (76 respondents) and in November 2018-May 2019 (28 respondents). RESULTS: About 34.2% of respondents stated that tenofovir/emtricitabine (TDF/FTC) was licensed for use in their country in 2017, and 66.7% that it was licensed for use in 2018 (P = 0.02). PrEP was recommended in national guidelines in 39.5% of responses in 2017 and 40.7% in 2018 (P = 0.378). About 70.7% of respondents were aware of "informal" PrEP use in 2017, while 66.6% were aware of this in 2018 (P = 0.698). In 2018, there were 53 centres offering PreP (the highest numbers in Poland and Romania), whereas six countries had no centres offering PreP. The estimated number of HIV-negative people on PreP in the region was 4500 in 2018. Generic TDF/FTC costs (in Euros) ranged from €10 (Romania) to €256.92 (Slovakia), while brand TDF/FTC costs ranged from €60 (Albania) to €853 (Finland). CONCLUSIONS: Although the process of licensing TDF/FTC use for PrEP has improved, this is not yet reflected in the guidelines, nor has there been a reduction in the "informal" use of PrEP. PrEP remains a rarely used preventive method in CEE countries.

Temporal changes and regional differences in treatment uptake of hepatitis C therapy in EuroSIDA.

OBJECTIVES: All HIV/hepatitis C virus (HCV)-coinfected patients with chronic HCV infection and ≥ F2 fibrosis should be considered for HCV therapy. This study aimed to determine the rate of HCV treatment uptake among coinfected patients in Europe. METHODS: EuroSIDA patients with viraemic HCV infection were included in the study. Poisson regression was used to identify temporal changes and regional differences in HCV treatment uptake. RESULTS: A total of 1984 patients were included in the study, with a median follow-up time of 168 months [interquartile range (IQR) 121-204 months]. To date, 501 (25.3%) HIV/HCV-coinfected patients have received HCV therapy. Treatment incidence rose from 0.33 [95% confidence interval (CI) 0.16-0.50] per 100 person-years of follow-up (PYFU) in 1998 to 5.93 (95% CI 4.49-7.38) in 2007, falling to 3.78 (95% CI 2.50-5.07) in 2009. After adjustment, CD4 cell count > 350 cells/µL [incidence rate ratio (IRR) 1.33 (95% CI 1.06-1.67) vs. CD4 count 200-350 cells/µL] and ≥F2 liver fibrosis [IRR 1.60 (95% CI 1.14-2.25; P = 0.0065) vs. < F2 fibrosis] were predictors of anti-HCV treatment initiation. However, 22% of patients who remain untreated for HCV, with fibrosis data available, had ≥F2 fibrosis and should have been considered for treatment, while only 36% of treated patients had ≥F2 fibrosis. CONCLUSIONS: Although treatment incidence for HCV has increased, there remain a large proportion of patients indicated for treatment who have yet to be treated.

Outbreak of West Nile virus infection among humans in Serbia, August to October 2012.

We describe the first reported outbreak of West Nile virus (WNV) infection in humans in Serbia in August to October 2012 and examine the association of various variables with encephalitis and fatal outcome. Enzyme-linked immunosorbent assay (ELISA) was used for detection of WNV-specific IgM and IgG antibodies in sera and cerebrospinal fluid. A total of 58 patients (mean age: 61 years; standard deviation: 15) were analysed: 44 were from Belgrade and its suburbs; 52 had neuroinvasive disease, of whom 8 had meningitis, while 44 had encephalitis. Acute flaccid paralysis developed in 13 of the patients with encephalitis. Age over 60 years and immunosuppression (including diabetes) were independently associated with the development of encephalitis in a multivariate analysis: odds ratio (OR): 44.8 (95% confidence interval (CI): 4.93­408.59); p=0.001 (age over 60 years); OR: 10.76 (95% CI: 1.06­109.65); p=0.045 (immunosuppression including diabetes). Respiratory failure requiring mechanical ventilation developed in 13 patients with encephalitis. A total of 35 patients had completely recovered by the time they were discharged; nine patients died. The presence of acute flaccid paralysis, consciousness impairment, respiratory failure and immunosuppression (without diabetes) were found to be associated with death in hospital in a univariate analysis (p<0.001, p=0.007, p<0.001 and p=0.010, respectively).

HIV care in times of the COVID-19 crisis - Where are we now in Central and Eastern Europe?

INTRODUCTION: The SARS-CoV-2 pandemic has hit the European region disproportionately. Many HIV clinics share staff and logistics with infectious disease facilities, which are now on the frontline in tackling COVID-19. Therefore, this study investigated the impact of the current pandemic situation on HIV care and continuity of antiretroviral treatment (ART) supplies in CEE countries. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was established in February 2016 to review standards of care for HIV in the region. The group consists of professionals actively involved in HIV care. On March 19, 2020 we decided to review the status of HIV care sustainability in the face of the emerging SARS-CoV-2 pandemic in Europe. For this purpose, we constructed an online survey consisting of 23 questions. Respondents were recruited from ECEE members in 22 countries, based on their involvement in HIV care, and contacted via email. RESULTS: In total, 19 countries responded: Albania, Armenia, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Greece, Hungary, Lithuania, Macedonia, Poland, Republic of Moldova, Russia, Serbia, Turkey, and Ukraine. Most of the respondents were infectious disease physicians directly involved in HIV care (17/19). No country reported HIV clinic closures. HIV clinics were operating normally in only six countries (31.6%). In 11 countries (57.9%) physicians were sharing HIV and COVID-19 care duties. None of the countries expected shortage of ART in the following 2 weeks; however, five physicians expressed uncertainty about the following 2 months. At the time of providing responses, ten countries (52.6%) had HIV-positive persons under quarantine. CONCLUSIONS: A shortage of resources is evident, with an impact on HIV care inevitable. We need to prepare to operate with minimal medical resources, with the aim of securing constant supplies of ART. Non-governmental organizations should re-evaluate their earlier objectives and support efforts to ensure continuity of ART delivery.

Comparison of nucleoside reverse transcriptase inhibitor use as part of first-line therapy in a Serbian and a UK HIV clinic.

BACKGROUND: Use of dideoxynucleoside reverse transcriptase inhibitors (dNRTIs) may lead to increased mitochondrial toxicity. We compared nucleoside reverse transcriptase inhibitor (NRTI) use as part of antiretroviral therapy (ART) in two HIV clinics: one in a low-middle income (HIV Centre Belgrade [HCB], Serbia) and one a high income (ICDC, Royal Free Hospital, London, UK) country. METHODS: Antiretroviral naïve patients starting ART from 2003 to 2005 were included. Specific NRTIs were compared between centers, focusing on dNRTI use. Kaplan-Meier estimates of the percentage of patients making changes to their NRTI backbone (a) for any reason or (b) for mitochondrial toxicity (peripheral neuropathy, pancreatitis, lactic acidosis) were calculated. RESULTS: Of 287 HCB patients, 89 (31.0%) received didanosine (ddI)-containing, 39 (13.6%) stavudine (d4T)-containing, and 39 (13.6%) ddI+d4T-containing regimens; for 539 ICDC patients, these were 18 (3.3%), 66 (12.2%), and 0 (0.0%), respectively (p < .0001). After 12 months, 57.5% and 52.6% at HCB and ICDC had switched their NRTI backbone. This was reduced to 34.5% at HCB after excluding changes due to drug supply interruption and to 11.2% and 1.3% at HCB and ICDC after changes were made for mitochondrial-related reasons. At 6 months, 73/80 (91.3%) and 385/488 (78.9%) had viral load below 50 copies/mL at HCB and ICDC, respectively. CONCLUSION: Patients treated at HCB faced higher levels of mitochondrial-related toxicity, likely due to greater dNRTI use.

Comparison of Demographic, Epidemiological, Immunological, and Clinical Characteristics of Patients with HIV Mono-infection Versus Patients Co-infected with HCV or/and HBV: A Serbian Cohort Study.

OBJECTIVE: The study aimed to correlate the status of hepatitis C (HCV) and hepatitis B virus (HBV) co-infection in patients with human immunodeficiency virus (HIV) infection with clinical and demographic data prior to starting highly active antiretroviral therapy (HAART) and assess the impact of HCV and HBV co-infection on the natural history of HIV infection. PATIENTS AND METHODS: The study involved a total of 836 treatment-naive patients with available serological status for HBV and HCV at the point of therapy initiation. Patients were stratified into four groups: HIV mono-infection, HIV/HCV, HIV/HBV, and HIV/HCV/HBV co-infection. Demographic, epidemiological, immunological and clinical characteristics were analyzed in order to assess the possible impact of HCV and HBV co-infection on HIV - related immunodeficiency and progression to AIDS. RESULTS: The prevalence of HCV and HBV co-infection in our cohort was 25.7% and 6.3%, respectively. Triple HIV/HCV/HBV infection was recorded in 1.7% of the patients. In comparison with those co-infected with HCV, patients with HIV mono-infection had lower levels of serum liver enzymes activity and higher CD4 cell counts, and were less likely to have CD4 cell counts below100 cells/µL and clinical AIDS, with OR 0.556 and 0.561, respectively. No difference in the development of advanced immunodeficiency and/or AIDS was recorded between patients with HIV monoinfection and those co-infected with HBV, or both HCV/HBV. CONCLUSION: HIV/HCV co-infection was found to be more prevalent than HIV/HBV co-infection in a Serbian cohort. Co-infection with HCV was related to more profound immunodeficiency prior to therapy initiation, reflecting a possible unfavorable impact of HCV on the natural history of HIV infection.

Reduced quantity and hydrogen-peroxide production of vaginal lactobacilli in HIV positive women.

It has been suggested that vaginal lactobacilli may influence heterosexual transmission of HIV infection. The aim of this study was to compare the vaginal flora on Gram's stained and isolation rate, quantity and H2O2 production of lactobacilli between HIV positive and HIV negative women. Although, the prevalence of abnormal vaginal flora was increased in HIV infected women, there was no significant difference in isolation rate of vaginal lactobacilli between the two groups (71.87 vs. 83.33%; P>0.05). However, the results of this study showed significantly reduced quantity of lactobacilli in HIV infected women (P<0.01). In particular, the prevalence of H2O2-producing lactobacilli was lower in HIV positive as compared to HIV negative women (80 vs. 56.52%), with borderline significance (P=0.057). Taken together, our findings showed altered vaginal microflora with reduced quantity and hydrogen-peroxide production of vaginal lactobacilli in HIV positive women, but further studies are needed to assess its actual significance and potential benefit from the use of probiotic therapy.

The dissociation between virological and immunological responses to HAART.

While HAART allows for the reconstitution of immune functions in most treated HIV patients, discrepant responses including failure to achieve a significant increase in circulating CD4+ T cells despite undetectable plasma viral loads (pVL), or a good immunological response while not reaching undetectable viremia, may occur. Thus, to evaluate the incidence of and risk factors for discrepant responses to HAART, we conducted a retrospective study of all 446 patients treated with HAART between 1 January 1998 and 31 August 2004 in our HIV unit. CD4+ T cell counts and pVL values at baseline and end of study were parameters of the type of response. Within a mean follow-up period of 33 months, discrepant immunological and virological responses occurred in even 50% patients. Of these, 174 (39%) did not have a rise in CD4+ T cells to above 400 per microl despite a good virological response (type 1 dissociation), while 49 (11.0%) had a rise in the CD4+ T cell count to at least 200 per microl but their pVL was not undetectable (type 2 dissociation). The risk factors for immunological failure despite an undetectable pVL were baseline CD4+ T cells below 100 per microl (OR 1.44, 95%CI 1.02-2.03) and HAART composed of three NRTIs (OR 1.92, 95%CI 1.35-2.73), while usage of two NRTIs in combination with PI(s) (OR 0.36, 95%CI 0.26-0.49), as well as simultaneous usage of all three drug classes (OR 0.37, 95%CI 0.26-0.53) were shown to be protective. The usage of PI-containing HAART regimens was protective against type 2 dissociation (OR=0.40, 95%CI 0.19-0.83). Importantly, there were no differences in the survival of HAART-treated patients irrespective of the type of response.

Incidence of acute pancreatitis and nucleoside reverse transcriptase inhibitors usage.

Acute pancreatitis (AP) is a well-known adverse effect of nucleoside reverse transcriptase inhibitors (NRTIs). Therefore, we performed a prospective, cohort study to examine the incidence rates (IRs) and rate ratios (RRs) of AP for each NRTI. A total of 116 HIV patients were included in the final analysis comprising 445.6 person-years of follow-up. Twelve cases of AP were recorded. The lowest IR for AP was for didanosine (ddI) (IR=0.03 per 100 person-years, 95% confidence interval [CI] = 0.01-0.05), and the highest for ddI + stavudine (d4T) (IR = 0.08, 95% CI = 0.07-012). Compared with ddI alone, the RR of AP was 2.21 (95% CI = 1.32-9.31) for d4T, and 3.13 (95% CI = 1.43-12.56) for ddI + d4T. Other risk factors for AP were CD4 cell count <200 cells/mm(3) and female sex. Our results suggest that the use of d4T alone or combined with ddI should not be used as first-line therapy, especially in women or patients with CD4-cell count <200 cells/mm(3).

The role of passive immunization in hiv-positive patients : a case report.

An HIV-positive patient presented with pulmonary tuberculosis as her AIDS-defining diagnosis in 1993 and was effectively treated with 12 months of standard antituberculosis medications (isoniazide, rifampin, and pyrazinamide for 2 months). She received zidovudine for 6 weeks at the time of her diagnosis; however, because of patient preference, she has not received subsequent standard HIV medications (7 years). Her CD4 count at the time of diagnosis (1993) was 297/microL. Monthly passive immunotherapy was administered (fresh frozen plasma from HIV-negative blood donors with a significant titer for the anti-vasoactive intestinal peptide [VIP]/NTM antibody) from December 1993 to June 1994. Her CD4 count increased to > 400/microL during the passive immunotherapy and has remained stable for the past 6 years. The rational for the use of anti-VIP/NTM antibodies preparations in HIV, the possible mode of action of anti-VIP/NTM antibodies, the use of Ig preparations, and the role of exercise as a natural source of anti-VIP/NTM antibodies are discussed. This case report supports the potential therapeutic use of anti-VIP antibodies for treatment of HIV disease.

Antigen/antibody content of circulating immune complexes in HIV-infected patients.

Dual infection with HIV and hepatitis B virus (HBV) is not an uncommon feature. Immunity impairment due to HIV infection can be the cause of a higher rate of HBV replication with less intensive liver damage and less effective immune response to HBV. Many HIV-infected patients have an elevated level of circulating immune complexes (CIC) in serum, throughout all stages of illness evolution. The aim of our study was to estimate p24 and HBsAg content of CIC in dually infected patients, and the prevalence of major classes of complexed antibodies (IgM and IgG). We examined 146 samples of sera from 105 HIV positive patients of the Institute for Infectious and Tropical Diseases during 1992 and 1993. On those sera we performed p24Ag and HbsAg detection, with and without prior dissociation of CIC, we determined serum level of CIC and immunoglobulin classes IgM and IgG level in sera and in polyethilenglycol (PEG) precipitates of sera. Acid dissociation of immune complexes revealed a high proportion of HIV antigen positive sera in all stages of HIV disease progression. HbsAg in serum of HIV positive patients was also found coupled in immune complexes much more frequently than in the HIV negative control group. In many instances both antigens were simultaneously found coupled in CIC. Immune complexes detected have been shown to contain both IgM and IgG immunoglobulins, while IgM antibodies were associated to immune complexes in higher proportion than IgG, compared to total serum immunoglobulins.

HBsAg as the antigen component of circulating immune complexes in HIV-infected patients.

Seeing the same transmission pattern of HIV and HBV coinfection by these two agents is not an uncommon feature. Immunity impairment due to HIV infection can be the cause of a higher rate of HBV replication with less intensive liver damage and less effective immune response to HBV, while the pathological course in both infections involves elevated levels of circulating immune complexes (CIC). These were the reasons for us to examine the frequency of HBsAg involvement as the antigen component of circulating immune complexes formed in sera of HIV-infected patients in different stages of HIV disease. We tested 67 sera of HIV-positive patients in different stages of HIV disease for the presence of HBsAg and HIV antigen p24 (with and without acid dissociation of immune complexes), for the presence of anti-Hbc antibodies and circulating immune complexes. HBsAg was positive in 13.8% sera prior to and 33.8% after acid pretreatment. Anti-HBc antibodies were present in 76.9% serum samples tested. Fifty percent of sera were positive for both HBsAg and p24 antigen after dissociation of immune complexes. The level of CIC was elevated in 65.9% of sera. Our results suggest that HBsAg is commonly associated in immune complexes formed in the sera of HIV-infected patients and that they may simultaneously contain HIV and HBsAg in patients coinfected with both agents. This may contribute to their mutual interaction and influence the diagnosis and follow-up of patients.

Neoplastic angioendotheliomatosis (NAE) of the CNS in a patient with AIDS subacute encephalitis, diffuse leukoencephalopathy and meningo-cerebral cryptococcosis.

A 12-year-old, hemophilic boy died with acquired immune deficiency syndrome (AIDS) after a clinical course characterized by progressive psycho-organic syndrome and opportunistic infections. Postmortem neuropathological examination revealed a cerebral form of neoplastic angioendotheliomatosis (NAE), leukoencephalopathy, giant cell encephalitis and meningo-cerebral cryptococcosis. The most unusual finding was the presence of proliferated neoplastic cells within lumina of some blood vessels throughout the central nervous system (CNS). These cells displayed cytologic features of malignancy and stained positively for common leukocyte antigen. Coronal sections showed diffuse cerebral and cerebellar leukoencephalopathy with most pronounced loss of myelin and axons in deep white matter, while the subcortical arcuate fibers and the corpus callosum were partially spared. In these areas numerous small foci of severe myelin loss were present. Microglial nodules and distinctive multinucleated giant cells (MGC) were numerous. Intracytoplasmic and intranuclear acidophilic inclusions were found in a few multinuclear and mononuclear cells. Close contact between mononuclear and multinuclear cells suggesting their fusion was also observed. As far as we know this is the first case of NAE encountered in AIDS, one of the rare primary cerebral forms and the youngest reported case of NAE up to now. This case could be considered as one proof more that NAE is a special form of malignant lymphoma.

Severe bacterial non-aids infections in HIV-positive persons: incidence rates and risk factors.

OBJECTIVES: This study aimed to determine incidence rates (IR) and identify risk factors for severe bacterial non-AIDS infections (SBnAI) requiring hospital admission. METHODS: Data from the prospective EuroSIDA cohort were utilized to determine IRs of first diagnosis of the following SBnAI requiring hospital admission: bacteremia, endocarditis, meningitis, peritonitis, pneumonia, osteitis, and pyolonephritis. Incidence rate-ratios (IRRs) and risk factors were assessed by Poisson regression. RESULTS: During 35,839 person-years of follow-up (PYFU), 275 patients were diagnosed with SBnAI (IR = 7.67 per 1000 PYFU, 95% confidence interval: 6.79-8.64). The most frequent infections were pneumonia (IR = 5.36, 4.63-6.17), bacteremia (IR = 1.14, 0.82-1.55), and pyelonephritis (IR = 0.67, 0.43-1.00). A strong risk factor for SBnAI was reduced estimated glomerular filtration rate [eGFR] (adjusted IRR = 5.07, 2.12-12.1 and IRR = 2.73, 1.63-4.56 for eGFR ≤ 60 and 60.1-90 compared to eGFR > 90, respectively). No current combined antiretroviral therapy (cART) compared with current cART use increased the risk of SBnAI (adjusted IRR = 2.96, 2.03-4.32). Other risk factors for SBnAI included current CD4+ count <350 cells/µL, female gender, age, infection with HIV through IDU, prior AIDS diagnosis, and anaemia. CONCLUSIONS: Enhanced attention directed towards people with comorbidity is warranted to limit the burden of these infections.

The comparison of chronic hepatitis C treatment outcome between intravenous drug users and non-intravenous drug users.

UNLABELLED: Despite the fact that the majority of prevalent and incident cases of HCV are associated with intravenous drug use (IVDU), these patients have largely been excluded from HCV care. The aim of this study was to examine the treatment outcome of chronic hepatitis C in IVDUs compared to non-IVDUs. PATIENTS AND METHODS: Patients with chronic hepatitis C (CHC) who initiated and completed combination antiviral therapy with pegilated interferon and ribavirin, at the Hepatology Department of the University Hospital for Infectious and Tropical Diseases in Belgrade, were retrospectively analyzed. The study included a series of 254 patients of which 100 (39.4%) were former IVDU. RESULTS: Sustained virological response (SVR) was recorded in a total of 172 patients (67.7%). The analyses of the favorable treatment outcome, regarding particular viral genotypes, revealed that among those with genotype 1 and/or 4, including patients with genotype 1 recombinants with genotype 3, SVR was achieved in 114 (63.3%), while it was almost equally distributed between subgroups of former IVDU and all others (P=0.079). Among patients infected with HCV genotypes 2 and/or 3 the SVR rate was as high as 86.6%. CONCLUSION: IVDU with CHC infection should be treated with standard combination antiviral therapy for CHC, since the success rate is equal or even better than in non-IVDU patients.

The prognosis of patients with dissociated virological and immunological responses to HAART.

BACKGROUND: While HAART allows for the reconstitution of immune functions in most treated HIV patients, failure to achieve a significant increase in circulating CD4+ T cells despite undetectable viremia occurs. METHODS: A retrospective study was conducted to evaluate the treatment outcome in a subgroup of 232 patients who after 3.1 years of treatment had not achieved desirable immune reconstitution despite a good virological response to HAART. RESULTS: After a further 3.6 ± 2.4 years of HAART, 82 (35.3%) patients achieved immune reconstitution (565.2 ± 174.6 CD4 cells/µl), while 149 (64.2%) patients did not (268.8 ± 91.1 cells/µl); the difference in the achieved CD4 counts between these subgroups was significant (P<0.01). One patient experienced treatment failure. Eleven patients died to the end of follow-up, of which 10 with a continuously dissociated response. Factors associated with immune recovery included clinical AIDS at HAART initiation (OR: 0.4, 95% CI: 0.24-0.81, P<0.01), usage of PIs and of drugs from all three classes (OR: 1.7, 95% CI: 1.0-3.0, P=0.046 and OR: 4.5, 95% CI: 1.15-18.19, P=0.03, respectively), and a rise in CD4 count to over 200 cells/µl after the first 3.1 years of treatment (OR: 5.3 95% CI: 2.6-11.0, P<0.01). Achievement of a rise in CD4 count to over 200 cells/µl after the first 3.1 years of treatment was an independent predictor of immune reconstitution in the following period. CONCLUSION: If patients on HAART reach CD4 cell counts of above 200 cells/µl in the first 3 years, immune recovery is possible after at least 6 years of treatment.

The metabolic syndrome, an epidemic among HIV-infected patients on HAART.

BACKGROUND: HAART has dramatically changed the prognosis of AIDS, but has led to long-term toxicities of antiretroviral drugs. A major chronic complication is the metabolic syndrome (MS), including hyperlipidemia, lipodystrophy (LD), and impaired glucose metabolism. METHODS: A cross-sectional study of a series of 582 patients from the Serbian HIV/AIDS cohort, treated with HAART for a mean period of 3.3+/-2.1 years (range 1-10), was performed to evaluate the prevalence and risk factors for MS during HAART. RESULTS: The prevalence of LD was 29.1%, with a 100% probability of development after 10 years of treatment. Risk factors for LD included female gender (OR 1.7, 95% CI 1.0-2.7, P=0.02), age>40 (OR 1.7, 95% CI 1.1-2.7, P=0.01) and AIDS at HAART initiation (OR 1.9, 95% CI 1.2-2.2, P<0.01), as well as prolonged usage of NRTIs (OR 2.7, 95% CI 1.6-4.5, P<0.01). The NNRTI-based regimens were less likely to induce LD than those PI-based (OR 1.87, 95% CI 1.2-2.9 vs. OR 3.7, 95% CI 2.3-6.1, respectively). Hyperlipidemia occurred in 47% of the patients, and was associated with male gender (OR 2.2, 95% CI 1.4-3.5, P<0.01) and prolonged usage of PI+NNRTI HAART (OR 3.0, 95% CI 1.8-4.9, P<0.01). In contrast, regimens composed of 2 NRTI+NNRTI were less likely to induce hyperlipidemia (OR 0.4, 95% CI 0.3-0.7, P=0.03). Glucose intolerance and/or diabetes mellitus was recorded in 9.6%, if with AIDS at HAART initiation (OR 3.7, 95% CI 1.2-11.4, P<0.01), male gender (OR 5.2, 95% CI 1.8-15.1, P<0.01) and age>40 (OR 2.6, 95% CI 1.1-6.3, P=0.02). CONCLUSION: MS seems an inevitable consequence of long-term successful HAART.

Long-term survival of HIV-infected patients treated with highly active antiretroviral therapy in Serbia and Montenegro.

BACKGROUND: Highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of HIV disease, even in terminally ill patients. Although these patients may survive many years after the diagnosis of AIDS if treated with HAART, some still die during treatment. METHODS: A retrospective study in a cohort of 481 HIV-infected patients treated with HAART between January 1998 and December 2005 was conducted to compare subgroups of long-term survivors (LTSs) and patients who died during treatment. RESULTS: A total of 48 patients survived for more than 72 months (mean 83.8+/-standard deviation 5.6 months). Thirty patients died during treatment (mean 35.3+/-25.0 months), of whom nine died from non-AIDS-related causes, 18 died from AIDS-related causes, and three died as a result of HAART toxicity. Although LTSs were significantly (P=0.015) younger at HAART initiation, age below 40 years was not a predictor of long-term survival. The subgroups did not differ in the proportion of clinical AIDS cases at HAART initiation, in the prevalence of hepatitic C virus (HCV) coinfection, or in pretreatment and end-of-follow-up CD4 cell counts. In contrast, the viral load achieved during treatment was lower in the survivors (P=0.03), as was the prevalence of hepatitis B virus (HBV) coinfection (P=0.03). Usage of either protease inhibitor (PI)-containing regimens [odds ratio (OR) 9.0, 95% confidence interval (CI) 2.2-35.98, P<0.001] or all three drug classes simultaneously (OR 7.4, 95% CI 2.2-25.1, P<0.001) was associated with long-term survival. Drug holidays incorporated in structured treatment interruption (STI) were also associated with a good prognosis (OR 14.9, 95% CI 2.9-75.6, P<0.001). CONCLUSIONS: Long-term survival was associated with PI-based HAART regimens and lower viraemia, but not with the immunological status either at baseline or at the end of follow up. STI when CD4 counts reach 350 cells/microL, along with undetectable viraemia, was a strong predictor of long-term survival.

The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy.

BACKGROUND: It is becoming increasingly clear that, during successful highly active antiretroviral therapy (HAART), a proportion of treated patients develop opportunistic infections (OIs), referred to in this setting as immune restoration disease (IRD). We examined the risk of developing IRD in HAART-treated HIV-infected patients. METHODS: A retrospective study of a cohort including all 389 patients treated with HAART between 1 January 1998 and 31 May 2004 in our HIV unit was performed to evaluate the occurrence of and risk factors for IRD during HAART. Baseline and follow-up values of CD4 T-cell counts and plasma viral loads (pVLs) were compared to assess the success of HAART. RESULTS: During successful HAART (significant increase in CD4 T-cell counts and decrease in pVL), at least one IRD episode occurred in 65 patients (16.7%). The median time to IRD was 4.6 months (range 2-12 months). IRDs included dermatomal herpes zoster (26 patients), pulmonary tuberculosis (four patients), tuberculous exudative pericarditis (two patients), tuberculous lymphadenitis (two patients), cerebral toxoplasmosis (one patient), progressive multifocal leucoencephalopathy (PML) (one patient), inflamed molluscum (one patient), inflamed Candida albicans angular cheilitis (three patients), genital herpes simplex (two patients), tinea corporis (two patients), cytomegalovirus (CMV) retinitis (two patients), CMV vitritis (one patient) and hepatitis B (three patients) or C (fifteen patients). A baseline CD4 T-cell count below 100 cells/microL was shown to be the single predictor [odds ratio (OR) 2.5, 95% confidence interval (CI) 0.9-6.4] of IRD, while a CD4 T-cell count increase to >400 cells/microL, but not undetectable pVL, was a negative predictor of IRD (OR 0.3, 95% CI 0.1-0.8). CONCLUSIONS: To avoid IRD in advanced patients, HAART should be initiated before the CD4 T-cell count falls below 100 cells/microL.

[Results of surgical treatment of retained testes]. / Rezultati hirurskog lecenja retencije testisa.

INTRODUCTION: Numerous papers discuss different opinions about determination of the best age for initiation of an appropriate medical or surgical therapy suggesting in this way modern dilemmas about this congenital malformation. All this emphasizes the importance of the problem, classification of professional disagreements and initiation of correct management of these malformations in order to reduce the consequences to the least possible level. The aim of the study was to emphasize the importance of the prompt diagnosis and surgical treatment at the best age in order to preserve the testicular function. MATERIAL AND METHODS: The study included 84 patients, aged 2-49 years, operated on at the Chachak Urological Ward of Surgical Department over the period 1990-1996. RESULTS AND DISCUSSION: The majority of the patients were between 6 and 10 years of age (3%) (Table 1, 2). Left side retention was predominant (48%), while bilateral retention was recorded in 14% of patients. Inguinal retention was the most common (76%), testicular ectopia (2%), while there was 7% of patients with testicular anorchia. SURGICAL METHOD: Funiculolisis and orchiopexy (Schoemaker's operation). Hernioplasty was performed in 38% and semicastration in 7% of patients.