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.

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.

Isoniazid-resistant Mycobacterium kansasii in an HIV-positive patient, and possible development of immune reconstitution inflammatory syndrome after initiation of highly active antiretroviral therapy: case report.

Non-tuberculous mycobacteria are rare but important causes of infection in HIV-positive individuals. A 28-year-old HIV-positive male presented with a high fever, non-productive cough, right subcostal pain, splenomegaly, a very low CD4 count, elevated C-reactive protein and erythrocyte sedimentation rate, and a normal white blood cell count. The suspicion of tuberculosis (TB) was very high, and sputum samples were positive for acid-fast bacilli. Standard quadruple anti-TB therapy was initiated, but once culture of the sample revealed Mycobacterium kansasii, pyrazinamide was withdrawn. Highly active antiretroviral therapy (HAART) was initiated soon after, consisting of abacavir/lamivudine and efavirenz. The patient's general condition deteriorated 2 weeks after HAART initiation, which could have been due to the development of immune reconstitution inflammatory syndrome (IRIS). The patient recovered and was discharged in good condition. However, the results of resistance testing of the isolated organism arrived after discharge, and showed isoniazid and streptomycin resistance. This is the first case report of M. kansasii infection from Serbia and shows the difficulties encountered during the course of treatment.

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 prognosis of highly active antiretroviral therapy (HAART) treated HIV infected patients in Serbia, related to the time of treatment initiation.

BACKGROUND: With the introduction of highly active antiretroviral treatment (HAART) an impressive improvement in patient survival and quality of life has bee observed. However, the optimal timing of initial HAART is still under consideration. OBJECTIVE: To investigate the prognosis of HAART treated patients in Serbia, related to the timing of HAART initiation. STUDY DESIGN: A series of 563 patients on HAART was retrospectively analyzed to investigate treatment response and survival. RESULTS: After a mean of 6 years (range 1-14) of treatment with PI-based and/or NNRTI-based regimens, a favorable response was achieved in 72.4%, treatment failure occurred in 7.9%, while 19.7% had a dissociative immunological/virological response. If treatment was initiated during primary HIV infection it took a shorter time to achieve a favorable response than in patients who began HAART in chronic HIV infection (2.7+/-2.2 years vs. 6.9+/-2.7 years, P<0.01). A higher proportion of patients with primary HIV infection then those treated in the chronic phase achieved a favorable response to HAART (88.4% vs. 71.9%, P=0.045). Patients who initiated HAART when their CD4 cell counts were below 200 cells/microL needed longer treatment for favorable response (8 years vs. 6 years, log rank P<0.01). Forty-seven (8.3%) patients died. The overall estimated survival was 13 years. Patients older then 40 and IVDU were more likely to die during HAART (OR 2.6, 95% CI 1.1-5.9, P=0.016, and OR 2.0, 95% CI 1.0-3.7, P=0.02, respectively). However, reaching and maintaining undetectable viremia was an independent predictor of longer survival (OR 11.3, 95% CI 4.6-27.7, P<0.01). CONCLUSION: Reaching and maintaining undetectable viremia during HAART predicted longer survival, even if sub-clinical immunodeficiency remained.

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.

The incidence of and risk factors for HIV-associated cognitive-motor complex among patients on HAART.

BACKGROUND: While highly active antiretroviral therapy (HAART) allows for the considerable decline in the incidence of HIV-related opportunistic infections and tumors, its effect on treating HIV infection of the brain, such as HIV-associated dementias (HADs), remains unclear. METHODS: A cross-sectional study of consecutive series of 96 patients from the Serbian HIV/AIDS cohort, treated with HAART in our HIV unit was performed to evaluate the incidence of and risk factors for cognitive/motor complex during HAART. CD4+T cell counts and pVL values at the time of neurological evaluation were parameters of the response to HAART. The mini-mental test and neurologic examination were performed at one point of time during treatment to reveal cognitive and/or motor disorders. RESULTS: After mean HAART duration of 47 months, unimpaired cognition, minor cognitive impairment, and HIV-associated dementia were recorded in 56 (58.3%), 27 (28.1%), and 13 (13.5%), respectively. Motor abnormalities had 39 (40.6%) patients. Of these, 21, 12, and 6 patients belong to the subgroups with normal cognition, minor cognitive impairment and HAD patients, respectively. Factors predictive for HAD were age over 40 (OR 3.7, 95% CI 1.07-13.28, P=0.039), and AIDS diagnosis prior to HAART initiation (OR 14.19, 95% CI 1.76-114.16, P=0.013). Conversely, factors shown to be protective against HAD were the usage of AZT and NNRTIs, as components of HAART regimens (OR 0.18, 95% CI 0.046-0.76, P=0.019, and OR 0.14, 95% CI 0.034-0.6, P=0.008). CONCLUSION: Cognitive/motor complex has still remained a significant neuropathology among late presenters and elder HIV/AIDS patients. Certain HAART regimens containing AZT, and/or NNRTIs, could be protective for these patients.

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.

The prognosis of CMV retinitis among patients with AIDS in Serbia.

BACKGROUND: Cytomegalovirus (CMV) end-organ diseases, including CMV retinitis, are major opportunistic events in terminal AIDS patients. METHODS: A retrospective study of 30 AIDS patients with CMV retinitis treated between 1997 and 2007 in Serbia was conducted to examine the prognosis and factors associated with survival. RESULTS: Eighteen (60%) patients survived the mean follow-up period of 46.4+/-36 months. Patients' sex, mode of HIV transmission or previous AIDS diagnosis did not affect survival. Bilateral CMV retinitis predicted dissemination of CMV disease and poor prognosis (OR 7.8, 95% CI 1.3-47.0, P=0.012), but was not associated with blindness (P=0.33). Among patients treated with HAART and CMV therapy the probability of surviving 10 years was 70%, while in those on CMV therapy alone, the median survival was 10 months (log rank P=0.00). However, HAART itself was not sufficient to prevent blindness and the major predictor of blindness was a baseline CD4 cell count of less than 50/microL (OR 6.8, 95% CI 1.1-41.8, P=0.03). After CMV disease, most patients suffered other opportunistic events regardless of HAART introduction. CONCLUSION: Even in the HAART era patients with advanced immunodeficiency and CMV retinitis may not escape from the high risk mortality group, while survivors commonly lose sight.

The prevalence and risk of hepatitis flares in a Serbian cohort of HIV and HCV co-infected patients treated with HAART.

Despite substantial benefits of HAART treatment of HIV-infected patients, cumulative long-term toxicity, including drug-induced hepatotoxicity, has emerged as an important complication. Thus, to examine the prevalence and risk of developing severe hepatic injury during HAART, we conducted a retrospective study in a cohort of 364 HIV-infected patients treated with HAART between January 1998 and May 2006, for whom data on alanine aminotransferase activity were available both before and during HAART. HCV co-infection was recorded in 35.4% of the series, but was found not to influence either the efficacy of HAART or survival (P>0.05). Severe hepatotoxicity occurred in a total of 24 patients (6.6%). Multivariate logistic regression defined HCV co-infection (OR 16.6, 95% CI 3.8-46.0, P<0.0001), and the use of SQV/RTV and d4T (OR 3.1, 95% CI 1.2-8.16, P=0.02, and OR 7.1, 95% CI 1.0-54.5, P=0.05, respectively) as independent risk factors for aggravation of hepatitis. In addition, there was a significant increase in the probability of developing liver damage over years of treatment (Log rank, P<0.01). Conversely, the probability of developing hepatotoxicity was not associated with an increase in the CD4 cell count to values greater than 350/microL (Log rank, P=0.59). In conclusion, in the setting of chronic viral hepatitis, hepatotoxicity during HAART may be attributed to the cumulative toxicity of drugs that induce mitochondrial toxicity, along with particular PIs and/or NNRTIs. Furthermore, our data suggest prudent use of D-drugs, still common in resource-limited countries, in HCV co-infected patients.

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 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.

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.

Focal tuberculosis of the liver with local hemorrhage in a patient with acquired immunodeficiency syndrome.

Tuberculosis of the liver is common in patients with acquired immunodeficiency syndrome (AIDS). Tuberculous liver granulomas in such patients are usually atypical. The liver granulomas may be even totally absent, but liver tissue usually reveals numerous acid-fast bacilli. Focal tuberculosis of the liver is a less common form of liver tuberculous infection. We present a 33-year old white homosexual man infected with the human immunodeficiency virus. He had three tumour-like lesions in the left liver lobe, which were subsequently diagnosed as focal hepatic tuberculosis with local hemorrhage. This unusual presentation of liver tuberculosis indicates the necessity of an aggressive diagnostic approach for the evaluation of focal liver lesions in patients with AIDS.

[Correlation between immunological markers and clinical course of HIV infection]. / Klinicko-imunoloske odlike razvoja HIV infekcije.

The interaction of human immunodeficiency virus (HIV) with CD4 molecule, which is expressed on various human cells is the crtical event in the pathogenesis of HIV infection. Decreased number and functional anergy of CD4+ T cells, which are the most important immunoregulatory cells, cause severe immunodeficiency. Having in mind that there is a significant correlation between clinical course of HIV infection and laboratory markers it is possible to predict progression of HIV infection toward acquired immunodeficiency syndrome (AIDS). These markers can be divided into four categories: (1) measures of viral production; (2) the specific immune response to HIV; (3) nonspecific immune system activation; (4) measurements of immune system damage. In addition, the use of these predictors can improve clinical management of HIV-infected individuals.

[Neurological disorders associated with HIV infection]. / Neuroloske komplikacije HIV infekcije.

Neurological diseases occur frequently in patients infected with human immunodeficiency virus (HIV). There are three main groups of central nervous system (CNS) dysfunction: (1) direct effects of HIV; (2) opportunistic infections; (3) opportunistic neoplasms. On the basis of clinical characteristics it is possible to differentiate focal and diffuse pathologic alterations of CNS. The starting point of evaluation of CNS dysfunction is computed tomography (CT). If the focal lesions are not present on CT scan, it is necessary to carry out cerebrospinal fluid (CSF) examination.

[Treatment and prophylaxis of opportunistic infections in individuals infected with HIV]. / Lecenje i profilaksa oportunistickih infekcija u bolesnika inficiranih HIV-om.

The primary causes of morbidity and mortality in persons infected with the human immunodoficiency virus are oportunistic infections. Infection with the human immunodeficiency virus (HIV) induces progressive quantitative and qualitative defects in CD4 (T helper) lymphocytes. Macrophage and monocyte function may also be impaired as a result of HIV infection. Consequently, patients in the later stages of HIV infection (ARC and AIDS) frequently experiency infections against which either cellular od humoral immunity, or both, are important. A large number of viruses, bacteria, fungi and protozoa are capable of infecting persons with ARC or AIDS. Much of recent research efforts has been targeted at new techniques to diagnose, treat and to prevent certain opportunistic infections. Treatment is often long and ardous for both patient and physician. This review provides a practical introduction to the treatment and prevention (primary prophylaxis, secondary prophylaxis, supression, or maintenance therapy) of the most common opportunistic infections associated with HIV.

[Diseases of digestive system in patients with AIDS]. / Oboljenja digestivnog sistema u bolesnika sa AIDS-om.

Human immunodeficiency virus infection can affect the entire gastrointestinal tract and hepatobiliary system. Gastrointestinal abnormalities in acquired immunodeficiency syndrome are common and may relate to opportunistic inections and tumors, diseases which are usual in the anti-HIV negative population also, and disease of unknown aethiology, such as wasting syndrome and recurrent diarrhoeal illness. Diarrhoea and weight loss are found in more than 50% of patients with AIDS. Gastrointestinal manifestations range in severity from the discomfort of oral and perianal infections, through life threatening diarrhoea due to intestinal cryptosporidiosis. The approach to the patient with AIDS and gastrointestinal or hepatobiliary disorders is oriented toward diagnosing treatable aethiologies and avoiding unnecessary invasive procedures. Although the final prognosis of full developed AIDS is poor, management of gastrointestinal disease may be improved by accurate diagnosis.

[Antiretroviral therapy of acquired immunodeficiency syndrome (AIDS)]. / Antiretrovirusna terapija sindroma stecene imunodeficijencije (AIDS-om).

The unique nature of the replication cycle of the retroviruses, including HIV, offera number of possible targets for chemotherapeutic agents. These are RNA viruses which have the capacity to make DNA copies through their characteristic enzyme, reverse transcriptase, encoded in the pole region of the viral genoma. Reverse transcription is an attractive target for therapeutic intervention as this event is uniquelly associated with retroviruses. Dideoxynucleoside analogues can compete with endogenous nucleosides that are the natural substrate for reverse transcriptase or may be incorporated intro the growing chain of proviral DNA and terminate elongation. Reverse transcriptase inhibition is the principal mechanism of action of zidovudine (AZT) and related nucleosides, dideoxyinosine (ddl) and dideoxycitidine (ddC), which all attach to reverse transcriptase to the same site. This review will discuss current approaches to the antiretroviral therapy in AIDS patients. Several well controlled clinical trials have established both the efficacy and toxicity of AZT in patients with AIDS and severe ARC and it was shown that this drug decreased the incidence and severity of opportunistic infections, with the highly significant reduction in early mortality. The efficacy of newer reverse transcriptase-inhibiting nucleoside derivatives will be discussed too, as well as the issue of combination therapies.

[Pulmonary manifestations of acquired immunodeficiency syndrome (AIDS)]. / Plucne manifestacije sindroma stecene imunodeficijencije (AIDS-om).

The lungs are the principal target organ in the infectious complications of acquired immunodeficiency syndrome (AIDS) and this predisposition to infections is not the regional manifestation of systemic immunologic deficiency induced by human immunodeficiency virus (HIV) only, because HIV also affects lung's own complex system of local defense mechanisms. It was demonstrated that pulmonary host defenses were compromised by.direct infection of alveolar macrophages with HIV and decreased production of solubile factors by lymphocytes derived from bronchoalveolar lavage fluid was shown. The most common infectious causative agents are facultative intracellular pathogens including Pneumocystis carinii, Cryptococcus neoformans, Mycobacterium tuberculosis and cytomegalovirus, which reflects the specific defects of cell-mediated immunity. AIDS patints have, in addition, an increased incidence of infections with capsulated bacteria such as Haemophilus influenzae and Sterptococcus pneumoniae which are associated typically with the impairment of the humoral immune response. High-grade pathogens such as M. tuberculosis tende to reactivate early in the progression of immunodeficiency whereas low-grade pathogens such as P. carinii only emerge when the defect is more advanced. The profound immunodeficiency in AIDS patients means that clinical features may be quite atypical and blunted.