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anti-TB therapy was initiated, but once culture of the sample revealed Mycobacterium kansasii, pyrazinamide was withdrawn.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 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.

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 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.

[Systemic mixed connective tissue disease--Sharp's syndrome]. / Mesovita sistemska bolest vezivnog tkiva--Sarpov sindrom.

Sharp's syndrome is a systemic mixed connective tissue disease that is defined with specific ribonucleoprotein antibody (U1RNP). The key diagnostic criterion is positive antinuclear antibodies in stain form. The disease is primarily localized on joints, muscles and skin; however, there are not widely used diagnostic criteria. There are USA, Mexican and Japanese diagnostic criteria. A 18-year-old male who fulfilled Sharp's diagnostic criteria is presented in the paper. In this patient the disease was manifested in pleura and pericardium. We wish to point out the importance of immunologic approach to the aetiology of pleural and pericardial inflammatory effusions in young patients, as well as the therapeutical dilemmas in the treatment of the disease.

[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.

[Clinical spectrum of HIV infection and classification systems]. / Klinicki spektar HIV infekcije i klasifikacioni sistemi.

Diseases spectrum caused by the human immunodeficiency virus (HIV) manifests with a wide range of clinical symptoms, due to the involvement of different organs and systems. Patients infected with HIV may present with a spectrum of clinical manifestations ranging from asymptomatic infection to severe immunodeficiency associated with different secondary infections, tumors, or other conditions. Since 1981 when the acquired immunodeficiency syndrome (AIDS) was recognized and the causative agent discovered thereafter, various systems have been proposed to classify manifestations of HIV infection and AIDS definition has bean revised several times. The evolution of classification systems for HIV infection and revision of case definitions for AIDS have closely followed current knowledge of biologic features of this infection, primarily related to its natural hystory and predictive value of immunologic parametres. Various classification systems for HIV infection, which have been widely used in clinical practice will be discussed in this review.

[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.

[Immunologic thrombocytopenic purpura as a clinical manifestation of HIV infection]. / Imunoloska trombocitopenijska purpura kao klinicka manifestacija HIV infekcije.

Immune thrombocytopenic purpura may be the sole clinical manifestation of HIV infection. Results of the treatment of 6 patients with spontaneous bleeding due to severe thrombocytopenia, are presented. In all patients immune thrombocytopenic purpura was the only clinical manifestation of HIV infection. Four of them were intravenous narcotic addicts, and the other two patients did not belong to high risk groups. Prednisone treatment of 1 mg/kg daily was sufficient to resolve bleeding and achieve platelet count elevation above 50 X 10(9)/l in five of six patients. Lowering the dose of prednisone of therapy withdrawal were associated with a fall in the platelet count. In three patients the complete remission was not achieved and danazol was administered, 600-800 mg orally daily, with variable efficacy. One of these patients achieved platelet count elevation above 50 X 10(9)/l, while the two others did not respond.