Initial Therapy of Human Immunodefi ciency Virus Infection in 2009

Liječenje je zaraze virusom humane imunodeficijencije (HIV od engl. human immunodeficiency virus) i nakon više od jednog desetljeća primjene učinkovito. Usprkos tomu što nije potkrijepljeno randomizirnim kliničkim pokusom, današnje smjernice preporučuju ranije započinjanje antiretrovirusnog liječenja. Naime, mnoga opservacijska istraživanja uz analize kliničkog pokusa SMART pokazuju da je morbiditet i mortalitet u asimptomatskih osoba s CD4+ limfocitima T između 200 i 350/mm3 značajan. Uz to postoji povezanost nekontroliranog umnožavanja HIV-a s imunosnom aktivacijom koja je pak povezana s ne-AIDS-morbiditetom i mortalitetom. Smjernice iz razvijenih zemalja govore u prilog individualnom pristupu liječenju, a Svjetska zdravstvena organizacija zalaže se za javnozdravstveni pristup (definirane kombinacije prve i druge linije). U Hrvatskoj se primjenjuje individualni pristup, no on je ograničen manjim izborom antiretrovirusnih lijekova u odnosu na razvijene države. Većina smjernica u početnom liječenju preporučuje kombinacije analoga nukleozida(tida) tenofovir/emtricitabin ili abakavir/lamivudin. Dok se prema pojedinim smjernicama prednost daje nenukleozidnim analozima, većina daje mogućnost izbora između nenukleozidnih analoga i inhibitora proteaze u početnom liječenju. Od nenukleozidnih analoga, prema većini smjernica danas se daje prednost efavirenzu u odnosu na nevirapin. Inhibitori proteaze se danas daju isključivo s niskim dozama ritonavira. Izbor je u većini smjernica relativno velik i uključuje primjenu atazanavira, fosamprenavira, darunavira, lopinavira i sakvinavira.The treatment of human immunodeficiency virus (HIV) infections is still effective after more than a decade of antiretroviral drug usage. Current guidelines recommend the earlier initiation of treatment despite the fact that there is no such evidence from a randomized clinical trial. However, many observational studies and data from the SMART study showed significant morbidity and mortality rates in asymptomatic patients with CD4+ lymphocyte T counts between 200 and 350 per mm3. Additionally, there is an association between uncontrolled HIV replication, immune activation and non-AIDS morbidity and mortality. Guidelines from developed countries are recommending an individual approach to treatment initiation whereas the World Health organization (WHO) endorses a public health approach (with defined combinations for the first and second line regimens). In Croatia we are implementing an individual approach, but with limited choices of treatment options compared to developed countries. Most guidelines recommend to initiate the treatment with a combination of nucleoside(tide) analogues such as tenofovir/emtricitabine or abacavir/lamivudine. According to some guidelines, the initiation of treatment with non nucleoside analogues is preferred; however, the majority of guidelines have no clear preference between the classes of non-nucleoside analogues and protease inhibitors. The majority of guidelines prefer efavirenz to nevirapine. Protease inhibitors are only given with low-dose ritonavir. Most guidelines recommend a number of protease inhibitors: atazanavir, fosamprenavir, darunavir, lopinavir and saquinavir

Frequency of HIV-1 Viral Load Monitoring of Patients Initially Successfully Treated with Combination Antiretroviral Therapy

BACKGROUND: Although considered an essential tool for monitoring the effect of combination antiretroviral treatment (CART), HIV-1 RNA (viral load, VL) testing is greatly influenced by cost and availability of resources. ----- OBJECTIVES: To examine whether HIV infected patients who were initially successfully treated with CART have less frequent monitoring of VL over time and whether CART failure and other HIV-disease and sociodemographic characteristics are associated with less frequent VL testing. ----- METHODS: The study included patients who started CART in the period 1999-2004, were older than 18 years, CART naive, had two consecutive viral load measurements of <400 copies/ml after 5 months of treatment and had continuous CART during the first 15 months. The time between two consecutive visits (days) was the outcome and associated factors were assessed using linear mixed models. ----- RESULTS: We analyzed a total of 128 patients with 1683 visits through December 2009. CART failure was observed in 31 (24%) patients. When adjusted for the follow-up time, the mean interval between two consecutive VL tests taken in patients before CART failure (155.2 days) was almost identical to the interval taken in patients who did not fail CART (155.3 days). On multivariable analysis, we found that the adjusted estimated time between visits was 150.9 days before 2003 and 177.6 in 2008/2009. A longer time between visits was observed in seafarers compared to non-seafarers; the mean difference was 30.7 days (95% CI, 14.0 to 47.4; p<0.001); and in individuals who lived more than 160 kilometers from the HIV treatment center (mean difference, 16 days, p=0.010). ----- CONCLUSIONS: Less frequent monitoring of VL became common in recent years and was not associated with failure. We identified seafarers as a population with special needs for CART monitoring and delivery

The use of parenteral iodine contrast media in diagnosing intracranial infections with computer tomography – our experience

Postkontrastno snimanje kompjuteriziranom tomografijom (CT-om), ima ključnu ulogu u dijagnostici gnojnih infekcija središnjeg živčanog sustava. Vizualizacija tipičnih lezija omogućuje brzu dijagnostiku i pravovremene odluke o terapijskom postupku. Analizirali smo 456 postkontrastnih CT studija u pacijenata s kliničkim i laboratorijskim nalazima koji su upućivali na gnojne infekcije središnjeg živčanog sustava. Iznijeli smo karakteristične slikovne nalaze sukladno anatomskoj lokaciji i komplikacijama. Nismo imali teških anafilaktoidnih reakcija kao ni akutne renalne insuficijencije nakon primjene nisko-osmolalnih, neionskih, vodotopivih, parenteralnih jodnih kontrastnih sredstava. Ne postoji terapijski postupak koji može izliječiti ili poboljšati kontrastom induciranu nefropatiju kad se ona jednom dogodi, ali je moguća profilaksa koja ima dokazanu vrijednost. U nijednog pacijenta iz ove studije nije registriran razvoj akutne renalne insuficijencije nakon primjene kontrastnog sredstva.Post-contrast computer tomography (CT) scans play a crucial role in the diagnosis of pyogenic infectious central nervous system diseases. Visualisation of typical lesion pattern often allows rapid diagnosis and subsequent therapeutic decisions. We analyzed 456 post-contrast CT scan studies in patients with clinical and laboratory findings of pyogenic CNS infection. We reported characteristic imaging findings according to anatomic site and their complications. We did not have severe anaphilactoid reactions or acute renal failure developed after administering a low-osmolal, nonionic, water-solubile, parenteral iodine contrast media to participants of this study. No current treatment can reverse or ameliorate contrast- induced nephropathy once it occurs, but prophylaxis is possible and has a proven value

The use of parenteral iodine contrast media in diagnosing intracranial infections with computer tomography – our experience

Postkontrastno snimanje kompjuteriziranom tomografijom (CT-om), ima ključnu ulogu u dijagnostici gnojnih infekcija središnjeg živčanog sustava. Vizualizacija tipičnih lezija omogućuje brzu dijagnostiku i pravovremene odluke o terapijskom postupku. Analizirali smo 456 postkontrastnih CT studija u pacijenata s kliničkim i laboratorijskim nalazima koji su upućivali na gnojne infekcije središnjeg živčanog sustava. Iznijeli smo karakteristične slikovne nalaze sukladno anatomskoj lokaciji i komplikacijama. Nismo imali teških anafilaktoidnih reakcija kao ni akutne renalne insuficijencije nakon primjene nisko-osmolalnih, neionskih, vodotopivih, parenteralnih jodnih kontrastnih sredstava. Ne postoji terapijski postupak koji može izliječiti ili poboljšati kontrastom induciranu nefropatiju kad se ona jednom dogodi, ali je moguća profilaksa koja ima dokazanu vrijednost. U nijednog pacijenta iz ove studije nije registriran razvoj akutne renalne insuficijencije nakon primjene kontrastnog sredstva.Post-contrast computer tomography (CT) scans play a crucial role in the diagnosis of pyogenic infectious central nervous system diseases. Visualisation of typical lesion pattern often allows rapid diagnosis and subsequent therapeutic decisions. We analyzed 456 post-contrast CT scan studies in patients with clinical and laboratory findings of pyogenic CNS infection. We reported characteristic imaging findings according to anatomic site and their complications. We did not have severe anaphilactoid reactions or acute renal failure developed after administering a low-osmolal, nonionic, water-solubile, parenteral iodine contrast media to participants of this study. No current treatment can reverse or ameliorate contrast- induced nephropathy once it occurs, but prophylaxis is possible and has a proven value

Comparison of baseline demographics and clinical characteristics according to frequency of viral load testing.

<p>Standard, subjects having <50% of measurements <5 months apart. Less frequent, subjects having ≥50% of measurements >5 months apart.</p><p>Values are N (%) or median (interquartile range).</p><p>MSM, men who have sex with men; CART, combination antiretroviral therapy; NNRT, non nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.</p

Rate of viral load tests per one year according to different baseline patients characteristics.

<p>95% confidence intervals are in parenthesis.</p>a<p>Men who had sex with men <i>versus</i> other categories.</p>b<p>NNRT-based compared to PI-based.</p><p>VL, viral load; CART, combination antiretroviral therapy; NNRT, non-nucleoside reverse transcriptase inhibitor;</p><p>PI, protease inhibitor; NRT, nucleoside analogue reverse transcriptase inhibitor.</p

Relationship between baseline or time-varying characteristics and interval (days) between viral load measurements on multivariable mixed model analysis^a.

<p>The intercept represents the average interval for a non-MSM who is a seafarer, lives ≥160 kilometers from Zagreb, has high school or lower education, has had at least one CART change, is taking a non-NNRT regiment, has a CD4 cell count of 350 per µL, is treated in 2008/09 and has a follow-up time of 2 years.</p>a<p>Adjusted for the linear and quadratic term of time.</p>b<p>Least square means estimates from the model.</p>c<p>When 47 potential outlying observations were removed the result became insignificant (p = 0.376).</p><p>MSM, men who have sex with men; CART, combination antiretroviral therapy; NNRT, non nucleoside reverse transcriptase inhibitor.</p

Relationship between baseline or time-varying characteristics and interval (days) between viral load measurements using crude mixed model analysis.

a<p>Adjusted for the linear and quadratic term of time and one independent variable.</p>b<p>Least square means estimates from the model. MSM, men who have sex with men;</p><p>CART, combination antiretroviral therapy; NNRT, non nucleoside reverse transcriptase inhibitor;</p><p>PI, protease inhibitor.</p

CLINICAL CHARACTERISTICS AND OUTCOMES OF COVID-19 IN PATIENTS HOSPITALIZED AT THE UNIVERSITY HOSPITAL FOR INFECTIOUS DISEASES „DR. FRAN MIHALJEVIĆ“, ZAGREB, DURING THE FIRST WAVE OF THE EPIDEMIC

Cilj: Cilj ovog rada bio je ispitati klinička obilježja i ishode u bolesnika hospitaliziranih zbog bolesti COVID-19 u Klinici za infektivne bolesti „Dr. Fran Mihaljević“ (KZIB) u Zagrebu tijekom prvog vala epidemije. Metode: Provedena je retrospektivna analiza medicinske dokumentacije kohorte bolesnika hospitaliziranih u KZIB zbog COVID-19 u kojih je infekcija virusom SARS-CoV-2 bila etiološki potvrđena pozitivnim nalazom RT-PCR testa. U istraživanje su uključeni svi bolesnici hospitalizirani tijekom prvog vala epidemije, između 25. veljače i 18. lipnja 2020. godine. Rezultati: Tijekom promatranog razdoblja, u KZIB je zbog COVID-19 bilo hospitalizirano ukupno 175 bolesnika, od čega 110 (62,9 %) muškaraca. Svi su bolesnici bili stariji od 18 godina (medijan 59 godina, raspon dobi 22–99 godina). Ukupno 110 (62,9 %) bolesnika imalo je jedan ili više komorbiditeta od kojih su najčešći bili kardiovaskularna bolest, uključujući hipertenziju (49,1 %), dijabetes (16,6 %) i KOPB/astma (6,9 %). Najčešći simptomi bolesti bili su: febrilitet (89,7 %), kašalj (73,7 %), dispneja (45,7 %), proljev (45,3 %) i malaksalost (33,1 %). Blagi oblik bolesti imalo je 24 (13,7 %) bolesnika, srednje teški oblik 54 (30,9 %), teški oblik 64 (36,6 %), a kritični oblik 33 (18,9 %) bolesnika. Potrebu za liječenje kisikom imalo je 104 (59,4 %) bolesnika, a za liječenjem u jedinici intenzivnog liječenja (JIL) 33 (18,9 %) bolesnika. Mehanički je ventilirano 29 (16,6 %) dok je 11 (6,3 %) bolesnika zahtijevalo liječenje hemodijalizom. Među bolesnicima hospitaliziranima zbog COVID-19 veći izgled smrtnog ishoda imali su bolesnici u dobi > 65 godina, oni s više od jednog komorbiditeta ili s istovremenim kardiovaskularnim bolestima, oni koji su pri prijmu imali perifernu saturaciju kisikom (SpO2) ≤ 90 %, respiratornu frekvenciju ≥ 22/min, MEWS zbroj ≥ 3, patološke promjene na rendgenogramu pluća, oni s duljim trajanjem hospitalizacije te bolesnici s potrebom za nadomjesnim liječenjem kisikom, dijalizom ili liječenjem u JIL-u. Terapiju hidroksiklorokinom primilo je 59 (22,3 %) bolesnika, lopinavir/ritonavirom 12 (6,9 %), azitromicinom 8 (4,6 %), a glukokortikoidima svega 11 (6,3 %) bolesnika. Preminuo je 21 hospitalizirani bolesnik (12 %). Rasprava: Rezultati našeg istraživanja pokazuju da su tijekom prvog vala epidemije bolesti COVID-19 u KZIB u Zagrebu hospitalizirani isključivo odrasli bolesnici, češće muškarci, s jednim ili više komorbiditeta, nerijetko s blagim oblikom bolesti i bez respiratorne insufi cijencije te potrebe za liječenjem kisikom. Bivarijatnom analizom nađene su razlike u kliničkim obilježjima i laboratorijskim nalazima između preživjelih i umrlih bolesnika, a značajnim prediktorima smrtnog ishoda pokazali su se dob > 65 godina, prisutnost komorbiditeta (osobito kardiovaskularnih bolesti), odsutnost febriliteta, prisutnost dispneje, težina bolesti (viši MEWS i respiratorna frekvencija, niža periferna saturacija kisikom pri prijmu te potreba za nadomjesnim liječenjem kisikom, dijalizom i liječenjem u JIL-u) te povišene vrijednosti leukocita, limfocita, CRP, ureje, ALT, kreatinina, CK i LDH. Multivarijatna analiza pokazala je da skup prediktora koji najtočnije predviđa smrtni ishod bolesnika uključuje dob bolesnika, prisutnost kardiovaskularnih bolesti te vrijednosti CRP-a, ureje i AST-a, budući da su ove vrijednosti bile različite između skupina preživjelih i umrlih bolesnika neovisno o vrijednostima drugih prediktora. Zaključak: Bolest COVID-19 je postala velika opasnost tijekom 2020. godine s velikim brojem oboljelih i umrlih bolesnika uz letalitet od 12 % među našim hospitaliziranim bolesnicima. Nepovoljan ishod bolesti bio je povezan s više kliničkih i laboratorijskih parametara. U prvom valu epidemije zbog COVID-19 bili su hospitalizirani uglavnom odrasli bolesnici sa srednje teškim do kritičnim oblikom bolesti, a lošije ishode bolesti imali su bolesnici s jednim ili više čimbenika rizika. U budućnosti će biti potrebno uložiti dodatne napore u aktivno traženje i pravovremeno prepoznavanje bolesnika s potencijalnim rizičnim čimbenicima koji zahtijevaju pravovremeno antivirusno i imunomodulacijsko liječenje. U konačnici, bolest COVID-19 je multisistemska bolest s još puno nepoznanica, a koju još uvijek svakodnevno upoznajemo.Aim: The aim of this study was to examine the clinical characteristics and patient outcomes of patients hospitalized for COVID-19 in the University Hospital for Infectious Diseases „Dr. Fran Mihaljevic“ (UHID) in Zagreb during the fi rst wave of the epidemic. Methods: A retrospective analysis was conducted using medical records of a cohort of patients hospitalized due to COVID-19 in the UHID in which infection with the SARS-CoV-2 virus was etiologically confi rmed by a positive result of the RT-PCR test. Included were all the patients hospitalized during the fi rst wave of the epidemic, between February 25th and June 18th, 2020. Results: During the study period, 175 patients with COVID-19 were hospitalized in the UHID of which 110 (62.9%) were men. All patients were over 18 years old (median age 59, range 22–99 years). A total of 110 (62.9%) patients had one or more comorbidities, the most common of which were cardiovascular disease including hypertension (49.1%), diabetes (16.6%) and COPD/asthma (6.9%). The most common symptoms of the disease were: fever (89.7%), cough (73.7%), dyspnoea (45.7%), diarrhoea (45.3%) and fatigue (33.1%). Of the total number of patients, 24 (13.7%) had a mild disease, 54 (30.9%) moderate, 64 (36.6%) severe and 33 (18.9%) critical. 104 (59.4%) patients required oxygen therapy, while 33 (18.9%) patients required ICU care. 29 (16.6%) patients required mechanical ventilationand 11 (6.3%) patients required haemodialysis. Among patients hospitalized due to COVID-19, the higher chance of fatal outcomes had patients aged > 65 years, those with more than one comorbidity or with concurrent cardiovascular diseases, those with peripheral oxygen saturation (SpO2) ≤ 90% on admission, respiratory frequency ≥ 22/min, MEWS score ≥ 3, pathological changes on the chest X-ray, those with longer hospitalization duration and patients in need of oxygen replacement treatment, dialysis or ICU care. 59 (22.3%) patients were treated with hydroxychloroquine, 11 (6.3%) glucocorticoids, 12 (6.9%) lopinavir/ritonavir and 8 (4.6%) azithromycin. 21 (12%) of hospitalized patients died. Discussion: Results show that during the fi rst wave of the COVID-19 epidemic only adult patients were hospitalized in the UHID in Zagreb, more often men, with one or more comorbidities, often with mild disease, without respiratory insuffi ciency and need for oxygen treatment. The bivariate analysis found differences in clinical characteristics and laboratory fi ndings between surviving and deceased patients, while signifi cant predictors of fatal outcome proved to be age > 65 years, presence of comorbidities (especially cardiovascular diseases), absence of febrility, presence of dyspnoea, disease severity (higher MEWS and respiratory frequency, lower peripheral oxygen saturation on admission and need for oxygen replacement treatment, dialysis and treatment in ICU) and elevated values of leukocytes, lymphocytes, CRP, urea, ALT, creatinine, CK and LDH. Multivariate analysis showed that the set of predictors that most accurately predicts thefatal outcome includes the patient\u27s age, presence of cardiovascular diseases, and values of CRP, urea and AST, since these differed between surviving and deceased patients regardless of the values of other predictors. Conclusion: The COVID-19 disease became a great danger during 2020 with many ill and deceased patients and a fatality rate of 12% among our hospitalized patients. Unfavourable disease outcome was associated with several clinical and laboratory parameters. In the fi rst wave of the epidemic, mainly adult patients with moderate to critical COVID-19 disease were hospitalized, and those with one or more risk factors had worse disease outcomes. In the future, it will be necessary to invest additional efforts in active search and timely recognition of patients with potential risk factors that require timely antiviral and immunomodulating treatment. Ultimately, the COVID-19 disease is a multisystem disease with many unknowns, which we are still getting to know each day