New antiretrovirals: What\'s in it for southern Africa

The rise of novel antiretrovirals (ARVs) has introduced a new evolutionary phase in HIV care. In developed countries, the 1980s and early 1990s were characterised by palliative care and opportunistic infection prophylaxis; the late 1990s by an attempt to use a limited and toxic antiretroviral arsenal effectively while cycling through high levels of resistance; and finally, the first half of this decade by working out the easiest-to-take regimens, using the steadily rising number of safer drugs. At present, there are 8 nucleoside analogues (NRTIs), 3 non-nucleoside analogues (NNRTIs), 10 protease inhibitors (PIs), and one each of the fusion, entry and integrase inhibitors to choose from, along with a new drug pipeline that targets both existing and new targets in the viral replicative cycle. The choice may seem quite vast, but the reality is that many of these drugs cannot be used simultaneously or in patients with extensive drug resistance. In addition, some drugs have unacceptable toxicities and are not favoured in current treatment regimens. Southern African Journal of HIV Medicine Vol. 9 (4) 2008: pp. 44-4

Nurses at risk for occupationally acquired blood-borne virus infection at a South African academic hospital

Aim. We aimed to ascertain if there had been any improvement in thenumber of nurses being immunised against hepatitis B virus (HBV) infection in a large academic hospital in which, 10 years previously,only 30.6% of the nurses were immune to infection with the virus,and to ascertain the incidence of infection with hepatitis C virus(HCV) and human immunodeficiency virus (HIV) in these nurses.Methods. We studied 170 predominantly black nurses.Their blood was tested for the presence of active or past HBVinfection using appropriate immunoassays, HCV infection bychromatographic immunoassays confirmed by polymerase chainreaction assays, and HIV using a rapid test confirmed by enzymelinkedimmunosorbent assays.Results. Serum of 89 (52.4%) nurses was positive for hepatitisB surface antibody (anti-HBs). Of these nurses 18 said that theyhad not received the vaccine; the serum of 9 of these was positivefor anti-hepatitis B core antibody (anti-HBc) as well as anti-HBs,indicating natural infection with the virus. Of the nurses positivefor anti-HBs, 89 were tested for anti-HBc; 28.2% tested positive foranti-HBc. Three nurses gave dates of immunisation that fell outsideof their nursing careers; 3 (1.8%) were actively infected with thevirus; 2 (1.8%) were infected with HCV; 10 nurses (5.9%) werepositive for HIV.Conclusion. Nurses at this academic hospital remain at high riskof work-related HBV infection

Nurses at risk for occupationally acquired blood-borne virus infection at a South African academic hospital

Aim. We aimed to ascertain if there had been any improvement in the number of nurses being immunised against hepatitis B virus (HBV) infection in a large academic hospital in which, 10 years previously, only 30.6% of the nurses were immune to infection with the virus, and to ascertain the incidence of infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in these nurses. Methods. We studied 170 predominantly black nurses. Their blood was tested for the presence of active or past HBV infection using appropriate immunoassays, HCV infection by chromatographic immunoassays confirmed by polymerase chain reaction assays, and HIV using a rapid test confirmed by enzyme-linked immunosorbent assays. Results. Serum of 89 (52.4%) nurses was positive for hepatitis B surface antibody (anti-HBs). Of these nurses 18 said that they had not received the vaccine; the serum of 9 of these was positive for anti-hepatitis B core antibody (anti-HBc) as well as anti-HBs, indicating natural infection with the virus. Of the nurses positive for anti-HBs, 89 were tested for anti-HBc; 28.2% tested positive for anti-HBc. Three nurses gave dates of immunisation that fell outside of their nursing careers; 3 (1.8%) were actively infected with the virus; 2 (1.8%) were infected with HCV; 10 nurses (5.9%) were positive for HIV. Conclusion. Nurses at this academic hospital remain at high risk of work-related HBV infection

Impact of Empiric Antimicrobial Therapy on Outcomes in Patients with Escherichia coli and Klebsiella pneumoniae Bacteremia: A Cohort Study

<p>Abstract</p> <p>Background</p> <p>It is unclear whether appropriate empiric antimicrobial therapy improves outcomes in patients with bacteremia due to <it>Escherichia coli </it>or <it>Klebsiella</it>. The objective of this study is to assess the impact of appropriate empiric antimicrobial therapy on in-hospital mortality and post-infection length of stay in patients with <it>Escherichia coli </it>or <it>Klebsiella </it>bacteremia while adjusting for important confounding variables.</p> <p>Methods</p> <p>We performed a retrospective cohort study of adult patients with a positive blood culture for <it>E. coli </it>or <it>Klebsiella </it>between January 1, 2001 and June 8, 2005 and compared in-hospital mortality and post-infection length of stay between subjects who received appropriate and inappropriate empiric antimicrobial therapy. Empiric therapy was defined as the receipt of an antimicrobial agent between 8 hours before and 24 hours after the index blood culture was drawn and was considered appropriate if it included antimicrobials to which the specific isolate displayed <it>in vitro </it>susceptibility. Data were collected electronically and through chart review. Survival analysis was used to statistically assess the association between empiric antimicrobial therapy and outcome (mortality or length of stay). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Among 416 episodes of bacteremia, 305 (73.3%) patients received appropriate empiric antimicrobial therapy. Seventy-one (17%) patients died before discharge from the hospital. The receipt of appropriate antimicrobial agents was more common in hospital survivors than in those who died (p = 0.04). After controlling for confounding variables, there was no association between the receipt of appropriate empiric antimicrobial therapy and in-hospital mortality (HR, 1.03; 95% CI, 0.60 to 1.78). The median post-infection length of stay was 7 days. The receipt of appropriate antimicrobial agents was not associated with shortened post-infection length of stay, even after controlling for confounding (HR, 1.11; 95% CI 0.86 to 1.44).</p> <p>Conclusion</p> <p>Appropriate empiric antimicrobial therapy for <it>E. coli </it>and <it>Klebsiella </it>bacteremia is not associated with lower in-hospital mortality or shortened post-infection length of stay. This suggests that the choice of empiric antimicrobial agents may not improve outcomes and also provides data to support a randomized trial to test the hypothesis that use (and overuse) of broad-spectrum antibiotics prior to the availability of culture results is not warranted.</p

Empiric Antibiotic Therapy for Staphylococcus aureus Bacteremia May Not Reduce In-Hospital Mortality: A Retrospective Cohort Study

Appropriate empiric therapy, antibiotic therapy with in vitro activity to the infecting organism given prior to confirmed culture results, may improve Staphylococcus aureus outcomes. We aimed to measure the clinical impact of appropriate empiric antibiotic therapy on mortality, while statistically adjusting for comorbidities, severity of illness and presence of virulence factors in the infecting strain.We conducted a retrospective cohort study of adult patients admitted to a tertiary-care facility from January 1, 2003 to June 30, 2007, who had S. aureus bacteremia. Time to appropriate therapy was measured from blood culture collection to the receipt of antibiotics with in vitro activity to the infecting organism. Cox proportional hazard models were used to measure the association between receipt of appropriate empiric therapy and in-hospital mortality, statistically adjusting for patient and pathogen characteristics.Among 814 admissions, 537 (66%) received appropriate empiric therapy. Those who received appropriate empiric therapy had a higher hazard of 30-day in-hospital mortality (Hazard Ratio (HR): 1.52; 95% confidence interval (CI): 0.99, 2.34). A longer time to appropriate therapy was protective against mortality (HR: 0.79; 95% CI: 0.60, 1.03) except among the healthiest quartile of patients (HR: 1.44; 95% CI: 0.66, 3.15).Appropriate empiric therapy was not associated with decreased mortality in patients with S. aureus bacteremia except in the least ill patients. Initial broad antibiotic selection may not be widely beneficial

Outcomes of patients on dual-boosted PI regimens : experience of the Swiss HIV cohort study

Rapport de SynthèseLa thérapie antirétrovirale a progressée de manière significative depuis te début de l'épidémie du syndrome d'immunodéficience acquise (SIDA). Durant les 20 dernières années, plusieurs combinaisons de traitements ont été utilisées avec succès menant à une réduction de la mortalité associée. Par contre, le traitement a aussi engendré des cas de résistances multiples avec comme résultat, le besoin d'utiliser plusieurs molécules en combinaison, et une augmentation des cas de toxicité. Une stratégie souvent employée fût la combinaison de deux molécules inhibitrices de la protéase en même temps en combinaison avec une troisième molécule, le ritonavir. (DBPI).La cohorte Suisse sur le VIH existe depuis 1987 et permet d'étudier de façon longitudinale les patients qui y sont inscrits. Pour ce travail de thèse, nous avons étudié les patients inscrits à la cohorte suisse de 1996 à 2007 qui ont reçu une combinaison DBPI.Pendant la période étudiée, un total de 405 patients ont reçu un traitement DBPI, dont 295 patients ont reçu le DBPI pour plus de 6 mois. La durée médiane du traitement était de 2.2 ans. Sur les 287 patients qui étaient en échec viral au début du traitement (défini comme HIV RNA&gt;400 copies/ml), 64.1% ont réussi à supprimer la virémie et 54.4% ont eu une suppression dans les 24 semaines qui ont suivi le début de la thérapie. Les patients avaient reçu en moyenne 6 combinaisons de traitement différentes avant le début de la thérapie DBPi. Pour les patients qui ont arrêté le traitement DBPI, la cause principale de l'arrêt était due au souhait du patient (48.3%), à l'échec virologique (22.5%) et à la toxicité (15.8%). Les patients ayant reçu le traitement après 1999, ou ayant été traités avec une combinaison de Lopinavir-ritonvir/saquinavir ou lopinavir-ritonavir/atazanavir arrivaient à supprimer leur virémie plus souvent que ceux qui avaient reçu d'autres combinaisons.Cette étude constitue la plus grande étude publiée sur le sujet de l'utilisation des DBPI pour les patients à résistances multiples. Malgré le fait que c'est une étude observationnelle, nous pouvons attester que le taux de succès était de 64.4%, le taux de toxicité était relativement bas (15.8%) et que la plus part des patients ont toléré ces combinaisons, malgré le taux élevé d'effets secondaires souvent rapportés. En somme, cette approche pourrait être envisagée dans des situations ou les nouveaux traitements tels que les inhibiteurs de l'intégrase et du CCR5 ne sont pas encore disponibles

Causes of death by category.

<p>Categorized by duration of antiretroviral therapy (ART) at the time of death. Pre-ART deaths occurred in subjects who were HIV-positive and eligible for ART but had not yet received it (CD4 cell count <200 cells/mm³) or those who had received <7 days of ART. Early ART deaths occured between 7–90 days of ART. Late ART deaths occurred after >90 days of ART.</p>a<p>All causes of death (immediate and contributing) are included and each subject may have multiple causes of death.</p>b<p>Non-infectious organ dysfunction, ie. pulmonary embolus or end stage renal disease.</p>c<p>At least one cause of death was revealed only through the post-mortem investigations.</p

Immediate and contributing cause(s) of death with supporting clinical, microbiologic and histologic findings.

<p><b>Symbols</b>: ∧pre-mortem culture;</p>∼<p>post-mortem culture;</p>&<p>detected by PCR;</p>%<p>Ziehl-Neelson stain positive;</p>*<p>unsuspected at time of death;</p>#<p>not satisfactorily explained by post-mortem technique.</p><p><b>Abbreviations</b>: <b>AFB</b> – acid fast bacilli; <b>ag</b> – antigen; <b>ART</b> – antiretroviral therapy; <b>ATN</b> – acute tuberular necrosis; <b>BM</b> – bone marrow; <b>CN</b> – cranial nerve; <b>CSF</b> – cerebrospinal fluid; <b>CMV</b> – cytomegalovirus, <b>CVA</b> – cerebrovascular accident; <b>DIC</b> – disseminated intravascular coagulation;<b>ESRD</b> – end stage renal disease; <b>GI</b> – gastrointestingal; <b>gran.</b> – granulmonatous; <b>HA</b> – headache; <b>HSM</b> – hepatosplenomegaly; <b>HTN</b> – hypertension; <b>ICH</b> – intracerebral hemorrhage; <b>inflam. –</b> inflammation; <b>IRIS –</b> immune reconstitution inflammatory syndrome; <b>KS –</b> Kaposi sarcoma; <b>LAD –</b> lymphadenopathy; <b>LN –</b> lymph node; <b>MAC –</b> Mycobacterium avium complex; <b>MTB –</b> Mycobacterium tuberculosis; <b>nec. –</b> necrotizing; <b>NHL</b> – non-Hodgkins lymhoma; <b>PCR –</b> polymerase chain reaction; <b>PJP –</b> Pneumocystis iroveci pneumonia; <b>PNA –</b> pneumonia; <b>pulm –</b> pulmonary; <b>TBT –</b> tuberculosis therapy; <b>vol. –</b> volume.</p