J. Pavie

Survival trends in critically ill HIV-infected patients in the highly active antiretroviral therapy era

IntroductionThe widespread use of highly active antiretroviral therapy (ART) has reduced HIV-related life-threatening infectious complications. Our objective was to assess whether highly active ART was associated with improved survival in critically ill HIV-infected patients.MethodsA retrospective study from 1996 to 2005 was performed in a medical intensive care unit (ICU) in a university hospital specialized in the management of immunocompromised patients. A total of 284 critically ill HIV-infected patients were included. Differences were sought across four time periods. Risk factors for death were identified by multivariable logistic regression.ResultsAmong the 233 (82%) patients with known HIV infection before ICU admission, 64% were on highly active ART. Annual admissions increased over time, with no differences in reasons for admission: proportions of patients with newly diagnosed HIV, previous opportunistic infection, CD4 counts, viral load, or acute disease severity. ICU and 90-day mortality rates decreased steadily: 25% and 37.5% in 1996 to 1997, 17.1% and 17.1% in 1998 to 2000, 13.2% and 13.2% in 2001 to 2003, and 8.6% in 2004 to 2005. Five factors were independently associated with increased ICU mortality: delayed ICU admission (odds ratio (OR), 3.04; 95% confidence interval (CI), 1.29 to 7.17), acute renal failure (OR, 4.21; 95% CI, 1.63 to 10.92), hepatic cirrhosis (OR, 3.78; 95% CI, 1.21 to 11.84), ICU admission for coma (OR, 2.73; 95% CI, 1.16 to 6.46), and severe sepsis (OR, 3.67; 95% CI, 1.53 to 8.80). Admission to the ICU in the most recent period was independently associated with increased survival: admission from 2001 to 2003 (OR, 0.28; 95% CI, 0.08 to 0.99), and between 2004 and 2005 (OR, 0.13; 95% CI, 0.03 to 0.53).ConclusionsICU survival increased significantly in the highly active ART era, although disease severity remained unchanged. Co-morbidities and organ dysfunctions, but not HIV-related variables, were associated with death. Earlier ICU admission from the hospital ward might improve survival.

Cohort Profile: French hospital database on HIV (FHDH-ANRS CO4)

The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

Efficacy and safety of a switch to unboosted atazanavir in combination with nucleoside analogues in HIV-1-infected patients with virological suppression under antiretroviral therapy

BACKGROUND Limited data are available on the use of unboosted atazanavir in combination with nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced HIV-infected patients. METHODS We conducted a multicentre, retrospective study among patients with plasma HIV-1 RNA levels <50 copies/mL under antiretroviral therapy who switched to unboosted atazanavir + NRTIs between January 2002 and December 2008. Virological failure during follow-up was defined as a confirmed plasma HIV-1 RNA level >50 copies/mL. Baseline risk factors for virological failure were identified using Cox proportional hazards models. RESULTS A total of 886 patients were analysed. At baseline, median age was 44 years, 71.5% were males and median CD4 cell count was 490 cells/mm(3). NRTIs used in combination with atazanavir were tenofovir, abacavir and emtricitabine/lamivudine in 36.9%, 44.1% and 94.4% of patients, respectively. Median follow-up was 21 months. The 3 year probability of virological failure was 20.1%. Only a history of virological failure under NRTIs [hazard ratio (HR) 1.63, P = 0.049] and under protease inhibitors (HR 2.04, P = 0.006) were significantly associated with the risk of virological failure. Among the 431 patients without a prior history of virological failure, the 3 year probability of virological failure was 11.3%, and only hepatitis C virus co-infection (HR 2.25, P = 0.026) and abacavir use (HR 0.43, P = 0.04) were associated with the risk of virological failure. Safety of the switch was satisfactory, with improvement of the lipid profile. CONCLUSIONS In patients with virological suppression and no prior history of virological failure, a switch to unboosted atazanavir in combination with NRTIs is associated with a low probability of virological failure and a good safety profile.

Prevalence of opportunistic intestinal parasitic infections among HIV-infected patients with low CD4 cells counts in France in the combination antiretroviral therapy era

BACKGROUND The use of combination antiretroviral therapy (cART) has dramatically reduced the prevalence of opportunistic infections, however data on the prevalence of intestinal parasitic infections in HIV-infected patients with low CD4 cell counts in the cART era are scarce. METHODS We performed a prospective cohort study among HIV-infected patients with CD4 cell counts <100/mm(3) seen at a university hospital in Paris. Medical records were reviewed and stool samples were obtained for macroscopic examination and detection of parasites including cryptosporidia and microsporidia, whether or not the patient had diarrhea. Stool cultures were performed for patients with diarrhea. Factors associated with the detection of parasites were then identified. RESULTS Stools samples from 143 consecutive patients were analyzed. Patients were mostly men (76%), and the median patient age was 41 years. The median CD4 cell count was 32/mm(3), and 59% were receiving cART. Diarrhea was present in 85 patients (59%), 19 of whom (22%) had intestinal parasites detected in stools. Three patients with diarrhea were diagnosed with Salmonella typhimurium, Campylobacter coli, and Clostridium difficile infections. Among the 58 patients without diarrhea, parasitic intestinal pathogens were still identified in six (10%). The overall prevalence of intestinal parasites was 17%, with cryptosporidia (n=8), microsporidia (n=6), and Giardia duodenalis (n=5) being the most frequent pathogens. Patients with intestinal parasites had diarrhea more often (76% vs. 56%, p=0.025) and were more often at US Centers for Disease Control and Prevention (CDC) clinical stage C (84% vs. 69%, p=0.024) than patients without parasites. CONCLUSIONS The prevalence of intestinal parasitic infections remains significant in HIV-infected patients with low CD4 counts in the cART era. A systematic search for parasitic pathogens including microsporidia, cryptosporidia, and G. duodenalis should be performed even in the absence of diarrhea.

Prevalence and clinical predictors of pulmonary tuberculosis among isolated inpatients: a prospective study

Guidelines help to prevent the transmission of Mycobacterium tuberculosis in healthcare settings, but may also result in the unnecessary isolation of many patients. We performed a prospective study to assess the prevalence and identify clinical predictors of culture-proven tuberculosis among inpatients isolated for suspected pulmonary tuberculosis (PTB) at our hospital. We also wished to validate a pre-existing clinical decision rule to improve our isolation policy. From August 2005 to January 2007, 134 patients isolated on admission to the ward for suspicion of PTB were prospectively enrolled. The admitting team made the decision to isolate patients on the basis of clinical and radiological findings, without the use of the clinical decision rule, and graded the overall suspicion of PTB. Twenty-six of the 134 isolated patients had PTB (prevalence: 19.4%), as well as one patient not isolated at admission. Univariate analysis revealed that PTB was significantly associated with young age, lack of human immunodeficiency virus (HIV) infection, weight loss, night sweats, fever, upper lobe disease and, especially, cavitary lesions on chest X-ray (adjusted OR 25.4, p <0.0001). Low suspicion of PTB by the admitting team and low clinical decision rule score had negative predictive values of 98.5% and 95.8% for PTB, respectively. Use of the clinical decision rule in addition to the team assessment would have led to the isolation of the patient with PTB not isolated on admission, and avoided 16 (14.8%) unnecessary isolations. In conclusion, the prevalence of PTB among isolated inpatients was high, and the use of a clinical decision rule in addition to clinical impression might improve isolation decisions.

Severe peripheral neuropathy following HAART initiation in an HIV-infected patient with leprosy.

We report a case of peripheral neuropathy following highly active antiretroviral therapy (HAART) initiation in a patient coinfected with HIV and Mycobacterium leprae and review the literature on leprosy-associated immune reconstitution inflammatory syndrome (IRIS). Physicians in charge of HIV-infected patients originating from countries endemic for leprosy should be aware of this risk of leprosy-associated IRIS when starting HAART.

Efficacy and safety of once-daily ritonavir-boosted atazanavir or darunavir in combination with a dual nucleos(t)ide analogue backbone in HIV-1-infected combined ART (cART)-naive patients with severe immunosuppression: a 48 week, non-comparative, randomized, multicentre trial (IMEA 040 DATA trial)

OBJECTIVES Boosted PIs are commonly prescribed in patients presenting with advanced HIV infection. We assessed the efficacy and tolerability of once-daily ritonavir-boosted atazanavir or darunavir plus two NRTIs in HIV-1-infected ART-naive patients with severe immunosuppression, targeting at least an 85% success rate at week 48. METHODS This 48 week, open-label, non-comparative, randomized, multicentre trial included ART-naive patients with CD4 cell counts <200 cells/mm(3), with plasma HIV-1 RNA >1000 copies/mL and without genotypic mutations conferring resistance to the study drugs. Patients were randomized (1:1) to receive once-daily atazanavir/ritonavir (300/100 mg) or darunavir/ritonavir (800/100 mg) plus tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine. The primary endpoint was treatment success, defined as plasma HIV-1 RNA ≤50 copies/mL at week 48 and no permanent PI/ritonavir discontinuation. The study was registered with ClinicalTrials.gov (NCT01928407). RESULTS One hundred and twenty patients were enrolled: 77% were men, 30% were born in Africa and 39% had AIDS. The median baseline CD4 and plasma HIV-RNA values were 69 cells/mm(3) and 5.4 log10 copies/mL. All but four patients received tenofovir disoproxil fumarate/emtricitabine. The week 48 treatment success rate was 66% (95% CI 54%-78%) with atazanavir/ritonavir and 80% (95% CI 68%-89%) with darunavir/ritonavir. The median CD4 cell count increased similarly in the two groups (Δweek 48 to week 0: +194 cells/mm(3)). Adverse events occurred in 23 and 18 patients, respectively. CONCLUSIONS Despite good adherence, neither study regimen reached the predefined objective, suggesting a need for more potent regimens for patients with advanced HIV infection.

Risk of HIV transmission during combined ART initiation for HIV-infected persons with severe immunosuppression

Background Individuals presenting for care with severe immunosuppression typically have high plasma HIV viral load (pVL) and may transmit HIV before and after initiation of combination antiretroviral therapies (cART). Patients and methods Using risk equations and data collected in the IMEA 040 DATA trial on sexual behaviour and pVL level of 84 HIV-infected patients (23 women), we estimated monthly rates of HIV transmission for each virologically unsuppressed participant (pVL >50 copies/mL) who reported sex with HIV-negative or unknown serostatus (HNUS) partners at cART initiation, 24 weeks (W24) and W48 after; rates were considered negligible for other participants. Results At cART initiation, median pVL was 5.4 log10 copies/mL. The percentage of virologically unsuppressed patients decreased, from 100% at cART initiation to 27% (95% CI 16%-43%) for heterosexuals and 8% (95% CI 2%-22%) for MSM at W48 (P < 0.001). The percentage of patients reporting sex with HNUS partners increased between cART initiation and W48, from 23% (95% CI 10%-42%) to 42% (95% CI 25%-61%) for heterosexuals (P = 0.042) and from 41% (95% CI 21%-64%) to 73% (95% CI 52%-88%) for MSM (P = 0.004). Median monthly HIV transmission rates were 0.0540 (IQR 0.0339-0.0742) for MSM and 0.0018 (IQR 0.0014-0.0191) for heterosexuals at cART initiation, and were reduced by 95% (95% CI 87%-100%) for heterosexuals and 98% (95% CI 95%-100%) for MSM as early as W24. Conclusions Risk of onward transmission for severely immunosuppressed individuals is high before and within the first weeks of cART, and persists, at a substantially reduced level, beyond 24 weeks of cART for some individuals. Earlier cART and protecting HIV-negative partners until full viral suppression is achieved could reduce HIV transmission.

J-08 Qualité des prescriptions au centre de vaccinations internationales de l’hôpital Saint Louis

Introduction et objectifs Dans les centres de reference, les conseils aux voyageurs (de plus en plus nombreux) doivent etre homogenes et conformes aux recommandations nationales (BEH actualise chaque annee). Materiels et methodes Une etude prospective a ete menee du 5 mai au 5 aout 2008 au centre de vaccinations internationales de l’hopital Saint louis a Paris ou se relaient 14 medecins. Resultats Au total, 730 patients ont ete inclus dont 409 (56 %) avaient moins de 30 ans. Les destinations principales etaient l’Afrique Sub-saharienne (58 %), l’Asie (21 %) et l’Amerique du sud (18 %). Les sejours etaient en moyenne de 4 semaines, principalement pour tourisme (72 %) ou retour au pays (16 %). Parmi les 608 (83 %) voyages en zone d’endemie palustre, 568 (93 %) concernaient une zone 3 de resistance. Une chimioprophylaxie a ete prescrite pour 591 patients (81 %), en accord avec les recommandations dans 99,9 % des cas. Le cout etait le critere de choix dans 49 % des cas. La molecule la plus prescrite etait la doxycycline (48 %). La vaccination contre la fievre jaune et l’hepatite A a ete pratiquee respectivement chez 461 (57 %) et 442 (60 %) voyageurs. Le DTP a ete mis a jour chez 261 (36 %) consultants. Seulement 39 sur 67 (58 %) patients âges de moins de 18 ans etaient correctement vaccines contre l’hepatite B (3 ont ete vaccines a la consultation). Parmi les 74 (10 %) prescriptions de vaccins en desaccord avec les recommandations, 29 etaient par exces et 45 par defaut (dont 12 hepatite A). Conclusion La grande majorite des prescriptions etaient homogenes et adaptees aux recommandations. Chaque erreur a pu etre discutee. Les prescriptions de chimioprophylaxie doivent etre maintenues a un niveau d’excellence. Les prescriptions vaccinales pourraient etre ameliorees : promotion du vaccin anti-hepatite A et mise a jour de l’hepatite B chez les jeunes.

M-07 Évolution et pronostic de la co-infection VIH-tuberculose (TB) sur une cohorte de 64 patients

Problematique Le moment optimal pour debuter une tritherapie (HAART) chez les patients co-infectes VIH-TB est difficile a definir (risques d’effets secondaires cumules des traitements, interactions medicamenteuses, syndrome de restauration immunitaire [IRIS], risques d’infections opportunistes [IO] ). Methodes Etude retrospective de 01/98 a 12/03 a l’hopital Saint-Louis des cas de tuberculose prouvee (culture + a M. tuberculosis ) chez des patients VIH + avec evaluation des facteurs pronostiques par un modele de Cox. Resultats 64 patients VIH+ ont eu une TB prouvee durant l’etude, 58 % venaient d’Afrique subsaharienne avec un âge moyen de 41 ans. La TB etait disseminee dans 77 % des cas. Les CD4 medians au diagnostic etaient a 81/mm 3 , 69 % des patients etait naif de HAART. Initialement, 86 % des patients a recu une quadritherapie antituberculeuse. Des effets secondaires sont apparus chez 27 % des patients, surtout lors du 1 er mois (toxicite hepatique : 41 %). Apres un suivi moyen de 26 mois, 84 % des patients a acheve le traitement avec seulement 5 % de rechutes, 1,5 % de deces attribuables a la TB (patient avec une TB XMDR) et 6 % d’IRIS ont ete notes. Le delai median d’instauration du HAART apres le debut du traitement antituberculeux etait de 108 jours. Des IO et deces sont survenus respectivement chez 17 % et 11 % des patients. Le risque de progression de la maladie VIH (IO et deces) etait significativement associe a l’âge > 40 ans ( p = 0,025) et a un taux de CD4 3 ( p = 0,0015). Conclusion Dans notre etude, l’efficacite et la tolerance du traitement de la TB etaient satisfaisantes. Cependant, une introduction plus precoce de la tritherapie devrait etre envisagee chez les patients âges et tres immunodeprimes (CD4 3 ).