Pauline Campa

Assistance Publique – Hôpitaux de Paris, Lutetia Parisorum, Île-de-France, France

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Publications (36)183.05 Total impact

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    ABSTRACT: Background. Multidrug-resistant Enterobacteriaceae (MRE) are widespread in the community, especially in tropical regions. Travelers are at risk of acquiring MRE in these regions, but the precise extent of the problem is not known. Methods. From February 2012 to April 2013, travelers attending 6 international vaccination centers in the Paris area prior to traveling to tropical regions were asked to provide a fecal sample before and after their trip. Those found to have acquired MRE were asked to send fecal samples 1, 2, 3, 6, and 12 months after their return, or until MRE was no longer detected. The fecal relative abundance of MRE among all Enterobacteriaceae was determined in each carrier. Results. Among 824 participating travelers, 574 provided fecal samples before and after travel and were not MRE carriers before departure. Of these, 292 (50.9%) acquired an average of 1.8 MRE. Three travelers (0.5%) acquired carbapenemase-producing Enterobacteriaceae. The acquisition rate was higher in Asia (142/196 [72.4%]) than in sub-Saharan Africa (93/195 [47.7%]) or Latin America (57/183 [31.1%]). MRE acquisition was associated with the type of travel, diarrhea, and exposure to β-lactams during the travel. Three months after return, 4.7% of the travelers carried MRE. Carriage lasted longer in travelers returning from Asia and in travelers with a high relative abundance of MRE at return. Conclusions. MRE acquisition is very frequent among travelers to tropical regions. Travel to these regions should be considered a risk factor of MRE carriage during the first 3 months after return, but not beyond. Clinical Trials Registration. NCT01526187.
    Clinical Infectious Diseases 04/2015; DOI:10.1093/cid/civ333 · 9.42 Impact Factor
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    ABSTRACT: Objectives: to describe in a cohort of HIV-infected patients from Sub-Saharan origin, the incidence of metabolic syndrome, insulin resistance, and lipodystrophy after three years of combined antiretroviral therapy, and model the 10-year risk of cardiovascular diseases, while taking into account environmental factors. Design: Multinational, prospective cohort study. Setting: HIV outpatients' clinics from four tertiary care centers set in France and Cote d'Ivoire Participants: HIV-infected, treatment naive patients eligible to start antiretroviral treatment and from Sub-Saharan African origin. Main outcome measures: incidence of metabolic syndrome, insulin resistance, and lipodystrophy, and assessment of 10 year-risk of cardio-vascular diseases using Framingham risk prediction, D.A.D. Cardiovascular Disease Risk and WHO/ISH prediction charts. Results: Of 245 patients followed up to 3 years, the incidences of metabolic syndrome, insulin resistance, and lipodystrophy were 5.5, 8.5 and 6.8 per 100 person-year of follow-up (cumulative incidence: 14.4, 21.9 and 18.1%, respectively). Living in France, as well as female gender and overweight, were risk factors for metabolic disorders as whole and only first generation protease inhibitors were marginally associated with metabolic syndrome. Cardiovascular risk as modeled through the 3 equations was high in all patients with the synergistic and deleterious effect of living in France compared to Cote d'Ivoire. Conclusions: this cohort study shows how the synergy between HIV, ARV exposure and westernization of life style in a cohort of HIV-infected patients from Sub-Saharan origin leads to a progressive increase in the risk of lipodystrophy, but also metabolic syndrome and insulin resistance, all associated with increased cardio-vascular risk.
    AIDS Research and Human Retroviruses 02/2015; 31(4). DOI:10.1089/AID.2014.0164 · 2.46 Impact Factor
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    ABSTRACT: Background. Dolutegravir has shown in vitro activity on HIV-2. We report safety and efficacy data of dolutegravir (50 mg twice-daily) containing-regimens in antiretroviral-experienced HIV-2 infected-patients. Methods. HIV-2 infected-patients experiencing virological failure to raltegravir received dolutegravir with optimized background antiretroviral combinations within the French Named Patient Program (NPP). Plasma HIV-2 RNA (pVL) was assessed at time of dolutegravir initiation (baseline), Month 3 (M3) and M6. Antiretroviral trough plasma concentrations (C12h) were determined using liquid chromatography coupled with tandem mass spectrometry. Results. Thirteen HIV-2 infected-patients, with 15 years infection median duration and given 16 previous antiretroviral regimens were included in NPP. Median follow-up was 9 months (min: 3-max: 15). Median baseline pVL and CD4 cells count were 9,544 copies/mL (3,096-23,120) and 100/mm3 (77-171), respectively. Available integrase genotypic resistance patterns were: Y143C/G/H/R(n=5), Q148R/K(n=2), N155H(n=4). Optimized background antiretroviral regimens conferring genotypic sensitivity score<2 in 10 patients, included: nucleoside reverse transcriptase inhibitors associated with darunavir/r (n=12), saquinavir/r (n=2), maraviroc (n=3). At M3 and M6, pVL was undetectable in 6/13 and 4/12 patients respectively, and median CD4 was 161 (101-188) and 167/mm3 (135-1353). Median dolutegravir C12h was 4,086 ng/mL (1,756-5,717) in 9 patients. No serious events were notified except one death from progressive multifocal leukoencephalopathy at M4. Conclusion. Optimized dolutegravir containing antiretroviral regimens supported by good plasma exposure provide a substantial initial efficacy rate for salvage therapy in heavily antiretroviral experienced HIV-2 infected-patients with virus harboring resistance to first-generation integrase inhibitors. Larger number of patients and longer follow-up are needed to confirm these findings.
    Clinical Infectious Diseases 02/2015; DOI:10.1093/cid/civ124 · 9.42 Impact Factor
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    ABSTRACT: Travel-related schistosomiasis can be detected in patients without symptoms of acute or chronic infection. A case of Schistosoma mekongi acquired in an endemic area of Laos and discovered unexpectedly from colon biopsies taken 5 years after infection is presented here. A literature review of previous cases of S. mekongi infection specifically associated with travelers is then presented.
    Journal of Travel Medicine 06/2014; DOI:10.1111/jtm.12137 · 1.53 Impact Factor
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    ABSTRACT: In low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing. During a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals. 85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8-100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0-93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3-47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6-32.6). Using multivariable logistic regression, HBsAg-positive status was significantly associated with the following: males, originating from high HBV-endemic region, contact with HBV-infected individual, without national healthcare, and intravenous-drug user (IDU). Of these risk-factors, physician's discretion for testing HBV was not significantly associated with participants' geographical origin or IDU. Missed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of HBV-testing strategies is necessary, especially before severe disease occurs.
    PLoS ONE 03/2014; 9(3):e92266. DOI:10.1371/journal.pone.0092266 · 3.53 Impact Factor
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    ABSTRACT: Each year, thousands of cases of uncomplicated malaria are imported into Europe by travellers. Atovaquone-proguanil (AP) has been one of the first-line regimens used in France for uncomplicated malaria for almost ten years. While AP's efficacy and tolerance were evaluated in several trials, its use in "real life" conditions has never been described. This study aimed to describe outcome and tolerance after AP treatment in a large cohort of travellers returning from endemic areas. Between September 2002 and January 2007, uncomplicated malaria treated in nine French travel clinics with AP were followed for 30 days after AP initiation. Clinical and biological data were collected at admission and during the follow-up. A total of 553 patients were included. Eighty-eight percent of them were born in Africa, and 61.8 % were infected in West Africa, whereas 0.5 % were infected in Asia. Migrants visiting friends and relatives (VFR) constituted 77.9 % of the patients, the remainder (32.1 %) were backpackers. Three-hundred and sixty-four patients (66 %) fulfilled follow-up at day 7 and 265 (48 %) completed the study at day 30. Three patients had treatment failure. One-hundred and seventy-seven adverse drug reactions (ADR) were reported during the follow-up; 115 (77 %) of them were digestive ADR. Backpackers were more likely to experiment digestive ADR compared to VFR (OR = 3.8; CI 95 % [1.8-8.2]). Twenty patients had to be switched to another regimen due to ADR. This study seems to be the largest in terms of number of imported uncomplicated malaria cases treated by AP. The high rate of reported digestive ADR is striking and should be taken into account in the follow-up of patients since it could affect their adherence to the treatment. Beside AP, artemisinin combination therapy (ACT) is now recommended as first-line regimen. A comparison of AP and ACT, in terms of efficacy and tolerance, would be useful.
    Malaria Journal 11/2013; 12(1):399. DOI:10.1186/1475-2875-12-399 · 3.49 Impact Factor
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    ABSTRACT: Impairment of the intestinal barrier and subsequent microbial translocation (MT) may be involved in chronic immune activation, which plays a central role in HIV pathogenesis. Th17 cells are critical to prevent MT. The aim of the study was to investigate, in patients with primary HIV infection (PHI), the early relationship between the Th17/Treg ratio, monocyte activation and MT and their impact on the T-cell activation set point, which is known to predict disease progression. 27 patients with early PHI were included in a prospective longitudinal study and followed-up for 6 months. At baseline, the Th17/Treg ratio strongly negatively correlated with the proportion of activated CD8 T cells expressing CD38/HLA-DR or Ki-67. Also, the Th17/Treg ratio was negatively related to viral load and plasma levels of sCD14 and IL-1RA, two markers of monocyte activation. In untreated patients, the Th17/Treg ratio at baseline negatively correlated with CD8 T-cell activation at month 6 defining the T-cell activation set point (% HLA-DR(+)CD38(+) and %Ki-67(+)). Soluble CD14 and IL-1RA plasma levels also predicted the T-cell activation set point. Levels of I-FABP, a marker of mucosal damages, were similar to healthy controls at baseline but increased at month 6. No decrease in anti-endotoxin core antibody (EndoCAb) and no peptidoglycan were detected during PHI. In addition, 16S rDNA was only detected at low levels in 2 out 27 patients at baseline and in one additional patient at M6. Altogether, data support the hypothesis that T-cell and monocyte activation in PHI are not primarily driven by systemic MT but rather by viral replication. Moreover, the "innate immune set point" defined by the early levels of sCD14 and IL-1RA might be powerful early surrogate markers for disease progression and should be considered for use in clinical practice.
    PLoS Pathogens 06/2013; 9(6):e1003453. DOI:10.1371/journal.ppat.1003453 · 8.06 Impact Factor
  • Journal of Hepatology 04/2013; 58:S21. DOI:10.1016/S0168-8278(13)60049-5 · 10.40 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: The systematic use of rapid tests performed at points-of-care may facilitate hepatitis B virus (HBV) screening and substantially increase HBV infection awareness. The objective of this study was to evaluate the effectiveness of such tests for HBsAg and anti-HBsAb detection among individuals visiting a variety of healthcare centers located in a low HBV-prevalent area. METHODS: Three rapid tests for hepatitis B surface antigen (HBsAg) detection (VIKIA®, Determine(TM) and Quick Profile(TM)) and one test for anti-hepatitis B surface antibody (anti-HBsAb) detection (Quick Profile(TM)) were evaluated in comparison with ELISA serology. Sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV, respectively) and area under the ROC curve were used to estimate test performance. Non-inferiority criteria of the joint (Se, Sp) were set at (0.80, 0.95). RESULTS: Among the 3956 persons screened, 85 (2.1%) were HBsAg-positive and 2225 (56.5%) had a protective anti-HBsAb titer. Test Se and Sp (lower bound of 97.5%CI) were as follows: 96.5% (89.0%), 99.9% (99.8%) for Vikia®; 93.6% (80.7%), 100.0% (99.8%) for Determine(TM); and 90.5% (80.8%), 99.7% (99.5%) for Quick Profile(TM), with all three tests achieving minimal non-inferiority criteria. False negative tests were typically observed in inactive HBsAg carriers. The anti-HBsAb Quick Profile(TM) test had excellent specificity (97.8%) and PPV (97.8%) albeit low sensitivity (58.3%), thus failing to establish non-inferiority. CONCLUSION: All three HBsAg rapid tests could be considered ideal for HBV screening in low HBV-prevalent countries, given the ease of use, rapidity, and high classification probabilities. The anti-HBsAb Quick Profile(TM) could be considered reliable only for positive tests.
    Journal of Hepatology 11/2012; 58(3). DOI:10.1016/j.jhep.2012.11.016 · 10.40 Impact Factor
  • Journal of Hepatology 04/2012; 56:S11. DOI:10.1016/S0168-8278(12)60038-5 · 10.40 Impact Factor
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    ABSTRACT: In HIV-infected patients, data on immunogenicity of Yellow fever immunization are scarce, and there is conflicting evidence of the influence of CD4 T-cell count and plasma HIV RNA on neutralizing antibody titer (NT) after vaccine injection. In this prospective cohort study, NT was measured in all consecutive HIV outpatients who had previously received at least 1 injection of Yellow fever vaccine. Risk factors for vaccine failure (NT < 1:10) and magnitude of NT according to dates of HIV diagnosis and immunization were assessed by logistic regression and general linear models. Among 364 included patients, 24 (7%) had NT <1:10 after a mean delay of 8.4 years after immunization. Among patients immunized after HIV diagnosis (n = 240), NT <1:10 was associated only with detectable plasma HIV RNA at immunization. Among 79 patients with primary vaccination after diagnosis of HIV infection, higher HIV RNA at immunization was the unique independent risk factor for NT <1:10 [adjusted odds ratio (OR) = 3.73 per log10, 95% confidence interval (CI): 1.14 to 12.28]. Lower values of NT were independently associated with a shorter duration of undetectable plasma HIV RNA (OR = 1.05 per year, 95% CI: 1.005 to 1.09) and higher plasma HIV RNA (OR = 0.91 per log10, 95% CI: 0.84 to 0.99) at immunization. The key determinant of antibody response was the HIV replication status at immunization. No association was found between antibody response and CD4 T-cell count.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2012; 59(4):360-7. DOI:10.1097/QAI.0b013e318249de59 · 4.39 Impact Factor
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    ABSTRACT: Objective: Persistent immune activation plays a central role in the pathogenesis of HIV disease. Besides natural regulatory T cells (nTregs), ‘double negative’ T cells shown to exhibit regulatory properties could be involved in the control of harmful immune activation. The aim of this study was to analyze, in patients with primary HIV infection (PHI), the relationship between CD4+CD25+CD127lowFoxP3+ nTregs or CD3+CD4−CD8− double negative T cells and systemic immune activation. Design: A prospective longitudinal study of patients with early PHI. Methods: Twenty-five patients were included. Relationships between frequency of Treg subsets and T-cell activation, assessed on fresh peripheral blood mononuclear cells, were analyzed using nonparametric tests. Cytokine production by double negative T cells was assessed following anti-CD3/anti-CD28 stimulation. Results: No relationship was found between T-cell activation and frequencies of nTregs. In contrast, a strong negative relationship was found at baseline between the proportion of double negative T cells and the proportion of activated CD8 T cells coexpressing CD38 and HLA-DR (P = 0.005) or expressing Ki-67 (P = 0.002). In addition, the frequency of double negative T cells at baseline negatively correlated with the frequency of HLA-DR+CD38+CD8+ T cells at month 6, defining the immune activation set point (P = 0.031). High proportions of stimulated double negative T cells were found to produce the immunosuppressive cytokines transforming growth factor-β1 and/or IL-10. Conclusion: The proportion of double negative T cells at baseline was found to be predictive of the immune activation set point. Our data strongly suggest that double negative T cells may control immune activation in PHI. This effect might be mediated through the production of TGF-β1/IL-10 known to downmodulate immune activation.
    AIDS 01/2012; 26(2):139–148. DOI:10.1097/QAD.0b013e32834e1484 · 6.56 Impact Factor
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    ABSTRACT: Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. To identify the optimal CD4 cell count at which cART should be initiated. Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L. HIV clinics in Europe and the Veterans Health Administration system in the United States. 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis. Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. Limitations: CD4 cell count at cART initiation was not randomized. Residual confounding may exist. Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.
    Annals of internal medicine 04/2011; 154(8):509-15. DOI:10.1059/0003-4819-154-8-201104190-00001 · 16.10 Impact Factor
  • Jean-Louis Poirot, Pauline Campa
    La Revue du praticien 04/2011; 61(4):551-8.
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    ABSTRACT: Little is known in HIV-2 infection about the kinetics of disappearance of raltegravir (RAL)-resistant virus after RAL withdrawal. RAL was interrupted in four highly antiretroviral-experienced HIV-2-infected patients exhibiting a virological failure when receiving RAL. Integrase gene was sequenced from plasma samples collected at the time of RAL failure and at further time points following RAL withdrawal. At the time of RAL withdrawal, virus exhibited different integrase resistance pathways: G140S/Q148R, E92Q/N155H, T97A/N155H and T97A/Y143C. In patient 1, the G140S/Q148R double-mutant was still detected at month (M)7 and at M11 after stopping RAL, but was no longer detected at M15. Regarding patient 2, the double-mutant E92Q/N155H was still present at M2 and M8 after stopping RAL, and was no longer detected at M12. In patient 3, RAL-resistant virus with T97A/N155H mutations were still present 1 month after stopping RAL, and were no longer detected at M14. Regarding patient 4, the mutant T97A/Y143C was still detected at M1 and M3 following RAL withdrawal. At M18 after RAL stop, integrase genotypic pattern evolved to T97A/Y143G. Persistence of HIV-2 RAL-resistant mutants was observed in all the key genetic RAL resistance pathways. These findings have clinical implications especially in HIV-2-infected patients for whom therapeutic arsenal is limited compared to HIV-1, since the persistence of resistant mutants might compromise the possible efficacy of upcoming second-generation integrase inhibitors.
    Antiviral therapy 01/2011; 16(6):937-40. DOI:10.3851/IMP1826 · 3.14 Impact Factor
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    ABSTRACT: The emergence of non-AIDS-related events in the HIV-infected population experiencing a longer life expectancy implies the implementation of a comprehensive approach of HIV clinical management through better access to care, prevention, and early diagnosis of co-morbidities. The Orchestra program is a computer-assisted HIV care and support tool implemented since December 2004 in the outpatient clinic of a University Hospital set in Paris, France. The intervention aims at improving access to HIV information care and support specifically targeted five areas of actions: cardiovascular risk factors; gynecological follow-up; anti-hepatitis B virus (HBV) vaccine coverage; sexuality and prevention of sexually transmitted infections; and compliance to antiretrovirals. The impact of this program was examined prospectively on a "before-after" basis after a two-year implementation. In the two-year period, 1717 patients were regularly followed. The level of the database information significantly increased in time (low density lipoprotein (LDL) cholesterol and glycemia were informed in 74% of patients at inclusion versus 95% at two years, and 83% versus 97%, p < 0.001, respectively). The number of targeted interventions was also higher. For eligible women, papanicolaou smears and mammography were prescribed in 52% of cases after intervention, versus 44% at inclusion, p0.04 and 83% versus 50%, p < 0.001, respectively. Indicators of care eventually improved significantly. Initially 72% non-adherent patients declared to be adherent after the intervention ( p < 0.001) and 67% of patients with initial LDL-hypercholesterolemia normalized their LDL level within two years ( p < 0.001). The Orchestra program has provided a unique opportunity to assess and improve prevention and management of co-morbidities in HIV patients.
    AIDS Care 05/2010; 22(5):588-96. DOI:10.1080/09540120903280893 · 1.60 Impact Factor
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    ABSTRACT: In 29 antiretroviral-naive HIV-2-infected patients starting lopinavir/ritonavir-containing regimen, the median CD4 cell count change from baseline (142 cells/microl) was +71 cells/microl at week 24 and +132 cells/microl at week 96. Seventeen (59%) patients had a CD4 cell count increase of at least 50 cells/microl and undetectable HIV-2 RNA at week 24 and were considered as responders to treatment. This sustained elevation of CD4 cell count in the first 2 years of combination antiretroviral therapy shows the potential for lopinavir/ritonavir regimens as first-line therapy in HIV-2 infection.
    AIDS (London, England) 05/2009; 23(9):1171-3. DOI:10.1097/QAD.0b013e32832949f0 · 6.56 Impact Factor
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    ABSTRACT: Background: HIV-infected patients often travel in tropical areas where immunization against Yellow Fever is compulsory. There are no data about its efficacy and safety in the 2007-2008 era, where patients are mostly treated and with controlled immunosuppression. Methods: A cohort study including all consecutive HIV-patients immunized against Yellow Fever was conducted in our Travel Medicine Department between January 2003 and August 2007. Efficacy was assessed by measurement of neutralizing antibody response in serum (Pasteur Cerba, France) between October 2007 and February 2008. Titer ≥ 1/10 was defined as protective. CD4-T cell counts and plasma HIV-RNA were collected at time of immunization and serum control. Log-transformed titer was used to assess spearman ranked sum test correlation between antibody level and 1) CD4 cells count at time of immunization and of serology, 2) delay between immunization and serology. Results: 103 patients were included (75% ARV-treated). At time of immunization, mean CD4-T cell count was 490/mm3 (range: 16-1254) and median plasma HIV-RNA was1.60 log10 copies/mL (58% < 40 copies/ml). Mean interval from immunization to serology was 784 days (range: 57-1778). At time of serology, mean CD4-T cell count was 511/mm3 (range: 14-1523). All patients except one developed a protective antibody response (median titer: 1/40; range: 1/5-1/80), including the 6 patients with a CD4-T cell count under 200/mm3 at time of serology. A negative correlation between antibody titer and interval from immunization to serology control was noted (p=0.034). No correlation was found between antibody titer and CD4-T cell count at immunization or serology. No adverse event was reported. Discussion: Yellow Fever vaccination was found to be safe and effective in this cohort of non severely immunocompromised HIV-infected patients. Antibody response was dependent of time elapsed since immunization, but not of CD4-T cell count. This supports the large use of vaccination in HIV-infected patients who travel to endemic countries.
    Infectious Diseases Society of America 2008 Annual Meeting; 10/2008
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    ABSTRACT: We investigated the in vitro phenotypic susceptibility of HIV-2 isolates from integrase inhibitor (INI)-naive patients to INIs and its relation to HIV-2 integrase gene polymorphism. We determined the phenotypic susceptibility to raltegravir and elvitegravir of co-cultured isolates obtained from the HIV-2 ROD reference strain and from 14 clinical isolates. IC(50) values were compared with those for HIV-1 reference strains. HIV-2 integrase gene polymorphism was assessed in isolates from 52 INI-naive patients enrolled in the French HIV-2 cohort. Median raltegravir and elvitegravir IC(50) values for the 14 clinical HIV-2 isolates were 2.4 and 0.7 nM, respectively, and were similar to those observed for HIV-2 ROD and HIV-1 reference strains. Overall, 38% of HIV-2 integrase amino acids were polymorphic. The catalytic triad DDE and the HHCC and RKK motifs were fully conserved, at the same genomic positions as described in HIV-1. In subtype B isolates, the total length of the integrase gene varied, owing to the presence of stop codons at positions 288, 294, 297 and 302. Fourteen of the positions associated with substitutions conferring INI resistance in HIV-1 were polymorphic in HIV-2. Despite 40% heterogeneity between the HIV-1 and HIV-2 integrase genes, the phenotypic susceptibility of clinical HIV-2 isolates to INIs was similar to that of HIV-1. This new class of antiretroviral drugs thus represents a novel therapeutic possibility for HIV-2-infected patients who otherwise have few treatment options.
    Journal of Antimicrobial Chemotherapy 09/2008; 62(5):914-20. DOI:10.1093/jac/dkn335 · 5.44 Impact Factor
  • Revue d Épidémiologie et de Santé Publique 05/2008; 56(2):102-102. DOI:10.1016/j.respe.2008.03.036 · 0.66 Impact Factor

Publication Stats

702 Citations
183.05 Total Impact Points

Institutions

  • 2013
    • Assistance Publique – Hôpitaux de Paris
      • Département de Médecine Interne
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France
  • 2008–2009
    • Université Victor Segalen Bordeaux 2
      Burdeos, Aquitaine, France
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2004–2005
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      • Service des Maladies Infectieuses et Tropicales
      Paris, Ile-de-France, France