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ABSTRACT: Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) frequently follows the initiation of antiretroviral therapy (ART) in patients with tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection. Treatment recommendations are nearly exclusively based on expert opinion.
To assess the clinical outcomes of patients treated using various strategies for TB-IRIS.
In a retrospective analysis of patients treated in Paris hospitals from 1996 to 2008, we describe TB-IRIS outcome, frequency of relapses and CD4 cell count changes after 12 months of ART for the following strategies: no treatment, interrupted ART and use of steroids.
Among 34 patients, TB-IRIS outcome was favourable in 10/10 with no treatment, 11/13 with ART interruption, 3/3 with ART interruption and simultaneous use of steroids and 8/8 with steroids alone. Relapses were observed in both the ART interruption (6/13, 46%) and steroids (4/8, 50%) groups, but were less frequent in the no-treatment group (1/10, 10%). Steroids were prescribed in 61% of the patients and had no significant side effects; steroid use was associated with a trend towards a lower median CD4 cell count at 12 months of ART compared to the others (230 vs. 322 cells/mm(3)), despite no baseline differences.
TB-IRIS outcome was favourable regardless of the therapeutic strategies employed. Although steroids were widely used and well-tolerated, an initial wait-and-see attitude in the case of non-severe IRIS remains an interesting strategy to be evaluated.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 10/2012; 16(10):1365-70. · 2.73 Impact Factor
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T Bommenel,
O Launay,
J L Meynard,
J Gilquin,
C Katlama,
A S Lascaux,
A Mahamat,
V Martinez,
C Pradier,
E Rouveix,
A Simon,
D Costagliola, S Abgrall
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ABSTRACT: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir.
From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models.
The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79).
Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.
Journal of Antimicrobial Chemotherapy 06/2011; 66(8):1869-77. · 5.07 Impact Factor
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ABSTRACT: Pooled analysis of the TORO comparative clinical trial data sets showed a significantly higher incidence rate (IR) of bacterial pneumonia (BP) among patients treated with enfuvirtide-containing combination antiretroviral therapy (ENF-cART) than in those treated with other cART regimens.
To examine the possible impact of ENF-cART on the risk of BP.
From the French Hospital Database on HIV, we selected two groups of patients among cART-treated patients who were prescribed a new cART regimen during the period 2001-2006, when their CD4 counts were <350 cells/mm(3). The ENF-cART and cART groups consisted of 1220 and 9374 patients, respectively. Poisson regression models were used to quantify the relationship between ENF-cART therapy and the risk of BP.
At baseline the median CD4 counts were 100 and 211 cells/mm(3) and the median plasma viral load (pVL) values were 60 276 and 2702 copies/mL in the ENF-cART and cART groups, respectively. The respective BP IRs were 0.65 [95% confidence interval (CI) 0.25-1.06] and 0.31 (95% CI 0.25-0.38) cases per 100 person-years. After adjustment for age, the HIV transmission group, the time period, co-trimoxazole prophylaxis, and stratified CD4 cell counts and pVL values, we found that the BP risk ratio was not increased by enfuvirtide treatment (relative rate 1.39; 95% CI 0.46-4.13). In contrast, lower CD4 cell counts and higher pVL values were significantly associated with a higher risk of BP.
ENF-cART is not associated with a significantly higher risk of BP than other cART regimens, although the value of the adjusted risk and the upper limit of the CI do not allow us to exclude a small increased risk.
Journal of Antimicrobial Chemotherapy 11/2009; 65(1):138-44. · 5.07 Impact Factor
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N Simonney,
G Dewulf,
J-L Herrmann,
M C Gutierrez,
E Vicaut,
C Boutron,
M Leportier,
M Lafaurie, S Abgrall,
D Sereni,
B Autran,
G Carcelain,
A Bourgarit,
P H Lagrange
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ABSTRACT: A prospective and multi-centre study has allowed us to analyse antibody responses and Mycobacterium tuberculosis clinical isolate genotypes on 24 consecutive HIV-TB co-infected patients treated with Highly Active Antiretroviral Therapy (HAART) who either went on to develop a TB Immune Restoration Syndrome (TB-IRS), or not. Circulating free and immune-complexed antibodies against ManLAM, ESAT-6/CFP10 and PGL-Tb1 in HIV-TB co-infected patients were measured by ELISA at the initiation of anti-TB treatment, at the date of HAART initiation and thereafter. Presence of circulating B cells was also monitored by in vitro antibody production (IVAP) against ESAT-6/CFP10 and PGL-Tb1. Finally, 16 out of 24M. tuberculosis clinical isolates from patients with TB-IRS were genotyped using spoligotyping and MIRUs-VNTR typing. Eleven patients (45.8%) experienced TB-IRS (TB-IRS+). Significantly, lower anti-PGL-Tb1 antibody levels were identified in TB-IRS+ compared to TB-IRS-negative patients prior to TB-IRS development. These very low levels were neither related to CD4 counts nor with complexed antibodies. No difference in antibody levels was observed with the other tested antigens. In addition, no specific strain genotype was associated with TB-IRS. The presence of specific anti-PGL-Tb1 antibodies only in TB-IRS-negative patients represents for the first time an indicator of a potential protective response or a diagnostic biomarker for the detection of non-progression to TB-IRS in HIV-TB co-infected patients starting HAART.
Tuberculosis (Edinburgh, Scotland) 06/2008; 88(5):453-61. · 2.54 Impact Factor
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ABSTRACT: The occurrence of toxoplasmic encephalitis (TE) was studied among 19,598 and 17,016 patients enrolled in the French Hospital Database on human immunodeficiency virus whose CD4 cell counts decreased to < or =200x10(6) cells/L before (1992-1995) or after (1996-1998) the availability of highly active antiretroviral therapy, respectively. The incidence of TE decreased from 3.9 cases per 100 person-years in the first period (95% confidence interval [CI], 3.7-4.1) to 1.0 cases per 100 person-years in the second period (95% CI, 0.9-1.1). After adjustment for known risk factors for TE, patients who received cotrimoxazole prophylaxis had a lower risk of TE (adjusted relative hazard, 0.6 and 0.5, respectively, for the first and second periods; P < .001). For patients treated with cotrimoxazole at inclusion, discontinuation of cotrimoxazole increased the risk of TE in both periods (adjusted relative hazard, 4.8 and 4.2, respectively; P < .001). Among patients whose CD4 cell counts increased to > 200 x 10(6) cells/L while undergoing highly active antiretroviral therapy, the incidence of TE was 0.1 cases per 100 person-years (95% CI, 0.0-0.2) and was not increased by discontinuation of cotrimoxazole.
Clinical Infectious Diseases 11/2001; 33(10):1747-55. · 9.15 Impact Factor
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ABSTRACT: To assess the risk factors for esophageal candidiasis (EC), a cohort study and a case-control study were conducted using 1,368 French patients who were already participating in the Delta trial (which compared different types of antiretroviral therapy in HIV-infected patients) and who had no previous history of EC. During a median follow-up period of 19 months, 87 (6%) patients developed EC. The results of the cohort study showed an increased risk of EC associated with a low baseline CD4+ cell count (P<0.0001), a high baseline plasma HIV RNA level (P < 0.0001) and prior zidovudine therapy (P = 0.02) at entry to the study. The case-control study revealed an increased risk of EC in patients with a recent low CD4+ cell count (P < 0.0002), recent antibacterial chemotherapy (P = 0.01) and oral candidiasis (P < 0.05). Cotrimoxazole prophylaxis also increased the risk of EC (P = 0.04) in the case-control study.
European Journal of Clinical Microbiology 06/2001; 20(5):346-9. · 2.86 Impact Factor
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ABSTRACT: To assess the risk factors for esophageal candidiasis (EC), a cohort study and a case-control study were conducted using
1,368 French patients who were already participating in the Delta trial (which compared different types of antiretroviral
therapy in HIV-infected patients) and who had no previous history of EC. During a median follow-up period of 19 months, 87
(6%) patients developed EC. The results of the cohort study showed an increased risk of EC associated with a low baseline
CD4+ cell count (P<0.0001), a high baseline plasma HIV RNA level (P<0.0001) and prior zidovudine therapy (P=0.02) at entry to the study. The case-control study revealed an increased risk of EC in patients with a recent low CD4+ cell
count (P<0.0002), recent antibacterial chemotherapy (P=0.01) and oral candidiasis (P<0.05). Cotrimoxazole prophylaxis also increased the risk of EC (P=0.04) in the case-control study.
European Journal of Clinical Microbiology 04/2001; 20(5):346-349. · 2.86 Impact Factor
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ABSTRACT: The incidence and risk factors for Pneumocystis carinii pneumonia (PCP) recurrence were evaluated in 451 HIV-infected patients enrolled in the French Hospital Database on HIV who started highly active antiretroviral therapy (HAART) while receiving secondary PCP prophylaxis after a first episode occurring between January 1995 and December 1998. There were 18 episodes of recurrent PCP. On HAART, the CD4+ cell count increased to above 200 x 106/L in 274 patients, 51 of whom stopped PCP prophylaxis. None of these patients had PCP recurrences during 363 person-years (PY) of follow-up after the CD4+ cell count had reached 200 x 106/L (incidence rate [IR], 0.00 cases/100 PY; 95% confidence interval [CI], 0.00-0.82), and 37 PY of follow-up after the CD4+ cell count had reached 200 x 106/L and PCP prophylaxis had been discontinued (IR, 0.00 cases/100 PY; 95% CI, 0.00-7.84). The CD4+ cell count remained < 200 x 106/L in 177 patients; 9 patients stopped PCP prophylaxis, and 6 of these had a disease recurrence. Multivariate Cox analysis (time censored when CD4+ cell count > 200 x 106/L) showed that discontinuation of secondary prophylaxis (relative hazard [RH], 25.95; p <.0001) was associated with recurrence, whereas higher CD4+ cell counts during follow-up (RH, 0.39/50 x 106/L increment; p <.002) were protective.
JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2001; 26(2):151-8. · 4.43 Impact Factor
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European Journal of Clinical Microbiology 03/1997; 16(2):180-2. · 2.86 Impact Factor
