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1.  The French Connection: The First Large Population-Based Contact Survey in France Relevant for the Spread of Infectious Diseases 
PLoS ONE  2015;10(7):e0133203.
Empirical social contact patterns are essential to understand the spread of infectious diseases. To date, no such data existed for France. Although infectious diseases are frequently seasonal, the temporal variation of contact patterns has not been documented hitherto.
COMES-F is the first French large-scale population survey, carried out over 3 different periods (February-March, April, April-May) with some participants common to the first and the last period. Participants described their contacts for 2 consecutive days, and reported separately on professional contacts when typically over 20 per day.
2033 participants reported 38 881 contacts (weighted median [first quartile-third quartile]: 8[5–14] per day), and 54 378 contacts with supplementary professional contacts (9[5–17]). Contrary to age, gender, household size, holidays, weekend and occupation, period of the year had little influence on the number of contacts or the mixing patterns. Contact patterns were highly assortative with age, irrespective of the location of the contact, and gender, with women having 8% more contacts than men. Although most contacts occurred at home and at school, the inclusion of professional contacts modified the structure of the mixing patterns. Holidays and weekends reduced dramatically the number of contacts, and as proxies for school closure, reduced R0 by 33% and 28%, respectively. Thus, school closures could have an important impact on the spread of close contact infections in France.
Despite no clear evidence for temporal variation, trends suggest that more studies are needed. Age and gender were found important determinants of the mixing patterns. Gender differences in mixing patterns might help explain gender differences in the epidemiology of infectious diseases.
PMCID: PMC4503306  PMID: 26176549
2.  Clinical impact and cost-effectiveness of making third-line antiretroviral therapy available in sub-Saharan Africa: A model-based analysis in Côte d’Ivoire 
In sub-Saharan Africa, HIV-infected adults who fail 2nd-line antiretroviral therapy (ART) often do not have access to 3rd-line ART. We examined the clinical impact and cost-effectiveness of making 3rd-line ART available in Côte d’Ivoire.
We used a simulation model to compare four strategies following 2nd-line ART failure: continue 2nd-line ART [C-ART2]; continue 2nd-line ART with an adherence reinforcement intervention [AR-ART2]; immediate switch to 3rd-line ART [IS-ART3]; and continue 2nd-line ART with adherence reinforcement, switching patients with persistent failure to 3rd-line ART [AR-ART3]. Third-line ART consisted of a boosted-darunavir plus raltegravir-based regimen. Primary outcomes were 10-year survival and lifetime incremental cost effectiveness ratios (ICERs), in $/year of life saved (YLS). ICERs below $3,585 (3 times the country per capita GDP) were considered cost-effective.
Ten-year survival was 6.0% with C-ART2, 17.0% with AR-ART2, 35.4% with IS-ART3, and 37.2% with AR-ART3. AR-ART2 was cost-effective ($1,100/YLS). AR-ART3 had an ICER of $3,600/YLS and became cost-effective if the cost of 3rd-line ART decreased by <1%. IS-ART3 was less effective and more costly than AR-ART3. Results were robust to wide variations in the efficacy of 3rd-line ART and of the adherence reinforcement, as well as in the cost 2nd-line ART.
Access to 3rd-line ART combined with an intense adherence reinforcement phase, used as a tool to distinguish between patients who can still benefit from their current 2nd-line regimen and those who truly need 3rd-line ART would provide substantial survival benefits. With minor decreases in drug costs, this strategy would be cost-effective.
PMCID: PMC4146647  PMID: 24732870
3.  A Case of Aggregatibacter aphrophilus Multiple Abscess 
Open Forum Infectious Diseases  2015;2(2):ofv031.
We report a case of brain and lung abscesses caused by Agreggatibacter aphrophilus in a 43-YEAR-OLD man with past history of splenectomy and drug addiction, in the absence of endocarditis. Microbiological samples remain negatives and diagnosis was made by 16S rDNA PCR performance on abscess fluid for this coccobacillus that belongs to the HACEK group. The patient’s clinical symptoms resolved within 6 weeks of treatment with cefotaxim.
PMCID: PMC4566307  PMID: 26380332
Aggregatibacter aphrophilus; brain abscess; HACEK; lung abscess; 16S rDNA
4.  Effectiveness and cost of quick diagnostic tests to determine tetanus immunity in patients with a wound in french emergency departments 
BMC Infectious Diseases  2014;14:603.
Tétanos Quick Stick® (TQS) is a test for tetanus immunity screening for wounded patients in emergency departments (EDs), but represents additional costs compared with a medical interview on vaccination history. The study objective was to assess the effectiveness and cost of the TQS in French EDs.
We performed a model-based analysis that simulates screening of tetanus immunity and risk of tetanus based on prophylaxis administration. Strategies compared were: i) diagnosis of tetanus immunity by “TQS”; ii) “Medical Interview” (current practice). The study population was 1,658,000 French adults seeking ED care for a wound in 2012. Model parameters were estimated based on French national surveillance data, and published literature. Outcome measures were number of tetanus cases, life years gained and costs (2012 €) from a societal perspective.
Use of TQS had negligible impact on health outcomes (0.02 tetanus cases/year in France vs. 0.41 for “Medical Interview”), but resulted in a decrease in annual costs of €2,203,000 (−42%). Base case and sub-group analysis showed that with the same effectiveness, the average cost per patient was: €13 with “Medical Interview” vs. €11.7 with TQS for the overall cohort; €28.9 with “Medical Interview” vs. €21 with “TQS” for tetanus-prone wounds; €15 with “Medical Interview” vs. €14.1 with “TQS” for patients aged ≥65 years; and €6.2 with “Medical Interview” vs. €7.8 with “TQS” for non-tetanus-prone wounds.
Use of TQS is as effective and less costly than “Medical Interview” when applied in ED to wounded patients with tetanus-prone wounds or aged ≥65 years. However, it is more expensive in patients with non-tetanus-prone wounds.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-014-0603-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4246690  PMID: 25407690
Tetanus immunity; Diagnostic tests; Cost-effectiveness; Emergency department
5.  Trends in Condom Use and Risk Behaviours after Sexual Exposure to HIV: A Seven-Year Observational Study 
PLoS ONE  2014;9(8):e104350.
We aimed to determine the trends in numbers and percentages of sexually exposed persons to HIV (SE) consulting an ED for post-exposure prophylaxis (PEP), as well as predictors of condom use.
Study Design
We conducted a prospective-observational study.
We included all SE attendances in our Emergency Department (ED) during a seven-year study-period (2006–2012). Trends were analyzed using time-series analysis. Logistic Regression was used to define indicators of condom use.
We enrolled 1851 SE: 45.7% reported intercourse without condom-use and 12.2% with an HIV-infected partner. Significant (p<0.01) rising trends were observed in the overall number of SE visits (+75%), notably among men having sex with men (MSM) (+126%). There were rising trends in the number and percentage of those reporting intercourse without condom-use in the entire population +91% (p<0.001) and +1% (p>0.05), in MSM +228% (p<0.001) and +49% (p<0.001), in Heterosexuals +68% (p<0.001) and +10% (p = 0.08). Among MSM, significant rising trends were found in those reporting high-risk behaviours: anal receptive (+450% and +76%) and anal insertive (+l33% and +70%) intercourses. In a multivariate logistic regression analysis, heterosexuals, vaginal intercourse, visit during the night-shift and short time delay between SE and ED visit, were significantly associated with condom-use.
We report an increasing trend in the number of SE, mainly among MSM, and rising trends in high-risk behaviours and unprotected sexual intercourses among MSM. Our results indicate that SE should be considered as a high-risk population for HIV and sexually transmitted diseases.
PMCID: PMC4144812  PMID: 25157477
6.  Characterization of Binding of Raltegravir to Plasma Proteins 
Antimicrobial Agents and Chemotherapy  2013;57(10):5147-5150.
The objective of this study was to characterize raltegravir (RAL) binding to albumin and alpha-1-acid glycoprotein (AAG). Unbound and bound RAL were separated by ultrafiltration. The association constant (Ka) was estimated by a graphical method. In HIV-infected patients, the average plasma protein binding is 76%. RAL did not bind to AAG but bound to nonsaturable, low-affinity albumin sites with an n (number of sites) · Ka product of 9.8 × 102 liters/mol. A pH increase of 0.2 U led to a 2% increase in the bound fraction.
PMCID: PMC3811458  PMID: 23856784
7.  Is expert opinion reliable when estimating transition probabilities? The case of HCV-related cirrhosis in Egypt 
Data on HCV-related cirrhosis progression are scarce in developing countries in general, and in Egypt in particular. The objective of this study was to estimate the probability of death and transition between different health stages of HCV (compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma) for an Egyptian population of patients with HCV-related cirrhosis.
We used the “elicitation of expert opinions” method to obtain collective knowledge from a panel of 23 Egyptian experts (among whom 17 were hepatologists or gastroenterologists and 2 were infectiologists). The questionnaire was based on virtual medical cases and asked the experts to assess probability of death or probability of various cirrhosis complications. The design was a Delphi study: we attempted to obtain a consensus between experts via a series of questionnaires interspersed with group response feedback.
We found substantial disparity between experts’ answers, and no consensus was reached at the end of the process. Moreover, we obtained high death probability and high risk of hepatocellular carcinoma. The annual transition probability to death was estimated at between 10.1% and 61.5% and the annual probability of occurrence of hepatocellular carcinoma was estimated at between 16.8% and 58.9% (depending on age, gender, time spent in cirrhosis and cirrhosis severity).
Our results show that eliciting expert opinions is not suited for determining the natural history of diseases due to practitioners’ difficulties in evaluating quantities. Cognitive bias occurring during this type of study might explain our results.
PMCID: PMC4003824  PMID: 24635942
Delphi method; Expert knowledge elicitation; Methodological bias; Risk perception; Cognitive bias; HCV in Egypt
8.  Timing of Intermittent Seminal HIV-1 RNA Shedding in Patients with Undetectable Plasma Viral Load under Combination Antiretroviral Therapy 
PLoS ONE  2014;9(3):e88922.
It was demonstrated that combination antiretroviral therapy (cART) reduces the HIV-1 viral load (VL) in the blood and the seminal compartment. Some studies have reported that the seminal HIV-1 VL is undetectable in individuals with an undetectable blood plasma viral load (bpVL) under cART. However, some recent studies have demonstrated that seminal HIV-1 RNA may still be detected, and potentially infectious, even in the case of an undetectable bpVL. The aim of this retrospective study was to determine the detection rate of a seminal VL and whether shedding could be intermittent over a very short time.
From January 2006 to December 2011, 88 HIV-1 infected men, enrolled in an Assisted Reproduction program, provided 306 semen samples, corresponding to 177 frozen sperm samples (two samples delivered at a one-hour interval (n = 129) or one sample (n = 48)). All enrolled men were under cART, with an undetectable bpVL for more than 6 months. HIV-1 RNA was quantified in seminal plasma using a Roche COBAS Ampliprep COBAS TaqMan HIV-1 test.
Seminal HIV-1 RNA was detected in 23 samples (7.5%) from 17 patients (19.3%). This detection rate was stable over years. With regards to the freezing of two samples delivered at a one-hour interval, the proportion of discordance between the first and second samples was 9.3% (12/129).
Our results confirm the intermittent shedding of HIV-1 in semen. While this finding has been shown by studies examining longer time intervals, to our knowledge, this has never been demonstrated over such a short time interval.
PMCID: PMC3940424  PMID: 24594873
9.  Predictive Factors of Cytomegalovirus Seropositivity among Pregnant Women in Paris, France 
PLoS ONE  2014;9(2):e89857.
Cytomegalovirus (CMV) is the most frequent cause of congenital infection. The objective of this study was to evaluate predictive factors for CMV seronegativity in a cohort of pregnant women in Paris, France.
Pregnant women enrolled in a prospective cohort during the 2009 A/H1N1 pandemic were tested for CMV IgG antibodies. Variables collected were age, geographic origin, lifestyle, work characteristics, socioeconomic status, gravidity, parity and number of children at home. A multivariate logistic regression model was used to identify independent predictive factors for CMV seropositivity.
Among the 826 women enrolled, 389 (47.1%) were primiparous, and 552 (67.1%) had Metropolitan France as a geographic origin. Out of these, 355 (i.e. 57.0%, 95% confidence interval (CI): [53.6%–60.4%]) were CMV seropositive: 43.7% (95% CI:[39.5%–47.9%]) in those whose geographic origin was Metropolitan France and 84.1% in those with other origins (95% CI:[79.2%–88.3%]).
Determinants associated with CMV seropositivity in a multivariate logistic regression model were: (i) geographic origin (p<0.001(compared with Metropolitan France, geographic origins of Africa adjusted odds ratio (aOR) 21.2, 95% CI:[9.7–46.5], French overseas departments and territories and other origin, aOR 7.5, 95% CI:[3.9–14.6], and Europe or Asia, aOR 2.2, 95% CI: [1.3–3.7]); and (ii) gravidity (p = 0.019), (compared with gravidity = 1, if gravidity≥3, aOR = 1.5, 95% CI: [1.1–2.2]; if gravidity = 2, aOR = 1.0, 95% CI: [0.7–1.4]). Work characteristics and socioeconomic status were not independently associated with CMV seropositivity.
In this cohort of pregnant women, a geographic origin of Metropolitan France and a low gravidity were predictive factors for CMV low seropositivity. Such women are therefore the likely target population for prevention of CMV infection during pregnancy in France.
PMCID: PMC3933677  PMID: 24587077
10.  Routine HIV Screening in Portugal: Clinical Impact and Cost-Effectiveness 
PLoS ONE  2013;8(12):e84173.
To compare the clinical outcomes and cost-effectiveness of routine HIV screening in Portugal to the current practice of targeted and on-demand screening.
We used Portuguese national clinical and economic data to conduct a model-based assessment.
We compared current HIV detection practices to strategies of increasingly frequent routine HIV screening in Portuguese adults aged 18-69. We considered several subpopulations and geographic regions with varying levels of undetected HIV prevalence and incidence. Baseline inputs for the national case included undiagnosed HIV prevalence 0.16%, annual incidence 0.03%, mean population age 43 years, mean CD4 count at care initiation 292 cells/μL, 63% HIV test acceptance, 78% linkage to care, and HIV rapid test cost €6 under the proposed routine screening program. Outcomes included quality-adjusted survival, secondary HIV transmission, cost, and incremental cost-effectiveness.
One-time national HIV screening increased HIV-infected survival from 164.09 quality-adjusted life months (QALMs) to 166.83 QALMs compared to current practice and had an incremental cost-effectiveness ratio (ICER) of €28,000 per quality-adjusted life year (QALY). Screening more frequently in higher-risk groups was cost-effective: for example screening annually in men who have sex with men or screening every three years in regions with higher incidence and prevalence produced ICERs of €21,000/QALY and €34,000/QALY, respectively.
One-time HIV screening in the Portuguese national population will increase survival and is cost-effective by international standards. More frequent screening in higher-risk regions and subpopulations is also justified. Given Portugal’s challenging economic priorities, we recommend prioritizing screening in higher-risk populations and geographic settings.
PMCID: PMC3867470  PMID: 24367639
11.  Rapid detection of glycopeptide-resistant enterococci: impact on decision-making and costs 
According to French national recommendations, the detection of a patient colonized with glycopeptide-resistant enterococci (GRE) leads to interruption of new admissions and transfer of contact patients (CPs) to another unit or healthcare facility, with weekly screening of CPs.
We evaluated the medical and economic impact of a pragmatic adaptation of national guidelines associated with a real-time PCR (RTP) (Cepheid Xpert™ vanA/vanB) as part of the strategy for controlling GRE spread in two medical wards. Screening was previously performed using chromogenic selective medium (CSM). Turn around time (TAT), costs of tests and cost of missed patient days were prospectively collected. In February 2012, the identification of GRE in one patient in the diabetology ward led to the screening of 31 CPs using CSM; one secondary case was identified in a CP already transferred to the Nephrology ward. Awaiting the results of SCM (median TAT, 70.5 h), 41 potential patient days were missed, due to interruption of admissions. The overall cost (screening tests + missing patient.days) was estimated at 14, 302.20 €. The secondary case led to screening of 22 CPs in the Nephrology ward using RTP. Because of a short median TAT of 4.6 h, we did not interrupt admissions and patients’ transfers. Among 22 CPs, 19 (86%) were negative for vanA, 2 were positive for vanB and 3 had invalid results needing CSM. The overall cost of the strategy was estimated at 870.40 € (cost of screening tests only), without missing patient days.
The rapid PCR test for vanA-positive GRE detection both allowed rapid decision about the best infection control strategy and prevented loss of income due to discontinuation of patient transfers and admissions.
PMCID: PMC4175105  PMID: 24180674
Screening; Glycopeptide; Resistant; Enterococci; Cost; Decision-making; Search and isolate
12.  Intensification of Antiretroviral Therapy through Addition of Enfuvirtide in Naive HIV-1-Infected Patients with Severe Immunosuppression Does Not Improve Immunological Response: Results of a Randomized Multicenter Trial (ANRS 130 Apollo) 
We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm3 or stage B/C disease with CD4 counts of <200/mm3. Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥200/mm3 at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm3, and the median HIV-1 RNA load was 5.4 log10 copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥200/mm3 at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression.
PMCID: PMC3553717  PMID: 23165467
13.  Investigating Recent Testing among MSM: Results from Community-Based HIV Rapid Testing Attendees in France 
Background. We aimed to identify factors associated with recent HIV testing in MSM who attended two experimental community-based and nonmedicalized voluntary counselling and testing programmes (CB-VCT) targeting MSM in France. Methods. This analysis was based on data collected in 2009–2011 through a self-administered pretesting questionnaire. An index measuring the level of participants' sexual orientation disclosure was built: the higher the index, the greater the disclosure. Factors associated with recent HIV testing (last test ≤ 1 year) were identified using a multivariate logistic regression model adjusted for the CB-VCT programme of enrolment. Results. 716 MSM provided data on testing history. Overall, 49% were recently tested for HIV and 51% were not. Recently tested MSM had a higher homosexuality disclosure index (adjusted OR [95% confidence interval]: aOR = 1.2 [1.1–1.4]), reported more inconsistent condom use during anal sex with men (aOR = 1.6 [1.2–2.1]), and were less likely to have sex under the influence of club drugs (aOR = 0.6 [0.4–1.0]). Conclusion. New testing strategies should focus on those who live their homosexuality relatively secretly and those who use club drugs before sex. Governments should develop policies which encourage improved social acceptance of homosexuality as concealment of sexual orientation represents a major barrier to testing.
PMCID: PMC4437427  PMID: 26316962
14.  A Single HIV-1 Cluster and a Skewed Immune Homeostasis Drive the Early Spread of HIV among Resting CD4+ Cell Subsets within One Month Post-Infection 
PLoS ONE  2013;8(5):e64219.
Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI). We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM]) and short-lived (transitional-memory [TTM] and effector-memory cells [TEM]) resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells), although 10-fold less (p = 0.0005) than in equally infected TCM (4.5), TTM (4.7) and TEM (4.6) cells. CD3−CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells), unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells). The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility, suggesting that subset activation and skewed immune homeostasis determine the conditions of viral dissemination and early establishment of the HIV reservoir.
PMCID: PMC3653877  PMID: 23691172
15.  Missed opportunities for HIV testing in newly-HIV-diagnosed patients, a cross sectional study 
BMC Infectious Diseases  2013;13:200.
In France, 1/3 HIV-infected patients is diagnosed at an advanced stage of the disease. We describe missed opportunities for earlier HIV testing in newly-HIV-diagnosed patients.
Cross sectional study. Adults living in France for ≥1 year, diagnosed with HIV-infection ≤6 months earlier, were included from 06/2009 to 10/2010. We collected information on patient characteristics at diagnosis, history of HIV testing, contacts with healthcare settings, and occurrence of HIV-related events 3 years prior to HIV diagnosis. During these 3 years, we assessed whether or not HIV testing had been proposed by the healthcare provider upon first contact in patients notifying that they were MSM or had HIV-related conditions.
1,008 newly HIV-diagnosed patients (mean age: 39 years; male: 79%; MSM: 53%; diagnosed with an AIDS-defining event: 16%). During the 3-year period prior to HIV diagnosis, 99% of participants had frequented a healthcare setting and 89% had seen a general practitioner at least once a year. During a contact with a healthcare setting, 91/191 MSM (48%) with no HIV-related conditions, said being MSM; 50 of these (55%) did not have any HIV test proposal. Only 21% (41/191) of overall MSM who visited a healthcare provider received a test proposal. Likewise, 299/364 patients (82%) who sought care for s had a missed opportunity for HIV testing.
Under current screening policies, missed opportunities for HIV testing remain unacceptably high. This argues in favor of improving risk assessment, and HIV-related conditions recognition in all healthcare facilities.
PMCID: PMC3652743  PMID: 23638870
HIV/AIDS; HIV testing; Late diagnosis; Risk assessment; Access to care
16.  Predictive Value of Liver Enzymes and Inflammatory Biomarkers for the Severity of Liver Fibrosis Stage in HIV/HCV Co-Infected Patients 
PLoS ONE  2013;8(3):e59205.
The aim of our study was to assess a possible association between plasma inflammatory biomarkers (CRP, IL-6, soluble CD14) and the extent of fibrosis or cirrhosis using a FibroScan® in HIV/HCV co-infected patients.
This cross-sectional study assessed 60 HIV/HCV co-infected patients who had paired plasma samples and FibroScan® values available. All included patients were controlled for HIV infection (HIV-1 RNA <50 copies/mL) and had detectable HCV RNA levels. Levels of three biomarkers were measured in all samples using commercial ELISA kits. Multivariate logistic regression models identified factors associated with the METAVIR stages of fibrosis (F0–F2 vs. F3–F4).
In univariate logistic regression analyses, in addition to sCD14 (odds ratio [OR] = 3.23, 95% confidence interval [95%CI] = 1.30–7.97, P = 0.01), aspartate aminotransferase (AST), alanine aminotransferase, platelet counts, and CD4 cell counts were associated with the stage of liver fibrosis and, thus, were introduced into the model. However, only AST (OR = 1.06, 95%CI = 1.02–1.10, P = 0.0009) was independently associated with F3–F4 stage liver fibrosis.
In our study of HIV/HCV co-infected patients, sCD14 plasma level, a biomarker of monocyte activation, was not independently associated with the F3–F4 stage of liver fibrosis. We hypothesize that the higher levels of inflammation markers observed in HIV/HCV co-infected patients, compared to HCV mono-infected patients, prevent this association being observed within this population.
PMCID: PMC3602202  PMID: 23527135
17.  Average Adherence to Boosted Protease Inhibitor Therapy, rather than the Pattern of Missed Doses, as a Predictor of HIV RNA Replication 
Consecutive missed doses may differentially impact the efficacy of antiretroviral therapy associated with the use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) and a ritonavir-boosted protease inhibitor (PI). In a cohort of 72 subjects receiving a boosted PI, average adherence to dosage was a better predictor of human immunodeficiency virus (HIV) replication than was the duration or frequency of treatment interruption. In contrast with an NNRTI, consecutive missed doses of a boosted PI did not emerge as a major risk factor for HIV replication.
PMCID: PMC3591724  PMID: 20210643
18.  Role of Baseline HIV-1 DNA Level in Highly-Experienced Patients Receiving Raltegravir, Etravirine and Darunavir/Ritonavir Regimen (ANRS139 TRIO Trial) 
PLoS ONE  2013;8(1):e53621.
In the ANRS 139 TRIO trial, the use of 3 new active drugs (raltegravir, etravirine, and darunavir/ritonavir), resulted in a potent and sustained inhibition of viral replication in multidrug-resistant treatment-experienced patients. The aim of this virological sub-study of the ANRS 139 TRIO trial was to assess: (i) the evolution of HIV-1 DNA over the first year; and (ii) the association between baseline HIV-1 DNA and virological outcome.
Among the 103 HIV-1-infected patients included in the ANRS-139 TRIO trial, HIV-1 DNA specimens were available for 92, 84, 88, and 83 patients at Week (W)0, W12, W24, and W48, respectively. Quantification of total HIV-1 DNA was performed by using the commercial kit “Generic HIV DNA Cell” (Biocentric, Bandol, France).
Baseline median HIV-1 DNA of patients displaying virological success (n  = 61), viral blip (n  = 20), and virological failure (n  = 11) were 2.34 log10 copies/106 PBMC (IQR  = 2.15–2.66), 2.42 (IQR  = 2.12–2.48), and 2.68 (IQR  = 2.46–2.83), respectively. Although not statistically significant, patients exhibiting virological success or viral blip had a tendency to display lower baseline HIV-1 DNA than patients experiencing virological failure (P  = 0.06). Median decrease of HIV-1 DNA between baseline and W48 was -0.13 log10 copies/106 PBMC (IQR = -0.34 to +0.10), mainly explained by the evolution from W0 to W4. No more changes were observed in the W4-W48 period.
In highly-experienced multidrug-resistant patients, HIV-1 DNA slightly decreased during the first month and then remained stable during the first year of highly potent antiretroviral regimen. In this population, baseline HIV-1 DNA might help to better predict the virological response and to tailor clinical therapeutic management as more aggressive therapeutic choices in patients with higher baseline HIV-1 DNA.
PMCID: PMC3547918  PMID: 23349724
19.  Impact of Herpes simplex virus load and red blood cells in cerebrospinal fluid upon herpes simplex meningo-encephalitis outcome 
BMC Infectious Diseases  2012;12:356.
Herpes simplex encephalitis (HSE) often leads to severe disability or death. Factors usually associated with outcome include Simplified Acute Physiology Score, age and delay of initiation of acyclovir treatment.
Our aim was to determine the impact of Herpes simplex virus (HSV) load in cerebrospinal fluid (CSF) upon HSE outcome.
We retrospectively determined HSV load in the CSF of 43 patients with confirmed HSE, hospitalized in northern France from 1998 to 2005, using CSF samples collected the day of hospital admission and stored at −20°C. We analyzed the association between HSV load and mortality/morbidity by the Glasgow Outcome Scale. Fisher’s exact test and Wilcoxon’s test were used for statistical analysis.
The M/F sex ratio was 1.7 and median patient age was 61 years. Median HSV load in CSF was 2.0 log copies/μL (IQR 25-75=1.2-2.6). The mortality rate was 32.6% six months after HSE diagnosis. Higher age was associated with mortality (p=0.03). Longer delay in acyclovir initiation tended to be associated with higher mortality but did not reach statistical significance (p=0.08). Severe disability and death due to HSV were associated with a higher Knaus score (p=0.004), later acyclovir initiation (p=0.006), older age (p=0.04) and presence of red blood cells in CSF (p=0.05). HSV load in CSF was neither associated with mortality (p=1.00) nor with morbidity (p=0.90).
In this study, HSV load in CSF was not found to be associated with poor outcome in patients with HSE. These data do not support measurement of HSV load at admission in patients with HSE.
PMCID: PMC3560250  PMID: 23245564
Herpes virus; Prognosis; Neurological/brain; Viral load
20.  Pharmacologic Boosting of Atazanavir in Maintenance HIV-1 Therapy: The COREYA Propensity-Score Adjusted Study 
PLoS ONE  2012;7(11):e49289.
Among HIV-1 infected patients who achieved virologic suppression, the use of atazanavir without pharmacologic boosting is debated. We evaluated the efficacy and tolerance of maintenance therapy with unboosted atazanavir in clinical practice.
Methods and Results
This multicenter retrospective cohort study evaluated the efficacy of switching HIV-1-infected patients controlled on triple therapy to unboosted (ATV0, n = 98) versus ritonavir-boosted atazanavir (ATV/r, n = 254) +2 nucleos(t)ide reverse transcriptase inhibitors. The primary endpoint was time to virologic failure (VF, >200 copies/mL). ATV groups were compared controlling for potential confounding bias by inverse probability weighted Cox analysis and propensity-score matching. Overall and adjusted VF rates were similar for both strategies. Both strategies improved dyslipidemia and creatininemia, with less jaundice in the ATV0 group.
In previously well-suppressed patients, within an observational cohort setting, ATV0–based triple-therapy appeared as effective as ATV/r- based triple-therapy to maintain virologic suppression, even if co-administered with TDF, but was better tolerated.
PMCID: PMC3494679  PMID: 23152890
21.  Should highly active antiretroviral therapy be prescribed in critically ill HIV-infected patients during the ICU stay? A retrospective cohort study 
The impact of highly active antiretroviral therapy (HAART) in HIV-infected patients admitted to the intensive care unit (ICU) remains controversial. We evaluate impact of HAART prescription in HIV-infected patients admitted to the ICU of Tourcoing Hospital from January 2000 to December 2009.
There were 91 admissions concerning 85 HIV-infected patients. Reasons for ICU admission were an AIDS-related diagnosis in 46 cases (51%). Fifty two patients (57%) were on HAART at the time of ICU admission, leading to 21 immunovirologic successes (23%). During the ICU stay, HAART was continued in 29 patients (32%), and started in 3 patients (3%). Only one patient experienced an adverse event related to HAART. Mortality rate in ICU and 6 months after ICU admission were respectively 19% and 27%. Kaplan-Meier estimates of the cumulative unajusted survival probability over 6 months were higher in patients treated with HAART during the ICU stay (Log rank: p = 0.04). No benefit of HAART in ICU was seen in the adjusted survival proportion at 6 months or during ICU stay. Prescription of HAART during ICU was associated with a trend to lower incidence of new AIDS-related events at 6 months (respectively 17% and 34% with and without HAART, p = 0.07), and with higher incidence of antiretroviral resistance after ICU stay (respectively 25% and 7% with and without HAART, p = 0.02).
Our results suggest a lower death rate over 6 months in critically ill HIV-infected patients taking HAART during ICU stay. The optimal time to prescribe HAART in critically ill patients needs to be better defined.
PMCID: PMC3544704  PMID: 23020962
HIV; Intensive care; HAART
22.  Is Universal HBV Vaccination of Healthcare Workers a Relevant Strategy in Developing Endemic Countries? The Case of a University Hospital in Niger 
PLoS ONE  2012;7(9):e44442.
Exposure to hepatitis B virus (HBV) remains a serious risk to healthcare workers (HCWs) in endemic developing countries owing to the strong prevalence of HBV in the general and hospital populations, and to the high rate of occupational blood exposure. Routine HBV vaccination programs targeted to high-risk groups and especially to HCWs are generally considered as a key element of prevention strategies. However, the high rate of natural immunization among adults in such countries where most infections occur perinatally or during early childhood must be taken into account.
Methodology/Principal Findings
We conducted a cross sectional study in 207 personnel of 4 occupational groups (medical, paramedical, cleaning staff, and administrative) in Niamey’s National Hospital, Niger, in order to assess the prevalence of HBV markers, to evaluate susceptibility to HBV infection, and to identify personnel who might benefit from vaccination. The proportion of those who declared a history of occupational blood exposure ranged from 18.9% in the administrative staff to 46.9% in paramedical staff. Only 7.2% had a history of vaccination against HBV with at least 3 injections. Ninety two percent were anti-HBc positive. When we focused on170 HCWs, only 12 (7.1%) showed no biological HBV contact. Twenty six were HBsAg positive (15,3%; 95% confidence interval: 9.9%–20.7%) of whom 8 (32%) had a viral load >2000 IU/ml.
The very small proportion of HCWs susceptible to HBV infection in our study and other studies suggests that in a global approach to prevent occupational infection by bloodborne pathogens, a universal hepatitis B vaccination of HCWs is not priority in these settings. The greatest impact on the risk will most likely be achieved by focusing efforts on primary prevention strategies to reduce occupational blood exposure. HBV screening in HCWs and treatment of those with chronic HBV infection should be however considered.
PMCID: PMC3436880  PMID: 22970218
23.  ANRS–COM'TEST: description of a community-based HIV testing intervention in non-medical settings for men who have sex with men 
BMJ Open  2012;2(2):e000693.
To describe a community-based HIV testing programme.
Design and setting
An intervention of HIV voluntary testing conducted in non-medical settings in four French cities.
Men who have sex with men (MSM).
Counselling and rapid HIV testing staffed by trained personnel from an HIV/AIDS community-based organisation.
Primary and secondary outcome measures
The population that has taken hold of the intervention and the satisfaction of participants. Data were collected on demographics, HIV testing history, sexual practices and satisfaction with the testing programme.
532 MSM were tested between February 2009 and June 2010, of whom 49 (9%) were tested two or more times. 468 MSM (88%) had casual male partners in the previous 6 months, and 152 (35%) reported having unprotected anal intercourse with risky casual partners (HIV infected or HIV serostatus unknown). 159 men (30%) had not been tested in the previous 2 years, and 50 (31%) of whom had unprotected anal intercourse with risky casual partners. Among the 15 patients who tested positive (2.8%), 12 (80%) received confirmation and were linked to care (median CD4 cell count =550/mm3). Satisfaction was high: 92% reported being ‘very satisfied’ with their experience. Steps of counselling and testing procedure were respected by testers and difficulties in handling tests were rare.
This community-based HIV testing programme reached high-risk MSM, of whom a substantial proportion had not been tested lately. This novel service supplements pre-existing HIV testing services and increases access to HIV testing in high-risk groups.
Article summary
Article focus
How extend testing facilities to reach and test for HIV more MSM and diagnose HIV-infected MSM earlier?
The presence of peers and non-clinical staff members who address sexuality more openly and avoid medical jargon during counselling sessions could offset cultural barriers and reduce fears of HIV and associated stigma.
The article describes an experimental programme of community-based HIV testing: the population reached, the quality of the programme and the satisfaction of participants.
Key messages
This community-based HIV testing and counselling programme reaches MSM with high-risk sexual behaviour, a substantial proportion of whom has not tested for HIV recently.
Community testers are able to perform rapid HIV test into a comprehensive prevention approach in line with participant's life.
2.8% of participants tested positive. Infection was confirmed in all cases, 80% were linked to care. Cases were diagnosed at early stages of disease.
Strengths and limitations of this study
This HIV testing and counselling programme is exclusively based on MSM community, and continuing the prevention counselling with the awareness of the HIV serostatus includes testing into a comprehensive prevention approach.
Community-based HIV testing programmes may be attractive and efficient in large urban areas (like Paris), but perhaps less so in smaller cities, where an outreach approach may work better.
The number of HIV diagnoses was small; the prevalence and median CD4 count among the few HIV-infected participants should therefore be interpreted with caution.
PMCID: PMC3323802  PMID: 22466158
24.  CD4-guided structured treatment interruptions of antiretroviral therapy in HIV disease: Projecting beyond clinical trials 
Antiviral therapy  2010;15(3):351-361.
International trials have shown that CD4-guided structured treatment interruptions (STI) of antiretroviral therapy (ART) lead to worse outcomes than continuous treatment. We simulated continuous ART and STI strategies with higher CD4 interruption/reintroduction thresholds than those assessed in the trials.
We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) Model to simulate cohorts of African adults with different CD4 counts at presentation (≤200/μl, 201–350/μl, 351–500/μl). We varied ART initiation criteria (immediate, CD4<350/μl or severe opportunistic event, CD4<200/μl or severe opportunistic event), and ART interruption/reintroduction CD4 thresholds (e.g. 350/250/μl, 500/350/μl, 700/500/μl). First-line therapy was non-nucleoside reverse transcriptase inhibitor (NNRTI)-based and 2nd-line was protease inhibitor (PI)-based.
STI generally led to a lower life expectancy than continuous ART, regardless of ART initiation criteria and interruption/reintroduction thresholds. Life expectancy increased with earlier ART initiation and higher interruption/reintroduction thresholds. STI reduced life expectancy by 48–69 months and by 11–30 months, compared to continuous ART when interruption/reintroduction thresholds were 350/250/μl and 500/350/μl, depending on ART initiation criteria. When patients interrupted/reintroduced ART at CD4 700/500/μl, life expectancies for STI ranged from 2 months lower to 1 month higher than continuous ART. Life expectancy for patients on STI increased with decreased risk of virologic resistance after ART interruptions.
STI with NNRTI-based regimens was almost always less effective than continuous treatment, regardless of interruption/reintroduction thresholds. The risks associated with STI decrease only if patients start ART earlier, interrupt/reintroduce treatment at very high CD4 thresholds (700/500/μl) and use first-line medications with higher resistance barriers, such as PIs.
PMCID: PMC3220615  PMID: 20516555
Africa; antiretroviral therapy; CD4-guided structured treatment interruptions; models/projections
25.  Laboratory Monitoring to Guide Switching Antiretroviral Therapy in Resource-Limited Settings: Clinical Benefits and Cost-Effectiveness 
As 2nd-line antiretroviral therapy (ART) availability increases in resource-limited settings, questions about the value of laboratory monitoring remain. We assessed the outcomes and cost-effectiveness (CE) of laboratory monitoring to guide switching ART.
We used a computer model to project life expectancy and costs of different strategies to guide ART switching in patients in Côte d'Ivoire. Strategies included clinical assessment, CD4 count, and HIV RNA testing. Data were from clinical trials and cohort studies from Côte d'Ivoire and the literature. Outcomes were compared using the incremental CE ratio. We conducted multiple sensitivity analyses to assess uncertainty in model parameters.
Compared with 1st-line ART only, 2nd-line ART increased life expectancy by 24% with clinical monitoring only, 46% with CD4 monitoring, and 61% with HIV RNA monitoring. The incremental CE ratio of switching based on clinical monitoring was $1,670/year of life gained (YLS) compared to 1st-line ART only; biannual CD4 monitoring was $2,120/YLS. The CE ratio of biannual HIV RNA testing ranged from $2,920 ($87/test) to $1,990/YLS ($25/test). If 2nd-line ART costs were reduced, the CE of HIV RNA monitoring improved.
In resource-limited settings, CD4 count and HIV RNA monitoring to guide switching to 2nd-line ART improve survival and under most conditions are cost-effective.
PMCID: PMC3174771  PMID: 20404739
Laboratory monitoring; diagnostic tests; HIV RNA; viral load; HIV/AIDS; antiretroviral therapy

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