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Using ultrasensitive polymerase chain reaction–based techniques we assessed levels of cell-free and cellassociated human immunodeficiency virus (HIV)–1 in paired blood and genital samples of 30 clinically asymptomatic treatment-naive women. Levels of HIV-1 RNA in cervicovaginal-lavage samples were positively correlated with those in plasma samples (r=.50; P=.008) whereas levels of HIV-1 DNA in genital samples were loosely correlated with those in blood samples (r=.31; P=.041). In plasma of peripheral blood levels of HIV-1 DNA were positively correlated with those of HIV-1 RNA (r=.64; P < .001) whereas no correlation between HIV-1 DNA and HIV-1 RNA was evident in genital secretions. Our results indicate that levels of HIV-1 RNA and HIV-1 DNA are unrelated in the genital tracts of treatment-naive women and suggest that the level of genital HIV-1 RNA is influenced by systemic viral replication—in contrast to genital HIV-1 provirus which may be influenced as well by local cofactors triggering the migration of HIV-infected cells originating from the cervicovaginal submucosa. These features may be relevant for an understanding of HIV-1 transmission in heterosexual individuals. (authors)

The consequences of zidovudine (ZDV) replacement by other nucleoside reverse transcriptase inhibitors on the expression of resistance mutations at codons 215 and 41 of the reverse transcriptase (RT) gene was investigated prospectively in 66 patients harboring mutant genotypes who were changed to an effective two- or three-drug combination antiretroviral regimen. Quantitation of mutant (MUT) viral populations at codon 215 by means of RT-PCR with differential hybridization of amplicons specific for MUT and wild (WT) variants revealed no difference in the proportion of 215 MUT variants prior to (93.5 +/- 2.4%) and 12 to 20 months after (96.9 +/- 1.9%) ZDV replacement, independently of a therapeutic change for stavudine. The fitness of the variants harboring the ZDV-resistant MUT 215 genotype following drug withdrawal was calculated to be 96 to 99% of that of the variants harboring the WT 215 genotype. The apparent stability of ZDV-resistant variants in the study population may have two main complementary explanations: persistent selective pressure secondary to partial cross-resistance due to the new regimens given after the therapeutic alteration and suppression of viral replication after the therapeutic alteration that could have hampered the replacement of less fit variants by fitter variants. These findings indicate that, at least within 15 months following discontinuation of ZDV, an effective antiretroviral therapy is insufficient to allow for ZDV-resistant strains to disappear, and thus to allow for the safe re-introduction of the drug.

Summary Herpes simplex virus type 2 (HSV-2) is considered as a major co-factor of both sexual transmission and acquisition of the human immunodeficiency virus (HIV). The HIV epidemic in Senegal is characterized by a remarkable and stable low prevalence. Whether HSV-2 may also constitute a possible co-factor favouring the spreading of HIV epidemic in Senegal is yet unknown. This prompted us to evaluate the HSV-2 seroprevalence in the sentinel population of pregnant women in Senegal. Two hundred and sixty pregnant women attending Roi Baudouin maternity in the capital city Dakar (n = 135) and the antenatal clinic in Kaolack (n = 125), the third city of Senegal, were prospectively recruited between March and August 2003. Fifty-six women (22%) were positive for HSV-2 serology. The prevalence of HSV-2 seropositivity was higher in women living in Dakar (26%) than in those living in Kaolack (16%) (P < 0.01). Only two women from Dakar and two other from Kaolack were found to be HIV-1-infected. Our observations suggest a seemingly low seroprevalence of HSV-2 infection in adult women Senegal, comparable with those usually reported in Western countries. Further, epidemiological surveys are needed to confirm these results in the general population.

Mixed infections are one of the major therapeutic challenges, as the current strategies have had limited success. One of the most common and widespread conditions of mixed infection is respiratory syncytial virus-mediated pathology of the respiratory tract in children. There is a dire need for the development of novel therapeutic approaches during mixed infections. Therapeutic intravenous immunoglobulin preparations, obtained from plasma pools of healthy donors have been used in immune deficiencies. This study was thus designed to characterize the functional efficacy of RSV-specific antibodies in IVIg. To explore the functional ability of these affinity-purified RSV-specific antibodies, the antibody-dependent and complement dependent cytotoxicity was determined using peripheral cells of healthy donors. This study demonstrates the existence of highly potent RSV-specific antibodies in IVIg preparations and provides the basis for the use of IVIg as broad-spectrum protective shield to RSV-infected children during mixed infections.

BackgroundResistance of pandemic A(H1N1)2009 (H1N1pdm09) virus to neuraminidase inhibitors (NAIs) has remained limited. A new mutation I223R in the neuraminidase (NA) of H1N1pdm09 virus has been reported along with H275Y in immunocompromised patients. The aim of this study was to determine the impact of I223R on oseltamivir and zanamivir susceptibility.MethodsThe NA enzymatic characteristics and susceptibility to NAIs of viruses harbouring the mutations I223R and H275Y alone or in combination were analyzed on viruses produced by reverse genetics and on clinical isolates collected from an immunocompromised patient with sustained influenza H1N1pdm09 virus shedding and treated by oseltamivir (days 0-15) and zanamivir (days 15-25 and 70-80).ResultsCompared with the wild type, the NA of recombinant viruses and clinical isolates with H275Y or I223R mutations had about two-fold reduced affinity for the substrate. The H275Y and I223R isolates showed decreased susceptibility to oseltamivir (246-fold) and oseltamivir and zanamivir (8.9- and 4.9-fold), respectively. Reverse genetics assays confirmed these results and further showed that the double mutation H275Y and I223R conferred enhanced levels of resistance to oseltamivir and zanamivir (6195- and 15.2-fold). In the patient, six days after initiation of oseltamivir therapy, the mutation H275Y conferring oseltamivir resistance and the I223R mutation were detected in the NA. Mutations were detected concomitantly from day 6-69 but molecular cloning did not show any variant harbouring both mutations. Despite cessation of NAI treatment, the mutation I223R persisted along with additional mutations in the NA and the hemagglutinin.ConclusionsReduced susceptibility to both oseltamivir and zanamivir was conferred by the I223R mutation which potentiated resistance to both NAIs when associated with the H275Y mutation in the NA. Concomitant emergence of the I223R and H275Y mutations under oseltamivir treatment underlines the importance of close monitoring of treated patients especially those immunocompromised.

Background A randomized controlled trial in South Africa found a beneficial effect of acyclovir on genital ulcer healing, but no effect was seen in trials in Ghana, Central African Republic and Malawi. The aim of this paper is to assess whether the variation in impact of acyclovir on ulcer healing in these trials can be explained by differences in the characteristics of the study populations. Methodology/Principal Findings Pooled data were analysed to estimate the impact of acyclovir on the proportion of ulcers healed seven days after randomisation by HIV/CD4 status, ulcer aetiology, size and duration before presentation; and impact on lesional HIV-1. Risk ratios (RR) were estimated using Poisson regression with robust standard errors. Of 1478 patients with genital ulcer, most (63%) had herpetic ulcers (16% first episode HSV-2 ulcers), and a further 3% chancroid, 2% syphilis, 0.7% lymphogranuloma venereum and 31% undetermined aetiology. Over half (58%) of patients were HIV-1 seropositive. The median duration of symptoms before presentation was 6 days. Patients on acyclovir were more likely to have a healed ulcer on day 7 (63% vs 57%, RR = 1.08, 95% CI 0.98–1.18), shorter time to healing (p = 0.04) and less lesional HIV-1 RNA (p = 0.03). Small ulcers (

Objectifs L’interet de la quantification dans le sang peripherique de l’ADN du virus d’Epstein-Barr (QEBV) dans le VIH reste controverse, contrairement a la transplantation. Le groupe ANRS de quantification EBV a evalue la QEBV de patients VIH+, en parallele dans le sang total (ST) et dans le plasma. Materiel et methods Les 12 laboratoires participants ont recrute chacun 50 patients, stratifies selon le nombre de CD4 (groupe 1 > 200/mm 3 et groupe 2 3 ). La QEBV se faisait avec la technique utilisee localement (technique maison ou trousse de quantification Lightcycler R -EBV quantification kit, Roche Diagnostics). Un controle qualite de la QEBV effectue par tous les laboratoires donnait de bons resultats ce qui a permis de realiser cette etude. Resultats 582 couples ST/plasma ont pu etre analyses (groupe 1 : 369 ; groupe 2 : 213) ; trois patients avaient un lymphome au moment de l’etude. L’ADN-EBV etait tres frequemment detectable dans le ST (66 %), surtout dans le groupe 2 (73 % versus 61 % ; p = 0,03). La QEBV etait egalement plus elevee dans le groupe 2 (3,7 log versus 3,4 ; p vs 17 % ; p L’ADN-EBV plasmatique etait detectable dans 5 % des cas, sans difference selon les CD4, et uniquement chez les patients ayant une QEBV dans le sang total > 2,9 log. Il y avait une correlation entre l’ADN-EBV dans le ST et l’ARN-VIH plasmatique ainsi qu’une correlation inverse avec le taux de lymphocytes CD4+. La QEBV des 3 lymphomes etait significativement plus elevee (4,8 versus 2,9 log10/ml ; p = 0,05). Un seul lymphome avait une QEBV plasmatique detectable. Conclusion La QEBV dans le sang total est correlee aux marqueurs de substitution du VIH et pourrait avoir une bonne valeur predictive positive dans certains cas de lymphomes.

Background Herpes simplex virus type 2 (HSV-2) is a major cofactor of human immunodeficiency virus type 1 (HIV-1) sexual acquisition and transmission. In the present study, we investigated whether HIV-1 and HSV-2 may interact at the cellular level by forming HIV-1 hybrid virions pseudotyped with HSV-2 envelope glycoproteins, as was previously reported for HSV type 1.

Human adenovirus (HAdV) infections constitute a major cause of morbidity in paediatric haematopoietic stem cell transplant (HSCT) patients. New antiviral treatments offer promising perspectives. However, it remains challenging to identify patients at risk for disseminated infection, and who should receive early antiviral intervention. We conducted a longitudinal study of allogeneic HSCT recipients, including weekly HAdV monitoring, to determine the risks factors associated with HAdV infection and dissemination, and to assess whether HAdV loads in stools may be used as surrogate markers for HAdV dissemination. Between September 2010 and December 2011, out of 72 patients, the cumulative incidence rates at day 100 of HAdV digestive infection, systemic infection and related disease were 35.9%, 24.0%, and 18.3%, respectively. In multivariate analysis, the risk factors for HAdV digestive and systemic infection were cord blood and in vitro T-cell depletion. Graft-versus-host disease (GVHD) grade >2 was also associated with systemic infection. In patients with HAdV digestive shedding, GVHD grade >2 and HAdV load in stools were the only risk factors for systemic infection. The median peak levels of HAdV in stool were 7.9 and 4.0 log10 copies/mL, respectively, in patients with HAdV systemic infection and in those without. HAdV monitoring in stools of paediatric HSCT recipients receiving cord blood or in vitro T-cell depleted transplants helps to predict patients at risk for HAdV systemic infection. Our results provide a rationale for randomized controlled trials to evaluate the benefit of anti-HAdV pre-emptive treatments based on HAdV DNA levels in stools.