larvae The three indigenous strains were screened by PCR amplifi

larvae. The three indigenous strains were screened by PCR amplification for the presence of binary toxin genes. Among the strains, only ISPC-8

showed the presence of bin genes, whereas these genes were absent in ISPC-5 and ISPC-6 strains. The results agree with the medium larvicidal activity of ISPC-5 and ISPC-6 strains, as also noted earlier (de Barjac et al., 1985; Charles et al., 1996). Most of the highly toxic strains (1593, 2362) of B. sphaericus showed the presence of these genes (Yousten, 1984; Baumann et al., 1987). The binA (1.1 kb) and binB (1.3 kb) genes from ISPC-8 were PCR amplified (Fig. 1). The sequences of binA (GenBank accession no. EU3753086) and binB (GenBank accession no. EU3753089) from ISPC-8 were compared with other highly toxic strains 1593/2362. The BinA protein differed by one amino acid (R197M), whereas BinB differs by two amino acids (H99P,

P174S) as compared with standard 1593/2362 strains. find more The insecticidal activity of this organism is mainly due to the presence of Bin (41.9 and 51.4 kDa) proteins (Broadwell & Baumann, 1987). The Bin proteins from ISPC-8 were purified using ion-exchange and gel-filtration chromatography. selleck inhibitor These proteins coeluted as a single peak on a gel filtration column with an elution volume that corresponded to an ∼65-kDa protein. The eluted peak showed two distinct bands of BinA and BinB when resolved on 12% SDS-PAGE (Fig. 2). The apparent molecular mass of ∼65 kDa is much lower than the complex of the BinA/BinB monomer, which essentially should show an elution volume corresponding to ∼93 kDa. These results indicate that the BinA and BinB proteins did not interact under these elution conditions, but coeluted, Niclosamide most likely due to the resolution in the gel

filtration. The purified proteins were tested against third-instar larvae of C. quinquefasciatus. The results showed higher toxicity of purified proteins with an LC50 value 6.32 ng mL−1 (Fig. 3). These results are particularly significant as there are very few reports on the toxicity of purified binary proteins. Baumann et al. (1991) have shown that the purified crystal from strain 2362 showed an LC50 value of 7 ng protein mL−1, whereas N NaOH-solubilized crystal yielded an LC50 dose of 2700 ng mL−1. The purified 51- and 42-kDa proteins from strain 2362 showed an LC50 value of 12 ng mL−1 (Baumann et al., 1991). When these Bin protein genes were expressed in Bacillus subtilis, the purified inclusion bodies showed an LC50 dose of 16 ng mL−1 (Baumann et al., 1991). Thus, a large variation in the LC50 doses and in the preparation methods has been observed. Perhaps more accurate estimates of toxicity profiles can be obtained using in situ folded BinA and BinB proteins in the assay, which may reveal the effect of amino acid substitutions observed in BinA and BinB proteins in our indigenous high-activity strain, ISPC-8.

larvae The three indigenous strains were screened by PCR amplifi

larvae. The three indigenous strains were screened by PCR amplification for the presence of binary toxin genes. Among the strains, only ISPC-8

showed the presence of bin genes, whereas these genes were absent in ISPC-5 and ISPC-6 strains. The results agree with the medium larvicidal activity of ISPC-5 and ISPC-6 strains, as also noted earlier (de Barjac et al., 1985; Charles et al., 1996). Most of the highly toxic strains (1593, 2362) of B. sphaericus showed the presence of these genes (Yousten, 1984; Baumann et al., 1987). The binA (1.1 kb) and binB (1.3 kb) genes from ISPC-8 were PCR amplified (Fig. 1). The sequences of binA (GenBank accession no. EU3753086) and binB (GenBank accession no. EU3753089) from ISPC-8 were compared with other highly toxic strains 1593/2362. The BinA protein differed by one amino acid (R197M), whereas BinB differs by two amino acids (H99P,

P174S) as compared with standard 1593/2362 strains. selleck The insecticidal activity of this organism is mainly due to the presence of Bin (41.9 and 51.4 kDa) proteins (Broadwell & Baumann, 1987). The Bin proteins from ISPC-8 were purified using ion-exchange and gel-filtration chromatography. selleck kinase inhibitor These proteins coeluted as a single peak on a gel filtration column with an elution volume that corresponded to an ∼65-kDa protein. The eluted peak showed two distinct bands of BinA and BinB when resolved on 12% SDS-PAGE (Fig. 2). The apparent molecular mass of ∼65 kDa is much lower than the complex of the BinA/BinB monomer, which essentially should show an elution volume corresponding to ∼93 kDa. These results indicate that the BinA and BinB proteins did not interact under these elution conditions, but coeluted, Carnitine palmitoyltransferase II most likely due to the resolution in the gel

filtration. The purified proteins were tested against third-instar larvae of C. quinquefasciatus. The results showed higher toxicity of purified proteins with an LC50 value 6.32 ng mL−1 (Fig. 3). These results are particularly significant as there are very few reports on the toxicity of purified binary proteins. Baumann et al. (1991) have shown that the purified crystal from strain 2362 showed an LC50 value of 7 ng protein mL−1, whereas N NaOH-solubilized crystal yielded an LC50 dose of 2700 ng mL−1. The purified 51- and 42-kDa proteins from strain 2362 showed an LC50 value of 12 ng mL−1 (Baumann et al., 1991). When these Bin protein genes were expressed in Bacillus subtilis, the purified inclusion bodies showed an LC50 dose of 16 ng mL−1 (Baumann et al., 1991). Thus, a large variation in the LC50 doses and in the preparation methods has been observed. Perhaps more accurate estimates of toxicity profiles can be obtained using in situ folded BinA and BinB proteins in the assay, which may reveal the effect of amino acid substitutions observed in BinA and BinB proteins in our indigenous high-activity strain, ISPC-8.

Distinction between “initiation,” “acceleration,” and “peak” pand

Distinction between “initiation,” “acceleration,” and “peak” pandemic intervals was made by application of enduring definitions (since Nutlin-3a cost 2008[5]) to best available information emanating from each country. Differentiation of acceleration from peak intervals would be most affected by limitations in interpretation of available information. In summary, we found that ill travelers with known countries of exposure can mirror significant transmission intensity within the source country and serve as a separate and important indicator from initial case detection

and reporting within that country. Other sensitive mechanisms for initial case detection otherwise exist in most countries. That travelers are important vectors of novel respiratory pathogens may be thought intuitive, however, our specific and detailed descriptive findings have not been documented elsewhere for H1N1pdm09 or other emerging respiratory pathogens.

For future novel respiratory events in which an age profile or predominance emerges early, travelers can function as sentinels for sustained transmission and could complement traditional surveillance systems and aid public health planning for targeted surveillance, interventions, see more and quarantine protocols at international borders. Additionally, these sentinel systems might fill the gaps in epidemiologically “silent” surveillance zones. This work was supported by the GeoSentinel Surveillance Network through a cooperative agreement with the Centers for Disease Control and Prevention (CDC; grant 5U50CI000359), by a tender from the European Centre for Disease Prevention

and Control (ECDC; tender OJ/2008/07/08-PROC/2008/019), and by funding from the International Society of Travel Medicine (ISTM). The findings and conclusions in this report are those of the authors and do not necessarily represent the views of very the Centers for Disease Control and Prevention. Payments from the CDC funding grant were made to authors or their institutions (D. A. P., P. L. L., E. C., F. C., P. E. K., and D. O. F). Consulting fees were paid by Baxter (to E. C.) and Crucell (to P. E. K.). Payment for development of educational presentations was paid by Sanofi (to P. E. K.). All other authors report no potential conflicts. Additional members of the GeoSentinel Surveillance Network who contributed data (in descending order) are: Alice Pérignon, Hôpital Pitié-Salpêtrière, Paris, France; Giampiero Carosi, University of Brescia, Brescia, Italy; Philippe Parola and Fabrice Simon, Hôpital Nord and Hôpital Lavaran, Marseille, France; Gerd-Dieter Burchard, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany; Natsuo Tachikawa and Hanako Kurai, Yokohama Municipal Citizen’s Hospital, Yokohama, Japan; Frank von Sonnenburg, University of Munich, Munich, Germany; Patrick W. Doyle and Wayne G.

The plasmid pGAD-PDC1 was made by replacing the 085-kb HindIII f

The plasmid pGAD-PDC1 was made by replacing the 0.85-kb HindIII fragment of pGAD GH (Clontech) with a PCR-amplified PDC1 open reading frame with HindIII linkers, Pexidartinib supplier and the 3.35-kb SphI fragment containing the ADH1 promoter-PDC1-ADH1 transcription termination sequence from pGAD-PDC1 was inserted into YIp5 at the unique SphI site. Then, the recombinant plasmid was linearized at the unique BglII site in PDC1 and transformed into YPH500. The PDC2 gene of the thus constructed strain NKC20 (LEU2::ADH1promoter-PDC1-ADH1termination in YPH500) was disrupted by

a PCR-directed integration method (Baudin et al., 1993) using HIS3 as a selectable marker. The newly constructed strain NKC21 (pdc2::HIS3 in NKC20) was a thiamin auxotroph, but grew normally in glucose medium containing thiamin. The mRNA levels of PHO3, THI20, and PDC5 in NKC21 were confirmed to be entirely depressed even under thiamin-deprived SRT1720 mw conditions (data not shown). To analyze the promoter activity of PDC5, all B593ΔX-derived plasmids were linearized with StuI to target integration to the ura3-52 locus and transformed

into YPH500. Single-copy integration was confirmed by restriction mapping of PCR-isolated fragments from the genomic DNA. Standard media and growth conditions for yeast cells were as described previously (Nosaka et al., 2005). Thiamin was added to the yeast minimal medium to a final concentration of 1 µM (high-thiamin medium) or 10 nM (low-thiamin medium). The concentration of the carbon source (glucose, raffinose, and galactose) was 2%. Yeast cultures (50 mL) were gently shaken with 1.5 mL of 36%

formaldehyde for 15 min at 30 °C, and the cross-linking reaction PAK6 was stopped with 2.5 mL of 2.5 M glycine. After two washes with cold PBS, the cells were suspended in 0.6 mL of lysis buffer (50 mM HEPES pH 7.5, 140 mM NaCl, 1% Triton X-100, 1 mM EDTA, and 0.1% sodium deoxycholate) containing 1 mM phenylmethylsulfonyl fluoride and 10 µL mL−1 protease inhibitor cocktail for Fungal and Yeast cells (Sigma), and lysed with glass beads in a bead beater (Biospec Products) by beating for three 60-s pulses with 5-min intervals on ice. After the lysate was drawn off the beads, the beads were again suspended with 0.6 mL of lysis buffer to recover the extracts. Then, the combined lysate was sonicated five times in ice-cold water using a Biorupter (Cosmo Bio, Tokyo) at 200 W for 30 s each time at 120-s intervals. Sonicated extracts were subsequently clarified by centrifugation. The lysate was divided into three fractions: the first and second (500 µL each) were used for immunoprecipitation, and the third (25 µL) was used as an input control.

In a more indirect way, the study of the multilayered

pro

In a more indirect way, the study of the multilayered

protective mechanisms also seems to lead to alterations in genetic expression. The earliest protective mechanisms that were studied included physical protection (typically by diffusion limitation/reduction) and physiological protection (through heterogeneous PF-02341066 price growth rates and nutrient concentrations within the biofilm). These mechanisms offer only transient protection (Cogan et al., 2005). Therefore, other mechanisms likely play a role. (3) What is the basis for biofilm persistence? Bacterial populations produce ‘persister’ cells that neither grow nor die in the presence of antibiotics. This phenomenon can lead to failure of antibiotic treatment in clinical situations. Persisters are different than drug-resistant mutants because their antibiotic tolerance is nonheritable and reversible (Lewis, 2007). These specialized cells, which are extremely tolerant to antibiotic application, can arise from a variety of

processes including gene expression, senescence, or niche expansion. Recent evidence indicates that this subpopulation may actively repress the expression of targets that are normally inhibited by antibiotics. This pathway is triggered in part by the SOS response and appears to involve toxin–antitoxin systems (Dorr et al., 2010; Kim & Wood, 2010). The process of persister cell formation has been incorporated into several mathematical models, sometimes indicating the predicted spatial location (Roberts & Stewart, 2005; Cogan, 2010), temporal find more stability (De Leenheer & Cogan, Progesterone 2009) or dynamic response to disinfection (Cogan, 2006). This is an area where the direct comparison of mathematical models and experimental studies has been explored helping to validate experimental hypotheses and suggest potential biological mechanisms (Balaban et al., 2004; Rotem et al., 2010). (4) How does the biofilm community contribute to ecological processes? The final question that

we will address is that of the developing ecology of the biofilm and its community. Understanding the phenotypic mosaic of developing biofilms is of importance in a variety of situations. For example, bioremediation often requires some control on the formation and elimination of an engineered biofilm. Also, biomineralization and other studies require detailed knowledge of the distribution of various species/phenotypes within the biofilm as well as their interactions. In general, ecological studies require the models to incorporate direct or indirect interaction between the biofilm components. In this way, the newest generation of models typically includes multiple species/phenotypes and often multiple substrates. It should be noted that the earliest models addressed some of these factors (Wanner & Gujer, 1986); however, based on the intermediate models it is clear that transport processes, mechanical structure, chemistry, and physics may be much more important than was initially assumed.

Such stringent conditions compromised signal intensities; however

Such stringent conditions compromised signal intensities; however, specific signals remained IDO inhibitor detectable at the highest stringency (at 75 °C hybridization) with negligible false negatives. These results suggest that, without any probe design or selection, genomic

fragments can provide a reasonable specificity for microbial diagnostics or species delineation by DNA–DNA similarities. Microarray-based technology, with its advantage of highly parallel detection, has been applied to both population profiling and to functional studies of complex microbial communities in the environment (Loy et al., 2002; Palmer et al., 2006; He et al., 2007; Iwai et al., 2008). Recent studies have used synthesized oligonucleotides as probes because of their flexibility in design and preparation, FK228 with intensive specificity evaluation applied to the probe design criteria (He et al., 2005). In addition, several studies have reported the

use of PCR-amplified genomic fragment sequences as probes. Such microarrays have been used for the detection of specific bacteria (Kim et al., 2004, 2005), species determination (Cho & Tiedje, 2001), and screening of environmental sequences related to a certain function within a community (Yokoi et al., 2007; Tobino et al., 2011). As the probes in these studies are randomly prepared by shotgun cloning of genomic DNAs, this kind of microarray is independent of sequence information found in public databases and hence offers unique potential for exploring unsequenced

microorganisms. Gemcitabine mw However, the specificity of genomic fragment probes has not been evaluated in detail. In this study, we prepared genomic fragment probes from pure cultures whose whole genome sequences are available and then evaluated hybridization specificity in terms of sequence similarity between probe and target. Genomic fragment probes were prepared from genomic DNAs of three Pseudomonas strains (Pseudomonas aeruginosa PAO1, Pseudomonas fluorescens Pf-5, and Pseudomonas putida KT2440) by shotgun cloning as described previously (Tobino et al., 2011). The probe set consisted of 167 fragment probes (55, 56, and 56 probes from PAO1, Pf-5, and KT2440, respectively) of ~ 2000 bp in length (Supporting Information, Table S1) and four control probes (see the figure legend of Fig. S1 for the preparation of control probes). Each fragment probe was spotted onto nylon membranes (5 ng per spot) in duplicate, and the spotted membranes were alkaline denatured, baked, and stored in a plastic bag until use (see Fig. S1 for probe layout). Genomic DNAs of pure cultures, plus control DNA (yeast gene ACT, included in the probe set as a positive control) were individually labeled with digoxigenin (DIG) by random priming according to the manufacturer’s instructions (DIG High Prime; Roche, Basel, Switzerland). Labeled products were sonicated to an average length of 400 bp.

Lopinavir/ritonavir was discontinued when the plasma viral load d

Lopinavir/ritonavir was discontinued when the plasma viral load dropped below 50 HIV-1 RNA copies/ml. After January 2008, zidovudine/lamuvidine

was replaced with tenofovir/emtricitabine (245/200 mg qd), and lopinavir/ritonavir tablets (600/150 mg bid) Hydroxychloroquine concentration replaced the capsules. Patients needed to have sufficient fluency in Dutch or English to complete a self-administered HRQL questionnaire. Recruitment of participants and the study design have been described previously [1, 11]. The study was approved by the Medical Ethics Committee of each participating site and written informed consent was obtained from all participants. Patients received a self-report questionnaire measuring HRQL when attending the out-patient clinic for the study visits at weeks

0, 8, 24, 36, 48, 60, 72, 84 and 96. The questionnaire consisted of two parts: the Medical Outcomes Study Health Survey for HIV (MOS-HIV) and a symptom checklist. The MOS-HIV is a widely used questionnaire comprising 10 subscales [12]. Physical health (PHS) and mental health summary (MHS) scores can be calculated on the basis of these subscale scores [13]. Higher scores indicate a better HRQL. The symptom checklist consisted of 14 items referring to symptoms related to PHI or to side effects of cART, i.e. difficulty with sleeping, lack of appetite, nausea, vomiting, diarrhoea, abdominal or stomach pain, fever, GDC-0199 mouse flu-like symptoms such as myalgia or chills, tingling of hands or feet, numb feeling in fingers or toes, dizziness,

itchiness and skin changes. These items were derived from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 and an HIV/AIDS-specific questionnaire [9]. The questions related to the experience of symptoms during the past week. Symptoms were scored on a four-point scale with the response categories ‘not at all’, ‘a little’, ‘quite a bit’, and ‘very much’. The four-point scale scores were linearly transformed to a scale of 0 to 100, with higher scores indicating more symptoms. We included patients who completed an HRQL questionnaire at baseline and at least one questionnaire during follow-up. Baseline characteristics Bortezomib manufacturer were compared using χ2 tests for categorical variables and general linear models or Kruskal–Wallis tests for continuous variables. Linear mixed effect models for repeated measurements were used to test for differences in MOS-HIV and symptoms scores during follow-up among the three groups, with baseline values included as a covariate. Model results were summarized by the estimated mean values during follow-up for the three groups, adjusted for baseline measurements. To investigate potential short-term toxicity of cART, we also compared the symptom scores among the three groups at week 8 using general linear models, with the baseline measurement included as a covariate.

broadinstituteorg, http://wwwgenomewustledu) G186A has four

broadinstitute.org, http://www.genome.wustl.edu). G186A has four chromosomes whereas G217B has only three (Steele et al., 1989). However, the total genome size of G217B is roughly 30% larger than G186A (41 megabases vs. 30.4 megabases, respectively) primarily due to repetitive DNA, which includes mobile DNA insertions, retrotransposons and multiple copies of a crypton (Goodwin et al., 2003). This suggests that the non-repetitive

‘core’ Histoplasma genome is roughly 26–28 megabases. Bioinformatics analyses of the sequence predicts that the Histoplasma genome encodes between 9000 and 10 000 genes (http://www.broadinstitute.org). Large regions of synteny exist between G186A and IDO inhibitor G217B and

much of the ‘extra’ DNA is located intergenically as clusters of repetitive sequence. Nucleotide sequence identity for homologous genes is roughly 97 ± 2% between G186A and G217B (J.A. Edwards and C.A. Rappleye, unpublished data) suggesting C59 wnt in vivo differential gene regulation, rather than amino acid change, is an important contributor to phenotypic differences between strains. Histoplasma capsulatum is a haploid organism and has a heterothallic mating system (Kwon-Chung, 1973). A mating type locus (MAT locus) is present in the genome and two MAT alleles are correlated with opposite mating types in clinical strains; G217B has the MAT1-1 allele whereas G186A has the MAT1-2 allele (Bubnick & Smulian, 2007). Some correlation exists between mating type and virulence. Considerable variation exists in the proportions of mating types (designated as + or −) in environmental sources of Histoplasma (Kwon-Chung et al., 1974; Gaur & Lichtwardt, 1980), however, in clinical samples – mating types predominate (Kwon-Chung et al., 1974, 1984). The significance of this correlation

is from presently unknown. Attempts to manipulate G186A and G217B in the lab have indicated differences in the efficiency of homologous recombination between the two strains. Whereas several gene deletion strains have been created through allelic replacement in the Panamanian background (G186A or G184A strains) (Woods et al., 1998; Sebghati et al., 2000; Tian & Shearer, 2002; Rappleye et al., 2004; Marion et al., 2006; Hwang et al., 2008; Hilty et al., 2011), only a limited number of gene knockout alleles exist in the NAm2 isolate G217B (Marion et al., 2006; Cooper & Woods, 2009). As a consequence, RNA interference (RNAi) has been adopted as a more practical means to deplete gene functions in Histoplasma (Rappleye et al., 2004) when efforts to delete genes through homologous recombination fail.

Baseline samples for CD4 cell count, VL and resistance should be

Baseline samples for CD4 cell count, VL and resistance should be taken. Treatment should be commenced immediately as per Recommendation 5.4.3 above. Triple therapy should be given to the neonate (see Section 8: Neonatal management). 5.5.1 Untreated women with a CD4 cell count ≥350 cells/μL and a VL <50 HIV RNA copies/mL (confirmed on a separate assay): Can be treated with zidovudine monotherapy

or with HAART (including abacavir/lamivudine/zidovudine). BTK inhibitor Grading: 1D Can aim for a vaginal delivery. Grading: 1C Should exclusively formula feed their infant. Grading: 1D Elite controllers are defined as the very small proportion of HIV-positive individuals who, without treatment, have undetectable HIV RNA in plasma as assessed by more than one different VL assay on more than one occasion. It is estimated that 1-in-300 HIV-positive individuals are elite controllers [95]. In the absence of data from RCTs on elite controllers, recommendations are based on RCT and observational data on all pregnant HIV-positive women. In the original zidovudine monotherapy study (ACTG 076) the transmission rate if maternal VL was <1000 HIV RNA copies/mL was 1% (range 0–7%) [16]. Treatment reduced transmission even among women with low or undetectable HIV VL, suggesting that the effects of treatment Ganetespib in vitro were not all related

to decreasing maternal viraemia but may also be related to reducing HIV in the genital tract and/or peri-exposure prophylaxis of the infant by placental transfer of zidovudine. A meta analysis of transmission outcomes in several major USA and European studies Immune system also demonstrated that an HIV VL <1000 HIV RNA copies/mL at delivery was associated with a relatively low risk of transmission and that ARV prophylaxis offered additional clinically significant protection [96]. Zidovudine has been shown to reduce cervicovaginal shedding of HIV [2] and there are no data to suggest that HAART is more effective than zidovudine at reducing cervicovaginal shedding in women with a plasma HIV

VL <50 copies/mL. Therefore, zidovudine monotherapy is an option in this setting. There are no data to support the use of intravenous zidovudine infusion during labour in elite controllers. HAART may provide more reassurance about prevention of MTCT but will also expose both mother and infant to more potential drug toxicities. The choice of HAART is as per Recommendation 5.3.3. Data on the mode of delivery in elite controllers are sparse and limited to case reports [97]. The benefits of PLCS at various levels of viraemia are discussed in Section 7.2 (Mode of delivery). There are no data to support the use of PLCS for PMTCT when the VL is <50 HIV RNA copies/mL in women on ART. The Writing Group therefore recommends vaginal delivery for all elite controllers on ART. 5.6.

Baseline samples for CD4 cell count, VL and resistance should be

Baseline samples for CD4 cell count, VL and resistance should be taken. Treatment should be commenced immediately as per Recommendation 5.4.3 above. Triple therapy should be given to the neonate (see Section 8: Neonatal management). 5.5.1 Untreated women with a CD4 cell count ≥350 cells/μL and a VL <50 HIV RNA copies/mL (confirmed on a separate assay): Can be treated with zidovudine monotherapy

or with HAART (including abacavir/lamivudine/zidovudine). E7080 purchase Grading: 1D Can aim for a vaginal delivery. Grading: 1C Should exclusively formula feed their infant. Grading: 1D Elite controllers are defined as the very small proportion of HIV-positive individuals who, without treatment, have undetectable HIV RNA in plasma as assessed by more than one different VL assay on more than one occasion. It is estimated that 1-in-300 HIV-positive individuals are elite controllers [95]. In the absence of data from RCTs on elite controllers, recommendations are based on RCT and observational data on all pregnant HIV-positive women. In the original zidovudine monotherapy study (ACTG 076) the transmission rate if maternal VL was <1000 HIV RNA copies/mL was 1% (range 0–7%) [16]. Treatment reduced transmission even among women with low or undetectable HIV VL, suggesting that the effects of treatment Sotrastaurin were not all related

to decreasing maternal viraemia but may also be related to reducing HIV in the genital tract and/or peri-exposure prophylaxis of the infant by placental transfer of zidovudine. A meta analysis of transmission outcomes in several major USA and European studies MG-132 mouse also demonstrated that an HIV VL <1000 HIV RNA copies/mL at delivery was associated with a relatively low risk of transmission and that ARV prophylaxis offered additional clinically significant protection [96]. Zidovudine has been shown to reduce cervicovaginal shedding of HIV [2] and there are no data to suggest that HAART is more effective than zidovudine at reducing cervicovaginal shedding in women with a plasma HIV

VL <50 copies/mL. Therefore, zidovudine monotherapy is an option in this setting. There are no data to support the use of intravenous zidovudine infusion during labour in elite controllers. HAART may provide more reassurance about prevention of MTCT but will also expose both mother and infant to more potential drug toxicities. The choice of HAART is as per Recommendation 5.3.3. Data on the mode of delivery in elite controllers are sparse and limited to case reports [97]. The benefits of PLCS at various levels of viraemia are discussed in Section 7.2 (Mode of delivery). There are no data to support the use of PLCS for PMTCT when the VL is <50 HIV RNA copies/mL in women on ART. The Writing Group therefore recommends vaginal delivery for all elite controllers on ART. 5.6.