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Purpose: To provide information about main pregnancy outcomes in HIV-HCV coinfected women and about the possible interactions between HIV and HCV in this particular population. Methods: Data from a multicenter observational study of pregnant women with HIV, conducted in Italian University and Hospital Clinics between 2001 and 2015, were used. Eligibility criteria for analysis were HCV coinfection and at least one detectable plasma HCV-RNA viral load measured during pregnancy. Qualitative variables were compared using the Chi-square or the Fisher test and quantitative variables using the Mann-Whitney U test. The Spearman's coefficient was used to evaluate correlations between quantitative variables. Results: Among 105 women with positive HCV-RNA, median HCV viral load was substantially identical at the three trimesters (5.68, 5.45, and 5.86 log IU/ml, respectively), and 85.7 % of the women had at least one HCV-RNA value >5 log IU/ml. Rate of preterm delivery was 28.6 % with HCV-RNA <5 log IU/ml and 43.2 % with HCV-RNA >5log ( p = 0.309). Compared to women with term delivery, women with preterm delivery had higher median HCV-RNA levels (third trimester: 6.00 vs. 5.62 log IU/ml, p = 0.037). Third trimester HIV-RNA levels were below 50 copies/ml in 47.7 % of the cases. No cases of vertical HIV transmission occurred. Rate of HCV transmission was 9.0 % and occurred only with HCV-RNA levels >5 log IU/ml. Conclusions: Coinfection with HIV and HCV has relevant consequences in pregnancy: HIV coinfection is associated with high HCV-RNA levels that might favour HCV transmission, and HCV infection might further increase the risk of preterm delivery in women with HIV. HCV/HIV coinfected women should be considered a population at high risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to determine the impact on human immunodeficiency virus (HIV) tropism of uncontrolled virus exposure during 2 years of intermittent highly active antiretroviral therapy (HAART). The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) randomized study compared the outcome of 2 years of structured treatment interruptions (STIs) versus standard continuous treatment in first-line HAART responder subjects. The STI schedule consisted of five STIs of 1, 1, 2, 2, and 3 months, respectively, separated by four periods of 3-month therapy. In the present study, coreceptor tropism was assessed in 12 patients of the STI arm at different time points over a period of 2 years. Tropism was determined on DNA and RNA by V3 loop region sequencing. The Geno2pheno algorithm (false-positive rate, FPR: 20 %) was used for data interpretation. At baseline, 9/12 subjects (75.0 %) had CCR5-tropic viruses in their HIV. Three had a CXCR4-tropic virus. Ten patients maintained the same coreceptor in DNA after 2 years, whereas in two patients, a shift occurred (one R5–X4, one X4–R5). In a patient with an R5 virus at baseline, a transient change to X4 tropism was seen in the rebounding virus during STI. Changes in tropism were not associated with the amplitude and duration of virus exposure during STIs, residual viremia at baseline, or the development of resistance mutations in the RT region. Our preliminary results suggest that viral replication, observed after short periods of treatment interruption, is not enough to drive the evolution of HIV tropism. [ABSTRACT FROM AUTHOR]

We evaluated rates and determinants of virological failure in triple-class experienced patients receiving raltegravir-based regimens from a national observational study over 48 weeks, defined by any one of the following: (1) no HIV-RNA suppression to undetectable levels (<50 copies/mL) during follow-up; (2) detectable viral load after obtaining undetectable levels; and (3) leaving the study before 48 weeks. Among 101 eligible patients, 26 (25.7%; 95% CI 17.2-34.2) had virological failure. No significant differences between patients with and without virological failure were observed for gender, age, route of transmission, baseline CD4/HIV-RNA, CDC group, hepatitis B or C co-infections, resistance (based on the last genotype available), type and number of concomitant drug classes, concomitant use of darunavir, atazanavir, etravirine, enfuvirtide or maraviroc, and health-related quality-of-life measures. A high rate of treatment response was observed. The analyses did not identify any baseline factor associated with failure, including resistance status. Even if we cannot exclude the presence of pre-existing minority resistant variants not captured by genotypic tests, the lack of baseline predictors of failure suggests the need to monitor patients closely during follow up for other factors, such as potential drug interactions and reduced levels of adherence, which may favour virological failure. [ABSTRACT FROM AUTHOR]

We evaluated rates and determinants of virological failure in triple-class experienced patients receiving raltegravirbased regimens from a national observational study over 48 weeks, defined by any one of the following: (1) no HIV-RNA suppression to undetectable levels (<50 copies/mL) during follow-up; (2) detectable viral load after obtaining undetectable levels; and (3) leaving the study before 48 weeks. Among 101 eligible patients, 26 (25.7%; 95% CI 17.2-34.2) had virological failure. No significant differences between patients with and without virological failure were observed for gender, age, route of transmission, baseline CD4/ HIV-RNA, CDC group, hepatitis B or C co-infections, resistance (based on the last genotype available), type and number of concomitant drug classes, concomitant use of darunavir, atazanavir, etravirine, enfuvirtide or maraviroc, and health-related quality-of- life measures. A high rate of treatment response was observed. The analyses did not identify any baseline factor associated with failure, including resistance status. Even if we cannot exclude the presence of pre-existing minority resistant variants not captured by genotypic tests, the lack of baseline predictors of failure suggests the need to monitor patients closely during follow up for other factors, such as potential drug interactions and reduced levels of adherence, which may favour virological failure. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the evolution of HIV-1 coreceptor tropism in proviral DNA of patients during maraviroc-based therapy.Methods: Fourteen heavily high active antiretroviral therapy (HAART)-treated patients with a CCR5 Trofile profile were monitored over a 24 month period from the start of maraviroc therapy. Whole-blood samples were obtained at different timepoints, and coreceptor tropism was determined for proviral DNA from the V3-loop region sequence using the Geno2Pheno algorithm [false positive rate (FPR): 20%].Results: At the start of maraviroc treatment, 13/14 patients were viraemic (median: 4.33 log copies/mL). Concordance in R5 tropism (R5/R5) was observed between circulating HIV-RNA (Trofile) and HIV-DNA provirus in 10/14 patients (median FPR = 54.0%), while 4 patients showed a CXCR4-tropic R5/X4 variant in their provirus (FPR: 5.8%, 5.7%, 16.6% and 1.1%, respectively). All R5/R5 patients showed a stable HIV-1 DNA coreceptor usage. Two out of four R5/X4 patients showed a tropism shift in their archived provirus and, after 6 months a prevalence of R5-tropic virus was detected in DNA. The other two R5/X4 patients harboured the 11/25 genotype, and maintained X4 tropism in provirus during the study. Virological response did not reveal differences in RNA decay and CD4+ cell recovery in patients with discordant tropism.Conclusions: A relatively good correlation between RNA and DNA tropism was observed at baseline. Proviral DNA tropism remained stable over 24 months of maraviroc-based therapy, indicating that determination of proviral DNA V3 sequence could be used in tropism prediction in clinical practice. The data also confirm the importance of the 11/25 rule in predicting viral tropism. [ABSTRACT FROM AUTHOR]

No data are available on the use of atazanavir (ATV) in patients with end-stage liver disease (ESLD), and guidelines discourage its use in this setting. The objective of our study was to evaluate the efficacy and safety of unboosted ATV in patients infected with HIV and suffering from ESLD who had been screened for orthotopic liver transplantation (OLTx). This was a single-arm, 24-week pilot study. Atazanavir-naïve patients undergoing a highly active antiretroviral therapy were switched to ATV 400 mg daily plus two non-thymidine nucleoside reverse transcriptase inhibitors. Fifteen patients (ten males and five females, age range 36–59 years) were enrolled in the study. Of these, 11 (73%) had a baseline CD4 cell count > 200 μl–1, and 12 had undetectable plasma HIV-RNA. 12 subjects (80%) were able to remain on ATV until week 24 (n = 10) or transplantation (n = 2). At the end of the study, the median CD4 cell count was 340 μl–1 , and nine of the ten patients had undetectable RNA. During the study period, two patients received a transplant, two died of intracerebral hemorrhage and lactic acidosis, respectively, and one discontinued ATV. Among the ten patients completing the 24-week study, no significant changes from baseline were observed for most of the liver function markers, with the exception of unconjugated bilirubin (from 1.15 mg/dl to 1.32 mg/dl, p = 0.047). Unboosted ATV treatment did not worsen liver disease and was able to maintain or gain immunovirological eligibility for OLTx in all patients, with a limited effect on unconjugated bilirubin. These results suggest that ATV is an easy-to-use drug in patients with ESLD. [ABSTRACT FROM AUTHOR]

Simian–human immunodeficiency virus (SHIV) 89.6P is considered to be one of the most pathogenic chimeric viruses in rhesus macaques. However, when crossing from one to another species of monkeys the pathogenicity of this virus may be affected. By using SHIV-89.6Pcy243, a virus obtained by passaging SHIV-89.6P in cynomolgus macaques, we investigated the dynamics of viral replication and the impact of the inoculum size (from 10 up to 50 monkey infectious dose) on the progression of the infection in 22 cynomolgus macaques. SHIV-89.6Pcy243 caused massive depletion of CD4+ T-cells within 4 weeks of the inoculum, followed by an irreversible immune deficiency in a high proportion of the infected monkeys. This study demonstrates that SHIV-89.6Pcy243 is pathogenic in cynomolgus macaques and that the dynamics of the viral replication and the rate of clinical progression depend on the size of the inoculum. Our findings provide unique and relevant data, particularly with regard to the value of the in vivo titration used to select the most appropriate infectious dose to study the “virus-host” interplay. [ABSTRACT FROM AUTHOR]

The present paper is part of a research program which aims at a quantitative analysis of the effects of light and gibberellic acid (GA) on growth of the first foliage leaf in durum wheat ( Triticum durum Desf.). Since leaf growth is the combined result of the increase in cell number (cell division) and cell enlargement, the influence of light and GA treatment on cell division in the basal meristem of the first leaf in two cultivars, Cappelli and Creso, was investigated. Creso is a short-strawed cultivar carrying the Gai 1 gene which influences both plant height and insensitivity to applied GA. Cell division, as measured by mitotic index, was similar in darkness, continuous red light and dichromatic irradiation (far-red plus red), while lower mitotic rates were observed under continuous far-red light: this indicates that the response of cell division is modulated by a high-irradiance reaction of phytochrome in both cultivars. The two cultivars showed different responses to blue light. In Cappelli, blue light and dichromatic irradiation (blue plus red) gave lower mitotic indices than the dark control, indicating the action of a specific blue-light-absorbing photoreceptor, whereas in Creso the response kinetics to all light regimes which included blue light were more complex. On the basis also of the results obtained with GA application in Cappelli, it appears that (i) the hormonal treatment is able to change the pattern of mitotic index only in the presence of the action of a blue-light receptor and (ii) the different responses of the two cultivars could be the result of different endogenous hormonal levels. The importance of the observations in relation to the data for first-leaf longitudinal growth reported in a previous paper (Baroncelli et al. 1984, Planta 160, 298-304) is discussed. [ABSTRACT FROM AUTHOR]

The first foliage leaf of Triticum durum Desf., cvs. Capelli and Creso, was studied for the action of light and gibberellic acid on different aspects of plant growth. Creso is a short-strawed cultivar carrying the Rht 1 gene, that influences both plant height and sensitivity to applied gibberellins. In this study, a cytophotometric analysis of chromosome endoreduplication in bulliform cells of the leaf epidermis was undertaken. The bulliform cells are arranged in long rows and comprise 4C, 8C, and 16C cells. The relative percentage of these cells was recorded under different light regimes and in the presence or absence of gibberellic acid (GA). Our data indicate that light strongly affects the occurrence of chromosome endoreduplication. Although cvs. Cappelli and Creso show the same frequency of endo-reduplicated cells in the dark, all light treatments induce lower endo-polyploidy in cv. Creso whereas, in cv. Cappelli, a reduction in endo-polyploidy is observed when plants are irradiated with blue-lacking lights. This indicates that the action of a blue-light responsive photo-receptor determines high endopolyploidy. With respect to GA treatment, cv. Creso is again shown to be insensitive to hormone application, whereas in cv. Cappelli, gibberellic acid influences endopolyploidy level in the dark, causing very high frequencies of 8C cells and relatively high frequencies of 16C cells. [ABSTRACT FROM AUTHOR]

The development of epidermal cell lines in the first foliage leaf of Triticum durum was studied with a combined cytological and DNA cytophotometric analysis. It was shown that: [ABSTRACT FROM AUTHOR]

Genetic variation induced by tissue culture has been characterized in many species. The present study was conducted to genetically and phenotypically characterize an albino mutant in sunflower induced by in-vitro culture. A single recessive gene defective in carotenoid biosynthesis eventually leads to a chlorophyll loss due to photobleaching, absence of seed dormancy, and a low level of endogenous abscisic acid (ABA) in cotyledons and leaves. Further characterization has shown that the endogenous level of the hormone does not increase after drought stress and that the mutation prevents anthocyanin synthesis. [ABSTRACT FROM AUTHOR]

A comparison has been made of the relative effectiveness of light quality and quantity and gibberellic acid (GA) treatment on the elongation growth of the coleoptile and the first foliage leaf in durum wheat ( Triticum durum Desf. cvs. Cappelli and Creso). The cultivar Creso is a shortstrawed variety carrying the Gai 1 gene on chromosome 4A, which influences both plant height and insensitivity to applied gibberellins. The main conclusions are as follows: 1) coleoptile elongation growth appears to be modulated via the fluencerate-dependent action of a blue-light receptor and via a low energy response of phytochrome; 2) the inhibition of first-foliage-leaf growth depends on the operation of a single blue-light-responsive photoreceptor; 3) high energy blue light produces the same inhibitory effect on the two wheat cultivars, whereas at relatively low fluences of white and blue light, the cultivar Creso is more sensitive; 4) the insensitivity to applied GA exerted by the gene Gai 1 in Creso is independent of light; 5) in Cappelli, the action of light on coleoptiles appears to be independent of the applied GA, whereas the hormone is able to change the pattern of growth inhibition of the first-foliage-leaf. [ABSTRACT FROM AUTHOR]

Adventitious buds were induced from in vitro culture of sunflower (Helianthus annuus L.) cotyledons. Four inbred lines (G1, G2, G3 and HA89), an open pollinated variety ('Argentario') and two hybrids with specific genetic markers were used. Cotyledons were cultured in vitro on MS medium (MURASHIGE and SKOOG 1962) containing various concentrations of kinetin and indole 3-acetic acid (IAA). The quantitative interactions between auxin and cytokinin, the age of the cotyledons and the 2,3,5-triiodobenzoic acid (TIBA) treatments have been found to influence shoot regeneration. The plantlets, after rooting, were successfully established on soil. Qualitative variation was noted in self- pollinated progeny of plants regenerated from culture of two inbreds. Chimerism in regenerated plants was indicated by sectoring of the genetic markers. Some culture-induced variant phenotypes were similar to known spontaneous mutation in sunflower but others have been not yet described. Preliminary data indicate that most of them may have single-gene recessive inheritance. [ABSTRACT FROM AUTHOR]

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CD8+ T cells are an essential component of an effective host immune response to tumors and viral infections. Genetic immunization is particularly suitable for inducing CTL responses, because the encoded proteins enter the MHC class I processing pathway through either transgene expression or cross-presentation. In order to compare the efficiency and persistence of immune response induced by genetic vaccines, BALB/c mice were immunized either twice intramuscularly with DNA plasmid expressing a codon-optimized HIV-1 gp120 Envelope sequence together with murine GM-CSF sequence or with a single immunization using an integrase defective lentiviral vector (IDLV) expressing the same proteins. Results strongly indicated that the schedule based on IDLV vaccine was more efficient in inducing specific immune response, as evaluated three months after the last immunization by IFNgamma ELISPOT in both splenocytes and bone marrow- (BM-) derived cells, chromium release assay in splenocytes, and antibody detection in sera. In addition, IDLV immunization induced high frequency of polyfunctional CD8+ T cells able to simultaneously produce IFNgamma, TNFalpha, and IL2. [ABSTRACT FROM AUTHOR]