Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness

<p>Abstract</p> <p>Background</p> <p>Two HIV-1 positive patients, L and P, participating in the Amsterdam Cohort studies acquired an HIV-1 superinfection within half a year from their primary HIV-1 infection (Jurriaans <it>et al</it>., <it>JAIDS </it>2008, <b>47:</b>69-73). The aim of this study was to compare the replicative fitness of the primary and superinfecting HIV-1 strains of both patients. The use of isolate-specific primer sets indicated that the primary and secondary strains co-exist in plasma at all time points after the moment of superinfection.</p> <p>Results</p> <p>Biological HIV-1 clones were derived from peripheral blood CD4 + T cells at different time point, and identified as the primary or secondary virus through sequence analysis. Replication competition assays were performed with selected virus pairs in PHA/IL-2 activated peripheral blood mononuclear cells (PBMC's) and analyzed with the Heteroduplex Tracking Assay (HTA) and isolate-specific PCR amplification. In both cases, we found a replicative advantage of the secondary HIV-1 strain over the primary virus. Full-length HIV-1 genomes were sequenced to find possible explanations for the difference in replication capacity. Mutations that could negatively affect viral replication were identified in the primary infecting strains. In patient L, the primary strain has two insertions in the LTR promoter, combined with a mutation in the <it>tat </it>gene that has been associated with decreased replication capacity. The primary HIV-1 strain isolated from patient P has two mutations in the LTR that have been associated with a reduced replication rate. In a luciferase assay, only the LTR from the primary virus of patient P had lower transcriptional activity compared with the superinfecting virus.</p> <p>Conclusions</p> <p>These preliminary findings suggest the interesting scenario that superinfection occurs preferentially in patients infected with a relatively attenuated HIV-1 isolate.</p

What do we know about children’s access to school and learning outcomes in Pakistan? Analysis of the risk factors to children’s proficiency in literacy and numeracy assessments

This paper discusses the research feasibility of Annual Status of Education Report (ASER), volunteering citizen-led social survey conducted in Pakistan. The paper presents a detailed commentary on the process of ASER data collection, discussing the strengths, limitations and quality of the data maintained. There are also findings of the ASER data analysis from 2013 to 2016 with a focus on 34 risk factors associated with children’s cognitive ability at age 8 (N=89,460).The results show that ‘not enrolled in school’ and ‘household poverty’ are the biggest risk factors for children to achieve an expected level in learning. However, school type attended by children does not explain variation in the learning outcomes. Children missing information on household characteristics are at high risk of failing to achieve. Social surveys are feasible for understanding the patterns of household poverty and access to education. Following the discussion on results, the paper considers policy implications of maintaining a national database of all children, ensuring a universal access to school education in Pakistan