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Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA.

ABSTRACT: HIV-1-infected individuals harbor a latent reservoir of infected CD4+ T cells that is not eradicated by antiretroviral therapy (ART). This reservoir presents the greatest barrier to an HIV-1 cure and has remained difficult to characterize, in part, because the vast majority of integrated sequences are defective and incapable of reactivation. To characterize the replication-competent reservoir, we have combined two techniques, quantitative viral outgrowth and qualitative sequence analysis of clonal outgrowth viruses. Leukapheresis samples from four fully ART-suppressed, chronically infected individuals were assayed at two time points separated by a 4- to 6-mo interval. Overall, 54% of the viruses emerging from the latent reservoir showed gp160 env sequences that were identical to at least one other virus. Moreover, 43% of the env sequences from viruses emerging from the reservoir were part of identical groups at the two time points. Groups of identical expanded sequences made up 54% of proviral DNA, and, as might be expected, the sequences of replication-competent viruses in the active reservoir showed limited overlap with integrated proviral DNA, most of which is known to represent defective viruses. Finally, there was an inverse correlation between proviral DNA clone size and the probability of reactivation, suggesting that replication-competent viruses are less likely to be found among highly expanded provirus-containing cell clones.

SUBMITTER: Lorenzi JC

PROVIDER: S-EPMC5150408 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA.

Lorenzi Julio C C JC Cohen Yehuda Z YZ Cohn Lillian B LB Kreider Edward F EF Barton John P JP Learn Gerald H GH Oliveira Thiago T Lavine Christy L CL Horwitz Joshua A JA Settler Allison A Jankovic Mila M Seaman Michael S MS Chakraborty Arup K AK Hahn Beatrice H BH Caskey Marina M Nussenzweig Michel C MC

Proceedings of the National Academy of Sciences of the United States of America 20161121 49

HIV-1-infected individuals harbor a latent reservoir of infected CD4<sup>+</sup> T cells that is not eradicated by antiretroviral therapy (ART). This reservoir presents the greatest barrier to an HIV-1 cure and has remained difficult to characterize, in part, because the vast majority of integrated sequences are defective and incapable of reactivation. To characterize the replication-competent reservoir, we have combined two techniques, quantitative viral outgrowth and qualitative sequence analy ...[more]

PMID: 27872306

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Project description:BackgroundIndigenous people tend to exhibit a higher burden of disability than their non-Indigenous counterparts, and are often underserved by disability services. Engaging appropriately with Indigenous communities, families and individuals in the initial stages of disability assessment and planning is crucial in order to build trust and understanding of disability service models and ensure that Indigenous people receive support that is tailored to their needs and cultural realities. This article aims to identify key elements of culturally competent communication in Indigenous disability assessment and planning, and provide recommendations for strengthening capacity in this area.MethodsThis qualitative research was designed to involve Aboriginal and Torres Strait Islander people at all stages and to reflect the views of Aboriginal and Torres Strait Islander researchers, people and families affected by disability and the community-controlled health sector. Semi-structured individual interviews were undertaken with staff implementing the National Disability Insurance Scheme (NDIS) (n = 4), NDIS participants (n = 24), disability support providers and organisational partners (n = 19) and Community Connectors (n = 8) in Queensland and the Northern Territory of Australia. Key themes derived from thematic analysis included appropriate and adequate engagement of individuals with disability and their families, the role of trusted relationships, and culturally safe and appropriate communication during planning meetings.ResultsOverall, the research findings highlight that a low level of cultural competence in the initial stages of the disability assessment and planning process exacerbated participant confusion and distrust towards assessment staff and the NDIS. Given difficulties in communication, participant understanding of the NDIS was generally limited. The necessity of culturally safe and appropriate use of interpreters was stressed, as was the role of trusted individuals, including existing service providers, Community Connectors and family members in providing a solid base for participant understanding of the NDIS.ConclusionsCultural competence in disability assessment and planning can be strengthened through multi-level engagement with the Aboriginal community-controlled sector and community leaders. Implementing mechanisms to enable the involvement of families, trusted service providers and Community Connectors can support a more meaningful understanding of individuals' needs within their cultural context and in relation to their cultural roles.

Dataset Information

Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA.

Publications

Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA.

Similar Datasets

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