Intensification of Antiretroviral Therapy With Raltegravir or Addition of Hyperimmune Bovine Colostrum in HIV-Infected Patients With Suboptimal CD4+ T-Cell Response: A Randomized Controlled Trial

“…However, a recent intensification study with raltegravir has tested also a combined therapy with anti-LPS, in order to inhibit translocation of bacterial products from the intestinal lumen. No improvement in immune activation was observed in the combined intervention compared with the raltegravir arm alone [108].…”

Section: Intensifications Of Haartmentioning

confidence: 82%

“…Treatment intensification studies of HIV-1-infected subjects receiving stable HAART have been not able to show a reduction of residual VL in concordant or immunodiscordant patients [73,76,106]. To date, short treatment raltegravir intensification strategies (12-or 24-weeks) in HAARTsuppressed subjects have been unable to demonstrate convincing evidence for decay of CD8 T-cell activation and/or CD4 T-cell increases in peripheral blood [106][107][108][109]. In contrast, a trend toward a decrease of CD8 T-cell activation and an increase of CD4 T-cell counts in ileum after 12 weeks of HAART intensification with raltegravir has been reported [110], whereas raltegravir-induced changes in CD8 T-cell activation markers in blood might require longer periods of time.…”

Section: Intensifications Of Haartmentioning

confidence: 99%

Immunodiscordant responses to HAART – mechanisms and consequences

Massanella

Negredo

Clotet

et al. 2013

Expert Review of Clinical Immunology

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A relevant fraction of HIV-1-infected individuals (ranging from 15 to 30%) presenting virologically successful highly active antiretroviral therapy fail to recover CD4 T-cell counts. These individuals, called immunodiscordant or immunological nonresponders, are at increased risk of clinical progression and death. Although older age, lower nadir CD4 T-cell count and HCV co-infection are some of clinical predictive factors, immunological mechanisms rely on impaired thymic production and accumulation of apoptosis-prone CD4 T cells. Indeed, immunodiscordant individuals may show increased tissue fibrosis and damage of gut-associated lymphoid tissue that results in higher hyperactivation, inflammation and immunosenescence, altered Treg/Th17 ratio and increased T-cell death. A better knowledge of the final pathogenic mechanism and factors influencing CD4 T-cell recovery will help to select the optimal therapeutic strategies for them.

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“…[23][24][25] Most evidence for increased microbial translocation in HIV is based on detection of increased levels of LPS and bacterial 16S rDNA. The latter is detected through a broad-range quantitative polymerase chain reaction (qPCR).…”

mentioning

confidence: 99%

Short Communication: Evidence That Microbial Translocation Occurs in HIV-Infected Children in the United Kingdom

Fitzgerald

Harris

Doyle

et al. 2013

AIDS Research and Human Retroviruses

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Microbial translocation (MT) from the gut is implicated in driving immune activation, increasing morbidity and mortality in HIV. We used bacterial 16S rDNA PCR, Sanger sequencing, and high-throughput sequencing to identify microbial DNA in the bloodstream of HIV-infected children in London, United Kingdom. Blood samples were collected from sequential children attending the HIV clinic at Great Ormond Street Hospital, London. DNA extraction, broad range 16S rDNA PCR, and standard Sanger sequencing were carried out. A subset of positive samples was analyzed by high-throughput sequencing (Roche 454 platform). Of 105 samples collected from sequential children, nine were positive using broad range 16S rDNA PCR (8.6%; 95% CI 4.4-16%). From three amplicons, 16S rDNA sequences were identified as Streptococcus, Propionibacterium acnes, and coagulase-negative Staphylococcus. Four positive samples were analyzed by high-throughput sequencing. In the three samples in which organisms were identified by Sanger sequencing, the same species were identified. Further species, in differing proportions, were identified in all four samples. The identified organisms included known gut orders Bifidobacteriaceae, Lactobacillaceae, Bacteroidales, and Clostridiales. In immunocompetent children of equivalent age, no bacterial DNA was detected in blood using this approach. This is the first study to our knowledge using molecular techniques to identify MT in children in the developed world. Our data indicate that 16S rDNA is detectable in 8.6% of HIV-infected children. Levels of DNA were low and from multiple bacterial species. Further studies are needed to ascertain the importance of MT in HIV-infected children.

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Intensification of Antiretroviral Therapy With Raltegravir or Addition of Hyperimmune Bovine Colostrum in HIV-Infected Patients With Suboptimal CD4+ T-Cell Response: A Randomized Controlled Trial

Abstract: ClinicalTrials.gov identifier: NCT00772590, Australia New Zealand Clinical Trials Registry: ACTRN12609000575235.

Cited by 55 publications

References 47 publications

Novel Sensitive Real-Time PCR for Quantification of Bacterial 16S rRNA Genes in Plasma of HIV-Infected Patients as a Marker for Microbial Translocation

Novel Sensitive Real-Time PCR for Quantification of Bacterial 16S rRNA Genes in Plasma of HIV-Infected Patients as a Marker for Microbial Translocation

Immunodiscordant responses to HAART – mechanisms and consequences

Short Communication: Evidence That Microbial Translocation Occurs in HIV-Infected Children in the United Kingdom

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