Dataset Information

Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials.

ABSTRACT:

Objectives

Interest in targeting HIV reservoirs is fueling trials that may decrease reservoir size and/or induce viral replication. Therefore, we aimed to develop strategies to sensitively measure changes in these parameters in patients on and off antiretroviral therapy (ART). Achieving these goals may help evaluate the effects of future clinical trials.

Design

To determine the relationship between measurements of total and integrated HIV DNA and their role as markers of reservoir size and ongoing replication, these parameters were measured during the first year of ART, during long-term effective ART, and during a clinical trial aimed at targeting reservoirs.

Methods

Total and integrated HIV DNA were measured in patient samples using quantitative PCR techniques. CD4(+)T cell counts and plasma viremia were also monitored.

Results

Unintegrated HIV DNA became undetectable during the first year of ART. Total and integrated HIV DNA levels were generally equal in well controlled patients on ART, and low-level plasma viremia correlated best with integration measures. Finally, patients who controlled plasma viremia (<400 copies/ml) during interferon-α monotherapy exhibited a decrease in the level of integrated but not total HIV DNA and a rise in the ratio of total to integrated HIV DNA over time.

Conclusion

Our findings suggest that appearance of unintegrated HIV DNA reflects residual HIV expression and de-novo reverse transcription, providing insight into the mechanism by which interferon-α reduces the HIV reservoir. We conclude that concurrent measurements of total and integrated HIV DNA provide information regarding reservoir size and ongoing replication in trials targeting HIV.

SUBMITTER: Mexas AM

PROVIDER: S-EPMC4692807 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Publications

Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials.

Mexas Angela M AM Graf Erin H EH Pace Matthew J MJ Yu Jianqing J JJ Papasavvas Emmanouil E Azzoni Livio L Busch Michael P MP Di Mascio Michele M Foulkes Andrea S AS Migueles Stephen A SA Montaner Luis J LJ O'Doherty Una U

AIDS (London, England) 20121101 18

<h4>Objectives</h4>Interest in targeting HIV reservoirs is fueling trials that may decrease reservoir size and/or induce viral replication. Therefore, we aimed to develop strategies to sensitively measure changes in these parameters in patients on and off antiretroviral therapy (ART). Achieving these goals may help evaluate the effects of future clinical trials.<h4>Design</h4>To determine the relationship between measurements of total and integrated HIV DNA and their role as markers of reservoir ...[more]

PMID: 23014521

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Project description:PurposeTo assess clinical antimicrobial efficacy results obtained with besifloxacin ophthalmic suspension, 0.6%, administered three times a day (TID) for 5 days, integrated across three clinical trials of bacterial conjunctivitis and to investigate any microbiological eradication failures.MethodsClinical microbiological eradication data from three randomized, double-masked, parallel group studies of patients with bacterial conjunctivitis (two vehicle controlled; one active controlled with moxifloxacin ophthalmic solution, 0.5%) were integrated. All bacterial samples isolated at baseline above the species-specific threshold value were subjected to antimicrobial susceptibility testing. Samples isolated at subsequent visits were subjected to susceptibility testing and pulsed-field gel electrophoresis (PFGE) to investigate the cause of eradication failures and the potential for drug resistance development.ResultsVisit 2 (day 4 or 5) and visit 3 (day 8) overall microbiological eradication rates were 92.2% and 88.4% for besifloxacin ophthalmic suspension compared with 61.4% and 72.5% for vehicle and 91.6% and 85.7% for moxifloxacin ophthalmic solution. Visit 2 and visit 3 microbiological eradication rates for Gram-positive and Gram-negative isolates and for individual species were consistent with the overall eradication rates. The majority of observed eradication failures in any treatment group were due to the persistence of the pathogen isolated at baseline. Eradication failures in the besifloxacin treatment group were not associated with lower antimicrobial susceptibility at baseline. PFGE data showed that the majority of bacterial strains in eyes with eradication failures were identical to the strain isolated at baseline; these eradication failures were not associated with a lower antimicrobial susceptibility at the follow-up visit.ConclusionTreatment with besifloxacin ophthalmic suspension, 0.6%, administered TID for 5 days resulted in microbiological eradication rates that were ≥ 90% across the three clinical studies for the common pathogens of bacterial conjunctivitis. The few eradication failures were not due to fluoroquinolone resistance at baseline and/or resistance development during treatment.

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Dataset Information

Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials.

Objectives

Design

Methods

Results

Conclusion

Publications

Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials.

Similar Datasets

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