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HIV-1 DNA predicts disease progression and post-treatment virological control.

Williams JP, Hurst J, Stöhr W, Robinson N, Brown H, Fisher M, Kinloch S, Cooper D, Schechter M, Tambussi G, Fidler S, Carrington M, Babiker A, Weber J, Koelsch KK, Kelleher AD, Phillips RE, Frater J, SPARTACTrial Investigato - Elife (2014)

Bottom Line: With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART.We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI.In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound.

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.

ABSTRACT
In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials.

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Related in: MedlinePlus

Distribution of log10 total and integrated HIV-1-DNA levels in untreated patients at baseline.Kernel density plot to show distribution of Total (blue) and Integrated (red) HIV-1-DNA at baseline.DOI:http://dx.doi.org/10.7554/eLife.03821.005
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fig1s1: Distribution of log10 total and integrated HIV-1-DNA levels in untreated patients at baseline.Kernel density plot to show distribution of Total (blue) and Integrated (red) HIV-1-DNA at baseline.DOI:http://dx.doi.org/10.7554/eLife.03821.005

Mentions: Traditionally, plasma viral load (VL) (Mellors et al., 1996) and CD4 cell count (Frater et al., 2014) are the only validated surrogate markers of progression used in the HIV-1 clinic. We therefore measured these biomarkers as well as HIV-1 DNA in 154 SPARTAC participants at enrolment to the trial and prior to any ART being given. The median (interquartile range) values of Total and Integrated HIV-1 DNA values in PHI (Figure 1—figure supplement 1) were 7707 (2477–18187) and 3830 (1563–6325) copies of HIV-1 DNA per million CD4 T cells, respectively. Total and Integrated HIV-1 DNA levels were closely associated (p < 0.0001; r2 = 0.72; Pearson correlation) (Figure 1—figure supplement 2) in these pre-therapy samples. Total and Integrated HIV-1 DNA were significantly associated with plasma viral load (both p < 0.001; r2 = 0.48 and 0.64, respectively; linear regression) (Figure 1A), and inversely with CD4 T cell count (both p < 0.001; r2 = 0.20 and 0.27, respectively; linear regression) (Figure 1B). Interestingly, the estimated time since seroconversion at recruitment did not correlate with HIV-1 DNA (both Integrated and Total) (Figure 1—figure supplement 3).10.7554/eLife.03821.004Figure 1.HIV-1 DNA correlates with baseline plasma viral load and CD4 T cell count.


HIV-1 DNA predicts disease progression and post-treatment virological control.

Williams JP, Hurst J, Stöhr W, Robinson N, Brown H, Fisher M, Kinloch S, Cooper D, Schechter M, Tambussi G, Fidler S, Carrington M, Babiker A, Weber J, Koelsch KK, Kelleher AD, Phillips RE, Frater J, SPARTACTrial Investigato - Elife (2014)

Distribution of log10 total and integrated HIV-1-DNA levels in untreated patients at baseline.Kernel density plot to show distribution of Total (blue) and Integrated (red) HIV-1-DNA at baseline.DOI:http://dx.doi.org/10.7554/eLife.03821.005
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199415&req=5

fig1s1: Distribution of log10 total and integrated HIV-1-DNA levels in untreated patients at baseline.Kernel density plot to show distribution of Total (blue) and Integrated (red) HIV-1-DNA at baseline.DOI:http://dx.doi.org/10.7554/eLife.03821.005
Mentions: Traditionally, plasma viral load (VL) (Mellors et al., 1996) and CD4 cell count (Frater et al., 2014) are the only validated surrogate markers of progression used in the HIV-1 clinic. We therefore measured these biomarkers as well as HIV-1 DNA in 154 SPARTAC participants at enrolment to the trial and prior to any ART being given. The median (interquartile range) values of Total and Integrated HIV-1 DNA values in PHI (Figure 1—figure supplement 1) were 7707 (2477–18187) and 3830 (1563–6325) copies of HIV-1 DNA per million CD4 T cells, respectively. Total and Integrated HIV-1 DNA levels were closely associated (p < 0.0001; r2 = 0.72; Pearson correlation) (Figure 1—figure supplement 2) in these pre-therapy samples. Total and Integrated HIV-1 DNA were significantly associated with plasma viral load (both p < 0.001; r2 = 0.48 and 0.64, respectively; linear regression) (Figure 1A), and inversely with CD4 T cell count (both p < 0.001; r2 = 0.20 and 0.27, respectively; linear regression) (Figure 1B). Interestingly, the estimated time since seroconversion at recruitment did not correlate with HIV-1 DNA (both Integrated and Total) (Figure 1—figure supplement 3).10.7554/eLife.03821.004Figure 1.HIV-1 DNA correlates with baseline plasma viral load and CD4 T cell count.

Bottom Line: With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART.We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI.In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound.

View Article: PubMed Central - PubMed

Affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.

ABSTRACT
In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials.

Show MeSH
Related in: MedlinePlus