Abstract
BackgroundHIV-1 RNA plasma concentration at viral set-point is associated not only with disease outcome but also with the transmission dynamics of HIV-1. We investigated whether plasma HIV-1 RNA concentration and CD4 cell count at viral set-point have changed over time in the HIV epidemic in the Netherlands.Methodology/Principal FindingsWe selected 906 therapy-naïve patients with at least one plasma HIV-1 RNA concentration measured 9 to 27 months after estimated seroconversion. Changes in HIV-1 RNA and CD4 cell count at viral set-point over time were analysed using linear regression models. The ATHENA national observational cohort contributed all patients who seroconverted in or after 1996; the Amsterdam Cohort Studies (ACS) contributed seroconverters before 1996. The mean of the first HIV-1 RNA concentration measured 9–27 months after seroconversion was 4.30 log10 copies/ml (95% CI 4.17–4.42) for seroconverters from 1984 through 1995 (n = 163); 4.27 (4.16–4.37) for seroconverters 1996–2002 (n = 232), and 4.59 (4.52–4.66) for seroconverters 2003–2007 (n = 511). Compared to patients seroconverting between 2003–2007, the adjusted mean HIV-1 RNA concentration at set-point was 0.28 log10 copies/ml (95% CI 0.16–0.40; p<0.0001) and 0.26 (0.11–0.41; p = 0.0006) lower for those seroconverting between 1996–2002 and 1984–1995, respectively. Results were robust regardless of type of HIV-1 RNA assay, HIV-1 subtype, and interval between measurement and seroconversion. CD4 cell count at viral set-point declined over calendar time at approximately 5 cells/mm3/year.ConclusionThe HIV-1 RNA plasma concentration at viral set-point has increased over the last decade of the HIV epidemic in the Netherlands. This is accompanied by a decreasing CD4 cell count over the period 1984–2007 and may have implications for both the course of the HIV infection and the epidemic.
Highlights
During the asymptomatic phase of HIV-1 infection, virus production and clearance are believed to reach a balance reflecting a relatively stable level of HIV-1 RNA concentration in plasma
The HIV-1 RNA plasma concentration at viral set-point has increased over the last decade of the HIV epidemic in the Netherlands
This is accompanied by a decreasing CD4 cell count over the period 1984–2007 and may have implications for both the course of the HIV infection and the epidemic
Summary
During the asymptomatic phase of HIV-1 infection, virus production and clearance are believed to reach a balance reflecting a relatively stable level of HIV-1 RNA concentration in plasma. Whether this balance, or viral set-point, is reached in all patients remains open to debate [1,2]. Viral set-point, is reached in all patients remains open to debate [1,2] It is agreed, that with a higher HIV-1 RNA plasma level, progression to AIDS is more frequent [3], as is the rate of HIV-1 transmission [4]. We investigated whether plasma HIV-1 RNA concentration and CD4 cell count at viral set-point have changed over time in the HIV epidemic in the Netherlands
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