Viral load levels measured at set-point have risen over the last decade of the HIV epidemic in the Netherlands

Abstract

Background: HIV-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 findings: We 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 log(10) 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 log(10) 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/mm(3)/year.

Conclusion: 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.

Figure 1. HIV-1 RNA concentration at viral set-point and mean HIV-1 RNA concentration at each time period.

In MSM patients from W-Europe or N-America with a proven or likely infection with subtype B: a) first HIV-1 RNA 9–27 months after seroconversion (n = 612), b) at 12 (n = 552), c) 18 (n = 370), and d) 24 months (n = 315). The solid black line shows the mean HIV-1 RNA concentration for patients with an estimated date of seroconversion from 1984 through 1995, 1996 through 2002, and 2003 through 2007 (as shown in Table 2). Dashed black lines are estimates obtained by continuous modelling of the estimated date of seroconversion using cubic splines.

Figure 2. CD4 cell count at viral set-point and mean CD4 cell count at each time period.

In MSM from W-Europe/N-America with a proven or likely subtype B infection: a) first CD4 cell count between 9 and 27 months after seroconversion (n = 578), b) at 12 months (n = 555), c) 18 months (n = 439), and d) 24 months (n = 347). The solid black line shows the mean CD4 cell count for patients with an estimated date of seroconversion from 1984 through 1995, 1996 through 2002, and 2003 through 2007 (as shown in Table 2). The dashed black lines were obtained using linear models assuming a constant decrease between 1984 and 2007.