HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders

Abstract

Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically linked HIV-1 founder variants represent a minority of HIV-1 infections, we found--n two different cohorts--hat more diverse HIV-1 populations in early infection were associated with significantly higher VL 1 year after HIV-1 diagnosis.

Figure 1

Positive relationship between HIV-1 diversity and viral loads over the first year since HIV-1 diagnosis. HIV-1 diversity was measured at the time of HIV-1 diagnosis. Individual log VL values and predicted means and 95% confidence intervals are shown at each post-infection visit. The upper panels correspond to Step (a) and RV144 (b) trial participants with homogeneous or heterogeneous viral populations; the lower panels correspond to low, medium, and high levels of env diversity in Step (c) and RV144 (d) trial participants. Models adjusted for baseline subject characteristics and assumed that the effects of heterogeneity and diversity are constant over time.

Figure 2

Negative relationship between HIV-1 diversity and CD4⁺ T cell counts over the first year since HIV-1 diagnosis. HIV-1 diversity was measured at the time of HIV-1 diagnosis. Individual CD4+ T cell count measurements and predicted means and 95% confidence intervals are shown at each post-infection visit. The upper panels correspond to Step (a) and RV144 (b) trial participants with homogeneous or heterogeneous viral populations; the lower panels correspond to low, medium, and high levels of env diversity in Step (c) and RV144 (d) trial participants. Models adjusted for baseline subject characteristics and assumed that the effects of heterogeneity and diversity are constant over time.