High Heritability Is Compatible with the Broad Distribution of Set Point Viral Load in HIV Carriers

Set point viral load in HIV patients ranges over several orders of magnitude and is a key determinant of disease progression in HIV. A number of recent studies have reported high heritability of set point viral load implying that viral genetic factors contribute substantially to the overall variation in viral load. The high heritability is surprising given the diversity of host factors associated with controlling viral infection. Here we develop an analytical model that describes the temporal changes of the distribution of set point viral load as a function of heritability. This model shows that high heritability is the most parsimonious explanation for the observed variance of set point viral load. Our results thus not only reinforce the credibility of previous estimates of heritability but also shed new light onto mechanisms of viral pathogenesis.Author Summary: Following an initial peak in viremia, the viral load in HIV infected patients settles down to a set point which remains more or less stable during chronic HIV infection. This set point viral load is one of the key factors determining the rate of disease progression. The extent to which it is determined by the virus versus host genetics is thus central to developing a better understanding of disease progression. Here we develop an analytical model that describes the changes of the distribution of set point viral load in the HIV carrier population over a full cycle of transmission. Applying this model to patient data we find that the most parsimonious explanation for the observed large variation of set point viral load across HIV patients is that set point viral load is highly heritable from donors to recipients. This implies that set point viral load is to a considerable extent under the genetic control of the virus.