From exposures to population interventions: pregnancy and response to HIV therapy.

Many epidemiologic studies identify contrasts between an "always-exposed" population and a "never-exposed" population. Such "exposure effects" are perhaps most valuable in discussing individual lifestyle changes, or in clinical care; they may be less valuable in estimating the potential effects of realistic public health interventions. Various methods, among them population attributable fractions and generalized impact fractions, attempt to obtain more policy-relevant estimates of "population intervention" effects, but such methods remain rare in the epidemiologic literature. Here, we describe the use of the parametric g-formula as a tool for the estimation of population intervention effects in longitudinal data. Our discussion is motivated by a previous study of the effect of incident pregnancy on time to virological failure among human immunodeficiency virus-positive women initiating antiretroviral therapy in South Africa between 2004 and 2011. We show that 1) interventional estimates of effect can be estimated in longitudinal data using the parametric g-formula and 2) exposure effects and population interventional effects can have dramatically different interpretations and magnitudes in real-world data. Epidemiologists should consider estimating interventional effects in addition to exposure effects; doing so would allow the results of epidemiologic studies to be more immediately relevant to policy-makers and to implementation science efforts.