title: The parametric g-formula to estimate the effect of highly active antiretroviral therapy on incident AIDS or death.
abstract: The parametric g-formula can be used to contrast the distribution of potential outcomes under arbitrary treatment regimes. Like g-estimation of structural nested models and inverse probability weighting of marginal structural models, the parametric g-formula can appropriately adjust for measured time-varying confounders that are affected by prior treatment. However, there have been few implementations of the parametric g-formula to date. Here, we apply the parametric g-formula to assess the impact of highly active antiretroviral therapy on time to acquired immune deficiency syndrome (AIDS) or death in two US-based human immunodeficiency virus cohorts including 1498 participants. These participants contributed approximately 7300 person-years of follow-up (49% exposed to highly active antiretroviral therapy) during which 382 events occurred and 259 participants were censored because of dropout. Using the parametric g-formula, we estimated that antiretroviral therapy substantially reduces the hazard of AIDS or death (hazard ratio = 0.55; 95% confidence limits [CL]: 0.42, 0.71). This estimate was similar to one previously reported using a marginal structural model, 0.54 (95% CL: 0.38, 0.78). The 6.5-year difference in risk of AIDS or death was 13% (95% CL: 8%, 18%). Results were robust to assumptions about temporal ordering, and extent of history modeled, for time-varying covariates. The parametric g-formula is a viable alternative to inverse probability weighting of marginal structural models and g-estimation of structural nested models for the analysis of complex longitudinal data.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine and Duke Global Health Institute, Duke University, Durham, NC, USA. daniel.westreich@duke.edu
authors.forename: Daniel
authors.initials: D
authors.lastname: Westreich
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Cole
authors.forename: Jessica G
authors.initials: JG
authors.lastname: Young
authors.forename: Frank
authors.initials: F
authors.lastname: Palella
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Tien
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kingsley
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernán
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D023241:Antiretroviral Therapy, Highly Active / Q000592:standards*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D015233:Models, Statistical; D011446:Prospective Studies; D019562:Viral Load