Searcharxiv⌕ Search
Home/Archive/arXiv

arXiv · 2507.10984

Causal indirect effect of an HIV curative treatment: mediators subject to an assay limit and measurement error

Vindyani Herath·Ronald J. Bosch·Judith J. Lok
View original source ↗Read source document ↗Export metadata ↓

Abstract

Causal mediation analysis decomposes the total effect of a treatment on an outcome into the indirect effect, operating through the mediator, and the direct effect, operating through other pathways. One can estimate only the pure indirect effect/indirect effect relative to no treatment, rather than the total effect by combining a hypothesized treatment effect on the mediator with outcome data without treatment. Furthermore, the mediation formula holds for the pure indirect effect (or the organic indirect effect relative to no treatment) regardless of whether there is an interaction between the treatment and mediator in the outcome model. This methodology holds significant promise in selecting prospective treatments based on their indirect effect for further evaluation in randomized clinical trials. We apply this methodology to assess which of two measures of HIV persistence is a more promising target for future HIV curative treatments. We combine a hypothesized treatment effect on two mediators, and outcome data without treatment, to compare the indirect effect of treatments targeting these mediators. Some HIV persistence measurements fall below the assay limit, leading to left-censored mediators. We address this by assuming the outcome model extends to mediators below the assay limit and use maximum likelihood estimation. To address measurement error in the mediators, we adjust our estimates. Using data from completed ACTG studies, we estimate the pure or organic indirect effect of potential curative HIV treatments on viral suppression through weeks 4 and 8 after HIV medication interruption, mediated by HIV persistence measures.

Explore related subjects

stat.AP

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Vindyani Herath, Ronald J. Bosch, Judith J. Lok. 2025-07-15. Causal indirect effect of an HIV curative treatment: mediators subject to an assay limit and measurement error. https://arxiv.org/abs/2507.10984

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Privacy-Preserving Causal Meta-Mediation Analysis with Survival Outcomes

Privacy and data-governance constraints often prevent pooling individual-level data across studies, limiting the use of conventional approaches for causal media- tion analysis in multicenter settings. We propose a federated causal meta-mediation framework for right-censored time-to-event outcomes that enables collaborative es- timation without sharing individual-level data. Our framework targets natural indirect effects in a prespecified population by combining information on mediator and outcome mechanisms across distributed data sources. A site-by-site identifi- cation strategy further allows heterogeneity across data sources to be character- ized, with a variance decomposition separating outcome-related, mediator-related, and interaction components. We develop federated one-step and targeted maxi- mum likelihood estimators that accommodate data-adaptive and machine-learning methods for nuisance-function estimation. The finite-sample performance of the proposed estimators is evaluated through numerical simulations. To illustrate the practical utility of the framework, we apply it on data from the French National Health Data System to evaluate the role of methotrexate coprescription in explain- ing the effect of TNFi versus IL-12/23 inhibitor therapy on treatment persistence among psoriatic patients.

stat.AP↗
arXiv2026

Geospatial Foundation Models Capture Health-Relevant Dimensions of Place Beyond Conventional Social Risk Indices

Area-based social risk indices summarize residents' socioeconomic conditions but incompletely capture physical features of place that may affect health. We evaluated whether numerical representations of physical place produced by four geospatial foundation model families from 2022 satellite data explained residual variance in tract-level associations between the Area Deprivation Index, Social Deprivation Index, and Social Vulnerability Index with health outcomes. We used LightGBM to predict variables from the American Community Survey and 40 chronic disease and health-behavior outcomes from CDC PLACES across 82,646 census tracts in the contiguous United States, evaluating performance across 10 held-out states. Among survey variables, models were moderately predictive of some variables including housing type (R-squared up to 0.54) but weak for disability, unemployment, and income disparity. For health outcomes, models explained up to 54% of variance left unexplained by social risk indices, with the largest gains for annual checkups, arthritis, and high blood pressure. Mean total variance explained by geospatial foundation models across the 40 health-related outcomes increased from 0.31 in the smallest tract-size decile to 0.39 in the largest. Geospatial foundation models capture health-relevant features of place not represented by conventional social risk indices and may usefully augment them in epidemiological analyses.

stat.AP↗
arXiv2026

A spatiotemporal negative binomial model with dynamic dispersion: An application to Tuberculosis infections

Tuberculosis (TB) remains a critical public health concern in Brazil, characterized by pronounced spatial heterogeneity and fluctuating temporal volatility. In this paper, we study monthly TB notifications across 61 microregions of Sao Paulo state from 2001 to 2024. To do this, we introduce a negative binomial spatial integer-valued generalized autoregressive conditional heteroskedastic (INGARCH) model featuring jointly dynamic conditional means and time-varying dispersion. To capture inter-regional spillovers, we incorporate both discrete adjacency structures and a novel continuous distance-based formulation leveraging the Matern correlation function. Parameter estimation via conditional maximum likelihood employs a two-step profile-likelihood iterative scheme, demonstrating solid finite-sample performance in simulation studies. Applied to the Sao Paulo TB surveillance data, the framework substantially outperforms standard Poisson and fixed-dispersion spatiotemporal baselines in empirical fit and uncertainty quantification, maintaining nominal 95% predictive coverage across both dense metropolitan centers and rural microregions. Our results reveal marked spatial heterogeneity in baseline incidence, dynamic overdispersion driven by localized outbreaks, and short-range spatial interaction decay. By accurately modeling spatiotemporal volatility, the proposed methodology provides a robust statistical tool to support public health surveillance, policy-making, and resource allocation.

stat.AP↗