# Estimating Mediation and Moderation Effects in HIV Incidence Prevention Trials

> **NIH NIH R01** · SAN DIEGO STATE UNIVERSITY · 2022 · $483,628

## Abstract

Project Summary/Abstract
The overall goal of this project is to analyze existing behavioral interventions designed to reduce HIV incidence
in order to examine the mechanisms (i.e., mediators) that predict efficacy, and the subgroups for whom (i.e.,
moderators) interventions are efficacious. We propose to use advanced approaches to analyzing mediators
and moderators. Specifically, we will utilize methods that allow indirect (mediated) effects to be directly tested
and quantified, even in interventions that do not find a significant total X ÞY effect (i.e., efficacy). We propose
to analyze data from four large-scale randomized controlled trials (RCTs) testing the efficacy of behavioral
interventions on an HIV incidence outcome; two trials were showed a significant effect on HIV, two had null
results on HIV. We will use the novel approach called “conditional process modeling” which simultaneously
models mediators and moderators and tests both how and for whom an intervention works, helping to identify
different processes leading to efficacy for different subgroups (AIM 1). We will compare the significant and the
null trials in their significant mediators and moderators and model characteristics to examine possible
situations of masked efficacy in the null trials (AIM 2). We will utilize cutting-edge advancements in causal
mediation analysis. Specifically, we will conduct sensitivity analysis to estimate the extent to which a mediator
is primarily responsible for producing effects on HIV, strengthening causal inference about mediators leading to
reduced HIV transmission in the interventions (AIM 3). To our knowledge these novel statistical approaches
have never been used to analyze mediators and moderators in HIV intervention RCTs. We will also explore the
use of biomedical strategies as moderators of mediated pathways to explore whether participants who reported
use of a biomedical tool show a different causal process in intervention efficacy (AIM 4). Understanding
mediators and moderators of existing behavioral HIV prevention interventions will help to inform how to pare
down or ramp up interventions to their most effective elements and which subgroups and contexts must be
targeted to produce briefer, cheaper, and more impactful interventions. These interventions could be used in
combination with biomedical prevention strategies.!By also analyzing biomedical tools (i.e., nPEP use and
male circumcision status) as potential moderators of mediated effects, we gain valuable insight into whether
and which behavioral mechanisms must be targeted in interventions when these specific biomedical strategies
are used. To meet our aims we will analyze data from studies using the “gold-standard” method for evaluating
HIV prevention interventions. Specifically, we will use data from four different two-arm RCTs that were
powered to test HIV incidence as the primary outcome. These RCTs tested the efficacy of behavioral HIV
prevention interventions among men who hav...

## Key facts

- **NIH application ID:** 10401780
- **Project number:** 5R01DA042666-06
- **Recipient organization:** SAN DIEGO STATE UNIVERSITY
- **Principal Investigator:** Eileen Virtusio Pitpitan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $483,628
- **Award type:** 5
- **Project period:** 2019-10-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401780

## Citation

> US National Institutes of Health, RePORTER application 10401780, Estimating Mediation and Moderation Effects in HIV Incidence Prevention Trials (5R01DA042666-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10401780. Licensed CC0.

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