Targeted Minimum Loss-Based Estimation of a Causal E ect Using Interval-Censored Time-to-Event Data - Interval-Censored-Time-to-Event Data: Methods and Applications - page 197

8.5 Alternative Target Parameters ::::::::::::::::::::::::::::::::::: 219

8.6 Concluding Remarks ::::::::::::::::::::::::::::::::::::::::::::: 223

8.7 Bibliography :::::::::::::::::::::::::::::::::::::::::::::::::::::: 225

Appendix: Equivalence of Candidate Interventions on m :::::: 227
Bibliography :::::::::::::::::::::::::::::::::::::::::::::::::::::: 228

8.1 Introduction

8.1.1 Motivation

The Adult Antiretroviral Treatment and Resistance Study, often referred to as

the Tshepo Study, was initiated in Botswana in 2002. It was the country's rst

large-scale trial of antiretroviral therapy in individuals infected with the Hu-

man Immunodeficiency Virus (HIV) or having developed the Human Acquired

Immunodeficiency Syndrome (AIDS). Its investigators aimed to evaluate the

potential for drug resistance and toxicity of six antiretroviral combination

therapies, and to determine the effectiveness of two proposed medication ad-

herence strategies. A total of 650 participants meeting inclusion criteria were

assigned to various treatment groups; treatment group allocation was ran-

domized and unblinded to participants. Study participants were followed for
a total of 3 years, with various measurements recorded on distinct sched-

ules. Basic clinical measures, including adherence assessments, were recorded

monthly. Disease progression measures, such as plasma CD4+ cell counts and

HIV RNA levels, were obtained bimonthly. Markers of drug toxicity were as-

sessed monthly for the first 6 months, bimonthly for the next 6 months, and

every 6 months subsequently. Further study details are provided elsewhere;

see, for example, Wester et al. (2010).

Disease status in patients with HIV infection can be ajudicated by mon-

itoring the evolution of HIV viral loads in the blood. High HIV viral load is