Mortality from competing risks and the spread of HIV-1 in human populations.

Abstract

In this dissertation I explore the contribution of behavioral variations between populations to heterogeneity in the spread of HIV-1, as well as the sources of those behavioral variations, particularly rates of mortality from competing risks. Chapter 2 provides a critical review of epidemiological explanations for heterogeneity in the spread of HIV-1. These explanations proceed from the proximate determinants of HIV-1 transmission, primarily the practices by which HIV-1 is transmitted and the factors that influence host susceptibility and infectiousness. I argue that a key assumption of the proximate determinants framework---that the rate of partner change is exogenously fixed---is unrealistic and produces misleading conclusions in empirical and simulation studies. It obscures interrelationships between the proximate determinants that may result from behavior change, and also limits the ways in which distal factors may operate to influence the spread of HIV-1. I conclude by introducing the concept of the risk-response function as a tool for organizing thinking and research on the dynamic and socially situated interrelationships between susceptibility, infectiousness, behavior, and prevalence. In Chapter 3 I present a modeling study focused on the relationship between mortality from competing risks and the equilibrium prevalence of HIV-1. The standard formulation of the proximate determinants framework predicts that the prevalence of HIV-1 at equilibrium is a decreasing function of competing-cause mortality, yet the most severe HIV-1 epidemics have occurred among populations with high mortality. I explore the potential for mortality-dependent behavior change to resolve this apparent contradiction. By incorporating a mortality-dependent behavior change function into standard compartmental models of HIV-1 transmission dynamics, I show that such a function can generate a positive association between background mortality and the equilibrium prevalence of HIV-1, but that this positive association occurs only over a restricted range of mortality. In Chapter 4 I explore the relationships between mortality from competing risks, the severity of the local heterosexual HIV-1 epidemic, and the timing of first sexual intercourse among adolescents in the neighborhoods of Chicago, Illinois. At the neighborhood level, male and female mortality from competing risks are strongly and positively correlated with a measure of the severity of the heterosexual HIV-1 epidemic. Local mortality rates also accelerate the initiation of sexual intercourse among adolescents, but do not condition the relationship between the severity of the local HIV-1 epidemic and the timing of first intercourse in the expected direction.