Projecting the benefits of antiretroviral therapy for HIV prevention: the impact of population mobility and linkage to care

Abstract

Background: Recent mathematical models suggested that frequent human immunodeficiency virus (HIV) testing with immediate initiation of antiretroviral therapy (ART) to individuals with a positive test result could profoundly curb transmission. The debate about ART as prevention has focused largely on parameter values. We aimed to evaluate structural assumptions regarding linkage to care and population mobility, which have received less attention.

Methods: We modified the linkage structure of published models of ART as prevention, such that individuals who decline initial testing or treatment do not link to care until late-stage HIV infection. We then added population mobility to the models. We populated the models with demographic, clinical, immigration, emigration, and linkage data from a South African township.

Results: In the refined linkage model, elimination of HIV transmission (defined as an incidence of <0.1%) did not occur by 30 years, even with optimistic assumptions about the linkage rate. Across a wide range of estimates, models were more sensitive to structural assumptions about linkage than to parameter values. Incorporating population mobility further attenuated the reduction in incidence conferred by ART as prevention.

Conclusions: Linkage to care and population mobility are critical features of ART-as-prevention models. Clinical trials should incorporate relevant data on linkage to care and migration to evaluate the impact of this strategy.

Figure 1.

In model 1, individuals who do not link in 1 year have an unchanged probability of linking in subsequent years (linkage is conditionally independent, as in Granich et al [5]). Model 2 incorporates a revised formulation of linkage to care, in which individuals who do not link initially join an unlinked compartment and link in late-stage disease. In model 3, we built upon the revised linkage structure and added migration (immigration and emigration). Mortality unrelated to human immunodeficiency virus (HIV) infection may occur from any compartment (background mortality; not shown). A, acute infection; D, dead; I, infected, not receiving antiretroviral therapy; S, susceptible; T, receiving antiretroviral therapy; U, unlinked to care (individuals who decline treatment or are lost to follow-up). Subscripts to the I, U, and T compartments denote stages of HIV infection progression.

Figure 2.

Incidence (A) and prevalence (B) (vertical axes) of human immunodeficiency virus (HIV) infection during antiretroviral therapy as prevention in linkage model 1 (individuals who do not link to care have an unchanged probability of linking in subsequent years) versus linkage model 2 (individuals who do not to link to care do not link until late-stage HIV infection), stratified by linkage proportion. The horizontal axis in both graphs is time in years following initiation of ART-as-prevention programs. The higher linkage proportion estimate (92%; used by Granich et al [5]) is depicted by solid lines, and an estimate from the study community (53%) is depicted by dashed lines. The horizontal dotted line in panel A indicates incidence of 0.1% (“elimination”). HIV incidence and prevalence decline substantially under both models, but incidence did not decrease to <0.1% at either linkage proportion in model 2.

Figure 3.

Human immunodeficiency virus (HIV) incidence (A), prevalence (B), and proportion of the population receiving antiretroviral therapy (ART; C) (vertical axes) in models with (gray lines) and without (black lines) migration, using a linkage proportion of 53%. Dotted lines indicate 95% confidence intervals. The horizontal axis in all graphs is time in years following initiation of ART-as-prevention programs. HIV incidence and prevalence initially decline substantially in both models, but they plateau at a higher incidences and prevalences in the model with migration. The proportion of individuals in the community who are receiving ART is initially lower in model 3, which accounts for migration, due to the lower prevalence of HIV infection among migrants and to the emigration of individuals receiving ART; after 12.7 years, the proportion of individuals receiving ART in the model accounting for migration is higher.

Figure 4.

Time-dependent partial rank correlation coefficients of model parameters in the full model (model 3, accounting for revised linkage and migration) with human immunodeficiency virus (HIV) incidence. The horizontal axis indicates time from initiation of an antiretroviral therapy (ART)-as-prevention program. Values above or below 0 on the y-axis correspond to the positive or negative effects of parameters on projected HIV incidence.

Figure 5.

Projected annual incidence of human immunodeficiency virus (HIV) infection at 30 years, according to linkage rate and immigration rate using model 3 (incorporating revised linkage and migration). Darker shades indicate higher HIV incidence at 30 years, with incidence values indicated in the shaded bar (right). HIV incidence is higher at 30 years for higher immigration rates and lower linkage rates. X, base case.