Trends of HIV-1 incidence with credible intervals in Sweden 2002-09 reconstructed using a dynamic model of within-patient IgG growth

• Published in: International journal of epidemiology 2015-06, Vol.44 (3), p.998-1006
• Main Authors: Romero-Severson, Ethan Obie, Lee Petrie, Cody, Ionides, Edward, Albert, Jan, Leitner, Thomas
• Format: Article
• Language: English
• Subjects: Bayes Theorem; Biomarkers - blood; Female; HIV Infections - epidemiology; HIV-1; Humans; Immunoenzyme Techniques; Immunoglobulin G - blood; Incidence; Infectious Diseases; Male; Medicin och hälsovetenskap; Models, Theoretical; Sex Factors; Sweden - epidemiology
• ISSN: 0300-5771; 1464-3685; 1464-3685
• DOI: 10.1093/ije/dyv034

HIV-1 is a lifelong disease, often without serious symptoms for years after infection, and thus many infected persons go undetected for a long time. This makes it difficult to track incidence, and thus epidemics may go through dramatic changes largely unnoticed, only to be detected years later. Because direct measurement of incidence is expensive and difficult, several biomarker-based tests and algorithms have been developed to distinguish between recent and long-term infections. However, current methods have been criticized and demands for novel methods have been raised. We developed and applied a biomarker-based incidence model, joining a time-continuous model of immunoglobulin G (IgG) growth (measured by the IgG-capture BED-enzyme immunoassay) with statistical corrections for both sample size and unobserved diagnoses. Our method uses measurements of IgG concentration in newly diagnosed people to calculate the posterior distribution of infection times. Time from infection to diagnosis is modelled for all individuals in a given period and is used to calculate a sample weight to correct for undiagnosed individuals. We then used a bootstrapping method to reconstruct point estimates and credible intervals of the incidence of HIV-1 in Sweden based on a sample of newly diagnosed people. We found evidence for: (i) a slowly but steadily increasing trend in both the incidence and incidence rate in Sweden; and (ii) an increasing but well-controlled epidemic in gay men in Stockholm. Sensitivity analyses showed that our method was robust to realistic levels (up to 15%) of BED misclassification of non-recently infected persons as early infections. We developed a novel incidence estimator based on previously published theoretical work that has the potential to provide rapid, up-to-date estimates of HIV-1 incidence in populations where BED test data are available.