A Conceptual Model of Interventions to Increase Diagnosis of Acute HIV Infection and Reduce Forward Transmission

Approximately 56,000 individuals in the US acquire HIV annually [1, 2]. Newly-infected persons are highly infectious during the first 2–4 months following HIV acquisition—a period known as acute HIV infection (AHI)—and consequently contribute disproportionately to HIV transmissions. In this paper, we discuss a conceptual model that incorporates interventions specifically targeting AHI that have the potential to greatly decrease new HIV infections. Two important properties distinguish acute HIV infection from the later, chronic stage of HIV infection. First, AHI is characterized by exceptionally high levels of virus circulating in the blood and in the genital tract [3–9]. Plasma and genital tract viral load levels are positively correlated with the risk of sexual transmission [4, 5, 10]. The high-level viremia observed during acute infection results in greatly increased risks of HIV transmission during sexual or syringe-sharing activities. The risk of transmission during acute HIV infection is approximately 8–22 times greater, on a per-act basis, than it is during the subsequent period of chronic infection [5, 11]. Consequently, and despite the relatively brief period during which persons are acutely-infected, the acute period of infection plays a disproportionate role in fueling nascent epidemics and sustaining more mature epidemics [12–16]. Simulation and mathematical models of the mature epidemics in the UK and US suggest that between 10 and 20% of sexually-transmitted infections can be attributed to acute-phase transmission [12, 17]. Moreover, phylogenetic analyses of persons with recent infection in England and Quebec suggest that 25–50% of recently-acquired infections are due to transmission during the early or acute-phase of HIV infection [13, 16]. The second distinguishing characteristic of AHI is that antibodies against HIV are not detectable during much of the acute period of infection. Formation of HIV antibodies usually occurs 2–4 weeks after HIV is acquired [7, 18]. Antibody levels detectable by standard enzyme-linked immunoassay (EIA, ELISA) screening tests are not reliably present until 4–8 weeks after infection. As a consequence, acutely-infected individuals usually have negative or indeterminate antibody test results [3, 18]. Current HIV screening strategies mainly rely on HIV antibody tests. Unfortunately, even the most aggressive antibody-based testing strategy will fail to identify HIV-infected individuals during AHI, when the risk of onward transmission is greatest. The annual incidence of new HIV infections in the US has remained relatively constant for more than a decade [1]. To reduce HIV incidence below the current plateau, innovative HIV prevention strategies are needed, including interventions to increase AHI diagnoses and prevent transmission of the virus during AHI. Currently, accurate diagnosis of AHI requires the use of HIV nucleic acid amplification tests that detect the presence of HIV RNA, rather than antibodies against the virus. We have developed a conceptual model of potential targets of AHI-specific interventions to increase AHI diagnoses and to reduce HIV transmission through a combination of increased RNA testing in both public health and clinical settings; education of at-risk individuals, health care providers, and HIV counselors; and implementation of timely and efficient partner notification programs.