Jeffrey W. Eaton

Bio: Jeffrey W. Eaton is an academic researcher from Imperial College London. The author has contributed to research in topics: Population & Acquired immunodeficiency syndrome (AIDS). The author has an hindex of 14, co-authored 16 publications receiving 1444 citations.

HIV treatment as prevention: Systematic comparison of mathematical models of the potential impact of antiretroviral therapy on HIV incidence in South Africa

Abstract: Background: Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. Methods and Findings: Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/ml and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. Conclusions: Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact. Please see later in the article for the Editors’ Summary.

Concurrent Sexual Partnerships and Primary HIV Infection: A Critical Interaction

Abstract: The combination of long-term concurrent sexual partnerships and high infectiousness early in HIV infection has been suggested as a key driver of the extensive spread of HIV in general populations in sub-Saharan Africa, but this has never been scientifically investigated. We use a mathematical model to simulate HIV spreading on sexual networks with different amounts of concurrency. The models show that if HIV infectiousness is constant over the duration of infection, the amount of concurrency has much less influence on HIV spread compared to when infectiousness varies over three stages of infection with high infectiousness in the first months. The proportion of transmissions during primary infection is sensitive to the amount of concurrency and, in this model, is estimated to be between 16 and 28% in spreading epidemics with increasing concurrency. The sensitivity of epidemic spread to the amount of concurrency is greater than predicted by models that do not include primary HIV infection.

A side door into care cascade for HIV-infected patients?

Abstract: HIV Prevention Trials Network studies are testing a number of new technologies for preventing HIV infections and reducing AIDS morbidity and mortality, but strengthening existing antiretroviral therapy (ART) programs may be among the most promising ways to generate greater health benefits using available resources. A cascade to care for HIV-positive patients has been described-HIV testing, retention in pre-ART care, treatment initiation, and sustained suppression on ART-and it has been noted that many patients are lost at each stage. We constructed a detailed representation by combining data from different sources about each stage. We found that, although currently available data were not sufficient to specify several key aspects, the traditional model of the cascade could not fully reconcile trends in HIV testing, linkage to care, retention in pre-ART care, and retention on ART with the large numbers of persons on ART and the large percentage of patients initiating treatment at late stages of infection. We hypothesize that supplementing the traditional linear cascade model with patient health-seeking behaviors that allow patients who are not in pre-ART care to be initiated on ART, is essential to fully characterizing the current functioning of ART programs. We have termed this additional channel to ART as the "side door." Understanding the relative roles of the different channels to care will be important to intervening effectively to improve the cascade to care, and we propose several new types of data that should be collected. With these insights, it may be possible to considerably strengthen the impact of ART programs.

Initiation of antiretroviral therapy in early asymptomatic HIV infection

Abstract: BACKGROUND Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non–AIDS-related event, or death from any cause. RESULTS A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 personyears), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non–AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P = 0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.)

Antiretroviral Therapy for the Prevention of HIV-1 Transmission

Abstract: BackgroundAn interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. MethodsWe randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked H...