Person:

Daniels, Norman

Background: In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. Methods: In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. Results: At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable. Conclusions: In settings with inadequate HIV treatment availability, trade-offs emerge between maximizing outcomes for individual patients already on treatment and ensuring access to treatment for all people who may benefit. While individuals may derive some benefit from ART even after virologic failure, the aggregate public health benefit is maximized by providing effective therapy to the greatest number of people. These trade-offs should be explicit and transparent in antiretroviral policy decisions.

In resource-limited settings, successful HIV treatment scale-up has been tempered by reports of funding shortfalls. We aimed to determine the priorities, including ethical considerations, of decision makers for HIV antiretroviral programs. We conducted qualitative interviews with 12 decision makers, identified using purposive sampling. Respondents engaged in one-on-one, semi-structured interviews. We developed an Interview Guide to direct questions about key priorities and motivations for HIV antiretroviral program decision making. We evaluated textual data from the interviews to identify themes. Among 12 respondents, 10 (83%) lived and worked in South Africa. Respondents came from Western Cape, Gauteng, and KwaZulu-Natal provinces and worked primarily in urban settings. The respondents supported prioritizing individual patients based on treatment adherence, pregnancy status to prevent maternal-to-child HIV transmission and/or orphans, and severity of illness. However, priorities based on severity of illness varied, with first-come/first-serve, prioritization of the most severely ill, and prioritization of the least severely ill discussed. Respondents opposed prioritizing based on patient socioeconomic characteristics. Other priorities included the number receiving treatment; how treated patients are distributed in the population (e.g, urban/rural); and treatment policy (e.g., number of antiretroviral regimens). Motivations included humanitarian concerns; personal responsibility for individual patients; and clinical outcomes (e.g., patient-level morbidity/mortality, saving lives) and/or social outcomes (e.g., restoring patients as functional family members). Decision makers have a wide range of priorities for antiretroviral provision in South Africa, and the motivations underlying these priorities suggest at times conflicting ethical considerations for providing HIV treatment when resources are limited.

Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set of prioritization criteria would be desirable. A decision process following the accountability for reasonableness framework was undertaken, including a multidisciplinary EuroGentest/PPPC-ESHG workshop to develop shared prioritization criteria. Resources are currently too limited to fund all the beneficial genetic testing services available in the next decade. Ethically and economically reflected prioritization criteria are needed. Prioritization should be based on considerations of medical benefit, health need and costs. Medical benefit includes evidence of benefit in terms of clinical benefit, benefit of information for important life decisions, benefit for other people apart from the person tested and the patient-specific likelihood of being affected by the condition tested for. It may be subject to a finite time window. Health need includes the severity of the condition tested for and its progression at the time of testing. Further discussion and better evidence is needed before clearly defined recommendations can be made or a prioritization algorithm proposed. To our knowledge, this is the first time a clinical society has initiated a decision process about health-care prioritization on a European level, following the principles of accountability for reasonableness. We provide points to consider to stimulate this debate across the EU and to serve as a reference for improving patient management.