Introduction

The United Nations has declared a goal of ending the AIDS epidemic by 2030 [1], an aspiration echoed by many individual countries. To achieve this goal, targets have been set for each step in the HIV diagnosis and care continuum. Specifically, besides primary prevention targets for voluntary medical male circumcision (VMMC) [2,3], pre-exposure prophylaxis (PrEP) [4,5], use of condoms [6], harm reduction [7], and opioid substitution treatment [8], the 90-90-90 goals aim for 90% of individuals infected with HIV to be aware of their status, 90% of those diagnosed to initiate antiretroviral (ARV) treatment, and 90% of those on ARVs to have viral loads suppressed below levels of detection, by 2020 [9,10]. These aspirational goals are laudable and, to the degree that they can be achieved, will have a meaningful impact on HIV incidence as well as mortality globally. However, the heterogeneity of the HIV epidemic globally raises challenges in terms of measuring success along the way. In a recently published article, Peter Ghys and colleagues have proposed six different metrics to measure transitions in different aspects (e.g., incidence, mortality) of the HIV epidemic [11].

Differing definitions of what it means for the epidemic to be “over” or “under control” can lead to confusion among stakeholders and the public. It is crucial to define quantifiable goals that will be clearly understood and can be used to measure progress toward vanquishing HIV/AIDS as a major public health problem. This will bring focus and provide benchmarks to measure success of HIV prevention and care programs globally. The purpose of this paper is to review concepts of epidemic control and apply them to the case of HIV. We identify aspirational but feasible goals for control and elimination of HIV transmission and HIV-related mortality. Finally, we will briefly discuss additional challenges and considerations that play an important role in controlling the HIV epidemic.

Epidemiological principles

Disease occurrence is typically measured in terms of incidence (all new cases of a disease during a given period of time) and prevalence (all existing cases of disease at a given point in time). Incidence and prevalence represent measures that we aspire to accurately count or estimate to characterize a certain disease at the population level. However, there are practical considerations, particularly with respect to HIV, that make estimating these measures difficult.

HIV incidence is difficult to measure because HIV infections are initially asymptomatic or cause minimal nonspecific symptoms. Therefore, most newly infected persons do not immediately seek HIV testing and are often diagnosed many months or years after infection. In addition, HIV infection is associated with a window period of one to three months, during which antibody tests cannot detect infection, meaning that early infection may be missed, even when people with very recent HIV infections are tested for antibodies to HIV. Because of these challenges, new infections are frequently measured in terms of new HIV diagnoses. Although this is a pragmatic approach, reporting diagnoses instead of incidence can be problematic in terms of understanding prevailing disease dynamics. For example, increases in diagnoses might be due to more effective HIV testing campaigns that identify previously undiagnosed individuals. The proportion of new diagnoses that occur among individuals with CD4 cell counts <350 (i.e., late-stage diagnosis) highlight the fact that many new diagnoses are not new cases of HIV. For example, a 2015 Dutch study found that 28% of men who have sex with men (MSM) had a CD4 count <350 at the time of diagnosis [12]. Similarly, the proportion of late-stage diagnoses in a 2013 South African study was 34% [13]. It is a goal to reduce the time between HIV infection and HIV diagnosis in order for persons to access ARV treatment and to reduce incident infections. As an alternative to using new HIV diagnoses as a proxy for HIV incidence, statistical modeling methods can be used to obtain estimates of HIV incidence in general and within specific populations [14,15].

In the absence of curative therapy, HIV is a lifelong infection. Thus, prevalence measures alone cannot provide a meaningful indication of changes in the epidemic in the short or near term; changes in prevalence must be interpreted in the context of HIV incidence, treatment outcomes, and mortality. Reducing HIV transmission and incidence requires identifying and counselling persons with HIV infection and providing lifelong ARV treatment in order to decrease the probability of transmission of the virus and reduce HIV-associated mortality, in addition to increasing coverage of primary HIV prevention methods among those at risk of infection. Programmatically, these are costly endeavors; estimates suggest that the cost of mounting a comprehensive AIDS response will be US$26–$36 billion annually [1,10,16].

Standard measures of epidemic control include control, elimination, eradication, and extinction (Box 1) [17,18]. These measures represent increasing levels of success with respect to ending disease incidence. The language surrounding epidemic control can be confusing, because the terms describing each level of control have common and imprecise meanings in colloquial language. In this paper, we use the words control, elimination, eradication, and extinction only in accord with their technical definitions.

Formulating goals for controlling the HIV epidemic

HIV has unique characteristics that affect the interpretation and utility of standard measures of epidemic control. Any measurable goals that are put forward in terms of reducing incidence of HIV must take into account the biological and sociological characteristics of the epidemic. Because eradication requires that a disease-causing agent is entirely removed from the natural environment on a global scale, eradication of HIV will not be an attainable goal until a vaccine and cure are developed and uniformly utilized. Table 1 presents aspirational epidemic control goals in terms of HIV transmission and HIV mortality that are attainable using current prevention methods. Control of the HIV epidemic includes both primary prevention of HIV among those at risk of infection and treatment of persons living with HIV (PLWH) to prevent HIV-related mortality and reduce the risk of onward transmission. Although these are distinct processes, there are some overlapping approaches that contribute to both.

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Table 1. Aspirational but feasible goals for control and elimination of HIV incidence and HIV-related mortality based on existing methods.

https://doi.org/10.1371/journal.pmed.1002729.t001

Current progress in controlling the HIV epidemic

Since the 90-90-90 targets were announced in 2014, substantial progress has been made. Compiling country-level data from around the world, the Joint United Nations Programme on HIV/AIDS (UNAIDS) has summarized progress through the end of 2017 [29]. Although progress—in some countries, substantial progress—has been made, a number of gaps and challenges remain. It is beyond the scope of this paper to fully review global progress, but there are some conspicuous trends. Gains in epidemic control have been notably slower among men and young people, highlighting that existing interventions and programs are not equally effective across demographic groups. This is evident in the faster declines in mortality from AIDS-related causes among women compared with men since 2000. This suggests that additional work will be necessary to increase uptake of HIV testing and treatment among groups that lag behind in the current environment. Additional marginal gains towards the 90-90-90 targets will require engaging these harder-to-reach groups.

There have also been consistent increases in HIV infections and AIDS-related deaths in Eastern Europe and Central Asia since 2000. This is in contrast to generally stable or declining rates of HIV infections and AIDS-related deaths in other regions globally. This suggests additional dynamics that need to be understood and managed in Eastern Europe and Central Asia, in order to halt the growing epidemic in this region.

Varying definitions of control: Defining feasibility

Control of the HIV epidemic should be measured at the local, national, and global levels. To achieve control of the HIV epidemic will mean identifying local goals that result in forward progress but are achievable for a given epidemiological context, as well as identifying and implementing the means to achieve those goals. In the 2016 Prevention Gap Report, UNAIDS identified a target of fewer than 500,000 new HIV infections globally by 2020 [30]. To achieve this goal, the report recommends implementing the Fast-Track strategy, including achieving the 90-90-90 targets in combination with primary prevention programs. Substantial progress will be required to achieve the 90-90-90 targets globally by 2020, and, under this aspirational goal, a substantial proportion, that is 27% of PLWH, will continue to have unsuppressed viral loads (i.e., if the goals are met, about 73% of PLWH will have a suppressed viral load [90% * 90% * 90% = 73%]).

Beyond identifying methods most appropriate to measure successes and identify challenges in HIV prevention, defining epidemic control also requires identifying aspirational yet feasible goals for a given geographical region and epidemiological context. Because control is achieved within a specific geographic region, the local dynamics and epidemic characteristics must be considered in order to identify appropriate goals. Thus, although benchmarks such as the 90-90-90 goals are helpful in planning at a global level, the target epidemiologic measures of incidence, prevalence, transmission rate, or mortality might need to be different depending on local epidemic characteristics. Goals must be identified in terms of what is aspirational, feasible, and measurable at the local, national, and global levels.

Additional considerations

Any discussion of epidemic control must acknowledge the sociocultural context in which HIV exists. It will be difficult, if not impossible, to achieve control of the HIV epidemic without addressing other factors that contribute to the epidemic, such as stigma and criminalization associated with HIV infection and the need for ancillary health services.

Stigma associated with HIV infection and HIV risk behaviors continues to pose a challenge to public health programs designed to reduce HIV incidence [31]. Stigma can reduce the likelihood that an individual is aware of their status and seeking treatment or effective prevention tools owing to fear of testing and disclosure. Joseph Amon and colleagues [32] have described the importance of measuring stigma in addition to other disease-specific indicators (e.g., HIV incidence, AIDS-related mortality) in order to track changes in the epidemic over time.

HIV prevention and treatment programs exist within larger healthcare and economic systems and PLWH, and those at risk of HIV seroconversion, have health needs beyond HIV treatment and prevention services. Mental health services, drug treatment programs, and programs ensuring continuity of care for incarcerated populations are all necessary components of a holistic approach to HIV prevention. Furthermore, these issues serve as a reminder that the populations of PLWH without a diagnosis and those at high risk of HIV infection are very heterogeneous, and there are additional challenges that can be barriers to reaching them. As programs approach the 90-90-90 goals, continued progress might be increasingly challenging because certain key populations have not been reached in individual settings, or different strategies might be required to make further progress.

Conclusions

In this paper, we have reviewed concepts related to epidemiological control in the context of the biology and epidemiology of HIV infection and considered sociobehavioral factors that contribute to the HIV epidemic. Substantial progress has been made in the past 35 years with regard to HIV prevention, treatment, and surveillance methods; however, significant challenges remain. The global commitment to ending the HIV epidemic, exemplified through the United Nations’ Political Declaration On HIV and AIDS [1], indicates a high degree of motivation from countries around the world to reduce morbidity and mortality due to HIV/AIDS. Existing strategies to measure and evaluate progress of HIV prevention interventions should be examined, and additional new measures should be considered in order to most effectively characterize current and future progress in stemming the epidemic. Targets related to controlling HIV incidence and AIDS-related mortality should reflect realistic capabilities of currently available interventions.

In addition to reliable data to track progress in controlling the HIV epidemic, continued research, including implementation science, will be needed to further our understanding of the most effective HIV prevention interventions and how to most effectively deploy these interventions. As outlined above, we identified elimination of HIV transmission due to mother-to-child transmission and blood transfusions as currently attainable. In order to meet this goal, however, resources will need to be allocated appropriately to ensure that appropriate interventions are broadly available, and studies will need to be conducted to understand barriers to implementation when those interventions are underutilized or ineffective. A holistic approach including surveillance, appropriate measures to track epidemic transition, and implementation science is key to continued progress in meeting global targets for control of the HIV epidemic.