Elsevier

The Lancet

Volume 382, Issue 9903, 2–8 November 2013, Pages 1525-1533
The Lancet

Review
The end of AIDS: HIV infection as a chronic disease

https://doi.org/10.1016/S0140-6736(13)61809-7Get rights and content

Summary

The success of antiretroviral therapy has led some people to now ask whether the end of AIDS is possible. For patients who are motivated to take therapy and who have access to lifelong treatment, AIDS-related illnesses are no longer the primary threat, but a new set of HIV-associated complications have emerged, resulting in a novel chronic disease that for many will span several decades of life. Treatment does not fully restore immune health; as a result, several inflammation-associated or immunodeficiency complications such as cardiovascular disease and cancer are increasing in importance. Cumulative toxic effects from exposure to antiretroviral drugs for decades can cause clinically-relevant metabolic disturbances and end-organ damage. Concerns are growing that the multimorbidity associated with HIV disease could affect healthy ageing and overwhelm some health-care systems, particularly those in resource-limited regions that have yet to develop a chronic care model fully. In view of the problems inherent in the treatment and care for patients with a chronic disease that might persist for several decades, a global effort to identify a cure is now underway.

Introduction

The idea of HIV as a chronic disease has emerged as a result of advances in treatment in the past three decades (table 1). Combination antiretroviral therapy (ART) improves health, prolongs life, and substantially reduces the risk of HIV transmission. In both high-income and low-income countries, the life expectancy of patients infected with HIV who have access to ART is now measured in decades, and might approach that of uninfected populations in patients who receive optimum treatment.1, 2

Advances in treatment and prevention have led some to ask whether the end of AIDS is possible.3 With the bold assumption that challenges of HIV testing and linkage to care can be overcome, we believe that, although AIDS is now preventable, substantial limitations of present therapeutic approaches persist (figure 1). First, ART does not fully restore health. For reasons that remain to be elucidated, antiretroviral-treated HIV disease is associated with new problems, generally referred to as non-AIDS morbidity. Second, health-care systems in regions where most people with HIV reside (eg, sub-Saharan Africa) were designed to provide acute care only and are ill equipped to provide the chronic care that is now required to manage this disease. Finally, ART is not curative, meaning that a young adult who acquires HIV will need to take expensive and potentially toxic drugs for several decades—a daunting task for both the individual and the health-care system. In this Review, we argue that although AIDS as a syndrome will diminish in frequency in people identified early and properly treated, solutions to three seemingly disparate issues—HIV-associated inflammation, an overburdened health-care system, and HIV persistence—are needed to further transform HIV disease.

Section snippets

The cascade of care

People have to access and adhere to ART if HIV infection is to become a genuinely chronic disease. Unfortunately, even within the most advanced health-care systems, effective delivery of HIV-related care is far from ideal. The treatment cascade is now a commonly used conceptual model that quantifies the delivery of services to people living with HIV across the entire continuum of care.4 To maximise the benefits of therapy at an individual and community level, at-risk individuals need first to

Disease persists during effective ART

When used correctly, ART results in rapid control of HIV and partial restoration of immune function, leading to prevention of the various complications that define AIDS. However, treatment does not fully restore health. Findings from studies undertaken in high-income countries show that HIV-infected adults who have durable treatment-mediated suppression of HIV replication are at risk for developing several non-AIDS disorders, including cardiovascular disease, cancer, kidney disease, liver

Does HIV infection accelerate ageing?

Because many non-AIDS events are typically associated with ageing in the general population,51 the popular but vague terms of accelerated ageing or premature ageing are often used to characterise the new range of HIV-associated diseases, but opinions about what defines these terms vary. Whether HIV-associated diseases that have been linked with ageing are simply more common at any given age, or are occurring earlier than expected, is debated. In either case, HIV-infected adults have a high

The health systems gap

HIV disease as a chronic illness requiring lifelong therapy and characterised by multiple comorbidities represents unique problems for health-care delivery. Identification of people with HIV, linking them to care, providing them with access to therapy, and addressing the multiple potential complications requires a well resourced health-care system.68 Barriers to success exist at every step and have been well documented.69

The absence of a well resourced chronic-care model is particularly urgent

HIV persistence and need for a cure

Despite the clinical effectiveness of ART, disease persists during effective treatment, and delivery of ART on a global level for decades to all in need of therapy will be a daunting and resource-expensive endeavour. Recognition of these limitations has led to growing recognition that a safe, affordable, and effective cure for HIV disease might be needed to address the limitations of present therapeutic strategies.92 Although a cure for HIV remains an aspirational goal, several clinical

Conclusions

By virtue of the success of ART, HIV has evolved into a chronic disease in which the typical complications of AIDS are no longer the dominant problem in many parts of the world. Rather than dealing with acute and potentially life-threatening complications, clinicians are now confronted with managing a chronic disease that in the absence of a cure will persist for many decades. HIV care requires new skills on the part of the clinical workforce and a reshaping of health-care systems that were

Search strategy and selection criteria

We searched PubMed, with no date restrictions, with the terms “HIV” in combination with “immune activation”, “inflammation”, “latency”, “cure”, “reservoirs”, “aging”, “non-AIDS morbidity”, and “HIV care delivery”, among others. In view of the very broad focus of our Review, we chose citations that are recent and that provide the strongest evidence to support our statements. We focused on papers published in the past 2 years, but cite older studies when appropriate. For larger topics that we

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