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When to initiate antiretroviral therapy in HIV-infected patients

Authors
John G Bartlett, MD
Paul E Sax, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Jennifer Mitty, MD, MPH

INTRODUCTION

Epidemiologic data have demonstrated that potent three-drug antiretroviral therapy (ART) regimens, which were introduced in 1996, have led to remarkable declines in morbidity and mortality among HIV-infected patients [1-3]. Initially, there was a "hit hard and hit early" approach to treatment, implying that all patients should be treated with combination therapy as soon as possible [4]. In the early 2000s, providers started to withhold therapy in patients with relatively preserved CD4 counts given the toxicity of early ART and the lack of clinical evidence proving a benefit of therapy for those with normal CD4 counts. However, advances in HIV therapy in the last decade have shifted the risk-benefit ratio back to earlier treatment. The standard of care today is to treat essentially all HIV-infected patients with ART.

This topic will discuss when to initiate ART and will review the evidence supporting early initiation of therapy. The selection of specific medications, patient evaluation, and laboratory monitoring are discussed elsewhere. (See "Considerations prior to initiating antiretroviral therapy" and "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient" and "Patient monitoring during HIV antiretroviral therapy".)

BENEFITS OF ANTIRETROVIRAL THERAPY

In HIV-infected individuals, antiretroviral therapy (ART) reduces mortality as well as serious AIDS- and non-AIDS-related complications. It also prevents transmission of HIV to others.

For the patient — For HIV-infected patients, ART can result in sustained suppression of HIV RNA. This leads to improvements in cellular immunity (ie, CD4 count), and a subsequent reduction in AIDS-related morbidity and mortality. Suppression in HIV RNA can also result in a reduction in HIV-immune activation (eg, proinflammatory cytokines, chronic inflammation, and T-cell activation), which can otherwise lead to end-organ damage (eg, coronary artery disease, liver and kidney disease, neurologic disease, malignancy) [5].

The benefits of ART can vary based upon the CD4 count. As an example, the patient's baseline CD4 count can impact treatment outcomes. This was illustrated in a collaborative study of 62,760 treatment-naïve patients in Europe and the United States [6]. Over a mean follow-up of 3.3 years, 2039 patients died. Although the overall risk of mortality was reduced by approximately 50 percent among those who initiated ART compared with those who did not, the absolute survival benefit depended upon the patient’s level of immunocompromise before treatment. In analyses stratified by CD4 count, the corresponding hazard ratios for all-cause mortality for treated versus untreated patients were:

                    

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Literature review current through: Nov 2016. | This topic last updated: Thu Oct 27 00:00:00 GMT+00:00 2016.
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