Antiretroviral Therapy for HIV Infection

Overview

Background

An estimated 33 million people are infected with HIV worldwide. [1] In the United States, approximately 1.1 million people have HIV infection, with 56,000 new infections occurring each year. [2]

Significant advances in antiretroviral therapy have been made since the introduction of zidovudine (AZT) in 1987.

With the advent of highly active antiretroviral therapy (HAART), HIV-1 infection is now manageable as a chronic disease in patients who have access to medication and who achieve durable virologic suppression. [3]

Excess mortality among patients with AIDS was nearly halved in the HAART era (see the image below), but it remains approximately 5 times higher in patients with AIDS than in HIV-infected patients without AIDS. The strongest risk factors for excess mortality were viral load greater than 400 copies/mL (compared with + count less than 200 cells/mL (compared with >200 cells/mL), and cytomegalovirus retinitis. [4]

Changes in survival of people infected with HIV. As therapies have become more aggressive, they have been more effective, although survival with HIV infection is not yet equivalent to that in uninfected people. Modified from an original published by Lohse et al (2007), "Survival of persons with and without HIV infection in Denmark, 1995-2005."

The CD4+ cell count thresholds for HAART initiation were recently raised from 350 to 500 cells/mL in the United States and from 200 to 350 cells/mL in mid- and low-income countries. Data suggest that these

recommendations mean a substantial increase in the number of patients who will require treatment and need early HIV testing. [5]

HAART provides effective treatment options for treatment-naive and treatment-experienced patients. Six classes of antiretroviral agents currently exist, as follows:

Nucleoside reverse transcriptase inhibitors (NRTIs)

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Protease inhibitors (PIs)

Integrase inhibitors (IIs)

Fusion inhibitors (FIs)

Chemokine receptor antagonists (CRAs)

Each class targets a different step in the viral life cycle as the virus infects a CD4 + T lymphocyte or other target cell. The use of these agents in clinical practice is largely dictated by their ease or complexity of use, side-effect profile, efficacy based on clinical evidence, practice guidelines, and clinician preference.

Resistance, adverse effects, pregnancy, and coinfection with hepatitis B virus, or hepatitis C virus present important challenges to clinicians when selecting and maintaining therapy.

This article reviews the mechanism of action, resistance, pharmacokinetics, and adverse effects of each of these classes, as well as current treatment guidelines for their use in adults and adolescents with HIV infection. Also discussed are the important challenges involved in selecting and maintaining antiretroviral therapy for pregnant women and patients with acute HIV infection, hepatitis B or C coinfection, or Mycobacterium tuberculosis coinfection.

For additional information on HIV disease, see the Medscape Reference articles HIV Disease and Pediatric HIV .

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