2010 Recommendations of the International AIDS Society-USA Panel Antiretroviral Treatment of Adult Infection
XVIII International AIDS Conference, July 18-23, 2010, Vienna

In January 2010, the current panel of the International AIDS Society–USA convened to review its 2008 antiretroviral therapy guidelines for the treatment of HIV-infected adults. In light of new and emerging data, the panel has updated its recommendations concerning when to start antiretroviral therapy, choice of initial regimens, patient monitoring, and changes for virologic failure.

When to Start Antiretroviral Therapy

“The risks associated with antiretroviral therapy have decreased, whereas concerns regarding the risks of long-standing untreated viremia have increased. Uncontrolled HIV replication and immune activation lead to a chronic inflammatory state, resulting in end-organ damage and comorbid conditions not previously thought to be associated with HIV infection,” the authors write. They add that there is currently no CD4+ cell count at which initiating therapy is contraindicated, although patient readiness is a key factor for deciding when to initiate antiretroviral therapy. Treatment is recommended for symptomatic patients regardless of CD4+ cell count, and for asymptomatic individuals with CD4+ cell counts of 500/µL or less. Therapy is also recommended in the following scenarios, regardless of CD4+ cell count: increased risk of disease progression associated with a rapid decline in CD4+ cell count or a plasma HIV-1 RNA level greater than 100,000 copies/mL; age older than 60 years; pregnancy; chronic hepatitis B or hepatitis C coinfection; HIV-associated renal disease; high cardiovascular risk; opportunistic infections, including tuberculosis; and circumstances with high risk of HIV transmission such as serodiscordant relationships. Additionally, risk reduction counseling should be a routine part of care at each patient–clinician interaction.

Choice of Initial Regimens

According to the authors, “the initial regimen should be individualized according to resistance testing results and predicted virologic efficacy, toxicity and tolerability, pill burden, dosing frequency, drug-drug interactions, comorbidities, and patient and practitioner preference.” Current evidence supports the combination of 2 nucleoside analogue reverse transcriptase inhibitors (nRTIs) and a potent third agent from another class. Tenofovir plus emtricitabine is the recommended nRTI combination in initial therapy, with efavirenz or a ritonavir-boosted (/r) protease inhibitor or raltegravir as the third agent, unless being reserved for later use when resistance mutations are present.

Patient Monitoring

When treatment is initiated or changed for virologic failure, plasma HIV-1 RNA levels should be monitored frequently until they decrease below detection limits and regularly thereafter. Once the viral load is suppressed for a year and CD4+ cell counts are stable at 350/µL or greater, viral load and CD4+ cell counts can be monitored at intervals of up to 6 months for patients with dependable adherence. Baseline genotypic testing for drug resistance should be performed for all treatment-naive patients and in cases of confirmed virologic failure. Tropism testing is essential before a CC chemokine receptor 5 - inhibitor is used.

Changes for Virologic Failure

According to the authors, when toxicity, intolerance, virologic failure, or other factors determine that switching antiretroviral therapy regimens is necessary, the goal is to maintain virologic suppression below the limits of detection of commercially available assays. Reasons for virologic failure should be assessed, including poor adherence, drug interactions, intercurrent infections and recent vaccinations. Virologic failure of an initial regimen should be identified and treated as early as possible with at least 2, preferably 3, fully active drugs (usually including a ritonavir-boosted protease inhibitor) to avoid the accumulation of resistance mutations. Design of a new regimen should consider the patient’s previous drug exposure, previous and current resistance profiles, drug interactions, and history of intolerance/toxicity. Treatment interruptions should be avoided. Other reasons for changing therapy include management of toxicity, enhancement of tolerability, and simplification of therapy.

“The IAS–USA Antiretroviral Guidelines Panel plays an important role in articulating optimal care approaches applicable to the resourced-world setting,” said Dr. Melanie Thompson, current panel chair. “However, we recognize that in countries of all resource levels, delivering optimal care requires addressing social and structural barriers as well as the ongoing stigma and discrimination associated with HIV infection. Therefore, the need to address these obstacles in order to benefit from our considerable scientific advances is also an important part of the panel’s message.”

Dr Paul Volberding, panel member and founding chair of the IAS–USA, as well as the vice-chair of the Department of Medicine at the University of California San Francisco and Chief of Medicine at San Francisco Veteran’s Affairs Medical Center, said, “The science of HIV medicine continues its rapid evolution. New drugs and the latest research results make it imperative that guidelines summarize the most recent developments. The IAS–USA, as a major source of education in HIV care, has a history of leadership in producing succinct, useful summaries to the international medical community involved in HIV care. The most recent updates address key questions, especially when HIV treatment is best initiated and how the newer drugs are best employed. We are proud to provide this information and grateful to the Journal of the American Medical Association for allowing the widest possible dissemination.”

The International AIDS Society–USA, established in 1995, is a 501(c)(3) professional organization with the mission of developing treatment guidelines for health care providers that will set a standard of care for HIV. The IAS–USA consists of an international panel of volunteers, none of whom participates in pharmaceutical marketing or promotional activities during their tenure on the panel. The authors of the report are Melanie A. Thompson, MD; Judith A. Aberg, MD; Pedro Cahn, MD, PhD; Julio S. G. Montaner, MD; Giuliano Rizzardini, MD; Amalio Telenti, MD, PhD; José M. Gatell, MD, PhD; Huldrych F. G?nthard, MD; Scott M. Hammer, MD; Martin S. Hirsch, MD; Donna M. Jacobsen, BS; Peter Reiss, MD, PhD; Douglas D. Richman, MD; Paul A. Volberding, MD; Patrick Yeni, MD; and Robert T. Schooley, MD.

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