The guidelines and recommendations for how to treat adults suffering from human immunodeficiency virus (HIV) infection have been updated after an evaluation of recent data. Scott M. Hammer, M.D. (Columbia University College of Physicians and Surgeons, New York, and the International AIDS Society-USA Panel) and colleagues published the recommendations in the August 6 issue of JAMA – a special issue focusing on HIV/AIDS.

In order to maintain the highest possible standard of care in a rapidly changing field such as antiretroviral therapy, specialists must regularly revise treatment guidelines. The authors note that, “For a disease that has been transformed from almost uniformly fatal to manageable over decades, the impact of treatment decisions is substantial.” These complex decision-making treatment processes are affected by the availability of new antiretroviral drugs and formulations as well as recent data on treatment options for antiretroviral patients.

After analyzing new data in the field from the last two years, Dr. Hammer and members of the International AIDS Society-USA panel developed new guidelines in the following important areas of antiretroviral management: when to begin therapy, initial regimen choice, patient monitoring, and approaches to treatment failure that require therapy change. Each is discussed below.

When Antiretroviral Therapy Should Begin

The panel has suggested that there is evidence from new data and other considerations that support beginning therapy before CD4 cell count falls below 350/μL. Patients who have CD4 counts of 350/µL or higher should be evaluated for therapy based on several factors including: patient readiness, potential drug interactions, difficulties adhering to therapy, toxicities, and cost.

It is also recommended that when deciding whether to initiate therapy in patients with CD4 counts of 350/µL, physicians should consider any rapid decline in CD4 cell count (more than 100/μL per year), a plasma HIV-1 RNA level higher than 100,000 copies/mL, cardiovascular disease risk factors, and the existence of other diseases that may affect treatment such as active hepatitis B or C virus and an HIV-associated disease that affects the kidneys called nephropathy.

Which Antiretroviral Regimen to Initiate

Individualized antiretroviral treatment is essential, especially because other illnesses and infections may affect a therapy’s efficacy. Most treatments will include efavirenz or a ritonavir-boosted protease inhibitor plus two nucleoside (or nucleoside plus nucleotide) reverse transcriptase inhibitors (nRTIs). The authors suggest that the initial regimen should contain nRTIs such as the fixed-dose combinations tenofovir/emtricitabine or abacavir/lamivudine. The choice of antiretroviral regimen will also be affected by the therapy’s degree of simplicity, pill number, tolerability, whether the patient wants to become pregnant, drug interactions and primary drug resistance.

Monitoring Patients

Since a primary purpose of antiretroviral therapy is to keep plasma HIV-1 RNA levels lower than 50 copies/mL, these levels should be checked frequently upon beginning treatment or changing it due to virologic failure. This may result in monitoring patients at 2, 4, 8, and every 4 weeks thereafter until the level is below assay detection limits, and 3 to 4 times per year thereafter. Some patients should also receive genotypic testing for drug resistance. Before beginning treatment as well as during follow-up, patients should be assessed for other conditions and monitored for toxicity.

Modifying Therapies

Recently, drugs have been approved that can be added to regimens to keep HIV suppressed even when strengthened by multidrug resistant virus. Three full active drugs should be prompted used in the event of virologic failure on an initial nonnucleoside reverse transcriptase inhibitor (NNRTI) – or ritonavir-boosted protease inhibitor-based regimen. In addition, three active drugs – including new classes of drugs – should be used in the event of multi-drug resistance.

Strategically combining old agents with new ones – such as raltegravir (an integrase strand transfer inhibitor), maraviroc (a CCR5 antagonist), and etravirine (a “second generation” NNRTI) – can aid in keeping HIV-1 RNA levels below 50 copies/ml even in patients who have multidrug resistant viruses or high degrees of treatment experience.

Although there have been several advances in the treatment of HIV, the authors write that, “Disease management remains challenged by toxicities, maintenance of adherence, clinical manifestations related to both the drugs and the HIV infection itself, and the threat of drug resistance. Sustainability and expansion of the progress achieved will depend on maintaining a robust drug development pipeline and the ability to deliver effective therapy and monitoring tools to the world’s affected populations.”

They conclude: “With creativity and political will, the progress and individualized approach to antiretroviral therapy evident in the developed world can be adapted to the public health approach in the developing world, where 90 percent of the world’s HIV-infected population lives.”

Antiretroviral Treatment of Adult HIV Infection: 2008 Recommendations of the International AIDS Society-USA Panel
Scott M. Hammer; Joseph J. Eron Jr; Peter Reiss; Robert T. Schooley; Melanie A. Thompson; Sharon Walmsley; Pedro Cahn; Margaret A. Fischl; Jose M. Gatell; Martin S. Hirsch; Donna M. Jacobsen; Julio S. G. Montaner; Douglas D. Richman; Patrick G. Yeni; Paul A. Volberding
JAMA(2008). 300[5]: pp. 555 -570.
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Written by: Peter M Crosta