Human Immunodeficiency Virus (HIV, AIDS) (cont.)
Eric S. Daar, MD
Eric S. Daar, MD
Dr. Daar received his undergraduate degree from UCLA and medical degree from Georgetown University School of Medicine. He completed an internship and residency in internal medicine at Cedars-Sinai Medical Center and his clinical and research fellowship in infectious diseases at Cedars-Sinai Medical Center and UCLA.
In this Article
When should antiviral therapy be started?
Guidelines for starting antiviral therapy have been proposed by panels of experts from several groups, including the DHHS (http://www.aidsinfo.nih.gov) and IAS-USA. For several years, these guidelines have recommended treating all patients who have symptoms of HIV infection as well as those who have CD4 cell counts of less than 350 cells/mm3. Recent data supporting even earlier initiation of therapy includes analyses of groups of patients followed over time. Although the data is imperfect, there are now several studies that suggest that outcomes are better amongst those who start when CD4 cells drop to below 500 cells/mm3, and at least one study, but not others, showing that those who started treatment with CD4 cells greater than 500 cells per mm3 actually were less likely to die than those who did not start treatment until their CD4 cells declined to less than 500 cells/mm3. In addition, there is increasing evidence that ongoing viral replication, even in the setting of high CD4 cells, may be associated with damage to the brain, kidneys, heart, and possibly even liver. Along with these studies arguing for earlier treatment, new regimens are increasingly easy to take, including a growing number of one-pill-per-day options and growing evidence that currently used treatments are very well tolerated and effective in suppressing viral load. Another compelling argument that can now be made for early therapy is the ability to reduce the risk of transmission to uninfected partners. A study called HPTN 052 demonstrated that amongst couples where one person is HIV-infected and the other is not, those that were on antiretroviral therapy were 96% less likely to transmit HIV to their uninfected partner than those not on treatment. Finally, there is now a large study that is specifically studying whether starting treatment with CD4 cells greater than 550 cells/mm3 results in better outcomes than those who defer treatment until CD4 cells are less than 350 cells/mm3. Based upon consideration of all these factors, current United States guidelines are now recommending that all HIV-infected individuals who are prepared to commit to treatment receive therapy regardless of CD4 cell count or symptoms of disease, much as is done for most infectious diseases for which there is effective therapy. It is worth noting that these recommendations for universal treatment of HIV-infected patients have not been adopted by all countries and may be limited by resources available for antiviral treatment.
Before starting treatment, patients must be aware of the short- and long-term side effects of the drugs, including the fact that some long-term complications may not be known. Patients also need to realize that therapy is a long-term commitment and requires consistent adherence to the drugs. In addition, clinicians and patients should recognize that depression, feelings of isolation, substance abuse, and side effects of the antiviral drugs can all be associated with the failure to follow the treatment program.
What is the initial therapy for HIV?
Guidelines for using antiviral therapy have been developed and are updated on a regular basis by an expert panel assembled by the DHHS, the IAS-USA panel, and others. The DHHS guidelines are available at http://www.aidsinfo.nih.gov. The most recent IAS-USA guidelines were published in the Journal of the American Medical Association (JAMA) in the summer of 2012 and will soon be updated.
Antiviral treatment options have primarily included combinations of two NRTIs, often referred to as "nucs," and one PI, typically with a low dose of RTV, a PI used at low doses to increase the level of the principle PI being used, so called "boosting." Alternative preferred options include the use of two NRTIs with an NNRTI, the latter often called "non-nucs." Some of these NNRTI-containing combinations are simpler to take than PI-containing combinations and tend to have different side effects. NRTIs can also be combined with the InSTIs RAL, dolutegravir (Tivicay, DTG), or EVG, the latter as part of a fixed-dose combination pill that also includes a new pharmacologic boosting agent called cobicistat (COBI) with very good viral suppression and tolerability.
Medically Reviewed by a Doctor on 8/5/2014
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