Important advances in understanding the biology and treatment of Human Immunodeficiency Virus (HIV) infection have occurred since 1995. As a result, new approaches to therapy have been developed that offer scientifically and medically sound options for persons with HIV infection. Although much is still unknown about anti-retroviral treatment, we do know that:
- Anti-retroviral therapy has been proven to slow disease progression and extend life;
- Anti-retroviral therapy does not eradicate the virus and is not a "cure;"
- In order for anti-retroviral therapy to be effective, the drugs must be used consistently and correctly; and
- Anti-retroviral therapy fails to help a significant portion of patients.
Anti-retroviral therapy proven to slow disease progression and extend life
In 1996, after more than a decade of relentless increase, deaths from AIDS finally declined in the U.S. and death rates from HIV infection in the U.S. declined an unprecedented 47 percent from 1996 to 1997. HIV incidence probably peaked in our area in 1983 and some of the drop stems from the effects of prevention efforts and behavior change. The introduction of powerful therapies able to retard the activity of HIV have also contributed to the reduced morbidity and mortality. Studies show that the use of anti-retroviral therapy (ART), in conjunction with the prevention of specific HIV-related opportunistic infections (OIs), has been associated with dramatic decreases in the incidence of OIs, hospitalizations, and deaths among HIV-infected persons. In addition, starting treatment as early as possible is associated with virologic, immunologic, and clinical benefits. Please see attached MMWR appendix for a summary of the principles of anti-retroviral therapy.
NOT a cure
Although anti-retroviral therapies impair the ability of HIV to multiply, spread and damage the immune system, they are NOT a cure. Effective drugs, taken properly, significantly decrease the amount of virus replicating in the blood and other body fluids, but they have not been shown to totally eliminate the virus from the body. People who have had undetectable "viral loads" (the amount of virus able to be found in the blood) for over two years still have virus in latent cells in the lymph nodes. We do not yet know how long ART will be effective in any individual and we do not know the long term effects of the drugs on the rest of the body.
Adherence and Effectiveness
In order for anti-retroviral therapy to be effective, the drugs must be used consistently and correctly. Correct use means that the drugs must be taken at appropriate intervals (with or without food as indicated), at correct doses and in correct combinations. The goal of antiretroviral therapy is to improve survival and decrease morbidity via continuous maximum suppression of HIV replication. Developing an effective treatment strategy requires combining medical science with patient history and preferences. Sub-optimal therapy (therapy that does not sufficiently suppress HIV replication) leads to viral resistance and treatment failure.
According to NIH guidelines, regular measurement of "viral load" and CD4+ T cell counts is needed to guide treatment decisions. The most effective therapy requires simultaneous initiation of combinations of effective anti-HIV drugs with which the patient has not been previously treated. Monotherapy (i.e., treatment with only one anti-retroviral drug)is not recommended and when changing treatment regimens, more than one drug should be changed. Women should receive optimal anti-retroviral therapy regardless of pregnancy status. (Although new studies show that Sustiva should not be taken when pregnant.)
Anti-retroviral therapy often requires patients to follow complicated pill taking regimens. Adherence is essential to treatment success. Non-adherence results in sub-optimal therapy and viral resistance. Clinical studies show that a significant portion of patients who are unable to follow the rigorous requirements of these regimens may ultimately fail therapy.,
Risks
Before starting therapy, patients should understand the short term risks and benefits and the uncertainties of long term use. They should also understand how to adhere to the regimen. Therapy should not be initiated until treatment goals and the need for close adherence to a treatment regimen are understood and endorsed by the patient. Encouraging the active particiation of HIV-positive persons in their own treatment may help patients take medications more successfully.
Quality of medical care impacts survival
As anti-retroviral therapy has become increasingly effective, it has also become increasingly complex. In order to ensure that newly available therapies are used in ways that most effectively improve the health and prolong the lives of HIV-infected persons, health care providers must be familiar with recent research advances and treatment recommendations. People who receive medical care from physicians with a great deal of experience treating HIV infection may live longer than those who see less experienced physicians. A physician's lack of knowledge of the most current data on effective HIV/AIDS drug regimens may contribute to treatment failure.
Anti-retroviral therapy fails to help a significant portion of patients
Many failures on current combination antiretroviral therapies can be attributed to intolerance of side effects, non-adherance due to the large numbers of pills required, and cross-resistance (resistance to one medication leading to resistance to other medications.) Currently available drugs often have inconvenient dosing schedules, high numbers of pills, significant side effects, and complex drug-drug interactions. There are several new treatments currently being studied to address these issues. In the future, patients should have treatment regimens that cause fewer side effects, require fewer pills and have more convenient dosing schedules.
Recommendations
- Persons who have engaged in high risk behavior should seek HIV testing and counseling as soon as possible.
- All HIV-positive persons should seek care as soon as possible and, with the help of an HIV-knowledgeable health-care provider, consider beginning anti-retroviral treatment.
References
- Centers for Disease Control and Prevention. Report of the NIH Panel to Define Principles of Therapy of HIV Infection and Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. MMWR 1998;47(No. RR-5).
- Births and Deaths: PreliminaryData for 1997. Vol. 47, No. 4. 42pp. (PHS) 99-1120
- Mann, Jonathan M Trantola, Daniel J.M. "HIV 1998: The Global Picture" Scientific American; July 1998 p. 82.
- Centers for Disease Control and Prevention. Report of the NIH Panel to Define Principles of Therapy of HIV Infection and Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. MMWR 1998;47(No. RR-5).
- Centers for Disease Control and Prevention. Report of the NIH Panel to Define Principles of Therapy of HIV Infection and Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. MMWR 1998;47(No. RR-5).
- Pantaleo, Giuseppe Perrin, Luc. "Can HIV be eradicated?" AIDS 1998;Vol 12, Supplement A pp. S175-S180.
- Chun, Tae-Wook et al. "Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy" Proc. Natl. Acad. Sci. USA Nov.1997; Vol 94 pp. 13193-13197.
- Carpenter, C et al. "Antiretroviral Therapy for HIV Infection in 1998" JAMA Vol 280, No. 1 p. 80.
- Centers for Disease Control and Prevention. Report of the NIH Panel to Define Principles of Therapy of HIV Infection and Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. MMWR 1998;47(No. RR-5).
- James John S. (ATN) Efavirenz (SUSTIVA ™)) Approved AIDS Treatment News Issue #304, October 2, 1998.
- Tebas P, Royal M, Fichtenbaum C, et al. Relationship between adherence to HAART and disease states. Presented at the 5th Conference on Retroviruses and Opportunistic Infections. Feb 1-4, 1998. Abstract 149/24.
- Wong JK, Gunthard HF, Havlir DV, et al. Reduction of HIV-1 in blood and lymph nodes following potent antiretroviral therapy and the virologic correlates of treatment failure. Proceedings of the National Academy of Sciences 1997;94:12574-12579.
- Carpenter C et al. "Antiretroviral Therapy for HIV Infection in 1998" JAMA Vol 280, No. 1 p. 80.
- Lerner Barron H et al. "Rethinking Nonadherence: Historical Perspectives on Triple-Drug Therapy for HIV Disease" Annals of Internal Medicine Oct. 1 1998; Vol 129, No. 7 p. 573.
- Centers for Disease Control and Prevention. Report of the NIH Panel to Define Principles of Therapy of HIV Infection and Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. MMWR 1998;47(No. RR-5).
- Kitahata Mari M. et al. "Physicians' Experience with the Acquired Immunodeficiency Syndrome as a Factor in Patients' Survival" NEJM Vol. 334 No. 11 p.701-729.
- Gallant, Joel E. Block, David S. "Adherence to antiretroviral regimens in HIV-infected patients: Results of a survey among physicians and patients" Journal of the International Association of Physicians in AIDS Care May 1998; p. 32.
- Murphy Mary J. "Four New Antiretroviral Medications will soon offer more options to HIV Patients" Handout from AIDS ATC.
- Deeks "Antiretroviral Agents: The Next Generation" AIDS Clinical Care May 1998;Vol 10, No. 5 p. 1.S
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