Antiretroviral treatment guidance updated: Revise your practice now
Executive Summary
For clinicians who are involved in care of HIV-infected patients, the newly revised "Guidelines for the Use of Antiretroviral Agents In HIV-1-Infected Adults and Adolescents" contains key treatment updates, as well as a new section on costs, including discussion of cost-sharing, prior authorizations, and use of generic drugs.
• In the past few years, several new antiretroviral agents and coformulations for treatment-naive individuals have been approved.
• Based on data from long-term follow-up studies and experience in clinical practice, the panel involved with developing the guidance now refers to options for initial treatment as "recommended" rather than "preferred" regimens.
For clinicians who are involved in care of HIV-infected patients, the newly-revised "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents" contains key treatment updates, as well as a new section on costs, including discussion of cost-sharing, prior authorizations, and use of generic drugs.1
The Department of Health and Human Services (HHS) guidelines provide an updated and concise review of the most recent evidence-based data concerning the use of antiretroviral therapy (ART), says William Short, MD, MPH, assistant professor in the Division of Infectious Diseases and Environmental Medicine in the Jefferson Medical College at the Thomas Jefferson University in Philadelphia and board member of the Washington, DC-based American Academy of HIV Medicine.
The May 1, 2014, revision includes a change in the classification of recommendations for initial treatment of HIV infection, explains Short. In the past few years, the Food and Drug Administration (FDA) has approved several new ART agents and coformulations for treatment-naive individuals. Based on data from long-term follow-up studies and experience in clinical practice, the panel involved with developing the guidance now refers to options for initial treatment as "recommended" rather than "preferred" regimens.
The guidance is further broken down into two categories: regimens recommended for ART-naïve patients, regardless of baseline CD4 cell count or viral load, and regimens that are recommended only for patients with baseline viral loads less than 100,000 copies/mL.
In the first category, clinicians will note three new recommended regimens, all involving the use of new integrase inhibitors:
• dolutegravir plus abacavir/lamivudine (only for patients who are HLA-B*5701 negative)
• dolutegravir plus tenofovir disoproxil fumarate/emtricitabine and tenofovir disoproxil fumarate/emtricitabine (only for patients with pre-ART creatinine clearance equal to or above 70 mL/min).1
"There is also a section on switching regimens for patients who may be intolerant of their current ART," says Short. "The recommendation emphasizes that the key to switching regimens is to maintain viral suppression without compromising future options."
Short points to an additional new table added to the "Adverse Effects of Antiretroviral Agents" section that offers recommendations on antiretroviral drug options when switching drugs due to adverse effects. Clinicians should consider a patient’s prior treatment history and responses, resistance profiles, and drug tolerance when selecting a new antiretroviral drug, the guidance recommends.
Monitoring is decreased
Viral load is the most important measure of response to ART, and it should be monitored during therapy to assure consistent viral suppression, according to the new guidance. Measurement of CD4 T lymphocyte cell count (CD4 count) is necessary when a patient enters into care, both to determine the urgency for ART initiation and the need for prophylaxis against opportunistic infections, the guidance states.1
Once therapy is initiated, CD4 count monitoring is most helpful in patients with advanced HIV infection to guide the timing of discontinuation of opportunistic infections prophylaxis or treatment, the guidance notes. Frequent monitoring of CD4 counts, especially in those with higher counts (> 300 cells/mm3) and consistently suppressed viral loads, is generally not required for patient management, the guidance states.
"Given the successes of ART, the guidelines now address the frequency at which CD4 count and viral load need to be monitored," says Short. "In the past, these were done every three months; now based on the patient’s history, less frequent monitoring is recommended."
For patients who have been on ART for at least two years with consistent viral suppression, the guidance states that those with a CD4 count between 300500 cells/mm3 can have a CD4 count monitoring every 12 months, while monitoring is optional for those with a CD4 count of more than 500 cells/mm3.1
The guidance recommends resumption of more frequent CD4 count monitoring in three situations:
• when patients experience virologic rebound;
• when patients develop new HIV-associated clinical symptoms;
• when patients develop conditions or initiate therapy that might lead to reduction of CD4 cell count.
Monitoring of lymphocyte subsets other than CD4, such as CD8 and CD19, is not clinically useful, is more expensive, and is not routinely recommended, the guidance states.1
Costs come into play
Look for a new section on drug costs and how they relate to ART, says Short. This discussion includes an overview of cost as it relates to adherence, prior authorizations, and the use of generic drugs, he notes.
In the past, the guidelines have not formally discussed costs related to antiretroviral therapy. The new section provides information, and it also elaborates on potential strategies for cost containment that do not compromise treatment effectiveness.
Clinicians who treat HIV-infected women of reproductive age should check the updated guidance for key drug to drug interactions, notes Short. Examples include oral contraceptives, medroxyprogesterone acetate, statins, and antimicrobials.
There can be potential interactions between antiretroviral drugs and hormonal contraceptives that can lead to lower contraceptive efficacy. Several protease inhibitors and non-nucleoside reverse transcriptase inhibitors have drug interactions with combined oral contraceptives; interactions include a decrease or an increase in blood levels of ethinyl estradiol, norethindrone, or norgestimate. These interactions potentially can decrease contraceptive efficacy or increases estrogen- or progestin-related adverse effects, such as thromboembolism. In the case of the contraceptive implant, contraceptive failure has been reported in two patients on efavirenz-based therapy.2
"Concerns about pharmacokinetic interactions between oral and implant hormonal contraceptives and antiretroviral [drugs] should not prevent clinicians from prescribing hormonal contraceptives for women on ART if that is their preferred contraceptive method," states the guidance. "However, when women wish to use hormonal contraceptives and drug interactions with antiretroviral [drugs] are known, additional or alternative contraceptive methods may be recommended."
What about other contraceptive options? Intrauterine devices (IUDs) appear to be a safe and effective contraceptive option for HIV-infected women.3-6 While most studies have looked at nonhormonal devices such as the Copper T380 IUD, data from several small studies also indicate levonorgestrel-releasing IUDs to be safe and not associated with increased genital tract shedding of HIV.7-8
No matter what contraceptive method is chosen, the guidance advises that clinicians should counsel all HIV-infected women and their partners on consistent use of male or female condoms to prevent transmission of HIV and protect against other sexually transmitted infections.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Rockville, MD: Department of Health and Human Services. Available at http://1.usa.gov/1fEQrl8.
- Leticee N, Viard JP, Yamgnane A, et al. Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz. Contraception 2012;85(4):425-427.
- Stringer EM, Kaseba C, Levy J, et al. A randomized trial of the intrauterine contraceptive device vs hormonal contraception in women who are infected with the human immunodeficiency virus. Am J Obstet Gynecol 2007;197(2):144.e1-8.
- Heikinheimo O, Lehtovirta P, Aho I, et al. The levonorgestrel-releasing intrauterine system in human immunodeficiency virus-infected women: A 5-year follow-up study. Am J Obstet Gynecol 2011; doi: 10.1016/j.ajog.2010.09.002.
- Curtis KM, Nanda K, Kapp N. Safety of hormonal and intrauterine methods of contraception for women with HIV/AIDS: A systematic review. AIDS 2009;23(1):S55-67.
- Centers for Disease Control and Prevention (CDC). U S. Medical Eligibility Criteria for Contraceptive Use, 2010. MMWR Recomm Rep 2010;59(RR-4):1-86.
- Heikinheimo O, Lahteenmaki P. Contraception and HIV infection in women. Hum Reprod Update 2009;15(2):165-176.
- Lehtovirta P, Paavonen J, Heikinheimo O. Experience with the levonorgestrel-releasing intrauterine system among HIV-infected women. Contraception 2007;75(1):37-39.
