Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV
Management of the Treatment-Experienced Patient
Discontinuation or Interruption of Antiretroviral Therapy
Last Updated: April 8, 2015; Last Reviewed: April 8, 2015
Discontinuation of antiretroviral therapy (ART) may result in viral rebound, immune decompensation, and clinical progression.1-5 Thus, planned interruptions of ART are not generally recommended. However, unplanned interruption of ART may occur under certain circumstances as discussed below.
Short-Term Therapy Interruptions
Reasons for short-term interruption (days to weeks) of ART vary and may include drug toxicity; intercurrent illnesses that preclude oral intake, such as gastroenteritis or pancreatitis; surgical procedures; or interrupted access to drugs. Stopping ART for a short time (i.e., less than 1 to 2 days) because of a medical/surgical procedure can usually be done by holding all drugs in the regimen. Recommendations for some other scenarios are listed below:
Unanticipated Short-Term Therapy Interruption
When a Patient Experiences a Severe or Life-Threatening Toxicity or Unexpected Inability to Take Oral Medications:
- All components of the drug regimen should be stopped simultaneously, regardless of drug half-life.
Planned Short-Term Therapy Interruption (Up to 2 Weeks)
When All Regimen Components Have Similar Half-Lives and Do Not Require Food for Proper Absorption:
- All drugs may be given with a sip of water, if allowed; otherwise, all drugs should be stopped simultaneously. All discontinued regimen components should be restarted simultaneously.
- Temporary discontinuation of all drug components is indicated. The regimen should be restarted as soon as the patient can resume oral intake.
- Stopping all drugs simultaneously may result in functional monotherapy with the drug with the longest half-life (typically a non-nucleoside reverse transcriptase inhibitor [NNRTI]), which may increase the risk of selection of NNRTI-resistant mutations. Some experts recommend stopping the NNRTI first and the other antiretroviral drugs 2 to 4 weeks later. Alternatively, the NNRTI may be replaced with a ritonavir- or cobicistat-boosted protease inhibitor (PI/r or PI/c) for 4 weeks. The optimal time sequence for staggered discontinuation of regimen components, or replacement of the NNRTI with a PI/r or PI/c, has not been determined.
Planned Long-Term Therapy Interruptions
Planned long-term therapy interruptions are not recommended outside of controlled clinical trials (AI). Several research studies are evaluating approaches to a functional (virological control in the absence of therapy) or sterilizing (virus eradication) cure of HIV infection. Currently, the only way to reliably test the effectiveness of these strategies may be to interrupt ART and closely monitor viral rebound over time in the setting of a clinical trial.
If therapy must be discontinued, patients should be aware of and understand the risks of viral rebound, acute retroviral syndrome, increased risk of HIV transmission, decline of CD4 count, HIV disease progression, development of minor HIV-associated manifestations such as oral thrush or serious non-AIDS complications (e.g., renal, cardiac, hepatic, or neurologic complications), development of drug resistance, and the need for chemoprophylaxis against opportunistic infections as a result of CD4 decline.
Patients should be counseled about the need for close clinical and laboratory monitoring during therapy interruptions.
- Holkmann Olsen C, Mocroft A, Kirk O, et al. Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or death. HIV Med. 2007;8(2):96-104. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17352766.
- Kousignian I, Abgrall S, Grabar S, et al. Maintaining antiretroviral therapy reduces the risk of AIDS-defining events in patients with uncontrolled viral replication and profound immunodeficiency. Clin Infect Dis. 2008;46(2):296-304. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18171266.
- Danel C, Moh R, Minga A, et al. CD4-guided structured antiretroviral treatment interruption strategy in HIV-infected adults in west Africa (Trivacan ANRS 1269 trial): a randomised trial. Lancet. 2006;367(9527):1981-1989. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16782488&itool=iconabstr&query_hl=147&itool=pubmed_docsum.
- DART Trial Team DTT. Fixed duration interruptions are inferior to continuous treatment in African adults starting therapy with CD4 cell counts < 200 cells/microl. AIDS. 2008;22(2):237-247. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18097226.
- El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355(22):2283-2296. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17135583.