Discontinuation of Antiretroviral Therapy

• Discontinuation of antiretroviral therapy (ART) may result in viral rebound, immune decompensation, and clinical progression 
• Treatment interruption, especially in established (>6 months) HIV infection, can be potentially dangerous. It could lead to dramatic increases in HIV viral load, which may exceed baseline viral load levels, and precipitous declines in CD4 cell counts, which may reach pre-treatment levels, with the risk of clinical events
• Planned interruptions of ART are not generally recommended. 

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

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.
• When All Regimen Components Have Similar Half-Lives and Require Food for Adequate Absorption, and the Patient Cannot Take Anything by Mouth for a Short Time:
• Temporary discontinuation of all drug components is indicated. 
• The regimen should be restarted as soon as the patient can resume oral intake.
• When the ARV Regimen Contains Drugs with Different Half-Lives:
• 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 ARV 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
• If therapy must be discontinued, patients should be aware of and understand the risks
• Patients should be counselled about the need for close clinical and laboratory monitoring during therapy interruptions.
• During a treatment interruption, patients may present as if they have acute HIV syndrome or the initial HIV-related symptoms may return. 
• Rebound in HIV-1 RNA plasma level may enhance horizontal and vertical transmission of HIV-1, which is of particular importance during pregnancy when a rebound in viral load may favor transplacental, peripartum, and breastfeeding-related transmission. 
• CD4 cell counts may take longer to decrease after the discontinuation of ART; therefore, clinicians should inform patients that a stable CD4 count after discontinuation of therapy does not predict long-term immunologic stability
• Reports have documented the association between discontinuation of an NNRTI, lingering low plasma levels, and emergence of resistance mutations. 
• The duration of these low detectable levels may vary widely from patient to patient. 
• There is no consensus regarding how best to manage treatment discontinuation. 
• Some experts would suggest replacing the NNRTI with a PI and continuing the two NRTIs and PI for approximately 1 week before interrupting therapy. Others would discontinue the NNRTI first and continue the NRTIs for several days (referred to as an “NRTI tail”)

Intermittent Anti Retroviral Therapy

• intermittent therapy group received ART whenever CD4 counts decreased to <250 cells/mm3 then discontinued treatment when CD4 counts increased again to >350 cells/mm3.
•  Patients in the intermittent treatment group had more than twice the risk of progression to AIDS or death compared with the continuous therapy group
• some investigators estimated patients with a nadir CD4 cell count between 2510 – 350 cells/mm3 with a CD4 cell count above 500 cells/mm3 at the time of treatment interruption would be able to interrupt therapy for a median of 61 week

Recommendation:

1. no specific indication on minimum period of treatment interuption or safety of duration of ART
2. this is because the morbidity and mortality depends on the individual levels of CD4 count and viral load. 
3. some studies showed patients with CD4 cell counts above 350 cells/mm3 - for a reasonably long time if they had previously attained a CD4 cell count above 500 cells/mm3 on therapy

References:

1. http://www.hivguidelines.org/clinical-guidelines/adults/antiretroviral-therapy/
2. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/18/discontinuation-or-interruption-of-antiretroviral-therapy
3. http://www.healthline.com/health/hiv-aids/structured-treatment-interruptions
4. http://www.prn.org/index.php/management/article/hiv_treatment_interruption_smart_study_68
5. http://www.aidsmap.com/HAART-can-be-safely-interrupted-for-over-a-year-by-patients-with-lowest-ever-CD4-cell-count-above-250-and-a-sustained-treatment-CD4-cell-count-of-500-or-more/page/1420127/