Targeting HIV-infected cells to reduce viral reservoirs

Inclusion criteria for participants are:

* Ability to provide signed written informed consent; age \>18 years
* Documented HIV diagnosis
* Continuous antiretroviral therapy for \> 4 years with no issues of adherence
* Taking a stable ART regimen, without the inclusion of a protease inhibitor
* At least 4 HIV viral loads \>20 and \< 400 copies/ml over the past two years
* No documented resistance to EFV in history, no PI including ritonavir in current ART regimen or during study period
* No evidence of EFV resistance by plasma virus sequencing at screening visit
* Non-pregnant throughout the study period, if female sex
* Good general health as shown by medical history and screening laboratory tests at the screening visit:

  * Hemoglobin ≥ 85 g/L, white blood cell count (WBC) \> 3,000 cells/mm3
  * Total lymphocyte count .750 X109/L
  * Platelets = 50 to 550 X109/L
  * Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase \< 5 times the institutional upper limit of normal (ULN);
* Willing to undergo either leukapheresis or blood draw at visits 2 and 7 (participants will be given the option to undergo blood draws rather than leukapheresis)
* Ability to add efavirenz to their current ART HIV medication re: avoid drug to drug interactions

Exclusion criteria

There will be no exclusion criteria based on gender/gender identity, ethnoracial composition, language, socioeconomic status, mode of HIV acquisition or sexual orientation/identity. Any participant who requires language interpretation can and will be accommodated for by the participation of translators, either at the patient's choice and/or with the assistance of the translator services provided by local ASO organizations. Exclusion criteria for participants include the following:

* Participants who would have difficulty participating in a trial due to non-compliance
* No active medications / illicit drugs that could adversely affect study compliance
* Currently prescribed and using EFV as part of ongoing ART treatment regimen for HIV suppression
* Currently prescribed a protease inhibitor or pharmacologic booster (cobisistat) as part of current ART regimen
* History of major psychiatric condition that would be adversely affected by efavirenz
* Diagnosed severe cognitive impairment or of strong concern in the judgement of investigators that efavirenz would adversely affect participant
* Documented or suspected history of resistance to any NNRTI including efavirenz, nevirapine or rilpivirine
* History of severe intolerance or documented allergy to efavirenz
* Participants with any of the following abnormal laboratory results at the screening visit:

  * Hemoglobin \< 85 g/L
  * Lymphocyte count \< .750 X109/L
  * Platelet count \< 50 X109/L or \> 550 X109/L
  * AST or ALT \> 5X the upper limit of normal
  * Creatinine \> 250 µmol/L
* Participants with a malignancy or undergoing chemotherapy
* Participants with other significant underlying disease (non-HIV-1) that might impinge upon disease progression or death
* Any concurrent condition requiring the continued use of immunoglobulin, antineoplastic agents, glucocorticoids (other than corticosteroid nasal spray for allergic rhinitis; topical or ophthalmic corticosteroids for acute, uncomplicated dermatitis or conjunctivitis; over the counter medications for acute, uncomplicated dermatitis for treatment period not longer than 14 days) or other immunomodulator medications (other than NSAIDS which will be allowed for any length of time)
* Active drug or alcohol use/dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
* Any illness or conditions including acute illnesses that, in the opinion of the investigator, may affect the safety of the participant or the evaluation of any study endpoints
* Any other conditions judged by the investigator that would limit the evaluation of a participant
* Any confirmed or suspected immunosuppressive or immunodeficient state (except HIV infection for Group-3), asplenia, recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within the past six months (topical steroids are allowed)