Emtricitabine/Tenofovir Alafenamide as Salvage ART

INCLUSION

• Age greater than or equal to 14 years
• Documented HIV-1 infection (written documentation of positive standard ELISA or rapid HIV-1/HIV-2 antibody test with confirmatory Western Blot, or documentation of repeated HIV RNA of > 1,000 copies/mL)
• Concurrent enrollment in the DOTCOM (14-I-0009) protocol
• For females of childbearing potential, willingness to use effective contraception for the duration of the study
• Willingness to be hospitalized for 10-15 days (with potential for day passes)
• Willingness to have blood samples stored for future research that may include genetic testing

• Multiple ART failure as defined by at least one of the following criteria:

  • HIV RNA > 1000 copies/mL and documented virologic failure on at least 1 prior ART regimen and at least 2 consecutive HIV RNA plasma measurements of > 1,000 copies/mL, including the last documented value, while on the currently prescribed ART regimen for at least 6 months; or
  • Documented extensive resistance to at least 3 antiretroviral (ARV) drug classes, and persistent plasma viremia (HIV RNA > 1,000 copies/mL for > 6 months) despite multiple regimen changes. The patient may be enrolled even if they have been prescribed their current regimens for less than 6 months.

• Where neither TDF nor ABC are optimal NRTI options as defined by at least one of the following criteria:

  • Presence of the M184V mutation plus TDF-associated resistance mutations based on genotypic/phenotypic testing, specifically K65R alone, or with TAMs (such as 41L, 67N, 70R, 210W, 215Y/F, or 219Q/E) with or without other NRTI-associated mutations; or
  • FTC/TDF is not considered an option due to impaired renal function (eGFR by Cockroft-Gault equation [eGFR(CG)]=30-60 mL/min), or risk of renal impairment because of conditions such as uncontrolled hypertension, diabetes mellitus, or history of renal toxicity while receiving a TDF-based regimen; and where ABC/3TC is contraindicated (ie, presence of HLA B*5701 allele or history of hypersensitivity reaction to ABC), or is a suboptimal option (eg, presence of ABC-associated resistance mutation(s) or in patients with HBV co-infection).

EXCLUSION

• Severe renal impairment (eGFR(CG) <30 mL/min)
• Acute medical illness stemming from a significant co-morbidity (eg, malignancy requiring chemotherapy, treatment of an acute opportunistic infection or acute renal failture). Enrollment may be deferred up to 3 months to allow a condition to resolve or stabilize.
• Pregnancy; however if a patient becomes pregnant while enrolled in the protocol, she may continue participation throughout her pregnancy.
• Breastfeeding
• Concomitant use of one of the following medications: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, bisphosphonate, St. John s wort, echinacea, milk thistle, sho-saiko-to, and probenecid.
• Any illness or condition that, in the investigator's opinion, may substantially increase the risk of participation in the study, or compromise the scientific objectives.