title: Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa.
abstract: BACKGROUND
  In HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine--in routine practice--the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment.
  
  
  RESULTS
  We conducted a retrospective review of HIV-infected patients who receiving second-line ART with a LPV/r-containing regimen who required concomitant TB treatment. We identified 29 patients; the median age was 36 years (IQR 29-40), 22 (76%) were female, the median CD4 cell count and viral load at first-line ART failure was 86 cells/mm³ (IQR 21-159) and 39,457 copies/mL (IQR 6,025-157,500), respectively. According to physician preference, 15 (52%) of 29 patients received super-boosted LPV/r (400 mg/400 mg) every 12 hours during TB treatment and 14 (48%) of 29 patients received standard dose LPV/r (400 mg/100 mg) twice daily during TB treatment. Among patients who received super-boosted LPV/r there was a trend towards a higher rate of symptomatic transaminitis (27% vs. 7%; p = 0.3), gastrointestinal toxicity (20% vs. 0%; p = 0.2) and a significantly increased need for treatment discontinuation (47% vs. 7%; p = 0.035. The durability of coadministered treatment was significantly shorter in patients who received super-boosted lopinavir/ritonavir with TB treatment compared to patients who received standard lopinavir/ritonavir dosing (log rank, P = 0.036). The rate of virologic failure was not higher in patients with unadjusted LPV/r dosing.
  
  
  CONCLUSIONS
  We observed a high rate of toxicity and need for treatment discontinuation among patients on standard rifampicin-based TB treatment who received super-boosted LPV/r.
authors.affiliation: Medical Unit, Médecins Sans Frontières/Doctors Without Borders, New York, New York, United States of America. ramurphy@gmail.com
authors.forename: Richard A
authors.initials: RA
authors.lastname: Murphy
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Marconi
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Henry
authors.initials: H
authors.lastname: Sunpath
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D060085:Coinfection / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D061466:Lopinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D013019:South Africa; D013997:Time Factors; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D061466:Lopinavir; D019438:Ritonavir; D012293:Rifampin