The Protease Inhibitor Transfer Study (PROTRA 1): abacavir and efavirenz in combination as a substitute for a protease inhibitor in heavily pretreated HIV-1-infected patients with undetectable plasma viral load.
OBJECTIVE
The aim of the study was to evaluate the safety and efficacy of abacavir (ABC) and efavirenz (EFV) instead of a protease inhibitor (PI) in HIV-1-infected subjects treated with two nucleoside reverse transcriptase inhibitors (NRTIs) and one PI with undetectable viral loads (< 50 HIV -1 RNA copies/mL). To be eligible for inclusion, patients had to have a history of viral load < 400 copies/mL for at least 3 months and had to be naive to treatment with nonnucleoside reverse transcriptase inhibitors (NNRTIs) and ABC, but multiple pretreatment and treatment failure were allowed.


METHODS
An open-label, single-centre pilot study of duration 48 weeks was conducted. ABC was added to the original treatment with two NRTIs and one PI at baseline, and at week 6 the PI was replaced by EFV. At each study visit, CD4 cell count, viral load [measured by polymerase chain reaction (PCR)] and clinical chemistry were measured. Fasting blood samples were taken at baseline and at weeks 12, 24, 36 and 48 to measure levels of cholesterol [high-density lipoprotein (HDL)/low-density lipoprotein (LDL)], triglycerides, insulin and C-peptide. Additionally, an oral glucose tolerance test (OGTT) was performed. A bioelectric impedance analysis (BIA) and a single slice abdominal and mid-thigh computed tomography (CT) scan were carried out to assess changes in body composition.


RESULTS
Thirty patients were included in the study. Three patients experienced ABC-hypersensitivity and one patient demonstrated virological failure caused by nonadherence. At week 48, all remaining patients had viral loads < 50 copies/mL with stable CD4 counts. The fasting metabolic parameters and abdominal fat distribution remained unchanged.


CONCLUSIONS
In heavily pretreated patients, ABC and EFV in combination provide an effective, simplified and well-tolerated alternative to PI treatment.
Bickel
M
M
Department of Infectious Disease, HIV Treatment and Research Unit, JW Goethe University, Frankfurt, Germany. markusbickel@hotmail.com
Rickerts
V
V
Stephan
C
C
Jacobi
V
V
Rottmann
C
C
Dauer
B
B
Carlebach
A
A
Thalhammer
A
A
Miller
V
V
Staszweski
S
S
D000328:Adult; D000368:Aged; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D001823:Body Composition / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000627:therapeutic use*; D010865:Pilot Projects; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D019562:Viral Load; D000099227:Abacavir
D000480:Alkynes; D048588:Benzoxazines; D008076:Cholesterol, HDL; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C098320:efavirenz