Minimizing resistance consequences after virologic failure on initial combination therapy: a systematic overview.
OBJECTIVE
To identify optimal first-line therapies based on the rate of virologic success (VS) and the preservation of future treatment options in antiretroviral therapy (ART)-naive subjects.


METHODS
Systematic overview of genotypic resistance mutations from clinical trials of combination ART.


METHODS
Various sources were searched for studies in ART-naive subjects providing virologic response rates and genotypes from subjects with virologic failure. The International AIDS Society-USA genotypic resistance guidelines were used to calculate regimen resistance cost (RCreg) and number of active drug (AD) scores for each regimen and to rank the regimens.


RESULTS
Intra- and interstudy comparisons showed higher VS rates for nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens (range: 51%-76%) and boosted protease inhibitor (boosted PI) regimens (range: 55%-79%). Boosted PI failures had the lowest RCreg (range: 0.12-0.21) and the highest AD (range: 19.80-20.18) scores. NNRTI failures had higher RCreg (range: 0.00-1.22) and lower AD (range: 16.83-21) scores.


CONCLUSIONS
NNRTI and boosted PI regimens provide the highest rates of VS in treatment-naive HIV-infected persons. Treatment option scores were higher in subjects who failed boosted PI- containing regimens versus NNRTI-containing regimens, however.
AIDS Research and Treatment Center, Duke University Medical Center, Durham, NC, USA. bartl004@mc.duke.edu
John A
JA
Bartlett
Jeffrey J
JJ
Buda
Birgitta
B
von Scheele
Josephine A
JA
Mauskopf
E Anne
EA
Davis
Robert
R
Elston
Martin S
MS
King
E Randall
ER
Lanier
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015201:Meta-Analysis as Topic; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors