Long term probability of detection of HIV-1 drug resistance after starting antiretroviral therapy in routine clinical practice.
BACKGROUND
Little is known about the long term risk of development of HIV-1 drug resistance for patients starting antiretroviral therapy (ART) with three or four drug regimens in routine clinical practice.


METHODS
We analysed a large cohort study of patients seen in one of six large HIV clinics in and around London, UK. The focus of this analysis was on patients who started ART with two nucleosides plus either a single protease inhibitor (PI), a PI with ritonavir, abacavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI).


RESULTS
4306 patients were followed; 1436 (33%) started with a single PI, 279 (6%) with a PI plus ritonavir, 156 (4%) with triple nucleosides and 2435 (57%) with an NNRTI. The overall cumulative risk of viral load failure was 38% by 6 years. Risk of > or =1 major IAS-USA mutation was 27% by 6 years; risk of mutations from at least two of the three main drug classes was 20% over the same period. These are lower limit estimates as test results were not available for many with viral load failure. Risk of PI mutations being detected in people who started ART with regimens containing a PI with ritonavir was significantly lower than the risk of NNRTI mutations being detected in those starting with NNRTI-containing regimens (relative hazard 0.3195% CI 0.15-0.61; p = 0.0008).


CONCLUSIONS
In routine practice, rates of viral load failure and of resistance detection in patients who started ART with three or four drugs are appreciable.
Phillips
Andrew N
AN
Dunn
David
D
Sabin
Caroline
C
Pozniak
Anton
A
Matthias
Ryanne
R
Geretti
Anna Maria
AM
Clarke
John
J
Churchill
Duncan
D
Williams
Ian
I
Hill
Teresa
T
Green
Hannah
H
Porter
Kholoud
K
Scullard
George
G
Johnson
Margaret
M
Easterbrook
Philippa
P
Gilson
Richard
R
Fisher
Martin
M
Loveday
Clive
C
Gazzard
Brian
B
Pillay
Deenan
D
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D015224:Dideoxynucleosides / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D019438:Ritonavir / Q000627:therapeutic use; D013997:Time Factors; D019562:Viral Load; D000099227:Abacavir
D044966:Anti-Retroviral Agents; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; D000099227:Abacavir