PMID- 16268823
OWN - NLM
STAT- MEDLINE
DCOM- 20060629
LR  - 20201209
IS  - 1464-2662 (Print)
IS  - 1464-2662 (Linking)
VI  - 6
IP  - 6
DP  - 2005 Nov
TI  - Indinavir/ritonavir 800/100 mg bid and efavirenz 600 mg qd in patients failing 
      treatment with combination nucleoside reverse transcriptase inhibitors: 96-week 
      outcomes of HIV-NAT 009.
PG  - 410-20
AB  - OBJECTIVE: Nucleoside reverse transcriptase (NRTI) sparing is a favourable option 
      for patients with NRTI failure or toxicity. METHODS: Patients judged to be 
      failing NRTI therapy were enrolled in a single-arm, open-label study of 
      indinavir/ritonavir (IDV/r) 800/100 mg twice a day (bid)+efavirenz (EFV) 600 mg 
      once a day (qd). The primary endpoint was the change in time-weighted average HIV 
      RNA from baseline. The initial 48-week protocol was extended to 96 weeks by a 
      single amendment. Analysis was by intention to treat. RESULTS: Sixty-one patients 
      (23 female) were enrolled in the study. Baseline median inter-quartile range 
      (IQR) NRTI exposure was 4.4 (3.9-4.7) years; baseline median viral load was 4.09 
      log(10) HIV-1 RNA copies/mL (range 3.75-4.61 log(10) copies/mL); baseline median 
      CD4 count was 169 cells/microL (range 60-277 cells/microL). The mean (SD) change 
      in time-weighted average HIV RNA from baseline at 48 and 96 weeks was -2.1 (0.7) 
      and -2.1 (0.8) log(10) copies/mL respectively, resulting in 87% and 69% of 
      patients with HIV RNA <50 copies/mL. Sixteen per cent of patients permanently 
      ceased therapy and 26% underwent temporary drug interruptions because of study 
      drug-related adverse events. Fasted-lipid values rose significantly over the 96 
      weeks of study, as did median blood glucose and median serum creatinine levels. 
      Twelve (20%) patients underwent IDV dose reduction, mainly because of 
      nephrotoxicity (nine of 12 patients). Blood pressure values deteriorated 
      following switch, but markers of nucleoside toxicity improved. CONCLUSIONS: IDV/r 
      800/100 mg bid+EFV 600 mg qd gave a potent, durable response in these NRTI 
      failures and was reasonably well tolerated. However, we observed adverse effects 
      on renal, metabolic and blood pressure parameters. Lower doses of boosted IDV 
      might improve toxicity while maintaining efficacy, and this possibility warrants 
      further investigation.
FAU - Boyd, M A
AU  - Boyd MA
AD  - The HIV Netherlands Australia Thailand Research Collaboration, the Thai Red Cross 
      AIDS Research Centre, Bangkok, Thailand. mark.boyd@fmc.sa.gov.au
FAU - Siangphoe, U
AU  - Siangphoe U
FAU - Ruxrungtham, K
AU  - Ruxrungtham K
FAU - Duncombe, C J
AU  - Duncombe CJ
FAU - Stek, M
AU  - Stek M
FAU - Lange, J M A
AU  - Lange JM
FAU - Cooper, D A
AU  - Cooper DA
FAU - Phanuphak, P
AU  - Phanuphak P
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - HIV Med
JT  - HIV medicine
JID - 100897392
RN  - 0 (Alkynes)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Benzoxazines)
RN  - 0 (Blood Glucose)
RN  - 0 (Cyclopropanes)
RN  - 0 (Lipids)
RN  - 0 (Oxazines)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 5W6YA9PKKH (Indinavir)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
RN  - JE6H2O27P8 (efavirenz)
RN  - O3J8G9O825 (Ritonavir)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alkynes
MH  - Anthropometry
MH  - Anti-HIV Agents/adverse effects/*therapeutic use
MH  - Antiretroviral Therapy, Highly Active
MH  - Benzoxazines
MH  - Blood Glucose/metabolism
MH  - CD4 Lymphocyte Count
MH  - Creatinine/blood
MH  - Cyclopropanes
MH  - Disease Progression
MH  - Female
MH  - HIV Infections/*drug therapy/immunology/virology
MH  - HIV Reverse Transcriptase/antagonists & inhibitors
MH  - HIV-1/*isolation & purification
MH  - Humans
MH  - Indinavir/adverse effects/therapeutic use
MH  - Lipids/blood
MH  - Male
MH  - Middle Aged
MH  - Oxazines/adverse effects/therapeutic use
MH  - Reverse Transcriptase Inhibitors/adverse effects/*therapeutic use
MH  - Ritonavir/adverse effects/therapeutic use
MH  - Treatment Failure
MH  - Treatment Outcome
MH  - Viral Load
EDAT- 2005/11/05 09:00
MHDA- 2006/06/30 09:00
CRDT- 2005/11/05 09:00
PHST- 2005/11/05 09:00 [pubmed]
PHST- 2006/06/30 09:00 [medline]
PHST- 2005/11/05 09:00 [entrez]
AID - HIV327 [pii]
AID - 10.1111/j.1468-1293.2005.00327.x [doi]
PST - ppublish
SO  - HIV Med. 2005 Nov;6(6):410-20. doi: 10.1111/j.1468-1293.2005.00327.x.