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Day 1 Report from Glasgow
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by Jules Levin
"New causes for optimism reported at International HIV Congress"
Note from Jules Levin: Highlighted at this year's Glasgow Conference are a number of posters presenting PK & clinical data for dual boosted PI regimens (2 PIs boosted by ritonavir low dose). The RESIST-2 data is an oral Late Breaker on Thursday and shows similar results as RESIST-1. With the availability of tipranavir are dual protease inhibitor regimens of use? Some researchers here feel tipranavir is preferable to dual PI-RTV boosted therapy. As far as I know there has never been a comparative study of dual boosted PI regimens vs boosted PI therapy. A comparative study with TPV/r may be in order. When should you use tipranavir? Is a new key question. BMS reports here 96 week results from '045' which compares Kaletra to ATV/r.
Swiss researchers reported in a poster abstract an evaluation of the clinical efficacy and safety of a once daily boosted PI regimen of lopinavir/ritonavir (Kaletra) plus indinavir in heavily pretreated patients with >1000 copies/ml HIV RNA and a history of poor adherence. Therapeutic drug monitoring of both PIs was performed after 2 or more weeks of therapy. 11 patients were included in this pilot study. 7/11 were men. 6/11 had previous AIDS defining events. All patients had severe psychiatric comorbidity and >3 therapy changes containing at least 1 PI. Median baseline CD4 count was 79 and viral load 4.34 log. No resistance to PI (genotype & phenotype) was observed in 8/8 patients. Direct Obseved Therapy (DOT) consisted of 5 pills (4-6) LPV/r and 2-4 pills of IDV. 6 patients were pretreated with IDv & 5 with LPV/r.
DOASGE OF OD BOOSTED DUAL PI THERAPY
| LPV/r dosage | IDV dosage | Pills | | [mg (n pills)] | [mg (n pills)] | Total (n) | | 666/166 (5) | 800 (2) | 7 | | 666/166 (5) | 1200 (3) | 8 | | 800/200 (6) | 800 (2) | 8 | | 533/133 (40 | 800 (2) | 6 |
Dose was adjusted by TDM in a number of patients.
RESULTS
| Baseline | WEEK 12 | WEEK 24 | | Median HIV RNA | 4.3 log | 2.1 log | 1.7 log | | VL <400 c/ml (n,%) | | 7 (87%) | 3 (75%) | | VL <50 c/ml (n,%) | | 3 (37%) | 2 (50%) | | Median CD4 count | 79 | 199 | 217 |
Study authors concluded our preliminary results suggest that boosted dual PI regimen is an important salvage option. Our preliminary data suggest that TDM of LPV/r & IDV can identify a favourable PK profile for both PIs when given once daily.
ATAZANAVIR/RITONAVIR/SAQUINAVIR (ATSAQ) 300/100/1600 twice daily. Schlomo Staszewski reported 24 weeks results from a pilot study of this dual boosted PI regimen. 40 patients were enrolled. Median CD4 of 266. VL 3.57 log. Median CD4 nadir 74. Median # of previous PIs: 3 (1-7). Median # of previous regimens: 8 (2-30). 15/40 had an STI before starting ATSAQ. Median follow-up: 32 weeks (12-60). 37/40 on-treatment. 3/40 off treatment. 34/40 (85%) <400 copies/ml. 24/40 (460%) <50 copies/ml. Median CD4 countincrease 6-80. No patients had new CDC B or C event or death. Taking an STI before new therapy did not improve response. Responses were similar whether baseline VL was above or below 100,000 c/ml. 6/40 were viral non-responders. Authors reported viral failure was not associated with previous PI mutations. STI before therapy had no influence on outcome. Lower SQV exposure was noted with viral failures. Hyperbilirubinemia was the only AE leading to discontinuation.
Virco presented interesting data on clinical cutoffs. They presented for the first time two cutoffs to evaluate drug resistance, which will be incorporated into their tests soon. The lower cutoff identifies fold-change response beginning to be lost (20%) reduction of wild-type response), and fold change where response is 'essentially lost': 80% reduction of wild-type response:
VIRCO-TYPE CLINICAL CUTOFFS FOR NUCLEOSIDES (TIDES) & FOR PIs & BOOSTED PIs
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Virco-TYPE predicted FC of wild-Type Clinical Isolates
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Viral response 20% reduction of wild-Type
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Viral response 80% Reduction of Wild-Type
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DRUG
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AZT
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1.1
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1.9
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14
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3TC
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0.9
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1.1
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3.7
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d4T
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0.9
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1.1
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2.2
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ddI
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0.8
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1.3
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3.0
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TDF
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0.9
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1.0
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2.0
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IDV*
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0.7
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0.8
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2.2
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IDV/r
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0.7
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4.1
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21
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NFV
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0.9
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1.0
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1.5
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SQV
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0.6
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0.7
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1.0
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SQV/r
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0.6
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1.1
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12
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APV
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0.6
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0.7
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1.4
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APV/r
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0.6
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0.9
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6.5
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LPV/r
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0.8
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10
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62
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*preliminary
FOR IMMEDIATE MEDIA RELEASE
MONDAY 15 NOVEMBER, 2004; GLASGOW, UK
"The goal of HIV therapy used to be just to keep someone alive a little longer but now, at least in the developed world, we are looking at a lifetime of therapy," commented Dr Robert Munk (University of New Mexico, USA). This shift of emphasis from survival to 'healthy survival' was a key talking point at the official Press Conference during the Seventh International Congress on Drug Therapy in HIV Infection (Scottish Exhibition and Conference Centre, 14--18 November, 2004).
The Press Conference, hosted by clinician and community representatives from the Congress Scientific Committee, covered important advances in how HIV infection is now managed, our understanding of existing drugs, and the development of new types of HIV drug treatment.
A key direction in HIV management is treatment simplification. "We have made remarkable progress in making treatments easier to take," commented Dr Roy Gulick (Cornell University, USA). "In the mid-1990s, patients were having to take their medication every 8 hours, while coordinating dosing with mealtimes, and having to swallow up to 20 pills a day. Now two pills a day taken at bedtime is common."
How has this progress been possible? Dr Gulick explained that "New drug developments, such as fixed-dose combinations (drugs combined into one pill) and advances in treatment monitoring have been largely responsible." Dr Munk also commented on the significance of treatment simplification in making it easier for patients to adhere to treatment long term. As several panellists also noted, unfortunately HIV can still be associated with stigma and discrimination, so a treatment that can be taken just once a day may help to protect confidentiality. Researchers are now investigating whether treatment can be simplified further with new management strategies, perhaps eventually allowing some patients to take single drug regimens. Optimism has also arisen in response to concerns over drug side effects. These have been a major barrier to treatment success over the past few years, with patients' quality of life sometimes being affected severely. Professor Ian Weller (University College, London, UK), Chairperson of the Congress Scientific Committee, explained that our increased understanding of individual drug profiles is allowing better tailoring treatment to the individual. "We now know which drugs are more likely to predispose to conditions such as high lipid levels, or the condition known as lipoatrophy. So if, for example, we know that a particular patient is at higher risk of heart disease, we can select a drug that is the least likely to contribute to this risk. We can also work with the patient to reduce other risk factors, such as quitting smoking," said Professor Weller. A note of caution was raised, however, by Alain Volny-Anne (European AIDS Treatment Group [EATG]). "The monitoring that surrounds HIV management is becoming increasingly complex and patients now spend a lot of time having hospital tests done to avoid potential side effects," he noted.
An increased understanding of individual HIV drugs is also giving clinicians increased awareness as to the best agents with which to initiate treatment. In addition, several promising new drugs are also in development. Dr Mauro Guarinieri (EATG) expressed particular interest in a new type of drug, the oral HIV entry inhibitors. He explained that, while still in an early phase of development, these compounds have important potential, and if clinical trials are successful they could become available in a few years.
The Panel was unanimous on the greatest concern surrounding HIV today -- the inequality of treatment access between developed world and resource-poor settings. Dr Munk made the analogy that "It's like we're quibbling over the choice on the menu in the West, while 90% of the world can't even get into the restaurant." Even then, Professor Eric Sandström (Karolinska Institute, Sweden) sounded a note of optimism by emphasising how seriously treatment-access issues are now being taken across all continents.
"This Congress is perhaps unique because we focus entirely on the treatment of HIV infection," commented Professor Weller "and it is great to see the meeting evolving to more fully encompass developing world issues." This trend can be seen in the high attendance at the session dedicated to treatment in resource-poor settings, sponsored by the International AIDS Society, and the allocation of scholarships facilitating participation at the Congress primarily to researchers and community workers from the developing world. The Congress -- which continues until Thursday --has attracted more than 2,500 delegates representing 69 countries.
For further information during the Congress, please contact:
Mandy Lakin/Steve Roxborough
Organising Secretariat
Tel: 0141 576 3825 (Secretariat office on site)
Fax: 0141 576 3823
For further information after the Congress, please contact:
Mandy Lakin/Steve Roxborough
Organising Secretariat
Thomson ACUMED®
Peakside House, Alder Court
Tytherington Business Park
Tytherington, Cheshire SK10 2XG, UK
Tel: +44 (0) 1625 668000
Fax: +44 (0) 1625 668121
E-mail: hiv7@acumed.thomson.com
Website: www.hiv7.com
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