1st Report From the Intl AIDS Conference in Geneva
from Jules Levin
Geneva, Switzerland, Sunday June 28, 6:30pm Geneva time
I arrived yesterday in Geneva after spending the past week in Lake Maggiori, Italy at the annual Resistance and Treatment Strategy Workshop where a good deal of interesting data and information was reported. NATAP will be holding a free community educational forum on Saturday July 18 at 10am to 4pm at NYU Medical Center to report the information from both conferences. Please call NATAP office to reserve seating at 212 219-0106 or 1-888-26-NATAP.
It's a pleasure to be in a dirty large city like Geneva after being in a humid desolate resort area (Lake Maggiori). Although the hotels and the food here in Geneva arent as good as in the USA. Cant wait to get back home.
The official conference starts tomorrow but today I attended three symposiums held by Merck, Roche and Glaxo Wellcome. The panelists included Dan Kuritzkes, Chip Schooley, Giuseppe Pantaleo, Melanie Thompson, Joe Eron, John Mellors, Julio Montaner and several European researchers. The opening plenary session is ongoing now but its mostly entertainment and Id rather do this.
Merck reported 32 weeks (n=12) of 1200 mg bid indinavir data where 60% were <50 copies/ml. More data reports will be forthcoming during the conference on IDV bid. Sustiva data was reported. At 60 weeks about 90% were <400 copies/ml using EFV/IDV or EFV/AZT/3TC. The EFV plus 2 NRTIs data (6 mos) so far is equal to IDV plus 2 NRTIs data. Rash of 10% is reported but very little or no severe grade 3 or 4 rash is reported. In fact, the EFV plus 2 NRTIs data is better than IDV plus 2 NRTIs possibly because of compliance difficulties with taking IDV. EFV is once a day with no dietary restrictions.
At the symposiums the speakers stressed treating hard and early. Pantaleo, a noted immunologist, said treating hard and early is important to raise a good immune response. He said the HIV specific CD4 response reported by Bruce Walker can be raised by early treatment but not by holding off treatment. Bruce Walker recommends treatment during primary infection to promote this effect but that the effect may be lost by holding off treatment (see current NATAP Reports). Another researcher here told me that Brigette Autran says she has never observed this HIV specific CD4 response reported by Walker and others (see NATAP Reports article in current issue). Melanie Thompson said we dont know when to begin therapy; that clinical studies are required to explore this question.
The speakers have stressed the need to reduce viral load to <50 copies/ml for durable responses. They have also said that if viral load is not reduced within a reasonable time period intensification of therapy should be considered. One speaker suggested 3 mos as a reasonable time period to intensify therapy if viral load is not below 50 copies/ml. This appears to be a theme at this meeting: that the goal of therapy should be to < 50 copies/ml. At Lake Maggiori a researcher said that viral load should be reduced to zero, that cells containing latent virus do decay and that eradication MAY be possible after 7-8 years of continual viral load suppression to zero or very low levels. Over time viral load may continue to decline even after initiallly reaching <50 copies/ml.
Melanie Thompson gave an interesting talk about the difference in clinical effect of HAART between studies and in real life. She and other speakers discussed factors in why some individuals respond better to therapy: adherence, baseline CD4 and viral load, pre-treatment, and their health status, in studies site staff promote and stress adherence, aggressive disease management is offered at study sites, study participants that are healthier are selected for participation, and more compliant patients are selected.
Chip Schooley mentioned three new classes of drugs in development: integrase inhibitors, fusion inhibitor, zinc finger chelators, and 3 new protease inhibitors (amprenavir, ABT-378 and Pharmacia & Upjohns PNU-140690). The first data (in naive persons) on ABT-378 will be reported at this meeting. It looks potent and tolerable. Its effect on protease resistant virus has yet to be explored in clinical study. Stay tuned for data on PNU-140690; its being reported here as well.
John Mellors discussed genotypic and phenotypic resistance testing. This was a major subject for discussion at Lake Maggiori Resistance Meeting. The NATAP forum on July 18 will focus on this subject. We will report and discuss this data. Data was reported correlating baseline geno and phenotypic testing with predicting clinical outcomes but there are some limitations. Phenotypic testing reports resistance in plasma not in lymph tissue. It may be more likely to predict insensitivity to a drug than sensitivity. That is, it may be more helpful in predicting what drugs may not work than what drugs may work.
Mellors tressed the importance of documenting a persons viral load decline after beginning therapy. Its important to see if they continue to decline to <50 copies/ml, he said. If such decline does not occu, he and others suggest intensification of therapy. Speakers refered to data from Dale Kempf, of Abbott, and ACTG 320 reported by Lisa Demeter that the nadir of viral load reduction (lowest level reached) is predictive of durability; and, that viral load reduction within a relatively short period after beginning therapy (4-8 weeks) is predictive of longer term viral load response.
I hope to report regular highlights of key info daily from here. Upon return to USA NATAP will report more details in newsletter, at forum and on web site. As well, NATAP will be conducting on site treatment education including data repors from Geneva at NYC ASOs over the next several months.
New data will be reported here on amprenavir, ABT-378, Fortovase, abacavir (1592U89), PNU-140690, IDV bid, ritonavir+saquinavir and other double PI combinations, adefovir, etc.
Im signing off for now because food is being served and Im starved and tired. See you later.