Brief Overview of ICAAC Highlights
From Julles Levin, NATAP
     Sept 29, 1998 San Diego

Below is a selection of abbreviated highlights from ICAAC. More extensive and expanded coverage is being posted to the NATAP web site.

• Although adherence considerations preclude it, taking amprenavir 3 times a day appears to improve its antiviral activity. The effectiveness of a particular drug based upon its concentration in blood may be associated with its daily AUC or its trough, and this difference may be class based. The effectiveness of protease inhibitors may be associated with the trough concentration of the drug. Abacavir appears to be associated with daily AUC. Eventually, abacavir may be explored as a once-a-day regimen
• Based on in vitro high tech study abacavir may have a synergy with amprenavir that it may not have with other PIs
• Agouron showed data associating plasma drug concentration, baseline viral load and initial 4-week change in viral load as early predictors of virological durability of nelfinavir at 48 weeks
• The new Bristol-Myers protease inhibitor has only been studied pre-clinically but may be once-a-day, more potent than current PIs, and may only have partial cross-resistance with current PIs. Clinical studies expected in early '99
• 4-drug regimen of 3TC+AZT+indinavir+nevirapine-" including drugs from 3 classes provided more rapid plasma HIV elimination than mono- or triple therapy suggesting incomplete inhibition of HIV replication by those treatments. This study and similar research from Amsterdam group reported at Geneva and Retrovirus suggest a potent 4-drug regimen may increase durability of virological suppression because of faster decline in viral decay
• The definition of "fat redistribution" or " lipodystrophy" remains unclear. It's proposed that the syndrome may be associated with protease inhibitor use , the magnitude of viral load reduction, the changes a body experiences due to partial immune reconstitution, and/or other effects due to HIV disease or recovery from HIV
• The use of genotypic and phenotypic resistance testing may detect pre-existing mutations to drugs prior to initial therapy . The use of such testing should help improve selection of drugs for a salvage regimen by evaluating a person's sensitivity to specific drugs. Testing appears to be better at showing which drugs a person may not be sensitive to than which they may be sensitive to
• Protease sparing NNRTI regimens show good short-term data but durability has not yet been shown-The 24 week data on EFV is holding up at week 36. Using the on-treatment analysis, it was reported at Geneva that 95% <400 copies/ml and 76% had <50 copies/ml. At ICAAC it was reported that Efavirenz+AZT/3TC had 88% <50 copies/ml (as-treated analysis) and about 95% <400 copies/ml. In a second but smaller study extending follow-up to 48 weeks (n=21) , 90% had <400 copies/ml at week 48. Using an on-treatment analysis at week 24, 88% (46/52) had <400 copies/ml using d4T+ddI+nevirapine; 30/41 had <50 copies/ml
• Two studies were reported about use of adefovir (ADV). In one study, adefovir+IDV+3TC+AZT was compared to ADV+IDV+AZT, ADV+IDV+3TC, ADV+IDV+d4T, and IDV+AZT+3TC. Using the on-treatment analysis, 20 week data was reported-- 79-83% had <400 copies/ml. Using the intent-to-treat analysis at week 20, 46% in 4 drug regimen had <400 copies/ml, while 57-60% had <400 copies in the 3-drug arms. Presenter said the low 46% rate was due to high drop-out rate. Adefovir's favorable resistance profile was discussed-presence of the 184 3TC resistance mutation increases adefovir efficacy and reduces AZT cross-resistance between adefovir and AZT. Side effects and toxicities are associated with use of ADV. Increased incidence of elevated LFTs may be associated with ADV, and kidney related (PRTD-Proximal Renal Tubular Dysfunction) toxicities are associated with use of ADV. In one study about 40% of participants experienced PRTD by week 48. PRTD does not begin to appear until 6 months of ADV treatment. PRTD symptomology appears to start resolving upon stopping ADV or reducing dose. It could take 12-16 weeks to return to normal. At week 16, 80% resolved symptomology
• Newly reported 16 week data from a pivotol NDA FDA submission study of amprenavir+AZT/3TC using the on-treatment analysis showed 88% had <400 copies/ml. Using the intent-to-treat observed data analysis, 82% had <400 copies/ml and 59% had <50 copies/ml. They reported 71% (as-treated analysis) with >100,000 copies/ml (10/14) had <400 copies/ml, and 96% (25/26) with viral load between 10,000 and 30,000 copies/ml had <400 copies/ml (as-treated). Side effects included parasthesia and rash.
• Ten rhesus macaques monkeys were infected intravenuously with SIV and then treated with placebo or PMPA during the acute phase of infection. After starting PMPA there was a little peak in viremia, then PMPA treatment kept virus load low. After PMPA was stopped virus load increased in 4/6 monkeys. In 2/6 animals, virus load decreased to below detection after PMPA was stopped. Author concluded PMPA induced immunity able to control replication in 2/6 monkeys, and that a vaccination effect could be achieved by post exposure therapy in these monkeys
• Use of HAART in a Ryan White Title program at Parkland Health & Hospital Systems in Dallas, Texas resulted in decreased inpatient utilization and costs, despite additional costs of HAART. For every $1 spent in HAART expenses there was a corresponding $3 savings in inpatient cost. Inpatient costs declined by 49% and incidence of opportunistic infections dropped from 22.3% to 10.1%. Data collected from 1/94 to 12/97. Specific hospital utilization was evaluated for the 12 months before and after availability of HAART in October '96.