Studies 398 and 400 will explore a number of questions including the influence of baseline genotypic and phenotypic protease inhibitor and RT inhibitor resistance profiles. As well, the studies will evaluate the genotypic and phenotypic resistance profiles to the study drugs that emerge on treatment. There will be several important substudies including a pharmacokinetics study to determine the PK relationships between the study drugs, and substudies evaluating immunological responses. Investigators will try to determine to the extent possible the relationship between drug exposure (as measured by a combination of PK and compliance) to drugs and the degree of duration of response and the emergence of resistance. As well, a PK relationship profile will be conducted for ritonavir+saquinavir when coadministered with efavirenz.

ICC study #006 will offer 5 different open-label treatment regimens. Three regimens will be for individuals who’ve failed protease inhibitors but are naive to NNRTIs, and two regimens with simplified dosing regimens for treatment naive persons. The study will be open label. Originally, the study was supposed to begin in February but its been delayed. The first few regimens are expected to begin enrollment in early June. The study will enroll 25 persons in each regimen at 7 different sites. The 3 regimens for protease failures are expected to be:

• adefovir+efavirenz+141W94+1592U89

• MKC-442+delavirdine+ddI+d4T

• MKC-442+nevirapine+ddI+d4T

MKC-442 is a NNRTI in early development which has shown a 1.30 log reduction in viral load in a 15 day study. This trial is the first to study the combination of two NNRTIs.

The two simplified dosing regimens are for protease inhibitor naive individuals:

• indinavir+nelfinavir+efavirenz (both indinavir and nelfinavir will be taken twice daily

• a once a day 4-drug regimen of adefovir+3TC+ddI+efavirenz

• NYU/Bellevue, ph- (212) 263-6565;

• Cornell Univ in NYC, (212) 746-7206;

• Univ of Cal at San Diego, (619) 543-8080;

• University of Colorado, (303) 372-5535;

• University of Minnesota, (612) 625-1462;

• AIDS Research Consortium Atlanta, (404) 876-2317;

• Pacific Oaks Medical Group-in LA, (310) 652-2562.

ACTG Sites. It is optional to a site whether or not they want to pick up an ACTG study. So, you have to check with your local site to determine if they offer these studies. If you are interested it may be important to contact the site quickly for information because enrollment could fill up quickly.

• NYU/Bellevue, NYC, (212)263-6565

• Mt Sinai Med Cen, NYC, (212) 241-0433

• Washington Univ, St Louis, (314) 454-0058

• Cornell Univ, NYC, (212) 746-4177

• Ohio State Univ, Columbus, (614) 293-8112

• Univ of Cincinnati, (513) 558-8373

• Case Western Univ, Cleveland, (216)844-8051

• Indiana Univ Hospital, (317) 274-8456

• Northwestern Univ, Chicago, (312) 908-4655

• Univ of North Carolina, Chapel Hill, (919) 966-7883

• Univ of Hawaii, (808)737-2751

• Howard Univ, Washington DC, (202)

• Univ of Puerto Rico, (787) 767-9192

• Massachusetts General Hospital, Boston, (617) 726-5598

• Johns Hopkins Univ, Baltimore, (410) 955-4370

• Stanford Univ, San Francisco, (650) 723-2804

• UCLA School of Med, Los Angeles, (310) 206-8029

• Univ of Cal at San Diego, (619) 543-8080

• San Francisco General Hospital, (415) 476-9296

• Univ of Miami, (305) 243-5765

• Univ of Rochester Med Cen- NY, (716) 275-2740

• Univ of Washington at Seattle, (206) 731-8877

• Univ of Minnesota, Minneapolis, (612) 625-1462

• Duke Univ, Durham- NC, (919) 681-6060

• Tulane Univ, New Orleans, (504) 584-3605

• Walter Reed Army Med Cen, (301) 295-0957

• Univ of Alabama at Birmingham, (205) 975-7925

• Univ of Colorado Health Sciences Cen, Denver, (303) 372-5535

• Univ of Pennsylvania, Philadelphia, (215) 349-8092

• Univ of Texas, Galveston, (409) 772-0361