January 31, 2001
|Study Title / Sponsor||ANRS 1000 "PRIMSTOP"|
|Population||Primary Infection (within 4 weeks of symptoms)|
|Study Type||Pilot -- no controls|
|Regimen||HAART + HU|
|Plan||3 STI of increasing length (2, 4 and 8 weeks) at 34, 48 and 72 weeks for patients with suppressed VL (<20 copies).|
|Follow-up||Until 108 weeks|
|Primary Endpoint||HIV RNA < 20 copies for at least 6 months from last TI.|
|Secondary Endpoints||1. Resistance; 2. Proviral DNA; 3. Cellular RNA; 4. HIV-1-specific T-lymphocyte response.|
Table 2 - Chronic Suppressed
|Study Title / Sponsor||TIBET||AUTOVAC II|
|Population||Chronic Suppressed <50 for 1 year; CD4 >500 for 6 months||Chronic suppressed <50 for 2 years|
|Study Type||Pilot, no controls||Randomized|
|Regimen||HAART||HAART w/without IL-2|
|Size||10 patients||50 patients|
|Comparison||None||Continuous versus STI w/without IL-2|
|Plan of Interruptions||Stop treatment until CD4+ count drops <350. Restart and continue until resuppressed.||Cycle between 2 weeks off and 4 weeks on treatment w/without IL-2. After 6 cycles, stop treatment in all arms and observe until CD4 drops <350.|
|Primary Endpoint||Safety||Time off treatment.|
|Secondary Endpoints||Time off treatment, cost, QOL, immune monitoring.||Immune monitoring.|
Table 3 - Chronic Suppressed
|Study Title / Sponsor||Philadelphia Wistar Institute||Gladstone Institute||Garcia/Gatell|
|Population||Chronic Suppressed Prior VL > 10,000; current VL < 50. Nadir CD4 count > 100 cells; current CD4 count > 400.||Chronic Suppressed||Chronic Suppressed|
|Study Type||Individualized Protocol - Randomized.||Pilot - no controls.||Randomized|
|Size||52 patients||20 patients||175 patients|
|Comparison||IT by group under continued ART versus group with previous periodic TI.||None||Multiple strategies: Continuing treatment vs. STI w/without HU; w/without Immune mod. w/without immunogen.|
|Plan of Interruptions||Continuous ART for 40 weeks - (non-adherent
patients will be excluded). Stop (comparison TI). Versus
1) Stop for 2 weeks (priming TI).
2) Restart and treat with ART until RNA <50 for 4 weeks.
3) Following suppression for 4 weeks, stop for 4 weeks (boost TI).
4) Restart and treat until RNA < 50 for four weeks.
5) Following suppression for 4 weeks, stop for 6 weeks (CD8 boost TI).
6) Restart and treat until RNA <50 for four weeks.
7) Following suppression for 4 weeks, open-ended TI (comparison TI).
After suppressed on HAART for 3 months:
1. Stop treatment for 2 months.
2. Restart and treat for 6 months. Repeat cycle 3 times.
1) Continue HAART for 1 year, then stop.
3) HAART/STI + HU
4) HAART/STO + general immune modulator
5) HAART/STI + immunogen.
|Duration||12 - 18 months||~ 3 years||18 months|
|Follow-up||~ 48 months||~ 3 years||-|
|Primary Endpoint||Time to RNA > 5000 during comparison TI. Demonstrated adherence by electronic monitors required.||Viral load levels||Proportion with VL set point < 10,000 after 6 months off treatment.|
|Secondary Endpoints||1. CD4+ proliferation.
2. CD8+ response.
3. Amplitude of successive VL rebounds.
4. T-cell phenotype; resistance; thymic function.
5. Quality of life
|Intensive immuno-logic monitoring. Quality of life.||
HIV-1 specific CTL response.
HIV-1 specific T-help response.
Table 4 - Chronic, Previously Untreated
|Study Title / Sponsor||ACTG A5102||SITACI|
|Population||Patients on first ART regimen; HIV RNA < 200 copies; CD4+ > 500 cells.||Chronic, previously untreated.|
|Regimen||HAART with or without IL-2||HAART|
|Size||80 patients||10 patients|
|Comparison||IL-2 versus no IL-2||Continuous versus STI|
|Plan of Interruptions||1) Treat w/without IL-2 for 18 weeks.
2) If CD4 > 500 then stop until CD4 drops < 350 (2x).
3) Restart and treat with ART for 6 months
4) If RNA < 200 continue w/without IL-2 for 18 weeks.
5) If CD4 > 500, stop until CD4 drops < 350 (2x).
6) Restart and treat with ART for 6 months
7) If RNA < 200, continue w/without IL-2 for 18 weeks.
|Cycle between 3 months on treatment and 1 month off. At 16 months, stop treatment in both arms and observe until CD4 drops <350.|
|Duration||~ 18 months to primary endpoint (end of step 2)||16 months +|
|Follow-up||~ 5 years||-|
|Primary Endpoint||CD4+ cell count at end of first 18 weeks w/without IL-2; rate of CD4 decline during TI.||Safety|
|Secondary Endpoints||1. Duration of 1st & 2nd TI.
2. Rate of resuppression.
3. Replicative capacity, fitness, resistance
|Resistance, time off treatment, immune monitoring|
Table 5 - Chronic, Unsuppressed or MDR
|Study Title / Sponsor||ANRS 097 "GigaHAART"||OPTIMA Tri-national study||ACTG A5086||CPCRA 064|
VL > 75,000;
CD4+ < 200.
|Chronic unsuppressed. MDR, have failed 2 regimes including 3 classes.||Chronic unsuppressed.
VL > 10,000; CD4 > 150.
At least one prior virologic failure; heavily pretreated.
MDR virus. VL > 10,000.
|Regimen||3-4 NRTI, an NNRTI, HU, RTV+APV or IDV, SQV, NFV||
MegaHAART is > 5 drugs.
Retreatment based on baseline genotype.
|Best available regimen based on baseline viral genotype, pheno-type and treatment history.||Regimen selected based on genotyping / phenotyping at baseline.|
|Size||90 patients||1300 patients||220 patients||480 patients|
|Comparison||Begin ""Giga-HAART"" immediately or wait 8 weeks to begin.||Continue, stop or switch to Mega-HAART||Begin new regimen immed-iately or wait 16 weeks to begin.||Begin new regimen immediately or wait 16 weeks to begin.|
|Plan of Interruptions||Deferred group has an 8-week washout before starting.||3 to 6 months drug-free period for interruption arm.||Deferred arm waits 16 weeks to begin new regimen.||Deferred arm waits 16 weeks to begin new regimen.|
|Duration||-||2 years||64 weeks||24 months|
|Primary Endpoint||Virological response = > 1.0 log reduction in VL at weeks 12 and 24.||Time to AIDS or death.||Proportion with VL < 400 at 48 weeks.||Progression to AIDS or death.|
|Secondary endpoints and monitoring||Toxicity, genotype, PI plasma concentrations.||Toxicity, illness, QOL, standard markers, economics.||VL < 50 at 24, 48, 64 weeks.
Adherence; Stratify above and below VL= 100,000; CD4+ above and below 200.
Resistance and Immunology substudies proposed.
|Genotype, VL, CD4+, drug levels, fitness assays. QOL adherence. Stored plasma and cells.|