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 |
| Size | 24 patients |
| Comparison | None |
| Plan | 3 STI of increasing length (2, 4 and 8 weeks) at 34, 48 and 72 weeks for patients with suppressed VL (<20 copies). |
| Duration | 82 weeks |
| 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. |
| Enrollment started: | 5/2000 |
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. |
| Duration | - | 9 months |
| Follow-up | - | - |
| Primary Endpoint | Safety | Time off treatment. |
| Secondary Endpoints | Time off treatment, cost, QOL, immune monitoring. | Immune monitoring. |
| Enrollment started: | - | - |
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 |
| Regimen | HAART | HAART | Multiple strategies |
| 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. 2) HAART/STI 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. |
| Enrollment started: | Underway | Underway | Proposal |
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. |
| Study Type | Randomized | Randomized |
| 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 4. Others |
Resistance, time off treatment, immune monitoring |
| Enrollment started: | 12/2000 | Proposed |
Table 5 - Chronic, Unsuppressed or MDR
| Study Title / Sponsor | ANRS 097 "GigaHAART" | OPTIMA Tri-national study | ACTG A5086 | CPCRA 064 |
| Population |
Chronic unsuppressed. 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. |
Chronic unsuppressed. MDR virus. VL > 10,000. |
| Study Type | Randomized | Randomized | Randomized | Randomized |
| 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 |
| Follow-up | - | 3 years | - | - |
| 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. |
| Enrollment started: | Underway | Proposed | Proposed | Underway |