Given the extensive immunologic and virologic data available from ACTG 315, follow-up studies of this advanced-disease population are indicated to primarily ascertain the impact of long-term suppression of viral replication on immunologic reconstitution or re-education and the durability of the antiviral effects of HAART.

Patients continue their current ACTG 315 regimen of zidovudine plus lamivudine plus ritonavir in an open-label fashion while undergoing 6 weeks of extensive evaluations. Treatment decisions are based on baseline viral load (mean of 2 viral load measurements taken during 6-week evaluations). Patients with HIV-1 RNA less than 100 copies/ml continue the ACTG 315 regimen. Patients with HIV-1 RNA 100-3000 copies/ml may continue the ACTG 315 regimen or initiate a new HAART regimen selected by the local investigator or primary care physician. Patients with HIV-1 RNA greater than 3000 copies/ml initiate a new HAART regimen selected by the local investigator or primary care physician. [AS PER AMENDMENT 4/10/00: Changes to regimens must be done in consultation with the study team. The team acknowledges that a viable regimen may not be available for a given patient when the plasma HIV RNA level is above 3,000 copies/ml. In this case, patients may remain on their failing regimen with evaluation every 8 weeks until a viable regimen becomes available to them.] All patients are required to maintain a HAART regimen that contains at least 3 drugs, 1 of which is a protease inhibitor. [AS PER AMENDMENT 3/5/01: All patients are required to maintain a HAART regimen that is approved by the protocol chairs.] Zidovudine (ZDV), lamivudine (3TC), stavudine (d4T), didanosine (ddI), delavirdine (DLV), ritonavir (RTV), and saquinavir soft gel capsules (SQV sgc) are provided on-study. [AS PER AMENDMENT 9/19/00: ZDV, 3TC, 3TC/ZDV combination tablet, d4T, ddI, DLV, RTV, and SQV sgc will be supplied by the protocol for 182 weeks.] [AS PER AMENDMENT 3/5/01: The following antiretroviral medications will be supplied by the protocol for Steps 1 and 2: ZDV, 3TC, 3TC/ZDV combination tablet, d4T, ddI, DLV, RTV, and SQV sgc.] Therapy is continued for 54 weeks. [AS PER AMENDMENT 10/6/98: The initial 54-week trial is followed by an additional 2 years of long-term evaluation. Also per this amendment, protocol therapy is initiated at Week 6.] [AS PER AMENDMENT 9/19/00: The initial 54-week trial is followed by an additional 2.5 years of long-term evaluation.] [AS PER AMENDMENT 3/5/01: Step 1 has an initial 54 weeks of treatment followed by 140 weeks of long-term follow-up. Step 2 has an additional 36 weeks of long-term follow-up. Patients who complete the final visit on Step 2 (Week 230) should return to the clinic 4 weeks after receiving the last dose of study-provided medication to complete the final evaluations.] [AS PER AMENDMENT 10/6/98: Patients may co-enroll in an immunology substudy.] [AS PER AMENDMENT 6/11/99: The immunology substudy is being piloted in 3 to 4 volunteers and may not proceed until the feasibility of the pilot project is reviewed.]