This study suggests that once-daily adefovir therapy reduces HIV RNA and is active against isolates resistant to lamivudine or lamivudine and zidovudine. Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.

HIV-1 Immunogen with unrestricted ART failed to demonstrate an increase in HIV progression-free survival. JAMA. 2000;284:2193-2202.

Background: Interleukin 2 (IL-2) administration increases CD4 counts in persons with higher counts. This study investigated persons with moderately advanced human immunodeficiency virus infection receiving highly active antiretroviral therapy (HAART). Methods: Two hundred four patients with CD4 T-cell counts from 50/µL to 350/µL who were treatment naive or had been treated only with reverse transcriptase inhibitors began a specified protease inhibitor HAART regimen. Virologic responders (Յ5000 copies/mL) at 12 weeks were randomized to open-label continuousinfusion IL-2 (IV IL-2), subcutaneous IL-2 (SC IL-2), or HAART alone. Thirty were not randomized and 15 enrolled in a substudy, leaving 159 for analysis. Subjects continued HAART alone for 72 weeks (n = 52) or with IV IL-2 (n = 53) or SC IL-2 (n = 54) for 5 days every 8 weeks. The IV IL-2 subjects could switch to SC IL-2 if their CD4 T-cell count increased by 100/µL or by 25%. Results: Patients receiving IV or SC IL-2 had greater increases in CD4 cell counts. At week 84, median increases were 459/µL, 312/µL, and 102/µL. Increases of greater than 50% at week 60 (primary end point) were achieved in 39 patients (81%) and 32 (67%) in the IV and SC IL-2 arms, respectively, compared with 13 (29%) in the HAART arm (PϽ.001 for both). Treatment with IL-2 did not increase plasma human immunodeficiency virus RNA levels. There were fewer new AIDS-defining events in the IV (P=.006) and SC (P=.03) IL-2 groups than in the HAART group (0, 1, and 7, respectively). Drug-related adverse events were more frequent with IL-2 treatment. Conclusion: Addition of IL-2 to HAART can significantly expand CD4 T-cell counts in moderately advanced human immunodeficiency virus infection, without loss of virologic control.

IL-2 before TI did not prolong time to CD4 of less than 350 cells/mm. A TI strategy utilizing a CD4 T-cell threshold of less than 350 cells/mm for restarting ART appears generally safe with most subjects in both arms remaining off ART for more than 1 year. Implications of our results for TI strategies include the potential advantage of starting ART at higher CD4 T-cell levels while avoiding any drug resistance and evaluating immunomodulators or drugs to reduce T-cell activation and HIV-1 RNA rebound during the TI.

In patients with baseline CD4 T-cell counts > or =300 cells/mm primarily treated with single- or dual-nucleoside ART, subcutaneously administered IL-2 at a dose of 1 million IU daily for up to 24 weeks had low toxicity but showed no consistent benefit in preventing decline in CD4 T-cell counts and minimal evidence of immunologic improvement vs. continued ART alone.