from Jules Levin

Wednesday, July 1

Following are data reported at this morning’s session called Clinical Immunology in HIV infection. The EARTH study explored immunological responses to HAART (AZT/3TC/RTV) initiated during early asymptomatic HIV. Baseline CD4 and HIV RNA were 534 cells and 3.74 log, respectively; naive CD4 were 322 and 214 memory cells; naive and memory CD8 were 603 and 556, respectively. Good adherence was reported by 14/15; 4/15 persons disct RTV. At weeks 12 and 24 13/15 (87%) and 14/15 (93%) had <200 copies/ml. One person failed and was noncompliant.

Investigator reported "slight increase" in naive CD4 from 322 to 417 at week 24. Absolute CD4 increased from about 550 to 700 cells. There was no significant increase in memory CD4. Activation markers CD8CD38 and HLA-DR decreased meaning a decrease in HIV antigen is occurring. The investigator characterized reconstitution of naive CD4 as modest, and said earlier start of therapy may counteract immune destruction.

This afternoon Bruce Walker delivered a talk reviewing his previously reported data. The recent May ‘98 NATAP Reports reviewed his talk on this subject at the Retrovirus Conference. He reported here observing that a HIV specific CD4 response to HAART during acute infection stimulates a CTL response which is sustained out 2 years and controls HIV. He said he saw this response in an individual not treated until after18 months post infection but did not see response in an individual initiating treatment after 3 months post infection.

Brigette Autran refutes his contention. In last month’s Lancet she discusses her findings. She reported here that the magnitude and stability of the viral load respnse to HAART in persons treated during advanced HIV (50-150 CD4) correlates with long term CD4 reconstitution. In 10 good responders none of them have so far experienced major events Ois) while in 10 non responders 3 have experienced major events. 50% responded to recall antigens. But only individuals with strong CD4 and viral load responses had such respnses. She emphasized that this good response must be accompanied by strong and continual viral load suppression. Both Autran and Walker said large studies are needed to address this question. I’m not convinced that their contentions are mutually exclusive based on their data but I will explore this further and report back on my findings. Nonetheless, Autran’s findings are encouraging. I will report an expanded discussion of these questions upon return to NYC from Geneva.

Two interesting reports on IL-2 in individuals with high (250-500) and low (<200) CD4s were presented. Briefly, Daniel Berger reported on a group with <200 CD4 who received HAART for 12 months: mean CD4 of 100 and mean viral load of 4.7 log. After 12 months 80% had <500 copies/ml by bDNA. Subsequently, they received treatment with 5-6 cycles of IL-2 administered subcutaneously at dosing of 9-18 million units daily for 5 days every 8 weeks. After 12 months of HAART alone baseline CD4 increased from 100 to 249; subsequent to IL-2 treatment CD4 increased from 249 to 470. The usual IL-2 asociated side effects were experienced: malaise, fatigue, fever. However, it is uncertain if 2nd CD4 increase was due to a continuing effect of HAART or the addition of IL-2. Berger thinks the IL-2 caused the effect but it is not certain.

I must leave now to attend two nighttime meetings. See you later.