11th International AIDS Conference Vancouver, British Columbia — July 7-12, 1996

Int Conf AIDS 1996 Jul 7-12; 11:26 (abstract no. LB.B.6022)
Holodniy M, Niu M, Bethel J, Standiford H, Schnittman S; VA Medical Center, Palo Alto, CA. Fax: (415) 858-3978. E-mail: hf.myh@forsythe.stanford.edu.

OBJECTIVES: To assess the role of ZDV initiated during primary HIV infection (PHI), prior to the establishment of chronic infection, and to provide insight into the pathogenesis of PHI.

METHODS: patients presenting with symptoms were screened for evidence of acute HIV infection; patients with p24 antigenemia and negative/indeterminate Western blot (WB) were randomized in a double-blind study to receive ZDV at 1000 mg/day or placebo for 24 weeks. Frequent clinical and laboratory evaluations were performed through week 24 and beyond study drug discontinuation. Virologic and immunologic assays included serial WB, flow cytometric phenotyping, p24 antigen, quantitative PBMC/plasma culture, plasma RNA, and viral phenotype and genotype.

RESULTS: The study was closed to enrollment in 12/95 after enrolling 28 patients. Twenty-three patients completed 24 weeks of therapy; 13 patients have completed their week 48 visit. Significant adverse events and minor clinical events (e.g., thrush, HSV, H. Zoster, OHL) were infrequent and comparable on the two arms. There were two deaths, one on the ZDV arm (wasting syndrome), and one on the placebo arm (bacterial pneumonia). CD4 counts (cells/mm³) were similar at baseline in the two arms (ZDV 604, placebo 619), but differed at 24 weeks (ZDV 672, placebo 502; p=0.19) and at 48 weeks (ZDV 701, placebo 362; p=0.02). Plasma RNA levels (log copies/ml) were similar at baseline for the two arms (ZDV 5.47, placebo 5.78), and declined comparably by week 48 (ZDV 3.93, placebo 4.00). In contrast, PBMC cultures (log IUPM), which were greater in the ZDV arm at baseline (ZDV 2.35, placebo 1.73) dropped substantially in both arms at week 24 (ZDV 1.65, placebo 1.10), but continued to fall in the ZDV arm while rebounding in the placebo arm by week 48 (ZDV 0.48, placebo 1.68; p=0.02).

CONCLUSIONS: Preliminary analysis of this study demonstrates that 6 months of high dose ZDV initiated during PHI results in immunologic and virologic benefit, which is maintained during early chronic infection following ZDV discontinuation. At 48 weeks, CD4 cells were significantly higher, and PBMC titer, but not RNA levels, were significantly lower. The long term clinical effect of ZDV intervention during PHI remains to be determined. Further studies with more potent antiretrovirals and combinations are warranted.

960707
LBB6022

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