GENEVA--Researchers at the 12th World AIDs Conference presented a number of papers on the use of highly active antiretroviral therapy (HAART) to reduce viral load in people infected with HIV. Perhaps the most dramatic illustration of the impact of HAART on individual patients was Mark Harrington’s presentation: "N of One Study: My Lymph Node During Asymptomatic, Progressive, and Post-HAART Disease."
Mr. Harrington is Senior Policy Director of the Treatment Action Group (TAG) in New York City. He illustrated his lecture with biopsies of his own lymph nodes taken at various points between 1992 and 1998 (see figure).
The First Biopsy
The first biopsy in 1992 was after Mr. Harrington had been infected with HIV for 7 years. "I had an active lymph node," he said. "However, it was crammed with HIV. The center of the node was already dying."
Just before the Vancouver World AIDS meeting in 1996, the picture had changed. "My CD4 cells, after gradually declining for 9 years, plummeted to 152 cells/mm³. My viral load rose to 190,000 copies/mL. I was losing weight and had developed oral hairy leukoplakia, thrush, and molluscum contagiosum. I had yet to go on treatment, and, as it turned out, I couldn’t have progressed at a better time."
This was because the results of studies with protease-inhibitor-based HAART were presented at the Vancouver meeting, and the standard for treating HIV changed to keeping the virus suppressed below detectable levels.
"I decided to start HAART when I got home," Mr. Harrington said. His second lymph node biopsy, taken just before he started triple therapy, showed follicular involution and fatty infiltration. The follicular dendritic cell network was disrupted and could no longer trap virus, and there were many "starburst-like" productively infected cells. "My blood was overflowing with infectious virus. My immune system was dying," he said.
After starting HAART, his viral load dropped by over 3 logs, his CD4 count rose to 600 cells/mm³, his skin conditions went into remission, and he gained 25 pounds.
"By June of this year, my viral load remained below 25 copies/mL and my CD4 count was 925 cells/mm³. My immune system regained previous abilities to respond to mitogens and alloantigens. The proportion of naïve CD4 cells quadrupled. The number of resting, latently infected CD4 lymphocytes is now about one per 2 million cells. I’m one of the lucky ones," Mr. Harrington said.
The third lymph node biopsy, from March 1998, showed virtually no HIV RNA. CD21 staining showed the restoration of a follicular dendritic cell network and lymph node architecture.
"My immune system is coming back to life," Mr. Harrington said. "I can live with a little provirus--and even with a little ongoing RNA replication--as long as my immune system recovers enough function so that I don’t have to die of AIDS."
