AIDS Biology

Edited by: Ricki Lewis IMPACT ON TREATMENT: John Mellors remarks that his papers "go a long way towards a more accurate assessment" of prognosis in people with AIDS. J.W. Mellors, L.A. Kingsley, C.R. Rinaldo, Jr., J.A. Todd, B.S. Hoo, R.P. Kokka, P. Gupta, "Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion," Annals of Internal Medicine, 122:573-9, 1995. (Cited in more than 150 publications through June 1997) J.W. Mellors, C.R. Rinaldo, Jr., P. Gupta, R.M. White, J.A. Todd, L.A. Kingsley, "Prognosis in HIV-1 infection predicted by the quantity of virus in plasma," Science, 272:1167-70, 1996. (Cited in more than 100 publications through June 1997) Comments by John W. Mellors, University of Pittsburgh Medical Center. Tracking progression of AIDS has evolved from observing symptoms to detecting antibodies against HIV to counting helper T cells to monitoring viral load. A team led by John W. Mellors, an associate professor of medicine and pathology and the director of the HIV-AIDS program at the University of Pittsburgh Medical Center, published papers in 1995, 1996, and 1997 that refine viral-load monitoring. The group's 1995 Annals of Internal Medicine and 1996 Science papers are featured here. The team's 1997 article (J.W. Mellors et al., Annals of Internal Medicine, 126:946-54, 1997) is too new to be included in the Hot Papers database. Mellors's team first demonstrated a correlation between increasing level of HIV RNA in plasma and disease progression, then utilized the measure's predictive power to establish risk classes of developing AIDS within six years. All three studies show that the prognosis worsens as the amount of virus in the bloodstream increases. "The amount of virus in the bloodstream is directly proportional to the number of productively infected cells in the body. With more productively infected cells, there is a greater rate of CD4+ cell destruction, which leads to earlier burnout of immunity," Mellors says. The 1995 study evaluated 62 men who had seroconverted at a known date. The researchers determined CD4+ count and viral load every six months for an average of 3.8 years, after which the men were divided into groups based on their status: Eighteen developed AIDS, 21 lost CD4+ cells but did not develop AIDS, and 23 maintained a stable CD4+ level. The researchers correlated this status to four levels of viral load. The link was clear: Sixteen of the 18 people with AIDS were in the highest viral load categories, as were 13 of the 21 with declining CD4+ counts and only four of the 23 stable men. The 1996 Science paper established the prognostic value of viral-load monitoring, finding it to more powerfully predict AIDS onset than CD4+ count. The 1997 study more clearly mirrored reality by evaluating "individuals who basically walked in the door [and were] diagnosed with HIV, with an unknown duration of infection," relates Mellors. The researchers measured viral load, CD4+ cells, and the immune system activation markers neopterin and b2-microglobulin. This study showed that considering viral load and CD4+ count can result in a better estimate of risk than either measure alone and established 12 risk levels based on these parameters. The lowest category predicts a 1.7 percent risk of progression to AIDS within six years; the risk for the highest category is 98 percent. These papers have been highly cited, Mellors speculates, because the ability to more precisely predict AIDS onset will impact treatment. "It's not absolute, but [the risk classes] go a long way toward a more accurate assessment of prognosis. It tells you in whom to initiate therapy, and when. It may also be useful to gauge the effectiveness of therapy," he concludes. The articles listed here, all approximately two years old, have received a substantially greater number of citations than others of the same type and vintage, according to data from the Science Citation Index of the Institute for Scientific Information, Philadelphia. Why have these research reports become such standouts? In conversations with The Scientist, the authors attempt to provide an answer.

AIDS Biology

The Scientist Staff

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