International AIDS Conference VIII: HIV Progression and Markers of HIV Infection
Seattle Treatment Education Project: STEP Perspective - Volume 4, Number 3 - October 1992 Lori Panther, M.D.
Interesting data was presented regarding in vivo study of how the HIV virus changes throughout infection. In addition, studies were discussed regarding the predictive value of several surrogate markers in predicting the course of HIV infection. Surrogate Markers and Disease Progression CD4 count. The value of CD4 count as an accurate measure of disease progression was under question. A few studies were presented as retrospective analyses of the predictive value of CD4 counts in drug trials. A group of 264 HIV-positive people followed for over five years revealed that CD4 count is a relatively insensitive predictor of HIV progression compared to beta-2 microglobulin, especially in situations when the CD4 count remains low for prolonged periods without the development of AIDS (Jacobsen, USA, MoC0084). Another study suggested the combination of CD4/CD8 ratio, beta-2 microglobulin and red cell count was a better predictor of HIV stage compared to CD4 count alone (Hirsch, USA, PoB3485). One clinical trial studying AZT effectiveness in 1986 showed that the change in CD4 count in the cohort under study did not correlate with clinical progression. Another retrospective analysis of the contribution of CD4 count in predicting clinical response in a drug trial found the CD4 count explained only 35 percent of the beneficial effect of the drug. These data suggest that the CD4 response to a given treatment may not always be a reliable predictor of treatment effect (Lagakos, USA, Session 114). Conversely, one study of ddI found that a sustained 10 percent increase in CD4 count significantly correlated with increased survival (Charlebois, USA, PoB3482). One confounding factor for the ability of CD4 count to accurately predict HIV progression is that improved opportunistic infection prophylaxis over the years has resulted in a downward shift of the CD4 count at which patients progress in their disease. For example, before mid-1987 CDC class IVC1 disease was diagnosed at an average CD4 count of 180; currently CDC class IVC1 disease occurs at an average CD4 count of 60 (Touraine, France, PoB3330). CD8 function. Confirming a previous report that CD8 cells inhibit replication of HIV in vitro, a small study of patient samples showed that the ability of CD8 cells to inhibit HIV replication correlated with the patients' CD4 cell count. Patients with higher CD4 counts tended to have greater CD8 cell-mediated inhibition of HIV replication in vitro. This offers clinical evidence that CD8 cells hold HIV replication "in check" early in the disease (Gomez, Canada, PoA2177). Syncytium-producing virus. Some intriguing work was presented addressing the question of viral "aggressiveness." In general, progression of any chronic infection is a result of three factors: loss of immune response, coinciding cofactors, and emergence of more virulent strains of the infecting agent. We can measure the aggressiveness of an HIV strain from a patient by taking the strain to the laboratory and measuring its ability to induce lymphocytes to fuse together into structures called syncytia. Two studies showed that syncytium-producing strains are more likely to be present in patients with a faster progression to AIDS, and emergence of syncytium-producing strains in a given patient who originally had non-syncytium-producing strains predicts an accelerated course to AIDS (Ho, USA, Session 114; Miedema, Netherlands, Session 114). The rate of progression to AIDS over 30 months in 45 patients with syncytium-producing virus was 67 percent compared to 16 percent in 45 patients with non- syncytium-producing virus. In addition, administration of AZT did not affect progression to AIDS in those with syncytium-producing virus whereas it slowed progression to AIDS in those with non- syncytium-producing virus (Miedema, Netherlands, Session 114). Neutralizing antibodies. One serologic study was presented with regard to HIV-enhancing antibodies. The concept of antibody production that actually enhances HIV infection was raised. Theoretically, antibody production against one viral population within a patient could actually be an enhancing antibody for another population of HIV within the same patient. If this holds true it may be an obstacle for the development of a vaccine to selectively induce only those antibodies that will be neutralizing and not enhancing for a wide range of HIV strains (Levy, USA, Session 114 ). PCR. "PCR," polymerase chain reaction, remains the most sensitive way to detect HIV in a blood specimen. This research technique is being refined to assess level of viral load and to monitor response to therapy. One three-year followup of 24 HIV-positive men who did not have detectable virus in their blood, by the PCR test, were found to have a five-fold decreased rate of progression to AIDS compared to 73 men who had HIV detectable by PCR (Woodfall, Canada, MoC0083). In another study of 70 patients, tested by PCR, increasing amounts of HIV per million cells in blood lymphocytes correlated with decreasing CD4 count and increased p24 antigen (Ko, Canada, PoA2139).
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Always watch for outdated information. This article first appeard in 1992. This material is designed to support, not replace, the relationship that exists between you and your doctor.
This information is designed to support, not replace, the relationship that exists between you and your doctor.