RTB: TCells fail again and again as surrogate markers; TCells do not correlate with Viral Load (“Virologic Failure”). What’s left? How about paying closest attention to actual health?
- “CD4 cell count monitoring does not accurately identify individuals with virologic failure among patients taking ART.”
BACKGROUND: CD4 T-lymphocyte (CD4) counts are widely used to monitor response to antiretroviral therapy (ART) in resource-limited settings. However, the utility of such monitoring in terms of predicting virologic response to therapy has been little studied.
METHODS: We studied participants aged 18 years and older who initiated ART in Tororo, Uganda. CD4 counts, CD4 percentages, and viral load (VL) were examined at 6-monthly intervals. Various definitions of immunologic failure were examined to identify individuals with VLs>or=50, >or=500, >or=1000, or >or=5000 copies per milliliter at 6, 12, and 18 months after treatment initiation. RESULTS: One thousand sixty-three ART-naive persons initiated ART. The proportion of individuals with virologic failure ranged between 1.5% and 16.4% for each time point.
The proportion with no increase in CD4 count from baseline did not differ between those with suppressed or unsuppressed VLs at 6, 18, and 24 months after ART initiation. No increase in CD4 cell counts at 6 months had a sensitivity of 0.04 [95% confidence interval (CI) 0.00 to 0.10] and a positive predictive value of 0.03 (95% CI 0.00 to 0.09) for identifying individuals with VL>or=500 copies per milliliter at 6 months.
The best measure identified was an absolute CD4 cell countor=500 copies per milliliter at 18 months which had a sensitivity of 0.13 (95% CI 0.01 to 0.21) and a positive predictive value of 0.29 (95% CI 0.10 to 0.44).
CONCLUSIONS: CD4 cell count monitoring does not accurately identify individuals with virologic failure among patients taking ART.
Global AIDS Program, US Centers for Disease Control and Prevention, Entebbe, Uganda. email@example.com
RTB: Here they go again – TCells and Viral Load don’t work as default markers of health, or drugging.
NIH News, February, 2009
It is unclear why increased CD4+ T cell counts did not translate into better health outcomes. James D. Neaton, Ph.D., of the University of Minnesota, principal investigator of the global clinical trials network that conducted ESPRIT, offers two possible explanations.
“It could be that the types of CD4+ T cells induced by IL-2 play no role in protecting the HIV-infected patient, and therefore the administration of IL-2 has no benefit,” says Dr. Neaton. “A second possibility is that the CD4+ T cells are at least somewhat functional or that IL-2 has some modest benefit, but that the side effects of IL-2 may neutralize any possible benefit.”
“In the end, the results of these two studies indicate that although a person’s number of CD4+ T cells is a key measure of success in the treatment of HIV with antiretroviral drugs, we can’t rely on CD4+ T cell counts to predict whether immune-based therapies such as IL-2 will improve the health of HIV-infected individuals,” concludes Dr. Levy, the principal investigator of SILCAAT.
“The purpose of clinical research is to clearly state and accurately test hypotheses with an ultimate goal of improving patient care,” notes H. Clifford Lane, M.D., director of clinical research at NIAID and a member of the executive committee of ESPRIT. “These two clinical trials successfully reached a definitive answer about the utility of IL-2 therapy for treating HIV infection. NIAID thanks the thousands of dedicated volunteers and investigators who made these studies possible. The results will have significant implications for the future development of immune-based therapies for HIV and studies of HIV pathogenesis.”