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Long-Term Nonprogression Rare and Transient in Large CASCADE Cohort Study
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XVIII International AIDS Conference, July 18-23, 2010, Vienna
Mark Mascolini
Fewer than 1% of more than 6500 CASCADE cohort members could be classified as long-term nonprogressors 15 years after HIV seroconversion in a large longitudinal study of this phenomenon [1]. The rare few who did meet the study definition of long-term nonprogression progressed in a median of 3.5 years.
Long-term nonprogression, broadly defined as stable HIV infection without antiretroviral therapy, has long intrigued researchers because of the clues it may hold to HIV pathogenesis. Most studies of long-term nonprogression are limited, however, because they evaluate individuals at a single time point and define progression only by CD4 count. CASCADE researchers planned this analysis to see how nonprogression rates evolve over time and what factors may influence that evolution. Unlike most nonprogression studies, they estimated progression-free survival without limiting progression criteria to CD4 count.
The CASCADE team defined progression as (1) a CD4 count falling below 500, (2) starting antiretroviral therapy, or (3) an AIDS diagnosis. For purposes of this analysis, long-term nonprogression meant going at least 10 years without one of these three progression markers.
The investigators focused on 6506 people (23% of them women) with a well-estimated date of HIV seroconversion. Median age at seroconversion stood at 28 years (interquartile range [IQR] 24 to 34). Half of the cohort acquired HIV through gay sex, about one quarter through heterosexual sex, about one quarter through injection drug use, and 1% because of hemophilia.
Estimated progression-free survival dwindled sharply with every additional 5 years since seroconversion. Nonprogression estimates were 9.5% (95% confidence interval [CI] 8.8 to 10.1) 5 years after seroconversion, 1.9% (95% CI 1.7 to 2.2) after 10 years, and 0.5% (95% CI 0.3 to 0.7) after 15 years.
Ten years after HIV seroconversion, 189 people (2.8%) could be classified as long-term nonprogressors, including 57 women (30%). Their median age at seroconversion was similar to that of the overall group at 27 years (IQR 23 to 32). But proportions by transmission risk differed somewhat from the whole group: 42% gay sex, 33% injection drug use, 23% heterosexual sex, and 1% hemophilia. Among these 189 long-term nonprogressors, median time to progression was 3.5 years (a median of 13.5 years since seroconversion, IQR 11.5 to 16.9). In this group, 38% had progression-free survival 15 years after seroconversion, as did 14% after 20 years with HIV infection.
Statistical analysis adjusted for age identified three predictors of losing long-term nonprogression status at the following hazard ratios (HR):
-- Female gender: HR 1.8 (95% CI 1.1 to 3.1)
-- Lower CD4 count 10 years after seroconversion:
500 to 613 vs over 760: HR 3.1 (95% CI 1.5 to 6.6)
614 to 760 vs over 760: HR 2.5 (95% CI 1.2 to 5.4)
-- Higher viral load 10 years after seroconversion:
Above 9275 copies versus lower: HR 2.6 (95% CI 1.3 to 5.3)
Year of HIV seroconversion, hepatitis C virus infection, and mode of HIV transmission did not affect loss of long-term nonprogression status in this analysis.
A possible limitation of this analysis, suggested Johns Hopkins researcher Richard Chaisson, is including starting antiretroviral therapy as a progression marker. He suggested reanalyzing the data after censoring for antiretroviral therapy as a progression marker to see how much that affected the results. Since the CASCADE researchers censored data for the analysis at December 31, 2008, it seems likely that most people who lost nonprogression status because of starting antiretrovirals would have had a CD4 count under 500.
Reference
1. van der Helm J, Jansen I, Porter K, et al. The characterization of long-term non-progression of HIV-1 infection since seroconversion. XVIII International AIDS Conference. July 18-23, 2010. Vienna. Abstract TUAC0106.
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