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Three Years With More Than 500 CD4s Normalizes Mortality in HIV+ Men
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17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
Reaching a CD4 above 500 and keeping it there for 3 years made the risk of death in HIV-infected men who did not inject drugs (non-IDUs) equivalent to that in the general population [1]. But HIV-infected women did not enjoy that advantage in this 7-year analysis of the COHERE cohort.
COHERE embraces 25 European cohorts of HIV-infected adults taking antiretrovirals. Charlotte Lewden and COHERE coworkers reckoned death rates per 100 person-years; they calculated standardized mortality ratios as observed/expected deaths, figuring the expected-death number by applying country-, age-, gender-, and calendar year-specific mortality rates to the HIV population.
The analysis included 80,642 cohort members, 30% of them women. Median age measured 34 years among women and 38 years among men. Overall median current CD4 count stood at 225 (interquartile range [IQR] 107 to 355). Median follow-up measured 3.5 years (IQR 1.5 to 6.1); 28% of cohort members started antiretrovirals in 1998-1999, 32% in 2000-2002, 21% in 2003-2004, and 19% in 2005-2008.
Deaths per 100 person-years fell steeply for both men and women in higher versus lower current CD4 echelons:
· Under 200: men 4.2, women 3.0
· 200 to 349: men 0.9, women 0.7
· 350 to 499: men 0.6, women 0.4
· 500 or over: men 0.4, women 0.2
Standardized mortality ratios also dropped at higher CD4 counts:
· Under 200: men 11.5, women 23.7
· 200 to 349: men 2.6, women 5.6
· 350 to 500: men 1.7, women 3.2
· 500 or over: men 1.4, women 2.2
But standardized mortality ratios differed in women and men according to how many years they spent with a CD4 count above 500. For IDUs, those ratios fell as years with a 500-plus CD4 count stretched from 1 to 5. But even after 5 years with more than 500 CD4s, standardized mortality ratios for male IDUs indicated about 3 times higher death rate than the general population, while ratios for female IDUs indicated more than a 4 times higher death rate than the general population.
For men who did not inject drugs, the standardized mortality ratio approached 1 (equivalent with the general population) after only 1 year with 500 CD4s, and the ratio stayed there through 2, 3, 4, and 5 years with a count above 500. After 3 years with 500 CD4s, the ratio stood at 1.1, indicating equivalence with the general population since the 95% confidence interval broadly overlapped 1 (0.8 to 1.3). For women who did not inject drugs, in contrast, the standardized mortality ratio remained around 1.5 no matter how long they kept their CD4s over 500.
Lewden and colleagues speculated that the stubbornly higher standardized mortality ratio in women "might be related to unmeasured confounding factors," such as lower socioeconomic status than men. This result underlines the need for health authorities and physicians to make sure HIV-infected women receive care equivalent to men.
"Though our results might be partly explained by other differences between HIV-infected and uninfected populations," the COHERE group concluded, "they point to the importance of maintaining high CD4 cell counts as well as long term treatment adherence."
The encouraging findings for men are at odds with several recent estimates of still-truncated life expectancy in Europeans and North Americans with HIV infection [2-5]. But another study detailed at this meeting concluded that life expectancy in the Dutch ATHENA cohort is approaching that in the general population [6]. NATAP will report the ATHENA results separately.
References
1. Lewden C, the Mortality Working Group of COHERE. Time with CD4 cell count above 500 cells/mm3 allows HIV-infected men, but not women, to reach similar mortality rates to those of the general population: a 7-year analysis. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 527.
2. Harrison KM, Song R, Zhang X. Life expectancy after HIV diagnosis based on national HIV surveillance data from 25 states, United States. J Acquir Immune Defic Syndr. 2010;53:124-130.
3. Losina E, Schackman BR, Sadownik SN, et al. Racial and sex disparities in life expectancy losses among HIV-infected persons in the United States: impact of risk behavior, late initiation, and early discontinuation of antiretroviral therapy. Clin Infect Dis. 2009;49:1570-1578. http://www.journals.uchicago.edu/doi/full/10.1086/644772.
4. Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008;372:293-299.
5. Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Ann Intern Med. 2007;146:87-95.
6. van Sighem Gras L, Reiss P, Brinkman K, de Wolf F, and ATHENA Natl Observational Cohort Study. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 526.
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