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Women With HIV Have Lower Mortality Than Men in Europe,
But Not in North America
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6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 17-20, 2011, Rome
Mark Mascolini
Death rate comparisons involving 33,000 HIV-positive women and men starting combination antiretroviral therapy (cART) in Europe, the United States, and Canada found that women had about a 25% lower death risk than men in Europe [1]. But mortality did not differ significantly between women and men in the US or Canada.
Perhaps because of differing access to medical care and cART in the United States versus Europe or Canada, earlier studies found higher death rates in women than men in the US [2-4], while in Europe women had slower HIV disease progression and lower mortality than men [5-10], and in Canada women had slower disease progression [11]. To compare mortality in women and men in these three regions, the ART-Cohort Collaboration (ART-CC), which combines 19 cohorts in Europe and North America, analyzed mortality in 33,291 women and men who started cART since January 1, 1998. All cohort members were infected heterosexually or through injection drug use.
The ART-CC team figured mortality hazard ratios separately for Europe, the US, and Canada, adjusting rates for age, CD4 count, and viral load when starting cART, HIV transmission category, geographic region or race/ethnicity, and AIDS diagnosis. Follow-up continued through December 2009. The investigators considered a person lost to follow-up if they did not have a cohort study visit for 2 years.
Most study participants, 29,355, lived in Europe, while 2772 were from the US and 1164 from Canada. In Europe and the US women were more likely than men to be infected heterosexually, to begin cART at a younger age, to be AIDS-free when starting cART, and to start cART at a higher CD4 count.
Proportions of men versus women were 53% and 47% in Europe, 85% and 15% in the US, and 67.5% and 32.5% in Canada. Median age was significantly older in men than women in Europe (38 versus 34), the US (45 versus 38), and Canada (40 versus 35) (P < 0.001 for all three comparisons). Proportions of men and women who were African or black were 16% and 30% in Europe, 63% and 62% in the US, and 9% and 19% in Canada. In Canada indigenous people accounted for 15% of men and 19% of women. Bigger proportions of men than women began cART with a viral load above 100,000 copies in Europe (44% versus 32%, P < 0.001), the US (39% versus 33%, P = 0.016), and Canada (49.5% versus 40%, P = 0.002).
Adjusted hazard ratios (HR) for death were significantly lower for women than men in Europe but not in the United States or Canada:
--Europe: HR 0.76 (95% confidence interval [CI] 0.68 to 0.85), P < 0.001
--United States: HR 1.19 (95% CI 0.86 to 1.64), P = 0.28
--Canada: HR 1.11 (95% CI 0.81 to 1.53), P = 0.52
Among people living in Europe, the ART-CC team found a significantly lower risk of death among women when they looked only at people infected during sex (HR 0.68, 95% CI 0.59 to 0.78, P = 0.006). But there was no death risk difference between women and men when the investigators looked only at people infected while injecting drugs (HR 0.94, 95% CI 0.78 to 1.13).
The researchers knew the cause of death for 26% who died in Europe, 75% in Canada, and 8% in the US. Among people with a recorded cause of death, 65% died of non-AIDS causes. Among people who died in Europe, 72% of men versus 62% of women died of a non-AIDS cause, and this difference approached statistical significance (P = 0.051). In the US and Canada women and men did not differ significantly in rates of non-AIDS death.
A lower percentage of women than men were lost to follow-up in Europe, the US, and Canada. In Europe this difference reached statistical significance (P < 0.001), but gender-based differences in loss to follow-up were small in all three regions (27.7% versus 25.5% in Europe, 17.1% versus 15.3% in the US, and 9.4% versus 6.9% in Canada).
The ART-CC investigators do not believe differing socioeconomic status or death ascertainment can explain can explain mortality differences (or lack of differences) in these cohorts. Instead, they suggested "it is likely that cART, in lowering the risk of death, renders visible again gender differences in mortality that exist in the general population."
References
1. Jarrin I, Del Amo J, the Antiretroviral Therapy Cohort Collaboration (ART-CC). Sex differences in mortality rates among HIV-positive patients: the Antiretroviral Therapy Cohort Collaboration (ART-CC). 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract TUPE145. http://pag.ias2011.org/EPosterHandler.axd?aid=1886.
2. Lemly DC, Shepherd BE, Hulgan T, et al. Race and sex differences in antiretroviral therapy use and mortality among HIV-infected persons in care. J Infect Dis. 2009;199:991-998.
3. Hessol NA, Kalinowski A, Benning L, et al. Mortality among participants in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study. Clin Infect Dis. 2007;44:287-294.
4. Poundstone KE, Chaisson RE, Moore RD. Differences in HIV disease progression by injection drug use and by sex in the era of highly active antiretroviral therapy. AIDS. 2001;15:1115-1123.
5. Jarrin I, Geskus R, Bhaskaran K, et al. Gender differences in HIV progression to AIDS and death in industrialized countries: slower disease progression following HIV seroconversion in women. Am J Epidemiol. 2008;168:532-540.
6. Garcia de la Hera M, Ferreros I, del Amo J, et al. Gender differences in progression to AIDS and death from HIV seroconversion in a cohort of injecting drug users from 1986 to 2001. J Epidemiol Community Health. 2004;58:944-950.
7. Porter K, Babiker A, Bhaskaran K, et al; CASCADE Collaboration. Determinants of survival following HIV-1 seroconversion after the introduction of HAART. Lancet. 2003;362:1267-1274.
8. Pezzotti P, Dorrucci M, Donisi A, et al. [Survival, progression to AIDS and immunosuppression in HIV-positive individuals before and after the introduction of the highly active antiretroviral therapy (HAART)]. [Article in Italian]. Epidemiol Prev. 2003;27:348-355.
9. Perez-Hoyos S, del Amo J, Muga R, et al; GEMES (Spanish Multicenter Study Group of Seroconverters). Effectiveness of highly active antiretroviral therapy in Spanish cohorts of HIV seroconverters: differences by transmission category. AIDS. 2003;17:353-359.
10. Moore AL, Sabin CA, Johnson MA, Phillips AN. Gender and clinical outcomes after starting highly active antiretroviral treatment: a cohort study. J Acquir Immune Defic Syndr. 2002;29:197-202.
11. Mocroft A, Gill MJ, Davidson W, Phillips AN. Are there gender differences in starting protease inhibitors, HAART, and disease progression despite equal access to care? J Acquir Immune Defic Syndr. 2000;24:475-482.
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