Sex Differences in Overall and Cause-Specific Mortality among HIV-Infected Adults on Antiretroviral Therapy in Europe, Canada and the US

Abstract

General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms 1 Sex differences in overall and cause-specific mortality among HIV-infected adults on Methods:The ART Cohort Collaboration (ART-CC) combines 19 cohorts of individuals started on cART in Europe and North America (NA). We analyzed patients infected via injecting drug use (IDU) or heterosexual sex using Cox proportional hazards models.Results: 32,443 European (45.9% women), 1,162 (32.5% women) Canadian and 2,721 (15.5% women) US patients were included. In Europe and NA, women were younger, more likely to have acquired HIV heterosexually, be AIDS-free and have higher CD4 counts and lower HIV-1 RNA at baseline. European women had lower rates of all-cause (adjusted Hazard Ratio:0.76; 95%CI: 0.68-0.84) and non-AIDS mortality (0.67; 0.57-0.78) than men, but AIDS-mortality rates were similar (0.90; 0.75-1.09). Women had lower mortality due to non-AIDS infections (0.6 versus 1.3 per 1000 person-years), liver diseases (0.4 versus 1.7), non-AIDS malignancies (0.6 versus 2.0) and cardiovascular diseases (0.6 versus 1.0). Between-sex differences in all-cause mortality were larger in heterosexuals (0.70; (interaction p-value=0.043). No sex differences in all-cause mortality were found in Canada (HR women 1.13; 0.82-1.56) or US (HR women 1.12; 0.79-1.58). Conclusions:The increasing importance of non-AIDS mortality is leading to emergent sex differences among HIV-positive patients in Europe, as in the general population. In spite of the better clinical characteristics at cART initiation, women in NA had similar mortality to men. 3 INTRODUCTIONHigher life expectancy in women compared with men has been well documented since the early and mid 20 th century in the general population of industrialised countries [1][2][3], and since 2006 in developing countries [4]. The reasons are not fully understood, but important reductions in between-sex mortality differences have occurred in countries with high female smoking rates and high levels of female participation in the work-force, supporting a strong contribution of lifestyle factors and gender roles [1][2][3][4].Among HIV-positive people, the introduction of combination antiretroviral therapy (cART) has led to dramatic reductions in mortality rates [5][6], with an increasing proportion of deaths in treated HIV-positive people being due to causes not conventionally considered HIV-related [7]. Such changes may lead to emergent differences between mortality rates in treated HIV positive men and women but, unfortunately, sex-stratified analyses are not commonly reported given the low proportion of women among the Western HIV epidemics.Studies reported to date have produced contradictory results. Reports from the United States, largely based on seroprevalent cohorts, continue to report worse outcomes in HIV-infected women than men [8][9][10]. In Canada, no se...

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy

“…Finally, regarding the association of gender and mortality for PLHIV, it should be taken into account that women have an overall higher life expectancy compared to men, at least in Western countries. Moreover, in PLHIV, a lower incidence of non-AIDS events in women compared to males has been described [ 22 ]. In our study, after controlling for other variables including pregnancy status and HIV viremia levels, females resulted more at risk of delayed ART initiation and therapy discontinuation, even if no differences in response rates to the first year of ART were evidenced.…”

Sex stratification of the trends and risk of mortality among individuals living with HIV under different transmission categories

“…Therefore, a lower proportion of HIV acquisition through injecting drugs in women may explain potential differences in mortality between transmission categories 26 , 27 . However, no sex differences in all-cause mortality were observed in the United States or Canada 20 . Moreover, differences in mortality by transmission category may also be modified by sex differences.…”

“…Notably, differences in mortality between different transmission categories may be confounded or modified by sex. Studies conducted in Europe 20 , China 15 , 21 , Kenya 22 , and South Africa 23 have reported that female PLWH have a lower risk of mortality than male PLWH. This is possibly because of women’s better adherence to ART 15 , 21 , lower rate of substance use 24 , or more favorable immune response to combined ART (cART) 25 .…”

British Columbia CARMA-CHIWOS Collaboration (BCC3): protocol for a community-collaborative cohort study examining healthy ageing with and for women living with HIV

“…[11][12][13] In Canada, WLWH have poorer health outcomes across the HIV care cascade compared with men, including lower rates of access to care and adherence to cART, 14 15 more comorbidities [16][17][18] and higher mortality rates. 19 20 WLWH also experience significant psychological stressors, including gender-based violence, substance use, discrimination, the impacts of colonisation and isolation. [21][22][23] These may further accelerate biological ageing and its health impacts.…”