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  1st International Workshop
on HIV and Women,
January 10-11, 2011
Washington, DC
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ART Response and Rebound Worse in Female IDUs Than Male IDUs
  1st International Workshop on HIV and Women, January 10-11, 2011, Washington, DC
Mark Mascolini
Injection drug users (IDUs) starting antiretroviral therapy (ART) had a higher risk of a poor virologic response and, among responders, a higher rebound risk than did non-IDUs in a large Canadian cohort [1]. Poor response and rebound risks were higher in female IDUs than in male IDUs compared with non-IDU males. Female IDUs also ran the highest risk of dying during follow-up after statistical adjustment for other death risk factors.
Numerous studies in high-income countries indicate that antiretroviral response rates can differ between men and women, with trends in the latest studies often favoring women. But findings are inconsistent from study to study because of differences in populations and study designs. There is little doubt that gender inequality often plays an important role in determining outcomes in HIV care in rich and poor countries. Injection drug use can compound gender-related obstacles to accessing and maintaining consistent care for HIV infection.
Because injection drug use is emerging as a more prominent HIV risk factor among Canadian women, CANOC cohort investigators planned this study to compare response and rebound rates in women and men with and without a history of injecting drugs. People defined as IDUs in this study did not have to be current IDUs. The cohort consists of all antiretroviral-treated people in British Columbia and people from selected sites in Ontario and Quebec.
Inclusion in this analysis required at least one viral load measurement after starting first-line ART on January 1, 2000 or later, as well as pretreatment CD4 and viral load data. The researchers defined virologic suppression of two consecutive viral loads below 50 copies after starting treatment; they defined rebound as a viral load above 1000 copies after suppression. The analysis compared four discrete groups: female IDUs, female non-IDUs, male IDUs, and male non-IDUs.
The study included 3902 people, 818 of them (21%) women. Median age stood at 40 years (interquartile range 34 to 46). Almost half of study participants (48%) lived in British Columbia, while 27% lived in Ontario and 26% in Quebec.
At the baseline visit, a higher proportion of women than men had a history of injection drug use (27% versus 17%, P < 0.001). Overall, women in the cohort were younger than men (36 versus 41, P < 0.001), had higher CD4 counts (median 199 versus 180, P < 0.001), and had lower viral loads (median 50,000 versus 100,000 copies, P < 0.001). A higher proportion of men than women had AIDS when they began treatment (15% versus 11%, P = 0.003). Follow-up lasted for a median of 37 months (interquartile range 18 to 61).
The CANOC team constructed a multivariate model that accounted for age, province, initial CD4 count and viral load, viral load testing rate, year ART began, and third antiretroviral agent in the regimen (that is, the nonnucleoside or protease inhibitor). In this analysis, male IDUs were about 25% less likely to reach an undetectable viral load than male non-IDUs (adjusted hazard ratio [AHR] 0.74, 95% confidence interval [CI] 0.66 to 0.83, P < 0.001), while female IDUs were half as likely and male non-IDUs to have a confirmed sub-50-copy load (AHR 0.51, 95% CI 0.42 to 0.61, P < 0.001). Female non-IDUs did not differ from male non-IDUs in chances of virologic suppression.
The viral rebound analysis considered age, province, pretreatment CD4 count and viral load, viral load testing rate, year ART began, and third antiretroviral. Compared with male non-IDUs, male IDUs were twice as likely to rebound from an undetectable viral load (AHR 1.96, 95% CI 1.52 to 2.53, P < 0.001), while female IDUs ran a tripled risk of virologic rebound (AHR 2.96, 95% CI 2.15 to 4.08, P < 0.001). Female non-IDUs were 40% more likely than male non-IDUs to have a virologic rebound (AHR 1.40, 95% CI 1.08 to 1.83, P = 0.013).
A time-to-death analysis factored in age, province, initial CD4 count, viral load testing rate, year ART began, and third antiretroviral. Compared with male non-IDUs, male IDUs were 64% more likely to die (AHR 1.64, 95% CI 1.24 to 2.16, P < 0.001) and female IDUs were 77% more likely to die (AHR 1.77, 95% CI 1.22 to 2.57, P = 0.003). Female non-IDUs did not differ from male non-IDUs in risk of death.
The researchers pointed out several study limitations: inclusion of people from only three provinces and lack of data on antiretroviral adherence, ethnicity, and pregnancy. They plan to consider those data, which they are collecting, in future analyses.
The CANOC investigators concluded that "female IDU were the least likely to virologically suppress, most likely to experience rebound, and had a greater risk of mortality." They called for further study exploring "the intersections between sex and other factors" in women and men starting ART, with goals of retaining people in care and maximizing the benefits of treatment.
1. Cescon AM, Palmer AK, Chan K, et al. Women with a history of injection drug use at greatest risk for poorer clinical outcomes in a cohort of HIV-positive individuals in Canada. 1st International Workshop on HIV and Women. January 10-11, 2011. Washington, DC. Abstract O_12.