At enrollment, the median age of the 2628 participants was 36 years; 56% were black, and 23% were Latina (). The median annual income was $4500, and 66% of participants reported a history of abuse or domestic violence. The likely causes of HIV infection were heterosexual sex in 42%, injection drug use in 34%, and transfusion in 4%; 20% had no identified cause. At baseline, the median CD4 cell count was 330 cells/mm3, and the median viral load was 22,000 copies/mm3.
Comparison of Baseline Characteristics of Women in the Women’s Interagency HIV Study Cohort, by HIV Status and Survival during Follow-up
The cohort included 2059 HIV-infected women and 569 who were not infected, of whom 9 seroconverted during follow-up. By April 2000, 468 participants had died (451 who were HIV infected [59.9 per 1000 woman-years] and 17 who were not HIV infected [8.5 per 1000 woman-years]). There were no deaths among the sero-converters. Causes of death were missing for 40 participants (37 of whom were HIV infected) (). For participants with HIV infection, AIDS accounted for 294 deaths (71% of those with available information), non-AIDS causes for 91 deaths (22%), and a classification could not be determined for 29 deaths (7%). Of these 29 indeterminate deaths, 14 (48%) had CD4 cell counts <200 cells/mm3 at their last measurement and 15 had CD4 counts ≥200 cells/mm3.
Causes of Death in the Women’s Interagency HIV Study Cohort
For deaths classified as AIDS, 138 (47%) were due to an AIDS-defining condition or malignancy and 90 (31%) were due to unspecified AIDS with CD4 cell count <200 cells/mm3. For non-AIDS deaths, the major causes were hepatic disease (21%); drug overdose (18%); non-AIDS malignancies (13%); cardiac causes (11%); accident, suicide or homicide (11%); and other gastrointestinal causes (10%). Deaths due to liver disease were about five times more common among HIV-infected women than among those who were not infected (P = 0.11).
Non-AIDS malignancies among the HIV-infected women included lung cancer (n = 3); oropharyngeal cancer (n = 2); hematologic cancer (n = 2); and liver, colon, stomach, ovary, and brain cancer (n = 1 each). Cardiac deaths in the non-AIDS group included coronary artery disease (n = 4, including 2 with renal failure), myocardial infarction (n = 1), hypertension (n = 2), and heart failure (n = 3). Four women who were not HIV infected died of cancer (3 with lung cancer, 1 with a hematologic malignancy).
All-cause and AIDS-related mortality rates () for HIV-infected women decreased markedly from October 1995 through April 1997, the period of introduction of combination antiretroviral therapy, and continued to decrease subsequently. Rates of all-cause mortality declined by an average of 26% per year (P = 0.03), and rates of AIDS-related mortality declined by an average of 39% per year (P = 0.01) among HIV-infected women. In contrast, rates of non-AIDS mortality among HIV-infected women (10% annual decrease, P = 0.73) and all-cause mortality among women who were not HIV infected (18% annual increase, P = 0.62) remained stable.
Change in Mortality in the Women’s Interagency HIV Study. HIV + indicates HIV infected; HIV– indicates not HIV infected. AIDS = acquired immunodeficiency syndrome; HIV = human immunodeficiency virus.
Women who died of AIDS-related conditions had higher median HIV-1 RNA counts than did those who lived or died of other causes (). Women who died of non-AIDS causes were older, had higher rates of hepatitis B antigenemia and hepatitis C infection, were more likely to have used injection drugs and smoked, and were more likely to have injection drug use as their likely cause of HIV infection than did those who survived. In general, women without HIV infection who died had similar characteristics as those with HIV infection who died of non-AIDS-related conditions ().
In unadjusted analyses, higher HIV-1 viral load, depressive symptoms, and use of combination antiretroviral therapy were associated with AIDS-related deaths. As expected, use of antiretroviral therapy was not independently associated with death due to AIDS after adjusting for HIV-1 RNA level ().
Associations between Selected Risk Factors and Causes of Mortality*
In the multivariate model, higher HIV-1 viral load, depressive symptoms, and past injection drug use were associated with death from non-AIDS causes among HIV-infected women. Although hepatitis B antigenemia, hepatitis C infection, and recent injection drug use were risk factors for non-AIDS deaths in univariate analyses, these effects were not observed after adjusting for a history of injection drug use.
In unadjusted analyses, hepatitis C infection and history of injection drug use were significant risk factors for non-AIDS-related deaths due to liver disease, drug overdose, and malignancy among HIV-infected women (). Depressive symptoms were a significant risk factor for deaths from drug overdose and non-AIDS malignancies, whereas recent drug injection use, use of cocaine or heroin, smoking, and frequent alcohol use were associated with death from drug overdose.
Univariate Associations between Selected Risk Factors and Specific Non-AIDS Causes of Death among HIV-Infected Women*
Among women who were not HIV infected, depressive symptoms, history of abuse, hepatitis C infection, history of injection drug use, recent injection drug use, frequent alcohol use, and use of heroine or cocaine were associated with mortality in univariate analyses (). There were too few deaths for multivariate models.