July 20, 2009
In the mid- to late 1990s, powerful anti-HIV therapies became available in high-income countries. The effect of these therapies was dramatic, as deaths due to AIDS-related infections fell. Today combination anti-HIV therapy, commonly called highly active antiretroviral therapy (HAART), has had such immense benefits that some researchers have forecasted something that would have been unbelievable just decades ago: HIV positive people starting therapy today and who have minimal or no co-existing health conditions will likely live near-normal life spans.
Research in the United States suggests that the gains from HAART are not evenly distributed across all HIV positive people. Scientists in that country have found that HIV positive women continue to see relatively high rates of illness and death. These problems have occurred particularly among women of colour. To try to understand why this is the case, a team of American researchers conducted an extensive investigation. Their findings suggest that some HIV positive women in the U.S. are experiencing a number of conditions that, if treated, could reduce their risk of death. These problems are not isolated to the United States. Researchers in Southern Alberta have also found similar issues among some HIV positive women there.
Beginning in 1994, HIV positive women and HIV negative women at high risk for this infection were recruited for the Women's Interagency HIV Study (WIHS) in the following cities:
The women were regularly interviewed, given physical examinations and had blood and other fluids collected for analysis. This report will focus on the results in HIV positive women. The average profile of 2,792 HIV positive women when they entered WIHS was as follows:
Major ethno-racial groups were as follows:
In that decade, about 25% of participants died. Although death rates initially declined, they then stabilized at rates higher than in HIV negative people of the same age.
In the first seven years of the study, AIDS-related complications were a major cause of death. For instance, in 1995 about 85% of deaths were related to AIDS. But by 2002 AIDS-related complications were responsible for 50% of deaths in that year.
The research team was deeply dismayed by the relatively high proportion of AIDS-related deaths because HAART was released in the U.S. during the first few years of the study.
In examining the medical records of the women who died between 1998 and 2004, the researchers found that only 37% of these women took HAART. Moreover, only four women had an undetectable viral load in the year before they died.
Non-adherence (not taking HAART exactly as prescribed and directed) was only part of the reason for this low degree of virologic control. The study team noted that when it came to initial therapy for HIV infection, many of the women were prescribed regimens consisting of only one or two anti-HIV drugs. The HIV virus would have quickly become resistant to such sub-optimal therapy. Thus, the women would have been burdened with a high level of drug-resistant HIV. Adding a third anti-HIV drug to a failing regimen would have been of little benefit.
Additionally, the researchers noted that the proportion of women dying from AIDS-related complications in this study is higher than seen in several other studies in Western Europe or in HIV positive men in the U.S. The research team noted that the following factors might have been responsible for the reduced survival seen in HIV positive women in the WIHS study:
Not surprisingly, researchers found that certain findings -- low CD4+ cell counts, high viral loads -- were linked to reduced survival. Also, women who had relatively low body weight or who had liver infections were at increased risk of death.
Importantly, the study team also found that women who had symptoms of depressive illness were at particular risk of death from the following:
According to the researchers, the most common cause of death unrelated to AIDS was this:
The researchers think that the high rates of "violent death and suicides" may be related to the effects of physical abuse and substance use in these women. But perhaps another factor may also be involved.
The study team made an unexpected finding: Women with high viral loads were more likely to die from violence or overdose.
Another study in the U.S. that focused on substance users was called ALIVE. In that study researchers found that HIV positive substance users were twice as likely to die from overdose as HIV negative users.
In a study of treatment interruption called SMART, researchers found that people who were randomly assigned to delayed initiation of HAART and who were injection drug users were more likely to die from a drug overdose compared to people who began HAART immediately.
The researchers found that nearly 70% of the WIHS women experienced chronic or episodic bouts of depression. Such high rates of depression could have easily led to the following:
Unfortunately, substance use may temporarily provide feelings of relief but can quickly make depression worse, perhaps pushing the women into a downward spiral and intensifying the despair that could have shortened their lives.
The WIHS research team suggests that providing broader access to medical care and treatment -- specifically treatment for depression, hepatitis C and HIV infection -- would likely have improved survival rates. They may be correct. However, given the relatively high rates of illicit drug use in the study -- 60% of women used cocaine, crack cocaine and/or heroin -- unless psycho-social support is made available to help these women recover from addiction and the underlying psychological trauma that led to such harmful behaviour, survival rates may not increase.
The problem described by the WIHS team is not restricted to the U.S. The destabilizing effects of addiction, substance use and undiagnosed or untreated mental health conditions have led to high rates of death from overdose and violence among drug users in Southern Alberta and likely elsewhere. Indeed, researchers in Bologna, Italy, have found broadly similar trends to the present WIHS study among people who inject street drugs.
Increasing the availability of addiction prevention, treatment and support services for HIV positive substance users may make a difference in their survival.
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