Compared with whites, blacks were 40% more likely not to reach and maintain an undetectable viral load after starting their first antiretroviral combination.1 That finding held true even after AIDS Clinical Trials Group (ACTG) researchers accounted for the impact of other diseases, adherence to antiretroviral therapy, education level, alcohol use, social support, and other important factors.
Previous studies also found a worse viral load response rate in blacks than whites in the United States. Researchers proposed that the worse response in blacks can be explained at least partly by social factors like poverty, poor access to healthcare, education level, and the impact of such factors on adherence -- how consistently a person takes prescribed drugs exactly as instructed. This new study by ACTG researchers combined data from five trials that included blacks and whites. In analyzing viral load response rates, the ACTG team used statistical methods that considered the impact of social factors, adherence, and diseases other than HIV.
- How the study worked. ACTG investigators focused
on 2495 adults in five completed trials of antiretroviral
therapy that took place between 1998 and 2005. The
study group included 1202 white men, 820 black men,
142 white women, and 331 black women. None of these
people identified themselves as Hispanic. One trial lasted
48 weeks, while the other four trials lasted more than
96 weeks. Everyone was starting their first antiretroviral
combination, which was chosen at random (as with tossing
a coin) as part of the clinical trial. The antiretroviral
combinations included many drugs in routine use today,
such as Sustiva (efavirenz), Kaletra (lopinavir/ritonavir),
Emtriva (emtricitabine), and Ziagen (abacavir). The
most-used drug was the combination pill Combivir (Retrovir
[zidovudine] plus Epivir [lamivudine]).
For every study participant in each trial, the researchers determined time to virologic failure, which they defined as time from study entry to the first of two consecutive viral loads (1) above 1000 copies from 16 weeks up to 24 weeks after treatment began, or (2) above 200 copies at or after week 24. Changes in CD4 count in blacks and whites were also measured.
Statistical analysis to determine the impact of race on viral load response considered personal factors like age and gender, HIV infection severity, other conditions such as hepatitis virus infection, mode of HIV transmission, depression, education level, alcohol use, social support, belief in the effect of antiretroviral therapy, and self-reported adherence. This kind of analysis can evaluate how race affects response to antiretroviral therapy apart from the impact of all the other factors analyzed.
- What the study found. Study participants had a
median age of 37 years when they entered the trials.
Participants had very different CD4 counts at the start of
each trial, ranging from 16 to 494; the median was 210.
Their median viral load was 100,000 copies. A small
proportion of study participants, 12%, ever had a positive
test for hepatitis C virus (HCV). Most people (82%) got
infected with HIV during sex. Compared with whites,
lower proportions of blacks had more than a high school
education (44% versus 61% of men, and 29% versus 38%
of women). Before the trials began, a somewhat smaller
proportion of blacks than whites believed antiretrovirals
would have a positive effect on their health.
Through 144 weeks of treatment, probability of viral load failure was higher in blacks than whites (45% versus 32%). This difference was statistically significant, meaning it was unlikely that the difference occurred by chance alone. The initial statistical analysis, which did not consider the impact of personal, clinical, and social factors, determined that blacks had a 60% higher risk of viral load failure than whites. This difference held true no matter what antiretroviral combination people were taking.
Figure 1. Compared with whites treated for the first time with antiretrovirals in five ACTG trials, blacks treated for the first time had a 40% higher risk of viral load failure, regardless of whatever other risk factors a person had. Less than perfect adherence to antiretroviral therapy more than doubled the risk of failure.
*Impact of every 10 times higher pretreatment viral load on failure in the first 6 months of therapy.
In the statistical analysis that considered many social and disease-related factors that might affect response to antiretroviral therapy, five factors independently raised the risk of failing to achieve and maintain an undetectable viral load (Figure 1). In other words, each of these factors raised the risk regardless of whatever other risk factors a person had. Compared with whites, blacks had a 40% higher risk of viral load failure. People with less than perfect adherence had more than a doubled risk of failure. Younger age, higher viral load, and having a positive HCV test at the time of starting treatment were also associated with a higher risk of failure. Of note, higher viral load at the time of starting treatment was associated with a higher risk of failure only during the first 6 months of treatment.
Two other factors also raised the risk of viral load failure somewhat, but it is possible that chance explained these associations. In other words, they did not raise the failure risk regardless of whatever other risk factors a person had: (1) Not graduating from high school raised the risk of failure about 20%. (2) Feeling little social support raised the risk about 20%. Risk of failure was not higher for women than men in this analysis.
Although blacks had a higher risk of viral load failure in this analysis, they gained more CD4 cells than whites. After 96 weeks of treatment, blacks gained an average of 33 more CD4 cells than whites. That finding held true regardless of what CD4 count a person had before antiretroviral therapy. The ACTG researchers cautioned that a 33-cell difference may not make a difference in health.
- What the results mean for you. This study goes beyond
previous research in explaining risk of viral load failure
in US blacks and whites starting their first antiretroviral
combination. In a statistical analysis that weighed the impact
of many personal, social, and disease-related factors,
blacks had a 40% higher risk of failure than whites. The
impact of poor antiretroviral adherence (inconsistent pill
taking) had an even greater impact on risk of viral load
failure. People who reported less than 100% adherence
in the past 4 days had a 2.6 times higher risk of failure
than people who reported perfect adherence.
The ACTG investigators considered a wide array of factors that might affect response to antiretroviral therapy, including important factors like education level, depression, and alcohol use. No earlier study tried to calculate the impact of race and all these other factors on treatment response. However, the ACTG team could not assess the impact of a few important factors, including income, housing status, and access to healthcare. These factors probably reflect challenging life situations that may be more common in black people in the ACTG trials. And some of these factors may have contributed to the higher treatment failure risk in blacks than whites.
Still, this study underlines the point that different people may respond to antiretroviral therapy in different ways. Although the study does not completely explain why the risk of antiretroviral failure was higher in blacks than whites, the results should encourage everyone to work hard to succeed with treatment. Most importantly, that means taking all antiretroviral drugs exactly as instructured by your doctor. Keeping all medical appointments is also essential to treatment success. As this study found, people who begin treatment with a higher viral load have to work especially hard to let their antiretrovirals get control of HIV. But once they attain this goal and keep taking their antiretrovirals regularly, this previously higher viral does not seem to affect their chances of continued treatment success.
Many problems can interfere with keeping appointments and taking pills reguarly, including difficulty getting to the medical clinic, problems at home, and poor support from family and friends. You should tell your HIV doctor about any problems that interfere with taking your medications or keeping appointments. Your doctors office probably has social workers who can help with these problems, or your doctor can help you find someone to address these problems. Community HIV groups also offer valuable help with these difficulties.