Race and gender may be important risk factors for some antiretroviral-associated side-effects, according to a US study published in the April 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators found that African-American patients had a higher risk of serious cardiovascular side-effects and that women were more likely to develop severe anaemia.
Antiretroviral therapy can mean a longer, healthier life, but many patients taking anti-HIV treatment develop side-effects. Previous research has identified a series of factors associated with an increased risk of side-effects including coinfection with hepatitis B or C virus, CD4 cell count, genetics and body mass index.
There is also some evidence that gender and race may be risk factors for some side-effects. For example, women are more likely than men to develop a rash when starting therapy with nevirapine (Viramune), and in patients of African descent, slower clearance of efavirenz (Sustiva) is associated with an increased risk of psychiatric side-effects.
Most of the clinical trials that lead to the formal approval of antiretroviral drugs included only a small percentage of patients from racial minorities or were women, so there is limited information about the role of these factors in the risk of side-effects.
Investigators from the US FIRST study therefore conducted an observational study lasting five years to see if race and gender were risk factors for antiretroviral-associated side-effects.
A total of 1301 patients were included in the investigators’ analysis. All were starting potent antiretroviral therapy for the first time. Patients were randomised into one of three treatment arms and prescribed either a protease inhibitor-based regimen, or NNRTI-based therapy, or treatment that included both a protease inhibitor and an NNRTI. Nelfinavir (Viracept) was the most commonly used protease inhibitor (61%), and efavirenz was the most widely used NNRTI (63%). The NRTI backbone prescribed to all patients was AZT (zidovudine) and 3TC (lamivudine, Epivir).
The study population was ethnically diverse, with 54% being African American and 17% Hispanic, and 20% were women.
Investigators recorded severe side-effects (grade 4) and conducted statistical analyses to see if these were associated with race or gender.
A total of 5929 person-years of analysis were available for analysis, and 409 patients experienced one or more severe adverse event, with an event rate of 9 per 100 person years. There were 176 deaths, a rate of 3 per 100 person years. Overall, black patients had a higher rate of serious side-effects than patients from other racial groups (p = 0.03), and were also statistically more likely to experience cardiovascular events (p = 0.03) and kidney-associated side-effects (p = 0.01). Black men were more likely to experience a psychiatric side-effect and women were more likely than men to develop anaemia (p = 0.01).
Overall, 523 (40%) patients changed treatment because of side-effects, but the investigators found that black patients were slightly less likely than patients of other ethnicities to do so.
The investigators then performed a series of multivariate analyses. This showed that, after controlling for other potential factors, women had an increased risk of grade 4 anaemia (adjusted HR = 2.34; 95% CI: 1.09 – 4.99). Black race was associated with an increased risk of cardiovascular events (adjusted HR = 2.64; 95% CI: 1.04 – 6.67), and kidney disease (adjusted HR = 3.83; 95% CI: 2.45; 95% CI: 1.13 – 5.30). Multivariate analysis also showed that black patients were less likely to change treatment because of side-effects (adjusted HR = 0.82; 95% CI: 0.66 – 1.01).
“After adjusting for baseline risk factors, this study demonstrated significant racial/ethnic- and gender-related differences for specific types of grade 4 adverse events but not for overall adverse events…or rates of toxicity-related discontinuation of therapy”, write the investigators.
The investigators note that African American patients had lower CD4 cell counts when antiretroviral therapy was started and also had a higher prevalence of high blood pressure, and these factors could have contributed to the higher risk of heart and kidney disease seen in the study.
A higher rate of severe anaemia amongst women was “not unexpected”, and the investigators would have expected high rates of anaemia amongst women taking a regimen that included AZT. However, when the investigators controlled for the use of AZT, they still found that women had a higher rate of anaemia “suggesting that other factors not assessed in this study may have contributed to the higher risk of anaemia.”
The investigators conclude, “the HIV clinician who treats women and racial/ethnic minorities needs to consider the underlying comorbid diseases and risk for cardiovascular, renal and psychiatric complications when selecting an antiretroviral regimen”, adding, “the long-term success of antiretroviral therapy, however, ultimately depends on earlier identification of HIV-infected individuals and entry into care to minimize antiretroviral toxicity and maximize survival.”
Tedaldi EM et al. Ethnicity, race and gender. Differences in serious adverse events among participants in an antiretroviral initiation trial: results of the CPCRA 058 (FIRST Study). J Acquir Immune Defic Syndr 47: 441 – 448, 2008.