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Heart attacks, non-AIDS cancers, more common in Botswana than US patients on HIV treatment
Carole Leach-Lemens, 2011-06-21 13:50:00
Incidence rates of non-AIDS-defining events (NADEs) in HIV-infected individuals on ART were fifty percent higher in a clinical trial cohort in Botswana compared to a routine care (observational) cohort in the United States (US), with especially high rates of heart disease and cancer, according to CW Wester and colleagues in a retrospective analysis published in the advance online edition of AIDS.
Liver disease, however, was only seen in the US cohort (4.0 per 1000 person years).
ART has significantly reduced HIV-related death and disease over the past two decades in resource-rich settings. However, those on long term ART have experienced continue to experience some negative health outcomes. These include heart, kidney, liver or non-AIDS-defining cancer related illnesses classified as non-AIDS-defining events.
The causes of NADEs are multiple and can include older age (which may also indicate longer exposure to antiretroviral therapy); smoking or alcohol use; long term viral replication (lengthy suppression of the immune system); co-infection with chronic diseases (for example hepatitis); as well as long term ART complications (for example diabetes).
US and Western European data have shown that the six-month cumulative risk of death from NADEs was three times greater compared to AIDS defining events in HIV-infected individuals with high CD4 cell counts. Heart and liver diseases and non-AIDS associated cancers were the most common causes.
While the majority of those on ART live in sub-Saharan Africa, few studies have looked at the effect of NADEs.
The authors retrospectively compared crude and standardised (based on the US cohort by age and gender) NADE rates in HIV-infected individuals on ART in two geographically distinct adult urban populations: a randomised clinical trial population in Gaborone, Botswana and an observational cohort in Nashville, Tennessee, US, with data from December 1, 2002 to December 31, 2007 and January 1, 2003 to December 31, 2007, respectively.
Of the 650 in the Botswana cohort, 65% were female, median age 33.3 years with a median CD4 cell count when starting ART of 199 cells/mm3. In contrast the US cohort of 1129 were predominantly male (75%) older (median age 40.1 years) with a higher median CD4 cell count at the start of ART (243 cells/mm3).
Overall crude incidence rates for NADEs were similar in the two cohorts 10.00 per 1000 person years (95% CI: 6.3-15.9, p=0.20) in Botswana compared to 12.4 per 1000 person years (95% CI: 8.4-18.4, p=0.20) in the United States.
However, when standardised to the US cohort (with an older and mostly male population) the rates were fifty percent higher in the Botswana cohort compared to the US cohort, 18.7 per 1000 person years (95% CI: 8.3-33.1, p=0.20) and 12.4 per 1000 person years (95% CI: 8.4-18.4, p=0.20),respectively.
Standardised rates of heart disease and non-AIDS defining cancers were higher in the Botswana population, 8.4 per 1000 person years (95% CI: 2.4-18.4), p=0.20 and 8.0 per 1000 person years (95% CI:1.3-20.8), p=0.015 compared to 5.0 per 1000 person years (95% CI: 2.7-9.2), p=0.20 and 0.5 per 1000 person years (95% CI: 0.1-3.5), p=0.015.
Hodgkin’s lymphoma was the primary non-AIDS defining cancer in Botswana. A finding that suggests it may be a significant cause of non-AIDS defining mortality in the region, note the authors. With improved diagnostic capacity, they add, cancer registers should be established to better describe cancer disease patterns.
Heart disease was the most common non-AIDS defining event in both settings, possibly because of ART or the chronic inflammatory state that is present in spite of viral suppression, note the authors.
Regardless of the differences in treatment regimens and socio-demographic factors in the cohorts, deaths linked to heart disease will increasingly be associated with non-AIDS defining mortality, they add.
Kidney NADE rates were similar in both groups, 3.0 per 1000 person years (95% CI: 1.3-6.6), p=0.92 and 2.4 per 1000 person years (95% CI: 0.0-7.2), p=0.92 in the US and Botswana, respectively. The authors expressed surprise at this outcome. Recent findings showed individuals of African descent infected with HIV to have a twenty-fold greater risk in developing HIV-associated nephropathy (kidney disease) than those of non-African descent.
The authors acknowledge the considerable challenges and limitations in undertaking this comparative analysis. These include, among others, differences in visit schedules, laboratory and clinical monitoring, ART regimens, death information – verbal reports in Bostwana and registry reviews and clinician assessments in the US, diagnostic capacity as well as differences in the definition of virological failure. The authors add trying to control for all possible confounders makes no sense.
Despite these limitations the authors conclude “NADEs appear to be as significant a problem in our sub-Saharan African setting and the monitoring, prevention and treatment of NADEs should be a critical component of care in resource-limited settings.”
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