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  20th Conference on Retroviruses and
Opportunistic Infections
Atlanta, GA March 3 - 6, 2013
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CD4 Count Affects Non-AIDS Risk in People Yet to Start Antiretrovirals
  20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
Mark Mascolini
A CD4 count below 350 more than doubled the risk of serious non-AIDS diseases in HIV-positive people who had not begun antiretroviral therapy [1]. Viral load in untreated people did not appear to affect risk of non-AIDS diseases in this 13,000-person ATHENA cohort analysis in the Netherlands.
Research has linked certain non-AIDS diseases to low CD4 count or high viral load in people taking antiretroviral therapy. But little is known about the impact of CD4 count and viral load on these morbidities in HIV-positive people who have yet to start antiretrovirals. To address these questions, ATHENA cohort investigators conducted this study of antiretroviral-naive cohort members.
This ATHENA analysis included 13,077 people in the Netherlands diagnosed with HIV in 1998 or later and not yet taking antiretrovirals. The researchers counted new diagnoses of major cardiovascular diseases (myocardial infarction, stroke, invasive coronary procedures), liver fibrosis or cirrhosis, and non-AIDS malignancies. A composite endpoint included diagnoses in all three disease clusters. The ATHENA team considered non-AIDS conditions that developed from the time of a cohort member's first CD4 count onwards. Follow-up continued until antiretroviral therapy began or the last follow-up visit.
The analysis included 18,641 person-years of follow-up. During that time, a new non-AIDS condition developed in 208 people (1.6%). Five people had two or more non-AIDS diagnoses. There were 53 cardiovascular events, 79 cases of liver fibrosis/cirrhosis, and 82 non-AIDS malignancies.
Overall incidence of combined events reached almost 6 per 100 person-years in people with a CD4 count below 200, meaning that 6 of 100 people had one of these diagnoses every year. (See Figure 1 in the poster linked below.) Among people with a sub-200 CD4 count, incidence of non-AIDS malignancies or cardiovascular disease was about 2 per 100 person-years, while liver fibrosis/cirrhosis incidence lay slightly below that. Among people with 200 to 349 CD4 cells, composite incidence of these non-AIDS conditions lay between 1 and 2 per 100 person-years, while incidence of non-AIDS malignancy and liver fibrosis approached 1 per 100 person-years.
The investigators used a Poisson regression model to assess associations between time-updated CD4 count and viral load and the composite non-AIDS endpoint. The model was adjusted for demographics, smoking history, alcohol use, CDC disease stage, hepatitis B or C, diabetes, and hypertension.
Compared with a CD4 count of 500 or higher, a count below 200 more than quadrupled the risk of the composite non-AIDS endpoint, while a count between 200 and 349 more than doubled the risk. A count between 350 and 499 did not significantly affect risk of the composite endpoint:
Relative risk (RR) of the composite non-AIDS endpoint (and 95% confidence intervals):
-- Below 200 CD4s: RR 4.36 (2.83 to 6.73)
-- 200 to 349 CD4s: RR 2.13 (1.45 to 3.14)
-- 350 to 499 CD4s: RR 1.23 (0.85 to 1.78
-- 500 or more CD4s: Reference
In contrast, time-updated viral load did not affect chances of the composite non-AIDS endpoint.
"In persons not yet receiving combination antiretrovirals therapy," the ATHENA team concluded, "a more severe degree of immunodeficiency rather than HIV RNA appears to be associated with an overall risk of our composite non-AIDS event endpoint." They call for larger studies to assess potential associations between individual non-AIDS diseases, CD4 count, and viral load in untreated people.
1. van Sighem A, Kesselring A, Gras L, et al. Risk of non-AIDS-defining events amongst HIV+ patients not yet on ART. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 1042. http://www.retroconference.org/2013b/PDFs/1042.pdf