Fewer CD4s at HIV Diagnosis Tied to Higher Risk of non-AIDS Deaths

20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta

Mark Mascolini

A lower CD4 count at HIV diagnosis raised the risk of death from non-AIDS cancer, non-AIDS infections, cardiovascular disease, and AIDS in a 5743-person analysis of the Austrian HIV Cohort Study [1]. A lower CD4 count when combination antiretroviral therapy (cART) began boosted the risk of death from non-AIDS cancers, non-AIDS infection, HBV/HCV-associated death, and AIDS.

The researchers divided observation time into three cART-era periods: 1997-2000, 2001-2004, and 2005-2011. They divided CD4 count at HIV diagnosis or cART initiation into four brackets: under 50, 50 to 199, 200 to 349, and 350 or higher. The researchers recorded deaths over the study period, checking for people lost to follow-up in death registries.

The study population included 4211 men (73%) and 1532 women. Nadir and latest CD4 counts averaged 227 and 510, and age at study entry averaged 36. Most cohort members acquired HIV heterosexually (38.2%) or during sex between men (34.1%). More than three quarters of study participants (79%) had ever taken cART, and 70.5% had taken cART for 6 months or more. Three quarters of study participants were Austrian, 12% came from other low HIV-prevalence countries, and 11% came from high-prevalence countries.

During follow-up, 876 people died, 311 (35.5%) from AIDS, 94 (10.7%) from non-AIDS cancers, 87 (9.9%) from HBV/HCV hepatitis, 79 (9.0%) from non-AIDS infections, and 48 (5.5%) from cardiovascular disease. More deaths were attributed to intoxication (6.5%) than to cardiovascular disease. Mortality fell from 3.61 deaths per 100 person-years in 1997-2000 to 2.42 in 2001-2004 and to 1.93 in 2005-2011. Median age at death rose in those three periods from 39.9 to 41.2 to 46.4, while median CD4 count before death climbed from 123 to 193 to 203.

From 1997-2000 to 2005-2011 mortality fell for AIDS (1.59 to 0.56 per 100 person-years), non-AIDS infections (0.25 to 0.20), HBV/HCV (0.38 to 0.16), and cardiovascular disease (0.28 to 0.10). But mortality from non-AIDS cancers climbed from 0.16 per 100 person-years in 1997-2000 to 0.21 in 2001-2004 and to 0.31 in 2005-2011. Mortality fell across the three study periods in every subgroup analyzed: age group, transmission mode, CD4s at diagnosis, CD4s at start of cART, and population in area of residence.

Compared with a CD4 count at or above 350 at HIV diagnosis or start of cART, lower CD4 counts at HIV diagnosis or cART start were associated with higher death rates at the following incidence rate ratios (IRR) and 95% confidence intervals (CI) in multivariable Poisson regression models:

Higher mortality by lower CD4 count at diagnosis compared with >350:
AIDS
200-349 CD4s: IRR 1.85 (1.04 to 3.29)
50-199 CD4s: IRR 5.75 (3.46 to 9.55)
Under 50 CD4s: IRR 16.05 (9.91 to 26.0)

Non-AIDS infection
50-199 CD4s: IRR 2.99 (1.23 to 7.28)
Under 50 CD4s: IRR 6.08 (2.43 to 15.24)

Non-AIDS malignancy
200-349 CD4s: IRR 2.39 (1.15 to 4.97)
50-199 CD4s: IRR 2.86 (1.29 to 6.35

Cardiovascular disease
50 to 199 CD4s: IRR 3.49 (1.36 to 8.96)

Higher mortality by lower CD4 count at start of cART compared with >350:
AIDS
50-199 CD4s: IRR 4.21 (2.75 to 6.43)
Under 50 CD4s: IRR 9.87 (6.40 to 15.23)

Non-AIDS infection
Under 50 CD4s: IRR 3.05 (1.41 to 6.60)

HBV/HCV
50-199 CD4s: IRR 2.46 (1.29 to 4.71)

Non-AIDS malignancy
50-199 CD4s: 2.16 (1.09 to 4.27)

The researchers warn that their statistical analysis is limited because it does not adjust for certain lifestyle factors, including smoking. It did adjust for gender, age, calendar year, duration of cART, HIV transmission category, and population of residence area. At the same time, the investigators cautioned that they may have underestimated mortality because of loss to follow-up of cohort members who left the country.

They proposed that ”the association of a lower CD4 cell count at HIV diagnosis with increased mortality for most causes of death suggests an urgency to prevent individuals presenting late for care.”

Reference
1. Sturm G, Sarcletti M, Gog S, et al. A lower CD4 cell count at presentation is associated with increased mortality for most causes of death. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 1044.  http://www.retroconference.org/2013b/PDFs/1044.pdf