High
HIV Viral Load Is a Risk Factor for Tuberculosis within 3 Months of Starting HAART
 By
Liz Highleyman
Worldwide,
tuberculosis (TB) is among the leading causes of death among people with HIV/AIDS,
and highly drug resistant TB is a growing public health problem. HIV-related
immune deficiency is a major risk factor for TB, and HAART
has been shown to improve long-term outcomes. However, the odds of developing
TB during the first 3 months after HAART initiation are high -- ranging from 1
to as high as 23 cases per 100 person-years (PY) in various prior studies -- and
the associated risk factors are poorly understood. Identifying these factors could
help target appropriate prevention strategies.  As
reported at the XVII International AIDS Conference
this month in Mexico City, Timothy Sterling and colleagues with the North American
AIDS Cohort Collaboration on Research and Design (NA-ACCORD), part of the International
Epidemiological Databases to Evaluate AIDS (IeDEA), looked at demographic and
clinical variables associated with developing TB either within 3 months or more
than 3 months after starting HAART.
Between
January 1995 and March 2006, the analysis included 12 cohorts in the U.S. and
Canada, consisting of a total of 10,820 HIV positive individuals who initiated
combination HAART (at least 3 drugs) and for whom TB endpoints were available.
People who had TB prior to or within the same month as HAART initiation were excluded;
persons with prior AIDS-defining events, however, were included. The median follow-up
duration after starting HAART was nearly 4 years.
Results
•
Overall, 48
study participants developed TB during 52,134 PY of follow-up (representing 92
cases per 100,000 PY).
•
9 cases occurred
during the first 3 months of HAART (335 cases per 100,000 PY).
•
39 cases occurred
after 3 months on HAART (79 per 100,000 PY) (P < 0.001).
•
8 of the 9
patients with TB during the first 3 months (89%) had a baseline CD4 count <
100 cells/mm3 and HIV RNA > 350,000 copies/mL.
•
In contrast,
just 11% of the full cohort met both these criteria.
•
Individuals
with TB cases occurring during the first 3 months had a significantly higher median
HIV RNA level than those who developed TB later (707,300 vs 67,406 copies/mL;
P = 0.02).
•
Individuals
with early TB also had a lower median pre-HAART CD4 cell count (73 vs 144; P =
0.25) and were more likely to be injection drug users (P = 0.12), but these differences
did not reach statistical significance.
•
There was no
difference in early vs delayed TB occurrence according to patient age, sex, race/ethnicity,
site of disease (pulmonary vs extrapulmonary), TB culture status (negative vs
positive), or type of HAART regimen (PI-based vs NNRTI-based).
•
1 of 9 patients
with early TB cases died (11%) compared with 9 of 39 later cases (23%), a difference
that also did not reach statistical significance (P = 0.43).
The
investigators concluded that high HIV RNA was the only factors significantly associated
with developing TB within 3 months of HAART initiation, though the small number
of early cases limited the study's statistical power.
They also noted
that TB risk during the first 3 months in this study was "several-fold lower
than reported in other cohorts, including those from developed world settings."
Based
on these findings, they recommended that "TB screening measures should be
focused on persons with advanced AIDS, before and shortly after HAART initiation."
Vanderbilt
University, Division of Infectious Diseases, Nashville, TN; Johns Hopkins University,
Baltimore, MD.
8/26/08
Reference
T Sterling, B Merriman,
and A Freeman. Risk factors for tuberculosis within 3 months of HAART initiation.
XVII International AIDS Conference (AIDS 2008). Mexico City. August 3-8, 2008.
Abstract
MOAB0304.
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