patients at greater risk of severe side-effects than AIDS
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HIV-positive individuals who take HAART are more likely to
serious or life-threatening treatment side-effect than develop
AIDS-defining condition, according to a US study published in
December 1st edition of the Journal of Acquired Immune
Syndromes. The study investigators suggest that doctors should
assess their patients' medical history and circumstances
prescribing anti-HIV therapy so they can avoid the use of
could aggravate existing health conditions.
Investigators analysed the results from five US multi-centre
trials that had a common system of reporting adverse events,
and deaths between 1996 and 2001. Partial findings from the
presented at the Ninth Conference on Retroviruses and
Infections in 2002.
The investigators wished to establish the incidence and
serious or life-threatening treatment side-effects,
illnesses and death.
Data were analysed from 2,947 patients who were followed for a
20.7 months, contributing 5,940 person-years of follow-up. At
of enrollment to the studies, 53% of individuals were
naïve, average age was a little over 39 years, 83% were male,
gay men, 16% had a history of injecting drug use, the median
count was 211 cells/mm3, and 40% had a previous AIDS
All the patients were prescribed anti-HIV therapy, and at the
month of follow-up 89% were receiving HAART (70% a protease
and 19% a non-nucleoside-based regimen), 3% mono- or
analogue treatment, and 8% had stopped anti-HIV treatment on
permanent or temporary basis.
A severe or life threatening side-effect (grade 4
adverse-event) was experienced by 675 individuals (11.4 cases
person years), 332 developed an AIDS-defining condition (5.6
100 person years), and 272 people died (4.6 cases per 100
The cumulative percentage of patients with a severe or life
side-effect at month twelve was 15.6%, at month 24, 23.7% and
36, 30.8%. The corresponding percentages for AIDS events were
10.8%, 16.5%, and the percentages for deaths were 3/9%, 7.9%
Liver-related side-effects were the most frequently reported
events (148 patients, 2.6 per 100 person years).
When the investigators looked at the risk factors for the
severe or life-threatening side-effects, they found that the
lower in younger patients (hazard ratio [HR] 0.83 for every
years, p=0.0001), and patients who had never taken anti-HIV
(HR=0.59, p=0.0001). The risks were increased for individuals
history of injecting drug use (HR=1.41, p=0.0006), lower
cell count (for every 100 cells/mm3, HR=1.06, p=0.04), and a
AIDS-defining illness (HR=1.22, p=0.03).
The investigators also found that women were at increased risk
experiencing severe or life-threatening neutropenia (HR= 1.76,
whilst African Americans were at increased risk of neutropenia
p=0.0001), anaemia (HR=2.46, p=0.008), and kidney-related
(HR=22.41, p=0.00250. People of Latino origin had an increased
neutropenia (HR=2.75, p=0.01).
Of the 272 people who died, 159 experienced both a grade 4
reaction and an AIDS-defining illness.
Coinfection with hepatitis B (HR=5.97, p=0.0001) and hepatitis
(HR=2.74, p=0.009) were significantly associated with the risk
experiencing a severe liver-related side-effect.
The investigators note, "our principal finding is that
the rate of grade
4 events is greater than the rate of AIDS events, and that the
death associated with these grade 4 events was very high for
They believe that their study has two important implications.
the procedure for collecting data of adverse events during
trials needs to be improved. Secondly, doctors need to
their patients for the existence of other medical problems,
account social and economic status and drug and alcohol use.
example, patients at increased risk of cardiovascular events
benefit from being placed on a protease inhibitor-sparing
Similarly, patients with a history of severe depression may be
off with an efavirenz-sparing HAART regimen."
Reisler RB et al. Grade 4 events are as important as AIDS
events in the
era of HAART. JAIDS 34: 379 – 386, 2003.