Withdrawal symptoms as a predictor of mortality in patients HIV-infected through drug use receiving antiretroviral treatment (HAART)
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Withdrawal symptoms as a predictor of
mortality in patients HIV-infected
through drug use receiving
antiretroviral treatment (HAART)
Michel L123, Giorgi R4, Villes V5, Poizot-Martin I6,
Dellamonica P7, Spire B5, Carrieri M.Patrizia5
1INSERM, U669, Paris, France ;
2Univ Paris-Sud and Univ Paris Descartes, UMR-S0669, Paris, France ;
3AP-HP, Emile Roux Hospital, Centre de Traitement des Addictions, Limeil-Brévannes, France ;
4 LERTIM, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille Cedex, France ;
5 Health and Medical Research National Institute, Research Unit 912 (INSERM UMR912), Marseilles, France
6 Southeastern Health Regional Observatory (ORS PACA), Marseilles, France
7 Sainte Marguerite Hospital, Marseilles, France
8 Archet Hospital, Infectious Diseases Service, Nice, FranceBackground:
HIV progression in IDUs
No difference
N diff iin d
death
th rates
t existed
i t d iin the
th
pre-HAART era
IDUs receiving HAART have an increased
risk of pre-AIDS death with respect to other
people living with HIV (PLWH)
This increased risk is not attributable to poor
p
response to HAART but rather to HCV, drug
use and social instability
y ((Mocroft 2002).
)
Self-reported heroin and cocaine use have
been associated with a development of new
Aids defining conditions (Lucas 2006).Background:
Life events and HIV progression
Higher cumulative average stressful life
events predict faster progression to AIDS in
gay men (Leserman 2002)
More lifetime
lif i trauma significantly
i ifi l predict
di
faster all-cause and AIDS-related mortality
i HIV-infected
in i f d men andd women (Leserman
2007).
Studies investigating to what extent life
events experience may be predictive of an
increased risk of death in IDUs are sparse.Objective
To explore the role that life events
events’
experience and particularly drug-
related events may play on the risk of
death in HIV-infected IDUs.Methods:
MANIF 2000 Study
the MANIF-2000
Multidisciplinary cohort to study social and
behavioral characteristics of patients HIV-
infected through injecting drug use since
1995
467 patients enrolled (criteria: clinical stage
A or B and CD4>300 mm3)
Participation of 12 hospital centers in two
French regions : Provence-Alpes-Côte
d’Azur and the Ile de France
Causes of death were retrieved either by y
death certificates or by hospital records.Methods : Questionnaires (1)
Standardized medical forms to collect clinical,
treatment and laboratory data
Face to face interviews to collect psycho
Face-to-face psycho-social
social
information including patient’s personal
experience with HIV infection,
infection care and
adherence to HAART
Self-administered questionnaires collecting
experience of negative life events, social
conditions, prison history, access to OST, drug
and alcohol use and depressive symptoms
(CES-D)Methods : Questionnaires (2)
Negative life events included:
• Financial problems
• Negative relational events
• Violence
• Hospitalizations
• Family member illnesses or accidents
• D
Drug-related
el ted problems
oble : Detoxification,
Deto ifi tio death
de th
from overdose of a family member or a friend,
experience of withdrawal symptomsMethods: Participants
467 patients enrolled
294 patients
p
receiving HAART during follow-up
accounting for 1430 person-years
(max follow up= 9 years)Statistical methods Kaplan Meier and Cox model to study the effect of possible baseline predictors and time dependant covariates on the risk of death. Variables with p
Results
During follow-up 26 deaths (1.8 deaths per 100 PY)
occurred in IDUs receiving HAART
HAART. These were
attributed as follows:
- 2 HIV
- 8 Liver disease
- 2 Suicides
- 1 Road accident
- C di l problems
4 Cardiovascular bl
- 4 “Unspecified” at home or in a car
- 5 other
th causes (aggression,
( i medullar
d ll aplasia,
l i sepsis,
i
hypopituarism, unknown)
41 patients reported negative experience with
withdrawal symptoms in 60 follow-up visitsCharacteristics of participants at
ART enrollment (n=294)
n (%)
Age (median [IQR]) 35 [32-38]
Men 215 (73.1)
High school certificate 63 (21.4)
Employment 92 (31.3)
(31 3)
Depressive symptoms 116 (39.5)
Injecting
jec g d drug
ug use 41 ((16.5)
6 5)
Drug-related problems * 20 (11.6)
Drug possession * 8 (4.7)
Withdrawal symptoms (WS) experience* 19 (11.0)
* Negative life eventsClinical characteristics of
participants at HAART enrollment
(n=294)
n (%)
Clinical stage A 125 (42.7)
(42 7)
B 156 (53.2)
C 12 (4.1)
CD4 /mm3 (median [IQR]) 390 [300-530]
U d t t bl viral
Undetectable i l lload
d 99 (33.7)
(33 7)
No OST 194 (66.0)
(66 0)
Buprenorphine 60 (25.8)
Methadone 36 (14.1)
Morphine sulfate 4 (1.3)Variables eligible for the multivariate Cox model (p
Kaplan-Meier
Kaplan Meier survival estimates, by withdrawal symptoms
00
1.0
stset fipoint0 ,id(id) failure(statut)
sts graph, by(qv41brok)
0.75
0.50
0.25
0.00
0
0 20 40 60 80 100
analysis time
No YesFactors independently associated
with the risk of death
Adjusted
Adj t d HR
[95% CI] P-value
Viral load ≥ 10000 copies/ml 4.7 [2.0-10.9]Why are withdrawal symptoms
predictive of survival ?
No significant difference in WS occurrence when
comparing
i methadone
h d anddbbuprenorphine
hi substituted
b i d
patients.
The incidence of withdrawal symptoms was
significantly
g y higher
g in the 1995-1998 p
period than in the
period after 1999
IR[95%CI] =27
=27.5[16.6;
5[16 6; 45.6]
45 6] - 1995
1995-1998
1998
IR[95%CI] =10.6 [7.3; 15.4] - 1999
Pharmacosurveillance data confirm that there was an
increase in dosage prescription for both methadone and
buprenorphine when comparing the two periods.Why are withdrawal symptoms
predictive of survival ?
Withdrawal symptoms may be a proxy of possible
interactions with HAART requiring an increase in OST
dosages
Withdrawal symptoms in patients receiving OST may be
a sign of under-dosing or inadequate care.
Underdosed substituted patients may use opioids to
manage withdrawal symptoms but they may die from
overdose because of their reduced tolerance to opioids.Conclusions (1)
Experience of withdrawal symptoms is a
predictor
di t off survival
i l iin IDUs
IDU on HAART
even after adjustment for HIV status (VL)
This association did not change even:
after adjustment for adherence and initial CD4
after exclusion of the two deaths due to suicide
after multiple imputation of missing data of the other
possible predictorsConclusion (2)
Withdrawal symptoms in IDUs living with HIV
mainly reflects difficulties in the management
of opioid dependence
dependence.
This association needs to be investigated
more thoroughly in other studies
Such symptoms should be detected and
managed more effectively to properly deliver
comprehensive care to IDUs on HAART and
prevent possible drug-related deathsThanks to :
The French National Agency for Aids Research
(ANRS, France), the charity organisation ECS-
SIDACTION (France), and the Departmental
Council (Bouches-du-Rhône, France).
Manif 2000 study group : C Boirot, AD Bouhnik, MP Carrieri, JP
Cassuto, M Chesney, P Dellamonica, P Dujardin, H Gallais, JA Gastaut, P Kurkdji, G
Lepeu, C Marimoutou, D Mechali, JP Moatti, J Moreau, M Nègre, Y Obadia, I Poizot-
Martin, C Pradier, D Rey, C Rouzioux, A Sobel, B Spire, F Trémolières, V Villes, E
Vi
Vincent,
t D Vl
Vlahov
h
All PLWH who accepted
p to p
participate
p in
the studyYou can also read
