Download HIV-1 containing the I50V mutation to amprenavir. Thus, if N88S can

HIV-1 containing the I50V mutation to
amprenavir. Thus, if N88S can be maintained, future treatment options for this
patient, who harbors I50V-containing virus, may include amprenavir, perhaps in
combination with ritonavir. Although the
change was less dramatic, N88S also lowered the level of resistance to lopinavir
imparted by I50V. The congruence of
directionality in the effect of N88S on amprenavir and lopinavir is consistent with
observations we have published elsewhere
with regard to cross-resistance between
these 2 PIs [6]. Although N88S is a relatively rare mutation in clade B viruses
from PI-experienced patients, recent reports indicate that it may be more common in other subtypes [7–9]. Thus, the
importance of the findings described here
may increase as PIs begin to be used in
areas where non–clade B HIV-1 is predominant, as well as after the introduction
of new PIs, such as atazanavir [4].
Eric Lam and Neil T. Parkin
ViroLogic, San Francisco, California
References
1. Patick AK, Duran M, Cao Y, et al. Genotypic
and phenotypic characterization of human immunodeficiency virus type 1 variants isolated
from patients treated with the protease inhibitor nelfinavir. Antimicrob Agents Chemother
1998; 42:2637–44.
2. Condra J, Holder D, Schleif W, et al. Genetic
correlates of in vivo resistance to indinavir, a
human immunodeficiency virus type 1 protease
inhibitor. J Virol 1996; 70:8270–6.
3. Ziermann R, Limoli K, Das K, Arnold E,
Petropoulos CJ, Parkin NT. A mutation in human immunodeficiency virus type 1 protease,
N88S, that causes in vitro hypersensitivity to
amprenavir. J Virol 2000; 74:4414–9.
4. Gong YF, Robinson BS, Rose RE, et al. In vitro
resistance profile of the human immunodeficiency virus type 1 protease inhibitor BMS232632. Antimicrob Agents Chemother 2000;
44:2319–26.
5. Parkin N, Chappey C, Maroldo L, Bates M,
Hellmann NS, Petropoulos CJ. Phenotypic and
genotypic HIV-1 drug resistance assays provide
complementary information. J Acquir Immune
Defic Syndr 2002; 31:128–36.
6. Parkin NT, Chappey C, Petropoulos CJ. Improving lopinavir genotype algorithm through
phenotype correlations: novel mutation patterns and amprenavir cross-resistance. AIDS
2003; 17:955–61.
7. Grossman Z, Paxinos E, Auerbuch D, et al.
D30N is not the preferred resistance pathway
in subtype C patients treated with nelfinavir.
Antivir Ther 2002; 7(Suppl 1):S30.
8. Gomes P, Diogo I, Goncalves MF, et al. Different pathways to nelfinavir resistance in HIV1 subtypes B and G [abstract 46]. In: Program
and abstracts of the 9th Conference on Retroviruses and Opportunistic Infections (Seattle).
Alexandria, VA: Foundation for Retrovirology
and Human Health, 2002.
9. Ariyoshi K, Matsuda M, Miura H, Tateishi S,
Yamada K, Sugiura W. Patterns of point mutations associated with antiretroviral drug treatment failure in CRF01_AE (subtype E) infection differ from subtype B infection. J Acquir
Immune Defic Syndr 2003; 33:336–42.
Reprints or correspondence: Dr. Neil T. Parkin, ViroLogic, 345
Oyster Point Blvd., South San Francisco, CA (nparkin@
virologic.com).
Clinical Infectious Diseases 2003; 37:1273–4
2003 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2003/3709-0022$15.00
Linezolid and Serotonin
Toxicity
Sir—The possibility, suggested by the report by Bernard et al. [1], that linezolid
may cause serotonin syndrome (serotonin
toxicity) via action as an monoamine
oxidase inhibitor (MAOI) is of great importance. The spectrum of the iatrogenic,
drug-induced reaction of toxicity ranges
from side effects to toxicity (thus, thinking
of it as a syndrome is less helpful) [2, 3].
General physicians need to know that severe serotonin toxicity—that is, toxicity of
a possibly life-threatening/fatal degree—
may be expected to result from combinations of MAOIs with serotonin reuptake
inhibitors [3].
If linezolid produces significant monoamine oxidase inhibition, then there will
be a risk of severe toxicity if it is coadministered with any serotonin reuptake inhibitor; serotonin reuptake inhibitors include
some narcotic analgesics (e.g., tramadol
and pethidine), all selective serotonin
reuptake inhibitors, and “dual action” antidepressants (i.e., serotonin and noradrenaline reuptake inhibitors), such as duloxetine and venlafaxine (and similar
drugs, such as sibutramine).
I have presented the evidence for the
accuracy of the spectrum model of sero-
1274 • CID 2003:37 (1 November) • CORRESPONDENCE
tonin toxicity in 2 major review articles
[3, 4]. The spectrum model aids persons
in understanding that the degree of elevation of serotonin levels dictates the severity of the toxicity, and that severe, lifethreatening toxicity only results from large
elevations in the serotonin level caused by
combinations of MAOIs and serotonin
reuptake inhibitors.
The features that distinguish serotonin
toxicity from other toxic syndromes are
hyperreflexia, hypertonia, myoclonus, fever, agitation, and late-stage/severe pyramidal rigidity [2]. Serotonin toxicity
typically presents as neuromuscular
hyperactivity (tremor, clonus, myoclonus,
and hyperreflexia), altered mental status
(excitement, agitation, and late-stage/
severe confusion), and autonomic hyperactivity (diaphoresis, fever, mydriasis,
tachycardia, and tachypnea).
Clinically, the onset of serotonin toxicity is often rapid; at first, the patient is
quick to detect the symptoms, with tremor
and hyperreflexia. Clonus and myoclonus
starts in the lower limbs and may become
generalized. Autonomic features (tachypnea, tachycardia, and hypertension) fluctuate and are not usually difficult to
manage. Other symptoms may include
shaking, shivering, chattering of the teeth,
and trismus. Pyramidal rigidity is a late
development and may impair respiration
if it affects truncal muscles. Rigidity and
fever (temperature, 139.5C) indicate serious toxicity.
The case reported by Bernard et al. [1]
illustrates the importance of knowing the
aforementioned information and what to
look for and report to establish the presence and severity of toxicity. The spectrum
concept predicts the high-risk cases that
may sometimes require aggressive treatment intervention with cyproheptadine;
endotracheal intubation, neuromusculaur
paralysis, and cooling; or chlorpromazine.
I maintain a summary (based on peerreviewed publications) of all aspects of
serotonin toxicity and the implicated
drugs on my Web site (http://www.psy
chotropical.com/SerotoninToxicity.doc).
P. Ken Gillman
Department of Clinical Neuropharmacology, Pioneer
Valley Private Hospital, and Department of Clinical
Neuropharmacology, James Cook University,
Mount Pleasant, Queensland, Australia
References
1. Bernard L, Stern R, Lew D, Hoffmeyer P. Serotonin syndrome after concomitant treatment
with linezolid and citalopram. Clin Infect Dis
2003; 36:1197.
2. Dunkley E, Isbister G, Sibbritt D, Dawson A,
Whyte I. The Hunter Serotonin Toxicity Criteria: a simple and accurate diagnostic decision
rule for serotonin toxicity. Q J Med 2003; 96:
635–42.
3. Gillman PK. Serotonin syndrome: history and
risk. Fundam Clin Pharmacol 1998; 12:482–91.
4. Gillman PK. The serotonin syndrome and its
treatment. J Psychopharmacol 1999; 13:100–9.
Reprints or correspondence: Dr. Ken Gillman, Dept. of Clinical
Neuropharmacology, Pioneer Valley Private Hospital, PO Box
8183, Mount Pleasant, Queensland 4740, Australia (kg@
matilda.net.au).
Clinical Infectious Diseases 2003; 37:1274–5
2003 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2003/3709-0023$15.00
Isolated Antibody
to Hepatitis B Core Antigen
in Individuals Infected
with HIV-1
Sir—We read with interest the article by
Gandhi et al. [1] concerning the factors
associated with the presence of isolated antibody to hepatitis B core antigen (antiHBc) in patients with human immunodeficiency virus type 1 (HIV-1) infection.
Patients in this study who were seronegative for hepatitis B surface antigen
(HBsAg) and for antibody to HBsAg (antiHBs) had a relatively higher CD4+ cell
count (median, ∼350 cells/mm3) and
lower plasma virus load (median, ⭐3.75
log10 copies/mL) than patients who were
not; 42% of these 142 patients had a history of percutaneous exposure to blood.
In order to determine whether the prevalence of isolated anti-HBc might be different among patients who had acquired
HIV infection mainly through sexual
transmission and who were at a late stage
of HIV infection, we analyzed the data in
a prospective observational study of 716
nonhemophiliac patients infected with
HIV-1, aged ⭓15 years, in an area where
hepatitis B (HBV) infection is hyperendemic [2, 3]. All statistical analyses were
performed using SAS statistical software
(Version 8.02, SAS Institute). Categorical
variables were compared using x2 or
Fisher’s exact test, whereas noncategorical
variables were compared using Wilcoxon’s
rank-sum test. The Spearman correlation
coefficient was used to compute the relationship between ordinal and continuous variables.
Of the 716 patients enrolled in our
study between June 1994 and June 2002,
416 (58.1%) had a complete diagnostic
study of hepatitis B status (i.e., the presence of HBsAg, anti-HBs, and anti-HBc)
performed at enrollment. Their clinical
characteristics are shown in table 1 (overleaf). Most of them were at the late stage
of HIV infection, with a depleted CD4 cell
count and a high plasma virus load (PVL),
and had acquired HIV infection through
sexual transmission; only 2.4% of the patients had a history of exposure to blood.
Approximately 10% of our patients had
chronic hepatitis C virus (HCV) infection.
Of the 416 patients who had a complete
study diagnostic study of hepatitis B status
performed, 140 (33.7%) were negative for
HBsAg and anti-HBs; isolated anti-HBc
was detected in 113 patients (80.7%). The
prevalence of isolated anti-HBc appeared
to increase with the severity of immunosuppression (Spearman correlation coefficient, ⫺0.84; P p .07) (table 1). In a
multivariate analysis, we did not find that
either chronic HCV infection or a history
of exposure to blood was associated with
presence of isolated anti-HBc (data not
shown), which finding may be related to
the small number of patients with chronic
HCV infection in our study. In addition,
isolated anti-HBc was not associated with
an increased risk for mortality or with progression of HIV infection either before or
after the introduction of HAART.
Our findings suggest that the prevalence
of isolated anti-HBc will vary with the epidemiologic characteristics of the patients
enrolled in the study and the background
seroprevalence of HBV infection. In an
area of hyperendemicity of HBV infection
and low endemicity of HCV infection, the
prevalence of isolated anti-HBc will be
high among patients at a late stage of HIV
infection.
Chien-Ching Hung,1,2 and Chin-Fu Hsiao3
Department of Internal Medicine and 2Department
of Parasitology, National Taiwan University
Hospital, National and Taiwan University College
of Medicine, and 3Division of Biostatistics
and Bioinformatics, National Health Research
Institutes, Taipei, Taiwan
1
References
1. Gandhi RT, Wurcel A, Lee H, et al. Isolated
antibody to hepatitis B core antigen in human
immunodeficiency virus type-1-infected individuals. Clin Infect Dis 2003; 36:1602–5.
2. Sheng WH, Chen MY, Hsieh SM, et al. Impact
of chronic hepatitis B infection on outcomes
of HIV-1-infected patients in an area hyperendemic for hepatitis B infection [abstract 823].
In: Program and abstracts of the 10th Conference on Retroviruses and Opportunistic Infections (Boston). Alexandria, VA: Foundation for
Retrovirology and Human Health, 2003.
3. Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A
prospective study of 22,707 men in Taiwan.
Lancet 1981; 2:1129–33.
Reprints or correspondence: Dr. Chien-Ching Hung, Dept. of
Internal Medicine, National Taiwan University Hospital, 7
Chung-Shan South Rd., Taipei, Taiwan ([email protected]
.ntu.edu.tw).
Clinical Infectious Diseases 2003; 37:1275–6
2003 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2003/3709-0024$15.00
CORRESPONDENCE • CID 2003:37 (1 November) • 1275