Jpn. J. Infect. Dis., 54, 2001

Laboratory and Epidemiology Communications

Rate of Subclinical Hepatitis A Virus Infection in
Adult HIV‑ 1 ‑Infected Patients
Setsuko Ida, Natsuo Tachikawa, Yoshimi Kikuchi, Akira Yasuoka and Shinichi Oka*AIDS Clinical Center, International Medical Center ofJapan,
Toyama 1‑21‑1, Shinjuku‑ku, Too,o ･162‑8655
Communicated by Hiroshi Yoshikura(Accepted March 13, 2001)

Hepatitis A virus (HAV) is usually transmitted orally

this period. Consequently, lt Was Calculated that 23 plus1 1through contaminated fわod or water (1,2). It can also be(i.e., 34 patients; 24.8% of the 137 homosexual men) Weretransmitted person‑to‑person as a sexually transmitted disease

infected with HAV in this outbreak. The rate of subclinical(STD) in homosexual men (315). We encountered an outbreak

infection was 32.3% (95% confidence interval lCI]: 16.6%‑
48.0%) in adult HIV‑ 1 ‑infected patients.

of acute HAY infection in HIV‑ 1 ‑infected homosexual men

livlng ln the Tokyo Metropolitan area from August 1998
through September 1999 (6). We here report the rate of sub‑

The characteristics of these patients are listed in Table 1.

There was no significant difference between HAV infection
manifest and non‑manifest groups with respect to age, CD4counts, CD8 counts, and anti‑HIV‑1 treatment. The HIV‑1

clinical HAY infection in adult HIV‑ 1 ‑infected cases.
A total of 404 HIV‑ I ‑infected patients visited the ambulant
clinic in September 1999. Among them, 137 patients werehomosexual men and 5 I (38%) of these homosexual patients
had anti‑HAV IgG antibodies.

viral load of patients with clinical manifestation was slgnif1‑

cantly higher than that of patients with subclinical HAV
infection. However, analysts Of the symptomatic patients

Twenty‑three of these patients had experienced typicalrevealed no correlation between severity of symptoms andclinical symptoms of acute HAY infection, such as fever,

HIVI viral load (data not shown). In geogr叩hical areas or

general fatigue, nausea, vomiting,and jaundice,inthe previousyear. The diagnosis was confirmed bythe presence of anti‑HAV
IgM antibodies in cases presenting with clinical symptoms.

high prevalence, most children infected are infected early inlife, and such infection is generally asymptomatic, while

initial infectioninadulthood results in greater clinical severity.
The rate of clinically manifest cases among HAV‑ infectedcases in HIV‑I‑infected patients reported here was thealmost same as that in adult non‑HIV cases (7), i.e., theimmunocompromised statusof HIV‑infected patients did not

Sera from 28 additional patients had been stored since

January 1998 (this outbreak started in August 1998). They
had not experienced any clinical manifestations of HAV
infection. However, serologlCal tests revealed that 1 7 patientsamong them had the lgG antibodies at that time; the remainlngll patients did not. Accordingly, the ll patients wereenhance the clinical manifestation.

seroconverted despite having no clinical symptoms during

Table 1. Demographic characteristics of HIV‑ I ‑infected homosexual subjects with
HAV infection
variables

symptomaticsubc

1

inicalHAV infection HAV infection
no. orpatients
agestagc (HIV)CD4+ T cell (/fLl)

CD8+ T cell (/LEI)

2311mean±SD34.8±8.1

33.2±5.6(range)(22‑54)

asymptomati c23mean±SD459± 142(range)( 1 73‑734)

mean±SD759±296(ran ge)(316‑161 1)

HIV‑1 viral load (/ml) medi an

4.8xl03(range)(<400‑8.6× 105)

(26‑45)11437±235(I 69‑872)
881 ±440(465‑1828)
1.6xIO3(<400‑3.4× 103)

receive anti‑HIV仙erapy

yes (%)

48%

73%

Data were obtained at the onset of symptoms in symptomatic patients and in January 1 999
in subclinical patients.

*Corresponding author: Teln;ax: +8 1 ‑3‑5273‑5 1 93, E‑mail: oka@
imcj.hosp.goJP

31

viral entry and cell‑to‑cellfusion. The ecotropic Friend MLV

domain of human CD4 (9). The CD4‑Env chimera was(FMLV) Env is oligomerized into a trimer in the endoplasmic
reticulum, cleaved into the surface protein (SU, gp70) and thetransmembrane protein (TM, p I 5E) in the Golgi apparatus,

processed, expressed on the cell surface, and incorporated

into the virion. When coexpressed, CD4‑Env bound to thewild‑type FMLV Env to form heter0‑0ligomers. Further, CD4‑
Env contributed the postbindingfusionfunction and comple‑
mented a fusion‑deficient TM mutant to induce membranefusion (10)･ Because the CD4‑Env and the TM mutant.aretransported to the cell surface, and incorporated intothe virion(1). At the time of virus budding or shortly thereaRer, pl5E
is cleaved into p12E and the C‑teminal 1 6‑amino‑acid long
R‑peptide (2). Expression of the wild‑type Env does not
induce syncytla in NIH 3T3 cells, whereas expression of therequired to form heter0‑01igomers in the complementatlOn,

the fusion efficiency may be dependent on the molar ratio of
the fbmer to the latter. In our previous study, however, we

良‑deleted Env does (3,4). No syncytia are induced by the R‑

deleted FMLV Env in HeLa cells lacking the FMLV receptor.
Env‑mediated membrane fuSion is initiated by the bindingof SU to the receptor followed by postbinding fusion (1).
The receptor‑binding domain (RBD) resides in the N‑terminal

examined the complementation between two molecules onlyat the molar ratio of日. In this study, the optlmal ratio f♭r

the complementation to induce syncytla Was detemined.
pCXN2 plasmids expressing FE (a wild‑type ecotropic

half of SU (5,6). Receptor‑binding and postbinding fusion

FMLV Env), FE.T470H (afusion‑deficient FMLV Env with afunctions can be contributed by two different molecules

point mutation in the extracellular domain ofTM), R‑deleted
FE.D86K (a binding‑deficient FMLV Env with a point muta‑

respectively (7,8)･ In a previousreport (7), a binding‑deficientEnv with a polnt mutatlOn in RBD and afusion‑deficient Env
with a polnt mutation in TM functioned in a complementarytion in R8D), and R‑deleted CD4‑Env, respectively, were used(10,1 1). Expression of R‑deleted FE.D86K did not induce
syncytia by itself, but did by co‑expression with FE in NIH

fasion to induce membrane fusion.

3T3 cells･ Similar Pomplementation in inducing syncytia was*Corresponding author: Tel: +81‑42‑561‑077l ext. 335, Fax: +81‑

obseⅣed in experlmentS uSlng R‑deleted CD4‑Env instead

42‑565‑33 1 5, E‑mail: matano@nih.gojp

of R‑deleted FE.D86K. Also, complementation was observed

32