Spectrum of Opportunistic Infections and Malignancies in Patients with Human Immunodeficiency Virus Infection in South Korea
Sang Won Park
Hong Bin Kim
Ui Seok Kim
Nam Joong Kim
Hee Jung Choi
Dong Hyeon Shin
Joo Shil Lee
Patients. We reviewed the medical records of 173 HIV-infected patients seen from May 1985 to April 1998 at the Seoul National University Hospital, a 1600-bed university-affiliated teaching hos-
Center for AIDS Research, National Institute of Health
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine
To determine the frequency and types of major opportunistic diseases in patients with HIV infection in South Korea, we reviewed the medical records of 173 HIV-infected patients. The patients were seen from 1985 to 1998 at a referral hospital for AIDS in South Korea. Most patients (85%) were male, and 107 (62%) were infected by heterosexual contacts. CD4+ lymphocyte counts at presentation were !200/mL in 27% of the patients. Tuberculosis was the most frequent opportunistic infection (25% of patients), followed by candidiasis (21%), herpes zoster (20%), Pneumocystis carinii pneumonia (10%), cytomegalovirus disease (9.8%). There were no cases of toxoplasmosis. Kaposi's sarcoma developed in 3 patients (1.7%), and nonHodgkin's lymphoma, in 2 (1.2%). Eleven patients (6.4%) developed peripheral neuropathy, and 8 (4.6%) had HIV encephalopathy. Tuberculosis was the single most important HIVrelated infection in South Korean patients.
pital and a referral center for patients with HIV infection or AIDS
in South Korea. The patients were referred because their CD41
lymphocyte counts were !500/mL or because they developed
symptoms presumed to be due to HIV infection.
Heterosexual transmission of HIV was presumed if the patients
sex partner was known to have HIV infection or the patient had
multiple sexual contacts with prostitutes. Homosexual transmission
of HIV was presumed only if the patient admitted having sex with
Patients with CD41 lymphocyte counts !200/mL received
trimethoprim-sulfamethoxazole as primary prophylaxis for
Pneumocystis carinii pneumonia. Prophylactic treatments for
tuberculosis and other opportunistic infections were not given. Bacille
Calmette-Guerin (BCG) vaccine has been recommended for
universal childhood immunization since 1960 in South Korea.
In South Korea, zidovudine has been available since 1991,
didanosine since 1996, and other antiretroviral drugs, including
lamivudine and indinavir, since 1997. Patients were treated with
zidovudine when they had CD41 lymphocyte counts !500/mL or
when they had symptomatic AIDS-related diseases. Of the 173
patients included in this study, 72 were prescribed zidovudine; 72,
didanosine; and 9, triple-drug therapy including a protease
Diagnoses of opportunistic diseases. Ziehl-Neelsen staining and
culture were routinely performed when tuberculosis was suspected.
Induced sputum specimens were obtained, and Diff-Quick staining
was used to identify P. carinii. Diarrheal stools were sent to a special
parasitology laboratory, where modified procedures for acid-fast
staining of stool concentrates were employed. For the diagnosis of
cytomegalovirus (CMV) retinitis, an ophthalmologist examined
patients at regular intervals. Diagnoses of other CMV diseases were
made by histological findings.
Cases of tuberculosis were classified as definite, probable, or
possible: definite if culture for Mycobacterium tuberculosis was
positive; probable if clinical symptoms and signs consistent with
tuberculosis were present and a stain was positive for acid-fast bacilli
or there were histological findings consistent with tuberculosis;
possible if clinical and radiological signs consistent with tuberculosis
were present and there was improvement with standard
antituberculous therapy . The other opportunistic diseases, including P.
carinii pneumonia, were diagnosed according to criteria suggested
by the Centers for Disease Control and Prevention ;
AIDSdefining diseases were also diagnosed according to the 1993 case
definition of AIDS by the Centers for Disease Control and
Prevention, but criteria for CD4 cell counts were not used.
Patient characteristics. Of the 173 patients, 85% were male,
90% were aged 2049 years, and 93% were infected by sexual
contact (table 1). Duration of follow-up ranged from 1 month
to 107 months; one-third of the patients were followed up for
!6 months. The annual number of patients, including those
who were hospitalized, is shown in figure 1.
Opportunistic infections. The frequency of opportunistic
infections among the 173 patients is shown in table 2. Herpes
zoster was by far the most frequent initial opportunistic
infection. Herpes zoster developed in 35 patients (20%), and recurred
in 8 (23%) of them. Seventeen patients (9.8%) had CMV
diseases: retinitis, 14 patients; esophagitis, 4; gastroenteritis, 2; and
disseminated disease, 1.
Tuberculosis was the most frequent opportunistic infection,
developing in 44 patients (25%). The diagnosis of tuberculosis
was definite for 18, probable for 10, and possible for 16 of these
cases. Of the 8 patients with CD41 lymphocyte counts >200/
mL, 2 (25%) had extrapulmonary tuberculosis, and 6 (75%) had
pulmonary tuberculosis. Of the 32 patients with CD41
lymphocyte count !200/mL, 24 (75%) had extrapulmonary
tuberculosis, and 8 (25%) had pulmonary tuberculosis.
Multidrugresistant M. tuberculosis was isolated from 1 patient. Three
patients died; 1 had an infection due to multidrug-resistant M.
tuberculosis and 2 had presented with advanced tuberculosis.
All other patients responded well to standard antituberculosis
P. carinii pneumonia developed in 18 patients (10%); definite
diagnoses were made in 10 cases, and presumptive diagnoses
were made in 8. None of these patients were receiving
prophylactic treatment for P. carinii pneumonia, because either their
HIV infection status was unknown or they were lost to
followup. Most of the patients with P. carinii pneumonia were in the
advanced stages of AIDS (median CD41 lymphocyte count,
Cryptosporidium and Isospora belli were the pathogens most
frequently isolated from patients with diarrhea. Nontyphi
Salmonella and Shigella species were not isolated when stool
cultures were performed. Amebic liver abscess developed in 3
patients. Four percent of the patients had serological tests positive
for Toxoplasma. CD41 lymphocyte counts at the time of
diagnosis of each opportunistic infection are shown in figure 2.
Malignancies. Kaposis sarcoma developed in 3 patients
Table 1. Baseline characteristics of 173 South Korean patients with
No. (%) of patients
(1.7%), including 1 with disseminated sarcoma involving the
stomach, lung, and thyroid gland. Two of the patients were
bisexual men, and 1 was a female prostitute. Non-Hodgkins
lymphoma developed in 2 patients (1.2%) patients: 1 with
primary CNS lymphoma and 1 with tongue lymphoma. Other
malignancies included squamous cell lung cancer (1 patient),
bladder cancer (1), and pancreatic cancer (1).
Neurological diseases. Eleven patients (6.4%) developed
peripheral neuropathy. Of the 11 patients, 2 were prescribed
zidovudine and didanosine, 6 zidovudine only, and 3 didanosine
only. Eight patients (4.6%) had HIV encephalopathy.
Neurological infections were rare. Only 3 patients developed
cryptococcal meningitis. There were no patients with tuberculous
or bacterial meningitis, nor any with cerebral toxoplasmosis.
Hypersensitivity reactions to drugs. Of the 46 patients who
were prescribed trimethoprim-sulfamethoxazole for
prophylaxis for or treatment of P. carinii pneumonia, none developed
hypersensitivity reactions. Of the 44 patients with tuberculosis
who were treated with antituberculosis drugs, only 1 developed
a hypersensitivity skin rash due to rifampin.
First AIDS-defining diseases. Of the 173 patients, 61
developed AIDS-defining diseases. The first AIDS-defining
diseases were tuberculosis in 39 patients (64%), esophageal
candidiasis in 6 (10%), P. carinii pneumonia in 6 (10%), HIV
encephalopathy in 3 (5%), CMV disease in 3 (5%), isospora
infection in 2 (3%), cryptococcal meningitis in 1 (2%), and
cryptosporidiosis in 1 (2%).
Causes of death. Twenty-four patients (14%) died. Causes
of death were as follows: pneumonia, 7 patients; disseminated
tuberculosis, 3; cryptococcal meningitis, 2; disseminated CMV
disease, 1; lung cancer, 1; bacterial peritonitis, 1; liver cirrhosis,
1; unknown, 4; and suicide, 4.
NOTE. CMV, cytomegalovirus; PML, progressive multifocal
No. (%) of patients
Since the first case of AIDS in South Korea was reported in
1985, the number of patients with HIV infection has been
increasing every year (figure 1). The total number of cases of HIV
infection officially reported as of September 1998 was 844 .
The prevalence of HIV infection in South Korea has been
estimated to be 0.01% (presumed total number of HIV-infected
individuals, 3100) . Our data show that the number of
symptomatic patients, especially those admitted to our hospital, has
been increasing since the mid-1990s. This epidemiological trend
reflects the fact that the AIDS epidemic did not begin until the
late 1980s in South Korea.
The major mode of transmission of HIV was heterosexual
contacts, accounting for 62% of the cases. Because
homosexuality is culturally unacceptable in South Korean, many
homosexuals will not disclose their sexual preferences. Therefore,
the rate of heterosexual transmission might be overestimated
in this study.
Tuberculosis was the single most prevalent disease in
HIVinfected patients in this study. Tuberculosis developed in 25%
of the patients and accounted for 64% of the first AIDS-defining
diseases. These findings are not unexpected given the fact that
tuberculosis is one of the most prevalent infectious diseases in
South Korea. A recent nationwide survey showed that the
prevalence of tuberculosis among people aged 029 years was 15.5%
and the prevalence of radiologically active tuberculosis was
1.0% . In countries with high rates of M. tuberculosis
infection, particularly in Africa, the number of cases of tuberculosis
has increased since the AIDS epidemic began . In contrast,
the prevalence of tuberculosis in South Korea has decreased
even after HIV infection was introduced in our population. This
occurrence could be attributed to the fact that the number of
patients with HIV infection is too small to influence the
incidence of tuberculosis.
The manifestation of tuberculosis in our patients varied
according to CD41 lymphocyte counts. For patients with early
HIV infection, radiographic findings resembled those seen for
patients with reactivation tuberculosis. However, most patients
with advanced HIV infection had disseminated tuberculosis,
and lymphadenopathy was also common. These findings are
consistent with those of previous studies .
Of note is the fact that there was only 1 case of infection
due to multidrug-resistant M. tuberculosis in South Korean
patients with AIDS. The recent nationwide survey  revealed
that the overall prevalence of drug-resistant M. tuberculosis was
9.9%; the prevalence of resistance to >2 drugs was 6.1%, and
the prevalence of resistance to >3 drugs was 4.6%. The fact
that iv drug abusers, one of the major groups not compliant
with antituberculous treatment, have not been found among
South Korean HIV-infected individuals may explain why
infection due to multidrug-resistant M. tuberculosis is rare in
P. carinii pneumonia developed in 10% of our patients.
Trimethoprim-sulfamethoxazole was prescribed to all the patients
with CD41 lymphocyte counts !200/mL as primary prophylaxis
for P. carinii pneumonia. One of the major drawbacks of
trimethoprim-sulfamethoxazole prophylaxis is an increased
frequency of hypersensitivity reactions in HIV-infected
individuals. The frequency of hypersensitivity reactions has been
reported to be as high as 25% . However, in our study there
were no cases of hypersensitivity reaction due to
trimethoprimsulfamethoxazole. Walmsley et al.  suggested that
genetically determined pathways of metabolism and detoxification of
sulfonamides might be involved in the pathogenesis of these
reactions, and that patients whose acetylator status is slow have
an increased risk for hypersensitivity reactions . To explain
the low incidence of hypersensitivity reactions to
trimethoprimsulfamethoxazole, further investigation is warranted to
elucidate whether the acetylator status of Koreans is fast.
Three of our patients had amebic liver abscess; 2 were
homosexual. In South Korea, the prevalence of amebic infections
has been decreasing rapidly . At our hospital, we have only
seen 4 patients with amebic liver abscess since 1995. Among
these patients, 3 were HIV-infected. It is of note that 2 of them
were found to be HIV-positive after amebic liver abscess was
diagnosed. In countries with low prevalences of amebic
infestation, amebic liver abscess may be regarded as an opportunistic
infection in immunocompromised patients.
No patients had toxoplasmosis. The prevalence of
Toxoplasma gondii antibodies among our HIV-infected patients was
4%. Most Koreans do not own pets, nor do they come into
close contact with dogs or cats (which may be the reason for
the low prevalence of toxoplasmosis in South Korea). In
contrast, in the United States, where 10%40% of adults with AIDS
are latently infected, one-third of these patients will develop
toxoplasmic encephalitis. In Africa, Europe, and Latin
America, where the incidence of latent infection is much higher, the
number of patients with AIDS who develop toxoplasmosis is
3 times greater than that in the United States .
Our study is limited by the relatively small number (173) of
patients, which accounts for 20% of all cases of HIV infection
reported in South Korea. A population-based, prospective
study on opportunistic diseases in patients with HIV infection
or AIDS is being launched by the Korean AIDS Research