Globally, an estimated 34 million people were infected with human immunodeficiency (HIV) at the end of 2011. In Korea, after the first case of HIV infection was reported in 1985, the number of cumulative HIV survivors rose to approximately 7,000 at the end of 2011, although the overall prevalence in the population was very low (< 1%) [1]. HIV infection leads to immunosuppression, which can result in life-threatening opportunistic diseases (ODs). Combination antiretroviral therapy reduced the mortality and morbidity [2,3], but despite advances in antiretroviral therapy, ODs remain one of the main causes of morbidity and mortality in HIV/AIDS patients.

The frequencies of ODs may vary across countries because of differences in genetic, environmental, and social backgrounds. Two studies have examined the epidemiology and clinical manifestations of ODs in Korean patients with HIV/AIDS [4,5]. The introduction of combination antiretroviral therapy and the use of prophylactic antimicrobials for ODs have changed the prevalence of ODs over time. Consequently, an understanding of the current epidemiology of ODs among HIV/AIDS patients should help to establish guidelines for the prevention of ODs. This study evaluated the prevalence of ODs among HIV-infected patients in the era of highly active antiretroviral therapy, and the risk factors associated with ODs.

The study enrolled 1,086 HIV-infected patients (1,007 males and 79 females; median age, 41 years) at 19 university hospitals from 2006 to 2012 (Table 1). The majority of patients (n = 601, 55.4%) were 30 to 50 years of age. The median CD4 T cell count at enrollment was 352 cells/mm³ (interquartile range [IQR], 207 to 514), and 22.9% of the patients (n = 206) had fewer than 200 cells/mm³. The median viral load at enrollment was 5.69 log copies/mL (IQR, 3.88 to 6.24),while 53.2% of the patients had undetectable viral loads. At enrollment, 76% of the patients (n = 355) were receiving antiretroviral agents (Table 1).

Before the introduction of combination antiretroviral therapy, ODs were the main cause of death in HIV-infected patients. However, advances in antiviral treatment led to a dramatic decline in ODs [2,8,9]. In our study, although 24.4% of the HIV-infected patients developed ODs, they were not the main cause of death, unlike previous studies.

In our series, the most prevalent OD was candidiasis, followed by TB and P. jirovecii pneumonia. In a study of 173 HIV-infected patients performed from 1985 to 1998, TB was the most frequent opportunistic infection (25% of patients), followed by candidiasis and herpes zoster [5]. In another study of 176 HIV-infected patients from 1985 to 2000, candidiasis was the most prevalent OD, followed by P. jirovecii pneumonia and TB [4]. Based on our data, TB can be considered a re-emerging OD in the HIV population in Korea. The prevalence of ODs in HIV patients varies by location and is 32.5% in China and 27.4% in Ethiopia and New York city [10-12]. In developing countries, TB remains the most common cause of death among HIV-infected patients, similar to the situation in Korea, and unlike countries with low risks of TB [13,14]. In Korea, the estimated TB incidence in 2012 was 108 per 100,000 population, the highest among Organization for Economic Cooperation and Development countries. The identification and treatment of latent TB infection has lowered the incidence of TB in developed countries. The current guidelines for the management of TB in Korea recommend treating latent TB in HIV-infected patients [7]. Until now, many doctors in Korea have tended to avoid giving TB treatment for latent TB for several reasons: toxicity, drug interactions, and concern about drug resistance. In addition, our data showed that TB developed in patients with a low CD4 T cell count, and many studies demonstrated that impaired cellular immunity was associated with TB reactivation [15,16]. After the guidelines for latent TB are applied to clinical practice in Korea, further studies must examine the effect on the incidence of TB. In our series, a history of TB was associated with ODs among HIV-infected patients. Several studies have also demonstrated that a history of TB was usually associated with TB infection [17,18]. In intermediate TB endemic areas, TB reactivation is more common in HIV-infected patients than de novo TB. There were two cases of nontuberculous Mycobacteria infection in our study. Our study used the patient data at the time of enrollment, and further studies will examine prospectively collected cohort data.

Our study found a low prevalence of Kaposi’s sarcoma and toxoplasmosis compared with other countries. This is because of the geographic variation in Kaposi’s sarcoma. de Sanjose et al. [19] reported that the prevalence of Kaposi’s sarcoma-associated herpesvirus in the general female population in Korea was only 4.93%.

The associated risk factors for ODs in our study were a low CD4 T cell count at the time of HIV diagnosis, smoking, alcohol consumption, and a history of TB. A low CD4 T cell count is associated with the development of ODs [10,20]. A study of homeless HIV/AIDS patients in Korea showed that they are at an advanced stage at admission, which leads to ODs and an unfavorable outcome [21]. Our results showed that 97% of HIV-infected patients with P. jirovecii pneumonia had CD4 T cell counts less than 200 cells/mm³; this supports recent guidelines that patients with such low CD4+ T cell counts should receive prophylaxis for P. jirovecii. Smoking could influence inflammatory and immune responses in the oral cavity, and smoking was associated with oral candidiasis in some studies [22,23].

This study had several limitations. First, we included only patient data at study enrollment; prospective longitudinal data will provide more accurate data on OD incidence and change in ODs in Korea. Second, we did not calculate the risk factors for ODs for each disease, and did not describe the clinical course of each OD. Third, we included only the data from patients in our cohort study. However, this study enrolled patients from multiple centers that covered most areas of Korea, so it is likely to be representative epidemiological data for Korea.

In conclusion, there was a range of ODs among HIV-infected patients in Korea, the most prevalent being candidiasis, M. tuberculosis infection, P. jirovecii pneumonia, CMV infection, and herpes zoster, while toxoplasmosis and HIV-related malignancy, such as Kaposi’s sarcoma, were rare. A major predictor of OD was a low CD4 T cell count at the time of HIV diagnosis. Based on our data, strategies to diagnose HIV at an early stage of infection, and timely antiretroviral therapy, are needed to reduce ODs among HIV-infected patients in Korea.