12

HIVI AIDS in

Yi-Ming Arthur Chen

AIDS Prevention and Research Center; Institute of Public Health, National Yang-Ming University, City, Taiwan

mSTORY AND CURRENT STATUS Thberculosis OF INFECTIOUS DISEASES IN As shown in Table 1, several important TAIWAN infectious diseases in Taiwan have been erad• icated or have been under control since 1948. Taiwan is located in the middle of East Every five years since 1957, the Department Asia. Since Taiwan is a frontier island, it expe• of Health (DOH) of Taiwan has conducted a rienced a complicated transformation in eth• survey on pulmonary tuberculosis (TB). The nicity during the 17th, 18th, and 19th cen• surveys showed that in 1957, 5.15% of per• turies. Taiwan had been occupied by both sons aged >20 had pulmonary TB, among the Dutch and Japanese. The main popula• them, 20% had infectious TB. By 1993, the tion of Taiwan now includes descendants from rates of pulmonary TB and infectious TB had four ethnic groups: aborigines, Fukienese, decreased to 0.65% and 0.06%. Currently, Hakka, and mainland Chinese. The native there are about 15,000 new TB cases every aborigines consist of nine different tribes. year in Taiwan (Center for Disease Control, The Fukienese and Hakka are early settlers Taiwan, 2003a). It is worth noting that the who immigrated from Fukien and Guangdong incidence of TB in the aborigines in 1998, provinces of China several hundred years ago. 239/100,000, was much higher than that in The mainland Chinese are people who came to other populations. Taiwan from the mainland after World War II. In the past few years, due to a new open• ness in society following the relaxation of Hand-Foot-and-Mouth Disease regulations, many immigrants from main• land China and southeastern Asia have come In 1998, an epidemic of enterovirus 71 to Taiwan through marriage arrangements. infection caused hand-foot-and-mouth dis• At present, Taiwan's population is about 23 ease (characterized by vesicular lesions on the million. hands, feet, and oral mucosa) and herpangina

Y. Lu et al. (eds.), AIDS in Asia 135 © Springer Science+Business Media New York 2004 136 HNIAIDS IN TAIWAN

TABLE 1. The Chronicle of the Control of identified in Guangdong Province, China in Infectious Diseases in Taiwan November 2002. By August 7,2003, SARS had spread to more than 30 countries, affected Year Event 8422 people and resulted in 916 deaths world• 1948 Eradication of plague wide (World Health Organization, 2003). In 1948 Initiation of vaccination program Taiwan, the first SARS case was diagnosed on 1955 Eradication of small pox March 14, 2003. This index case had traveled 1959 Eradication of rabies 1965 Eradication of malaria to Guangdong, China in February. On April 1984 Initiation of HBV vaccination program 24, the Taipei city government announced 1990 AIDS control law was launched that it was closing down Ho-Ping Hospital 1995 Initiation of HAV vaccination program for two weeks. Although the government im• 1997 Free HAART was provided posed mandatory 14-day quarantine on all air 1998 Initiation of influenza vaccination program, especially among elders travelers from China, Hong Kong, Singapore, 1998 Eradication of poliomyelitis was recognized Macau, and Toronto on April 28, the SARS 1999 Infectious disease control law was launched epidemic spread in Taiwan island-wide and 1999 Establishment of Taiwan CDC by merging more than 29 hospitals reported nosocomial three governmental organizations infection. According to the Center for Dis• 2001 Formation of AIDS Advisory Committee at the Executive Yuan ease Control of Taiwan, of the 664 proba• ble SARS cases reported to the World Health Organization, there were 346 SARS cases in thousands of people in Taiwan, some of confirmed by either RT-PCR or serological whom died. The sentinel physicians reported test (Figure 1) (Center for Disease Control, nearly 130,000 cases of hand-foot-and-mouth Taiwan, 2003b). disease or herpangina in two waves of the epi• demic' which probably represents less than 10% of the estimated total number of cases. mSTORY AND CURRENT STATUS There were 405 (0.3% of the total) patients OF HIV-l INFECTION IN TAIWAN with severe disease. Most of them were five years old or younger, and most of those who The first indigenous AIDS case in died were young. The majority died of pul• Taiwan was found in 1986, and as of Oct 2003, monary edema and pulmonary hemorrhage. 5464 people living with HIV-l (hereafter re• Enterovirus 71 infection was associated with ferred to simply as mV) and AIDS (PLWHA) most of the serious cases and with nearly had been reported to the Department of all the deaths. A laboratory-network was es• Health of Taiwan. This number included 5042 tablished linking 10 hospitals island-wide to• Taiwan citizens and 422 foreigners. The num• gether with the Center for Disease Control bers of PLWHA increased rapidly, with a (CDC) of Taiwan for laboratory diagnosis. rate of increase of more than 15% every year This network has been active since then and (Figure 2). The male-to-female ratio of the more laboratories were added to the net• reported cases was 13 to 1. According to work when severe acute respiratory syndrome risk factor analysis, 40.6% of the cases were (SARS) attacked Taiwan in 2003 (Ho et al., heterosexuals, 36.5% were men who have 1999). sex with men (MSM), 12.2% were bisexu• als, 2.0% were intravenous drug users (IDU), Severe Acute Respiratory Syndrome and 0.24% were infected by blood transfu• (SARS) sion; 53 cases were among hemophiliacs, and nine cases were due to vertical transmission The outbreak of SARS, originally re• (Center for Disease Control, Taiwan, 2003c). ferred to as atypical pneumonia, was first It has been speculated that the true number HNIAIDS IN TAIWAN 137

.. ~ ......

~ , m " ~ ~ 7 ~ ~ a 5 q ~ ~ 2 ~ ~ ~ \ A A A.... ____...... I Merch April Mey June 0818(2003)

FIGURE 1. Epidemiological curve of the probable and con finned SARS cases in Taiwan. The confinned cases were proved by either RT-PCR or serological test. (CDC Taiwan, 2003b)

Reported Cases of H1V/AIDS by Year In Taiwan , 1984-2003Il~31

769 HIV(+) OAIJS 652 659 534 478 402 350 228 277 136137 174 5 3

Qo __ ..J

FIGURE 2. The cumulative numbers of HIV/AIDS cases reported to CDC of Taiwan by the end of October 2003. (CDC Taiwan, 2003c)

of PLWHA in Taiwan is about 2-3 times the very rare. When the trends over time on reported cases. the distribution of different age groups in the There are several important characteris• HIV/AIDS patient cohort were analyzed, the tics of the HIV / AIDS epidemic in Taiwan: results showed that the percentage of patients more than 80% of infections have been due aged 19 or younger increased from 2% in to sexual transmission, less than 2% of in• 1995-1996 to 6% in 1997-1998. In addition, fections have been as a result of needle shar• since 1997-1998, the number of patients in ing, and mother-infant transmission has been their 20s has surpassed the number of those 138 HIVIAIDS IN TAIWAN

TABLE 2. The Prevalence Rates of HIV rates of syphilis infection than the heterosex• Infection among DitTerent Groups in ual men in Taiwan. In contrast to the high Taiwan, 2001. rate of sexual contact with sex workers in the male heterosexual subgroup, only 16.6% Group Prevalence Rate of the HIV-positive MSM had sexual con• Conscripts 5.3/100,000 tact with sex workers (Chen et al., 1998a; First-time blood donors 6.3/100,000 Chenetal., 2001b). Therefore, the high rate of Pregnant women 14.5/100,000 syphilis infection among HIV-positive MSM IDU 89.7/100,000 Prisoners 112.0/100,000 may reflect the prevalence rate of syphilis in• FSWa 200.01 100, 000 fection in the MSM population in Taiwan. In STI patients I, 900.01 100, 000 Taiwan, the HIV-positive MSM were much MSM in gay saunas 6,700.0/100,000 younger than the HIV-positive heterosexual a 1996 data. men were. According to the Yang-Ming AIDS Center database, about 55% of the HIV- pos• itive MSM were aged below 30, while about in their 30s and has become the largest age 30% of HIV-positive heterosexual men were group (Chen et al., 2oo1b). This is an alarm• aged below 30 (Chen et al., 2001b). In addi• ing sign that HIV1 AIDS education among tion, the group of MSM patients had a higher Taiwan's youth needs to be strengthened. percentage of persons aged below 20 than the heterosexual group, 3.0% vs. 1.7% (Chen The Prevalence of HIV Infection in et al., 2001b). This suggests that MSM DitTerent Groups in Taiwan might be engaging in high-risk behaviors at a younger age than heterosexual men in Taiwan. Men Who Have Sex with Men The synergistic relationship between HIV and certain STIs, especially genital ulcerative dis• As shown in Table 2, judging by the HIV eases, has been reported previously (Plum• prevalence rates in the populations of con• mer, 1998). The lack of sex education and scripts, first-time blood donors, and pregnant the existing stigmatization of homosexuality women, the general public in Taiwan had a both considerably increase the risk for MSM lower rate of HIV infection than other coun• of contracting HIV and other STIs in Taiwan. tries in Asia (Monitoring the AIDS Pandemic Therefore, it is important to develop an ef• Network, 2001). Among different high-risk fective HIV and STI prevention program groups in Taiwan, MSM in gay saunas had targeting MSM in Taiwan. the highest rate of HIV infection. Accord• ing to our surveys, the rates of HIV-1 infec• tions among MSM in gay saunas in different Heterosexual Population and HN Subtypes cities were: 15.8% (22/139) in in Changes over time in the distribution of 1999, 9.5% (33/348) in Taipei in 2000, 5.2% different HIV subtypes in the heterosexual (16/307) in Taipei in 2001, and 6% (6/100) population are very striking. According to our in Taichung in 2002. Besides HIV, this pop• analysis, more than half of heterosexual males ulation also had quite high rates of syphilis had HIV subtype B infection, but CRF01...AE infection, ranging from 8.1 to 13.8% (Center surpassed subtype B and became the major for Disease Control, Taiwan, 2oo3c). subtype between 1997 and 1998 (Figure 3) (Chen et al., 2oo1b). Sexually Transmitted Infections (STI) According to risk factor analysis, nearly half of the HIV-positive heterosexual males Both the male homosexual and bisexual admitted that they had sexual contact with sex HIV / AIDS patients had significantly higher workers when they went to Southeast Asia. HNIAIDS IN TAIWAN 139

Male Patients (No. =957) Female Patients (No. = 79)

B C 0

2 G Unknown 2 (0.2%) CRF01_AE 4 (0.4%) 55 (70.9%)

FIGURE 3. Proportions ofHIV-l sUbtypes in the male and female HIV/AIDS patients recruited by the Yang-Ming AIDS Center from 1988 to 2000 in Taiwan.

This is consistent with the results of the phy• (Hu et al., 2001; Hudgens et al., 2002). Stud• logenetic analysis which showed that most of ies on the virological characteristics of both the Taiwanese CRFOLAE clustered with iso• HIV SUbtype C and CRFO 1_ AE have revealed lates from Thailand (Figure 4). that they may have adapted better to trans• mission through the human population (Ping et al., 1999; Montano et al., 1998). Women with HIVIAIDS

As shown in Figure 3, about 85% of the Female Sex Workers (FSW) female HIV/ AIDS patients were infected with non-B clades, with CRFOLAE as the pre• In Taiwan, most FSW are infected with dominant sUbtype. In Taiwan, the most im• HIV CRFOLAE (Chen et al., 2001b). There portant risk factor for women was that their is a risk of an increasing spread of HIV E in the husbands were seropositive. Previously, we heterosexual population in Taiwan. In a sur• have reported the results of a study that found vey of HIV and STI prevalence among FSW 17 of 52 (32.7%) married couples were sero• in the Taipei metropolitan area from 1993 to concordant. When the HIV subtypes of the 1996, 0.2% (2/1036) of FSW from karaoke couples were analyzed, 14 of33 (42.4%) hus• bars were found to have HIV, while none of the bands infected with CRFOL AE had transmit• 725 FSW from massage parlors and 484 FSW ted HIV to their wives, while only 1 of 17 from brothels were infected with HIV (Chen (5.9%) men with SUbtype B had transmitted et al., 1998b). Due to the lack of subsequent the disease to their spouses (p < 0.01). Both follow-up study, the current prevalence of of the two husbands infected with SUbtype C HIV infection in this population is unknown. had also transmitted HIV to their wives (Chen et al., 2001 b ). Otherrecent studies in Thailand Injecting Drug Users (IDU) have also shown SUbtype differences, both in level of viral replication during seroconver• The prevalence of HIV infection among sion and in transmissibility in cohorts of IDU Taiwanese IDU has never been reported. 140 HIVIAIDS IN TAIWAN

A

E

c

K

"'netic Tr~ Analysis of HIV-1 Isolates from Taiwan

FIGURE 4. Pbylogenetic analysis of Taiwanese (TW-) mV-J isolates. The neigbbor-joining tree was obtained from 100 bootstrap samples of aligned env sequences corresponding to the nucleotide residues 7062-7379 of HXB2 from different HIV-l isolates.

There is relatively little control of the medical men and one MSM were infected with HIV supplies market in Taiwan, and syringes are CRFOLAE, and two female IOU were in• easy to obtain. Because of this, there appears fected with HIV B subtypes. Among hetero• to be a much lower rate of needle-sharing in sexual male IOU, five out of six (83.3%) men Taiwan, with the possible exception of the were infected with mv CRFOl_ AE, and only prison inmate population. Although less than one out of 12 (8.3%) men infected with mv 2% of the total number of reported cases of B had sexual contact history with FSW (p < HIVI AIDS were among IOU, it is importantto 0.01) (Chen et al., 2001b). Therefore, sexual note that according to a survey conducted by a transmission is a major risk factor of male IOU social worker visiting prisons island-wide, the infected with HIV CRFOLAE in Taiwan. numbers of HIV-positive inmates tripled be• tween 2001 and 2003 (Sr. TeresaHsieh,Direc• tor, Lourdes Home of Taiwan, personal com• ISSUES RELATED TO munication, October, 2003). In terms of sub• TREATMENT AND CARE types, according to our previous study on 22 IOU, 12 heterosexual men and one MSM were In Taiwan, the AIDS Control Law was infected with HIV B subtype, six heterosexual launched in 1990 and has been modified five HNIAIDS IN TAIWAN 141

.. ..

Numbers of PLWHAs c::=J 0-44 45-111 _ 112-224 0 NGO _ 225-359 360-1 ,235 6. Hospital

FIGURE 5. The distributions of AIDS designated hospitals and non-governmental organizations against the density of PLWHA in different prefectures and cities in Taiwan.

times since then. Under this law, the govern• person per month. According to the Bureau of ment has to provide free treatment to all Tai• the National Health Insurance (BNHI), by the wanese PLWHA. Currently, there are 27 des• end of 2002,2660 of 3425 (77.7%) PLWHA ignated AIDS hospitals in Taiwan. As shown had begun receiving HAART. The implemen• in Figure 5, the distribution of the hospitals is tation of the free HAART program in Taiwan not even and some prefectures and cities do has caused dramatic decreases of both mor• not have an AIDS hospital. The designated bidity and mortality of HIVIA IDS in Taiwan. AIDS hospital system should be expanded to A five-year prospective study on a cohort of meet the medical needs of patients. 309 PLWHA (83% with AIDS) admitted to a teaching hospital in Taipei City showed that Highly Active Anti-Retroviral Therapy the mortality rate declined significantly from 110.5-148.4 per 100 patient-years in 1995 to Since April 1997, the Taiwanese gov• 5.5-7.4 per 100 patient-years in 1999 (Hung ernment has provided protease inhibitors in et aI., 2000). The five leading HIV-associated conjunction with NRTIs (Nucleoside Reverse opportunistic infections (01) in the cohort Transcriptase Inhibitors) and NNRTIs (Non• were oroesophageal candidiasis, Pneumocys• Nucleoside Reverse Transcriptase Inhibitors). tis carinii pneumonia, tuberculosis, muco• The cost of the highly active anti-retroviral cutaneous herpes simplex infection and cy• therapy (HAART) is about US$ 1000 per tomegalovirus diseases (Hung et aI., 2000). 142 HNIAIDS IN TAIWAN

The clinical spectrum of HIV / AIDS patients NGOs-the Living with Hope Organiza• in Taiwan was very similar to that in the West• tion, Taiwan Hemophiliac PWA Association, ern countries, but the incidence of OI differed, PRAA, and Lourdes Home-were trained to be e.g. the incidence of tuberculosis in patients interviewers. In total, 50 PLWHA (45 men and with advanced illness (24.6%) was relatively five women) participated in the survey. The high, and the rate of an endemic fungal in• results showed that 16% had suffered from fection (Penicillium mameffei infection) was discrimination by medical staff and 30% had increasing (Hsieh et ai., 1996; Hsueh et ai., been refused or delayed when they sought 2000). medical care. In terms of education rights, our 1999 survey showed that two PLWHA HIV Drug Resistance were expelled and three were refused admis• sion by school authorities. Because of their Although the BNHI provided free vi• HIV status, three had lost their jobs, three ral load and CD4 cell counts tests, the cost had been offered early retirement, five had for genotyping of HIV drug resistance was lost their prospects for promotion, and 22 had not covered. Recently, we investigated the experienced harassment from their employ• prevalence ofHIV genotypic mutations in ret• ers. Three patients stated that their children rospective samples collected between 1997 had been taken away from them when they and 2000. The results showed that among revealed their status. At present, Taiwanese 136 treatment nalve PLWHA, none of the 31 PLWHA are still restricted from taking tests MSM, 32 bisexual males, seven females, or to become government employees and profes• four IOU had any primary mutation, while sional technologists. two of 62 (3.2%) MSM had M184V mutation In 2002, a survey of 1292 medical per• for RT inhibitors (Elbeik et ai., 2002). sonnel from 42 hospitals island-wide showed that 42.9% are not willing to care for PLWHA Non-Governmental Organizations and and 97.6% think there should be a law forcing Social Movement PLWHA to disclose their seropositive status to medical personnel (Taiwan Root Medical In response to the challenge of Peace Corps, 2002). HIV/AIDS, since 1992, there have been 15 To change the attitude of the general non-governmental organizations (NGOs) public toward PLWHA, family members of established in Taiwan to provide shelter, PLWHA and volunteers were invited to par• counseling, anonymous testing, social care, ticipate in a floating lantern ceremony at a and education for PLWHA, vulnerable riverside in Taipei City on World AIDS day groups, and the general public. As shown in 1994. This memorial has become an annual in Figure 5, there is only one NGO in the event since then. In 1995, Taiwan invited the middle region of the country and one in Names Project to bring 576 AIDS quilts for the southern part of Taiwan. It is worth a special exhibition at the Chiang Kai-Sheik mentioning that although there is no PLWHA memorial plaza on World AIDS day. The NGO in Taiwan, a PWA Rights' Advocacy Taiwan AIDS Memorial Quilt Project was Association (PRAA) was established in 1997. established under the Living with Hope Or• ganization in 1995. In 2001, Taiwan invited Issues on the Human Rights of PLWHA the Photographer Network to show the "Posi• tive lives" of PLWHA from different Asian In 1999, a survey was conducted to countries. The images created, of pink and understand the human rights issues of white lanterns floating on a river, and colorful PLWHA in Taiwan. Social workers from four quilts displayed in front of traditional Chinese HNIAIDS IN TAIWAN 143 theaters, have shocked and moved many peo• Chen, Y.M.A., Huang, KL., Jen, 1, Chen, S.c., Liu, Y.c., ple in Taiwan. Chuang, Y.c., Wong, lC., Tsai, J.J., and Lan, Y.C. (2001b). Temporal trends and molecular epidemi• ology of HIV-l infection in Taiwan from 1988 to 1998. J AIDS 26:274-282. CONCLUSION Elbeik, E., Lan, Y.C., Dileanis, lA., Marlowe, N., Ng, V., and Chen, Y.M.A. (2002). Prevalence of HIV- In conclusion, the mv/ AIDS epidemic 1 genotypic mutations in the protease and reverse in Taiwan is evolving. There are several is• transcriptase genes from infected individuals in Tai• wan: Treatment challenges. The XIV International sues that need to be addressed immediately: AIDS Conference, Barcelona, Spain, July 7-12, sentinel surveillance of HIY infection among 2002. (Unpublished paper). different high-risk groups should be imple• Ho, M., Chen, E.R., Hsu, KH., TWu, S.J., Chen, KT., mented; prenatal counseling for the HIV an• Tsai, S.F., Wang, lR., and Shih, S.R. (1999). An tibody test and chemoprevention of mother• epidemic of enterovirus 71 infection in Taiwan. N Engl J Med. 341:929-935. to-child transmission should be instituted Hsieh, S.M., Hung, C.c., Chen, M.Y., Hsueh, P.R., immediately; and NGOs should receive more Chang, S.c., and Luh, KT. (1996). 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