HAART and Decreased HIV Transmission
• JID 2004:190 (1 September) • 879
M A J O R A R T I C L E
Decreased HIV Transmission after a Policy
of Providing Free Access to Highly Active
Antiretroviral Therapy in Taiwan
Chi-Tai Fang,1Hsu-Mei Hsu,2Shiing-Jer Twu,2Mao-Yen Chen,1Yu-Yin Chang,3Jing-Shiang Hwang,4
Jung-Der Wang,1,3Che-Yen Chuang,1and the Division of AIDS and STD, Center for Disease Control,
Department of Health, Executive Yuan
1Department of Internal Medicine, National Taiwan University Hospital,
National Taiwan University, and
2Department of Health, Executive Yuan, and
3College of Public Health,
4Institute of Statistical Science, Academia Sinica, Taiwan
infection in 1989 and adopted a policy to provide all HIV-infected citizens with free access to highly active
antiretroviral therapy (HAART) beginning in April 1997. This provided an opportunity to determine the effect of
the widespread use of HAART on the evolution of the HIV epidemic.
We analyzed national HIV surveillance data. The HIV transmission rate was estimated by use of
an exponential model of HIV epidemic evolution, with statistical projection over the interval between infection
and detection to fit the surveillance data.
By the end of 2002, the cumulative number of HIV-infected citizens in Taiwan had reached 4390
(0.019% of the total population). After free access to HAART was established, the estimated HIV transmission
rate decreased by 53% (0.391 vs. 0.184 new cases/prevalent case-year [95% confidence interval, 31%–65%]). There
was no statistically significant change in the incidence of syphilis, in the general population or among HIV-positive
patients, during the same period.
Providing free HAART to all HIV-infected citizens was associated with a 53% decrease in the
HIV transmission rate and contributed to the control of the HIV epidemic in Taiwan.
Taiwan established a nationwide surveillance system for human immunodeficiency virus (HIV)
A higher HIV load is one of the major determinants of
the risk of HIV transmission [1–3]. Highly active anti-
retroviral therapy (HAART) [4, 5], which profoundly
suppresses HIV-RNA levels in body fluids [6–8], not
only remarkably prolongs the survival of treated pa-
tients [9, 10] but also reduces rates of mother-to-child
perinatal transmission [11, 12] and heterosexual trans-
mission , according to the results of clinicalstudies.
In theory, the widespread use of HAART could lead to
a reduction in the rate of HIV transmissionintheentire
population and contribute to the control of the HIV
Received 31 May 2003; accepted 30 January 2004; electronically published 22
1032); National Health Research Institutes, Taiwan (integrated grant NHRI-EX92-
Reprints or correspondence: Prof. Jung-Der Wang, Dean, College of Public Health,
National Taiwan University, Taipei 100, Taiwan (email@example.com).
The Journal of Infectious Diseases
? 2004 by the Infectious Diseases Society of America. All rights reserved.
pandemic [14–18]. Nevertheless, there is a lack of em-
pirical data to verify this argument, because of the ex-
pense of HAART, which is simply not affordable to the
majority of people with HIV, except those in affluent
countries [19, 20]. Furthermore, most countries lack
an effective surveillance system for tracking the inci-
dence of asymptomatic HIV infection [19, 21, 22]. A
possible negative consequence of the widespread use of
HAART is the potential increase in unsafe sexual be-
havior due to optimism about treatment [23, 24].
Mathematical simulations have suggested thata modest
increase in unsafe sexual behavior can offset the effect
of a large decrease in infectiousness by the widespread
use of HAART [25, 26]. Thus, the effect of widespread
use of HAART on the evolution of an HIV epidemic
Similar to other countries, Taiwan has been affected
by the HIV epidemic since the mid-1980s . To
counteract the threat of the HIV epidemic, the De-
partment of Health of Taiwan established a nationwide
active surveillance system for HIV infection in 1989.
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880 • JID 2004:190 (1 September) • Fang et al.
Unlike the majority of other countries, Taiwan adopted apolicy
to provide all HIV-infected citizens with free access to HAART
through the National Health Insurance program, beginning in
April 1997. The combination of an effective surveillancesystem
and a policy to provide free HAART to all HIV-infectedcitizens
made it possible to study theeffectof widespreaduseofHAART
on the evolution of the HIV epidemic in Taiwan. We analyzed
HIV surveillance data through statistical modeling, to estimate
the HIV transmission probability ratio in the Taiwanese popu-
lation, before and after the implementation of the free-HAART
policy. To differentiate the effect of HAART from that of be-
havioral changes, the incidence of syphilis in the general pop-
ulation and among HIV-positive patients was also analyzed,for
MATERIALS AND METHODS
Surveillance of HIV infection and AIDS.
and AIDS became reportable diseases in Taiwan in 1984. All
identified cases must be reported to the Center for Disease
Control (CDC; Taipei, Taiwan). To protect the rights of these
patients, all personal information was kept confidential. Cases
of HIV infection detected by ELISA must be confirmed by
Western blot. For each case of HIV, the date of first detection,
age, sex, HIV risk factors, date of development of AIDS, and
date of death are registered. AIDS was defined according to
Centers for Disease Control and Prevention (Atlanta, GA) cri-
teria . The identification of cases of AIDS depended on
reports from physicians. The identification of cases of asymp-
tomatic HIV infection depended on active screening. As both
a moral obligation and an incentive for voluntary testing, the
government offered free antiretroviral therapy (ART) to all
identified HIV-infected citizens. Nationwide routine screening
of blood donors was started in 1988. High-risk populations—
such as patients with syphilis, gonorrhea, or other sexually
transmitted diseases; prostitutes; male homosexuals; patients
with hemophilia; injection drug users; prisoners; and individ-
uals having multiple sex partners—were encouraged or per-
suaded to receivevoluntarytesting.Pre-andposttestcounseling
about safer sex and ART were routinely offered. Among the
general population, young couples were encouragedtoundergo
HIV testing before marriage. Pregnant women were also en-
couraged to undergo HIV testing as part of obstetric care. To
further improve the detection rate of asymptomatic HIV in-
fection, compulsory HIV testing was also enacted among en-
listed servicemen (military service is mandatory for all men at
20 years of age in Taiwan) in 1989. The performance of the
active surveillance system was measured by the proportion of
AIDS among newly identified cases. A lower proportion of
AIDS among newly identified cases indicates a shorter median
interval between infection and detection.
Policy of providing free access to ART.
At the beginning
of the HIV epidemic, the government decided to ensure that
all HIV-infected citizens would have free access to ART and
medical care. Initially, a special government fund, which was
subject to annual review by the legislature, was raised to pur-
chase the needed antiretroviral agents. After 1 January 1998,
the antiretroviral agents were purchased through the National
Health Insurance system. Under this policy, zidovudine was
introduced in 1987, followed by didanosine (in 1992) and de-
oxycytidine (in 1995). To maximize the benefits of ART, special
clinics were created where antiretroviral agents were prescribed
and their use monitored by qualified physicians. In 1997, the
government decided to provide free access to HAART to all
HIV-infected citizens, despite the high cost. On 7 April 1997,
saquinavir, indinavir, ritonavir, lamivudine, and stavudinewere
simultaneously introduced. The timing of the initiation of
HAART and the regimens were based on guidelines recom-
mended in the United States [4, 5]. Early intensive treatment
was encouraged, except for patients with blood HIV-RNAlevels
!5000 copies/mL and peripheral CD4 cell counts in the normal
range. Regular monitoring of adverse effects of drugs, blood
cell counts, blood chemistry, and CD4 cell counts was also
provided free of charge. To improve drug compliance, newer
agents that were more convenient to use, including efavirenz
(since 2000), nevirapine (since 2000), lopinavir/ritonavir(since
2001), and abacavir (since 2001), were added to the therapeutic
Estimating the rate of HIV transmission.
sumption of a stable interval distribution between infection
and detection, we can use a modified back-calculation method
[29–31] to predict surveillance results from theoretical inci-
dence curves. If the HIV prevalence is low and the incidence
curve therefore follows an exponential model [17, 32], then the
predicted surveillance data will also follow an exponential
model, which allows us to estimate the average HIV transmis-
sion rate (new cases/prevalent case-year), R, by regressing the
natural logarithm of numbers of newly detected cases against
time t. R will be equal to the slope of the regression line plus
the average risk of mortality, m. Because the magnitudes of R
and m during the HAART era might be different from that
during the pre-HAART era, the regression should be conducted
of R during the pre-HAART era but will slightly overestimate
R during the HAART era, because the interval distribution
between infection and detection caused a convex theoretical
surveillance curve after the implementation of the HAART pol-
icy. To obtain an exact estimate of R during the HAART era,
we can estimate the parameters of this interval distribution
from the proportionof thosewithAIDSamongnewlyidentified
cases, calculate the predicted surveillance curve, and then con-
duct a nonlinear regression procedure to adjust for the effect
of this nonlinearity.
Under the as-
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HAART and Decreased HIV Transmission • JID 2004:190 (1 September) • 881
Estimation of the total number of HIV-infected patients in
If all identified cases of HIV and AIDS are reported,
as in Taiwan, we can estimate the total number of HIV-infected
patients from the reduction in the transmission rate after the
implementation of the HAART policy. Because new patients
with HIV acquired their infection from either identified pa-
tients (x% of the total) or from unidentified patients, the re-
duction in R in Taiwan (denoted DR) is the weighted mean of
the reduction in R of identified patients (denoted DR?) and that
of unidentified patients (0, by definition). Therefore, DR p
(x%)(DR )(x%) p DR/DR
value of DR?is 100%, the minimal value of x% would be DR.
Incidence of syphilis and gonorrhea.
syphilis and gonorrhea in the general population was studied
using nationwide surveillance data. Syphilis and gonorrhea are
also reportable diseases in Taiwan. To be registered, patients
with syphilis must have compatible clinical symptoms or signs
and positive Venereal Disease Research Laboratory (VDRL)test
results or Treponema pallidum hemagglutination assay (TPHA)
titers; patients with gonorrhea must have compatible clinical
symptoms or signs and positive urethral-culture results. The
incidence of syphilis among HIV-positive patients was directly
measured in the 1152 HIV-positive patients who were treated
and monitored at the Taipei Municipal Venereal Disease Con-
trol Institute (TMVDC; Taipei, Taiwan), where regular VDRL
titer monitoring has been part of the treatment of HIV-positive
patients since 1989. To be counted as a case of newly acquired
syphilis after a diagnosis of HIV infection, there must be com-
patible clinical symptoms or signs, positive TPHA titers, and
a 4-fold increase in VDRL titer, compared with the baseline
titers at the time of diagnosis of HIV infection.
Linear regression was used for model
fitting in estimating R. The slopes of linear regression lines
during the pre-HAART and HAART eras were compared by a
. Because the maximal possible
The incidence of
Y p b +b X+b t+b tX+? .
X is a dummy variable that is used to describe the era (X p
for the pre-HAART era and
is the natural logarithm of the number of cases at time t. Here,
we assume that infections occur at discrete points in time, such
as the beginning of each 4-month period. Thus, b2and b2+b3
are the slopes of the regression lines during the pre-HAART
era () and during the HAART era (X p 0
b3, the coefficient of the slope dummy variable tX, is the dif-
ference in slopes between the regression lines during the pre-
HAART and HAART eras. Our test of slope change is therefore
based on the significance of the b3estimate. With the results
of linear regression used as the initial guess values, a nonlinear
regression curve was also fitted, by use of the least-squares
method, for surveillance data from the HAART era. The risk
for the HAART era). Yt
X p 1
), respectively.X p 1
of mortality was calculated as the number of deaths of HIV-
infected individuals during the 4-month interval, divided by
the mean number of prevalent cases at the beginning and end
of the interval; this was compared by use of the Wilcoxon rank-
sum test. The incidence of syphilis during the pre-HAART and
HAART eras was compared using the large-sample method for
person-time data. The software programs usedforcomputation
and illustration were SAS (version 8.0; SAS Institute), S-PLUS
2000 (MathSoft), and Excel 2002 (Microsoft). Two-tailed P !
was considered to be statistically significant.
Surveillance of HIV and AIDS, 1984–2002.
1984 to the end of December 2002, a total of 29,429,255 ELISA
tests for HIV were performed in Taiwan, including 20,635,116
tests for blood donors, 2,357,235 compulsory HIV tests for
enlisted servicemen, and 896,200 tests for prisoners. The num-
ber of newly detected HIV infections and cases of AIDS (im-
ported cases were not included) every 4 months is shown in
figure 1A. The proportion of AIDS among newly identified
cases remained stable before 2001 (
decreased (to) in 2001 and 2002 (
coxon rank-sum test). Up to the end of December 2002, the
reached 4390, or 0.019% of the total population (22,520,776
persons) in Taiwan. Among these 4390 patients, 3541 were still
alive at the end of 2002. The prevalence of HIV among people
15–64 years old (
n p 15,890,584
HIV seroprevalence rates were 0.009% (6 cases/67,443 popu-
lation) among enlisted servicemen, 0.014% (6 cases/41,379 pop-
ulation) among pregnant women, and 0.1% among patients
with other sexually transmitted diseases.
Among the 4390 HIV-positive patients, the majority were
men (92.9%). The most common age at diagnosis was 20–29
years (36.5%), followed by 30–39 (33.5%) and 40–49 (13.2%)
years. Sexual contact (96.4%) was the predominant risk fac-
tor, followed by injection drug use (1.9%), hemophilia (1.2%),
transfusion (0.3%), and mother-to-child transmission (0.2%).
The percentage of injection drug users (IDUs) decreased from
3.8% during the pre-HAART era (January 1990–April 1997,
) to 0.8% during the HAART era (May 1997–Decem-
n p 1149
ber 2002,) (; x2test). Among sexuallyacquired
n p 3094P ! .01
cases, 54.5% of patients reported they were men having sex
with men (MSM), but the actual percentage of MSM was prob-
ably much higher, because male homosexuality remained a so-
cial taboo in Taiwan, and patients were reluctant to disclosetheir
true sexual orientation. Because disposable needles can be easily
IDUs in Taiwan actually acquired HIV through sexual contact.
), but this rate
P p .0003
) was 0.021%. In 2001, the
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882 • JID 2004:190 (1 September) • Fang et al.
The national policy of providing free access to highly active antiretroviral therapy (HAART) was started 7 April 1997. B, Natural logarithm of the nos. of
all newly detected cases every 4 months in Taiwan, January 1984–December 2002. Regression lines are shown.
A, Nos. of newly detected cases, including asymptomatic HIV infection and AIDS, every 4 months in Taiwan, January 1984–December 2002.
Reduction of HIV transmission during the HAART era.
The natural logarithm of the numbers of newly detected cases
every 4 months is shown in figure 1B. The slopes of the linear
regression line during the pre-HAART (January 1990–April
1997) and HAART (May 1997–December 2002) eras were
R p 0.80 P ! .0001
p0.90; ), respectively, for each prevalent case-year.P ! .0001
The slope decreased significantly during the HAART era, com-
pared with that during the pre-HAART era (
ual analysis showed that the residuals had no autocorrelation
over time during either time period. On the basis of the average
proportion of AIDS (among newly identified cases) of 0.25, the
interval distribution between infection and detection was sim-
ulated by use of a Weibull model
with a median time from infection to detection of 2.35 years
(figure 2). Using 0.156 as the initial value, nonlinear regression
was conducted and converged on the slope value of 0.138/
prevalent case-year during the HAART era.
). Resid-P p .005
F(t) p 1?exp(?0.0982t)
The Kaplan-Meier survival curves of HIV-infected patients
during the pre-HAART and HAART eras are shown in figure
3. The average risk of mortality, m, which was calculated by
averaging the number of deaths per number of prevalent cases
every 4 months during 1991–1996, was
prevalent case-year, which was significantly reduced to (0.046?
0.019) cases/prevalent case-year during 1998–2002 (Pp.0002;
Wilcoxon rank-sum test).
Thus, the estimated R during the pre-HAART era was
new cases/prevalent case-year. After im-0.292+0.099 p 0.391
plementing the policy to provide free access to HAART, R was
reduced to0.138+0.046 p 0.184
The reduction in the average HIV transmission rate in Taiwan
wasthus (0.391?0.184)/0.391?100% p 53%
interval [CI], 31%–65%).
Estimation of the total number of HIV-infected patients in
Because , theminimalvalueofx%would
DR p 53%
be 53%. This implies that the upper limit of the total num-
new cases/prevalent case-year.
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HAART and Decreased HIV Transmission • JID 2004:190 (1 September) • 883
dicted surveillance curve (St) during the pre–highly active antiretroviral
therapy (HAART) era and after the introduction of HAART. The interval
distribution (Ft) between infection and detection caused a convex surveil-
lance curve after the implementation of the free-HAART policy.
Incidence curve (It) (simple exponential model) and the pre-
diagnosed between 1 January 1990 and 7 April 1997 (monitored until 7
April 1997) and 3117 HIV-infected patients diagnosed after 7 April 1997
(monitored until 31 December 2002). HAART, highly active antiretroviral
Kaplan-Meier survival curve of 1154 HIV-infected patients
ber of HIV-infected patients in Taiwan at the end of 2002 is
(95% CI, 6754–14,161). The 8283 patients4390/53% p 8283
would account for 0.036% of the total population, which does
not violate the low prevalence assumption.
Incidence of syphilis and gonorrhea.
nually reported numbers of cases of syphilis and gonorrheawere
3200 and 520 during 1993, 3240 and 263 during 1994, 3054 and
175 during 1995, 3172 and 121 during 1996, 3050 and 95 during
1997, 2407 and 91 during 1998, 3037 and 163 during 1999, 3854
and 367 during 2000, 3694 and 397 during 2001, and 4182 and
838 during 2002. There was no statistically significant change in
the reported numbers of cases of syphilis and gonorrhea during
this period. Among the 1152 HIV-positive patients who were
treated and monitored at TMVDC, the incidence of newly ac-
quired cases of syphilis after the diagnosis of HIV infection was
60 episodes/11,048 person-months during the pre-HAART era
(1 January 1990–31 March 1997) and 158 episodes/32,023 per-
son-months during the HAART era (7 April 1997–31 December
2002). There was no significant difference in incidence between
the 2 periods ( ), with an incidence ratio of 0.91 (95%P p .53
The nationwide an-
Our research shows that, after implementing a policy of pro-
viding free access to HAART to all HIV-infected citizens, the
HIV transmission rate decreased by 53% in Taiwan. This result
makes a strong case for the more widespread use of HAART
as a major control measure against the HIV and AIDS epi-
demics in countries with low prevalence. It should be empha-
sized that the Taiwan government also provided free access to
zidovudine, didanosine, and deoxycytidine to all HIV-infected
citizens during the pre-HAART era. Thus, the reduction in the
HIV transmission rate would probably be 153% if there had
been no ART in the baseline situation. This reduction in HIV
transmission contributed greatly to the control of the HIV ep-
idemic. The extremely low prevalence of HIV in Taiwan is a
testament to the success of the policy of providing free access
Study of the evolution of HIV epidemics has been hampered
by the asymptomatic nature of early HIV infection, which
makes the direct measurement of the incidence of HIV in large
populations, such as the entire Taiwanese population, very dif-
ficult. Before the HAART era, data on the evolution of HIV
epidemics were mainly obtained by backward projection from
AIDS surveillance data [30, 31]. The usefulnessof thisapproach
has diminished since the introduction of HAART, which can
delay or even prevent the development of AIDSinHIV-infected
patients [5, 10, 22]. In the present study, R was estimated by
use of an exponential model of HIV surveillance results, which
had been predicted by a modified back-calculation projection
from a theoretical exponential incidence curve to fit the ob-
served surveillance data. The validity of our model depends on
2 assumptions: a low prevalence of HIV, which is the pre-
requirement of the simple exponential incidence curve used in
the present study, and a stable interval distribution, for use in
the projection. In Taiwan, 129 million screening ELISA tests
were conducted during 1984–2002 among the population of
22 million persons, and the screening activity has been con-
stantly focused on persons who are at an increased risk of HIV
infection, with the incentive of free ART and medicalcare.Even
if the actual total number of cases of HIV and AIDS was 10-
fold higher than the detected 4390, it would still account for
a prevalence rate as low as 0.19% of the total population. For
the second assumption, the Department of Health of Taiwan
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884 • JID 2004:190 (1 September) • Fang et al.
made an extraordinary effort in establishing anationwideactive
surveillance system beginning in the late 1980s. Since 1990, the
active HIV screening and reporting system has functioned well.
This notion was supported by the high R2values of the linear-
regression model used to explain the surveillance data in the
2 studied time periods (0.80 for 1990–1997 and 0.90 for 1997–
2002) and the stable proportion of the development of AIDS
among newly identified cases before 2001. The decreased pro-
portion of cases of AIDS in 2001 and 2002, which was probably
due to the improved performance of HIV surveillance among
an increasing number of asymptomatic people who voluntarily
received testing, will yield a biased slope estimate higher than
it should be during the HAART era. Thus, the actual effect of
HAART on reducing the HIV transmission might be higher
than the 53% estimated in the present study.
For an observational study, any conclusion about a causal link
must be carefully examined to exclude the influence of potential
confounding factors. Thepresentstudyisalsoanecologicalstudy
and might be subject to ecological fallacy. However, the major
confounding factor (patterns of behavior) probably cannot ex-
plain the decrease in the average transmission rate of HIV after
April 1997 in Taiwan. Although we had no reliable way of ob-
taining an accurate estimation of trends of risky sexual behav-
ior, which was a private matter, the surveillance data on syphilis
can be used as the surrogate marker. If there indeed had been a
decrease in the rate of unprotected sex, there should have been
a corresponding decrease in the incidence of syphilis. Ourresults
showed that there was no such trend, either in the general pop-
ulation or among HIV-positive patients. This indicates that the
decreased rate of HIV transmission was unlikely to be caused by
and HIV-positive patients in Taiwan after 1997.
No specific intervention program, such as needle exchange
or methadone maintenance programs, has been put in place
for injection drug–related HIV infection in Taiwan. Because
disposable needle can be easily purchased from any drugstore
at a very low price (∼$0.03/needle), IDUs in Taiwan have not
usually shared needles during the past 2 decades. The most
likely explanation for the significantly lower proportion of
IDUs during the HAART era is that HIV-positive IDUs in
Taiwan did not transmit HIV to other IDUs. In fact, most
HIV-positive IDUs in Taiwan acquired HIV through sexual
Antiretroviral drug resistance among patients recently in-
fected with HIV has become a disturbing problemintheUnited
States [33, 34]. Widespread drug resistance will certainly di-
minish, or even nullify, any effect of the free-HAART policy
on HIV transmission. Thus, a well-functioning medical, nurs-
ing, and laboratory infrastructureisessentialtoensurethelong-
term success of HAART and to avoid the rapid emergence of
drug resistance. To conserve resources, the Taiwan CDC has
facilitated the establishment of special clinics that are capable
of delivering qualified medical care, including appropriate pre-
scription and the monitoring of CD4 cell counts, plasma HIV
load, and adverse effects of drugs. This has contributed to an
extremely low rate of treatment failure caused by primary drug
resistance for patients recently infected with HIV in Taiwan
. Further monitoring of the prevalence of drug resistance
Although our results support that the policy of providing
free access to HAART can significantly decrease the rate of HIV
transmission among a population, one must be aware that such
a policy alone cannot eradicate the HIV epidemic. The number
of newly detected cases of HIV is still slowly increasing in
Taiwan, which indicates a basic reproductive number 11 .
Because the HIV epidemic runs an exponential course during
its early phases [17, 21], a reduction in HIV transmission by
53% means that the evolution of the epidemicwassloweddown
by 53%. However, the epidemic will eventually catch up if we
cannot further reduce the transmission rate of HIV byadditional
preventive action. Although public education about safersexand
condom use has been widely distributed in Taiwan since the
mid-1980s, more effort is needed. There are still thousands of
new cases of syphilis each year, which indicates that unsafe sexu-
al practices are still common. To further reduce the rate of HIV
transmission, the ongoing challenge is how to make condom use
a social standard for sexually active young persons.
Our results of a significant reduction in the transmissionrate
of HIV may not be directly extrapolated to countries with a
high prevalence of HIV. For countries withlowprevalence,such
as Taiwan, an early adoption of a universal HAART policy will
result in a slower increase in the incidence and prevalence rates
when the epidemic is still in its early exponential phase. To the
contrary, for countries with a high prevalence, with a mature
epidemic and stable incidence rate, the provision of universal
access to HAART may result in a decrease in incidence rate of
HIV, but the prevalence of HIV and AIDS might not signifi-
cantly change for a relatively long period of time, because the
decrease in the number of new cases is offset by the longer
survival of existingpatients.ProvidingfreeaccesstoHAART
in countrieswith ahighprevalenceofHIVwillalsohavefinancial
constraints. Further studies are needed to determine the best
preventive and therapeutic strategies for HIV infectionandAIDS
under these conditions.
In conclusion, after implementing a nationwide policy of pro-
viding free access to HAART to all HIV-infected citizens, the
average transmission rate of HIV decreased by 53% in Taiwan.
The widespread use of HAART can be an effective measure to
control HIV epidemics in countries with a low prevalence.
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HAART and Decreased HIV Transmission • JID 2004:190 (1 September) • 885 Download full-text
1. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and hetero-
sexual transmission of human immunodeficiency virus type 1. Rakai
Project Study Group. N Engl J Med 2000;342:921–9.
2. Mofenson LM, Lambert JS, Stiehm ER, et al. Risk factors for perina-
tal transmission of human immunodeficiency virus type 1 in women
treated with zidovudine. Pediatric AIDS Clinical Trials Group Study
185 Team. N Engl J Med 1999;341:385–93.
3. Tovanabutra S, Robison V, Wongtrakul J, et al. Male viral load and
heterosexual transmission of HIV-1 subtype E in northern Thailand.
J Acquir Immune Defic Syndr 2002;29:275–83.
4. Centers for Disease Control and Prevention. Report of the NIH panel
to define principles of therapy of HIV infection and guidelines for the
use of antiretroviral agents in HIV-infected adults and adolescents.
MMWR Morb Mortal Wkly Rep 1998;47(RR-5):1–41.
5. Carpenter CC, Cooper DA, Fischl MA, et al. Antiretroviral therapy in
adults: updated recommendations of the International AIDS Society–
USA Panel. JAMA 2000;283:381–90.
of nucleoside analogues and a protease inhibitorreducesHIV-1RNAlevels
in semen: implications for sexual transmission of HIV infection. Antivir
7. Vernazza PL, Troiani L, Flepp MJ, et al. Potent antiretroviraltreatment
of HIV-infection results in suppression of the seminal sheddingofHIV.
The Swiss HIV Cohort Study. AIDS 2000;14:117–21.
8. Eron JJ Jr, Smeaton LM, Fiscus SA, et al. The effects of proteaseinhibitor
therapy on human immunodeficiency virus type 1 levels in semen (AIDS
Clinical Trials Group protocol 850). J Infect Dis 2000;181:1622–8.
9. Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and
mortality among patients with advanced human immunodeficiency
virus infection. N Engl J Med 1998;338:853–60.
10. Mocroft A, Vella S, Benfield TL, et al. Changing patterns of mortality
across Europe in patients infected with HIV-1.Lancet1998;352:1725–30.
11. Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-
dose nevirapine compared with zidovudine for prevention of mother-
to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012
randomised trial. Lancet 1999;354:795–802.
12. Cooper ER, Charurat M, Mofenson L, et al. Combinationantiretroviral
strategies for the treatment of pregnant HIV-1–infected women and pre-
vention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr
13. Musicco M, Lazzarin A, Nicolosi A, et al. Antiretroviral treatment of
men infected with human immunodeficiency virus type 1 reduces the
incidence of heterosexual transmission. Italian Study Group on HIV
Heterosexual Transmission. Arch Intern Med 1994;154:1971–6.
14. Garnett GP, Bartley L, Grassly NC, Anderson RM. Antiretroviral ther-
apy to treat and prevent HIV/AIDS in resource-poor settings. NatMed
15. Hosseinipour M, Cohen MS, Vernazza PL, Kashuba AD. Can antiret-
roviral therapy be used to prevent sexual transmission of human im-
munodeficiency virus type 1? Clin Infect Dis 2002;34:1391–5.
16. Wood E, Braitstein P, Montaner JS, et al. Extent to which low-level
use of antiretroviral treatment could curb the AIDS epidemic in sub-
Saharan Africa. Lancet 2000;355:2095–100.
17. Levin BR, Bull JJ, Stewart FM. Epidemiology, evolution, and future of
the HIV/AIDS pandemic. Emerg Infect Dis 2001;7(Suppl 3):505–11.
18. Anderson RM, Gupta S, May RM. Potential of community-wide che-
motherapy or immunotherapy to control the spread of HIV-1. Nature
19. Joint United Nations Programme on HIV/AIDS (UNAIDS). Report
on the global HIV/AIDS epidemic. Geneva: UNAIDS, 2002.
20. Berwick D. “We all have AIDS”: case for reducing the cost of HIV
drugs to zero. BMJ 2002;324:214–6.
21. Solomon PJ, Isham VS. Disease surveillance and data collection issues
in epidemic modeling. Stat Methods Med Res 2000;9:259–77.
22. Centers for Disease Control and Prevention. Guidelines for national
human immunodeficiency virus case surveillance, including monitor-
ing for human immunodeficiency virus infection and acquired immu-
nodeficiency syndrome. MMWR Morb Mortal Wkly Rep 1999;48(RR-
23. Van de Ven P, Rawstorne P, Nakamura T, Crawford J, Kippax S. HIV
treatments optimism is associated with unprotected anal intercourse
with regular and with casual partners among Australian gayandhomo-
sexually active men. Int J STD AIDS 2002;13:181–3.
24. Katz MH, Schwarcz SK, Kellogg TA, et al. Impact of highly active
antiretroviral treatment on HIV seroincidence among men who have
sex with men: San Francisco. Am J Public Health 2002;92:388–94.
25. Law MG, Prestage G, Grulich A, Van de Ven P, Kippax S. Modeling
the effect of combination antiretroviral treatments on HIV incidence.
26. Blower SM, Gershengorn HB, Grant RM. A tale of two futures: HIV
and antiretroviral therapy in San Francisco. Science 2000;287:650–4.
I. General health statistics. Taipei, Taiwan: Department of Health, Ex-
ecutive Yuan, 2002.
28. Centers for Disease Control and Prevention. 1993 revised classification
system for HIV infection and expanded surveillance case definition for
AIDS among adolescents and adults. MMWR Morb Mortal Wkly Rep
29. Brookmeyer R, Gail MH. Back-calculation. In: Brookmeyer R, Gail
MH. AIDS epidemiology: a quantitative approach. New York: Oxford
University Press, 1994:194.
30. Brookmeyer R, Gail MH. Minimum size of the acquired immunode-
ficiency syndrome (AIDS) epidemic in the United States. Lancet 1986;
31. Brookmeyer R, Gail MH. A method for obtaining short-term projec-
tions and lower bounds on the size of the AIDS epidemic. J Am Stat
32. Halloran ME. Concept of infectious disease epidemiology.In:Rothman
KJ, Greenland S, eds. Modern epidemiology. 2nd ed. Philadelphia: Lip-
33. Little SJ, Holte S, Routy JP, et al. Antiretroviral-drug resistance among
patients recently infected with HIV. N Engl J Med 2002;347:385–94.
34. Grant RM, Hecht FM, Warmerdam M, et al. Time trends in primary
HIV-1 drug resistance among recently infected persons. JAMA 2002;
35. Chen MY. Drug resistance in HIV isolates from Taiwan.In:Symposium
of HIV/AIDS Drug Therapy and Adherence, Taipei, Taiwan, 2002.
36. Gray RH, Li X, Wawer MJ, et al. Stochastic simulation of the impact
of antiretroviral therapy and HIV vaccines on HIV transmission:Rakai,
Uganda. AIDS 2003;17:1941–51.
37. Bracewell RN. The basic theorem of convolution. In: Bracewell RN. The
Fourier transform and its applications. 3rd ed. New York: McGraw-Hill,
38. Lui KJ, Lawrence DN, Morgan WM, Peterman TA, Haverkos HW, Breg-
man DJ. A model-based approach for estimating the mean incubation
period of transfusion-associated acquired immunodeficiency syndrome.
Proc Natl Acad Sci USA 1986;83:3051–5.
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