I N D I A
R U S S I A
K A Z A K H STAN
M O N G O L IA
Number of cases (thousands)
Lin Lu, Manhong Jia, Yanling Ma, Li Yang,
Zhiwei Chen, David D. Ho, Yan Jiang and
The HIV-1/AIDS epidemic in China is at a
critical juncture. Historically, HIV-1 infection
has been largely confined to certain high-risk
populations such as intravenous drug users and
former blood and plasma donors in geographi-
cally disparate rural areas1–3. However, HIV-1
prevalence has now increased rapidly among
men who have sex with men and among female
sex workers4,5. It seems that China is following
the path of some of the other Asian countries
where HIV-1 infection is no longer confined
to high-risk populations5.
Since the first cases among foreign tourists
and local recipients of imported factor VIII in
the mid 1980s, HIV-1 has spread to all of main-
land China1,4. The current epidemic comprises
largely of two affected populations: former
blood and plasma donors in Henan and neigh-
bouring provinces, and intravenous drug users
in Yunnan and along drug-trafficking routes1,2
(Fig. 1). Both of these populations stemmed
from the infection of drug users from Yunnan’s
Dai and Jingpo ethnic minority groups in Yun-
nan in the late 1980s6,7.
Statistics from the Chinese Ministry of Health
and UNAIDS have revealed a worrisome trend
of the HIV-1 epidemic in China. As of Octo-
ber 2007, an estimated 700,000 infections had
occurred4. Although the prevalence of infec-
tion remains low (0.04–0.07%), the new figure
represents an 8% increase since 2006 (refs 4, 5).
Remarkably, 38% of the cases were attributed
to heterosexual contacts — more than triple
the 11% in 2005 (ref. 4). In line with this trend,
the proportion of women infected has doubled
over the past decade4. As 90% of these women
are of child-bearing age (15–44), this is likely to
translate into more vertical transmission from
mother to child4. Additionally, the proportion
of cases among men who have sex with men
increased eight-fold from 0.4% in 2005 to 3.3%
in 2007 (ref. 4). These data suggest that the HIV-
1 epidemic is expanding, and that more effective
preventive measures are urgently needed.
The epidemic in Yunnan
Located in southwest China, Yunnan has
long been regarded as China’s Shangri-la
for its natural beauty. But now, with all of its
16 prefectures affected, it is a major site of
the AIDS epidemic. Yunnan’s ethnic diver-
sity is unrivalled in China, with 25 differ-
ent ethnic minority groups representing one
third of the province’s population. Of these
groups, 13 live along the border with Myan-
mar, Laos and Vietnam, and cross-border
travel and commerce are common. Yunnan
has a long history of opium/heroin trade, and
the vast majority of illicit drugs in China are
trafficked through Yunnan from the ‘Golden
triangle’ of illicit opium production, encom-
passing Myanmar, Thailand, Laos and
Vietnam (Fig. 1)8,9.
HIV-1 was detected in intravenous drug
users inYunnan in 1989 (ref. 10). It then also
spread among other populations11. Between
1989 and 2006, 3.2 million blood samples
were tested in Yunnan. This testing identi-
fied 48,951 HIV-1 cases, 3,935 AIDS patients,
and 1,768 resultant deaths — representing
about 25%, 8% and 13% of the national totals,
respectively. Prefectures bordering Myan-
mar and Vietnam were the first and the most
Although the cumulative HIV-1 case load
rose gradually from 1989 to 2003, there was
a sharp rise in 2004, when 13,486 new cases
were seen. This total is comparable to the
number identified in the previous 16 years.
Identification of these new cases was likely to
be due to increased surveillance and testing
since the estimated incidence rates remained
relative stable over time among the major risk
groups. These estimates were determined by
re-testing all seropositive samples from the
surveillance effort using the BED assay12 to
detect those with low-affinity antibodies to
HIV-1. Intravenous drug users had the high-
est incidence rate throughout the study, vary-
ing between 2.2% and 8.0% per year, whereas
that for outpatients attending sexually trans-
mitted infection (STI) clinics was 0.3–1.0%
The changing face of HIV in China
HIV has advanced from high-risk groups such as intravenous drug users to some in the general population,
according to comprehensive new data from the south of China. What needs to be done to halt its spread?
Figure 1 | Pervasive spread. The geographic distribution of cumulative reported HIV-1 infection in
mainland China (redrawn from ref. 4).
NATURE|Vol 455|2 October 2008
per year and for pregnant women it
was about 0.1% per year.
HIV-1 has hit different Yunnan popu-
lations disproportionately. Figure 2
shows provincial average HIV-1
prevalence rates over time among
intravenous drug users, female sex
workers, STI outpatients, pregnant
women and an ‘unlinked popula-
tion’ (patients admitted to the hospi-
tal who were willing to be tested for
HIV-1 anonymously) based on the
results from 97 sentinel surveillance
sites located through the province.
Within these groups, the highest
prevalence rate has always been found
in the intravenous drug users popula-
tion. From 1992 to 1995, the average
prevalence rate remained around 6%.
In 1996, it jumped to about 22%, and
then remained near that level. Preva-
lence rates among female sex work-
ers and STI outpatient groups have
been consistently lower, but follow
a similar trend. The ‘unlinked’ and
pregnant women populations have
also experienced a similar pattern of
prevalence increases, although the
jumps occurred in 1999 and 2003,
respectively. This sequential upsurge
of infection among intravenous drug users,
female sex workers, STI outpatients, then
among the ‘unlinked’ and finally pregnant
women, is reminiscent of what has been seen
in other countries, where HIV-1 infection has
spread from high-risk groups to some in the
This trend in transmission mode is further
illustrated by the fact that the proportion of
cases among intravenous drug users has
decreased from 100% in 1989 to 40% in 2006.
Concurrently, heterosexual transmission has
increased markedly, reaching 37.5% of infec-
tions in 2006.
Although most infections were in farmers
from 1989 to 1995, more factory workers are
now infected, and the number of infections
among unemployed persons have come to rival
those in farmers. In addition, whereas the Dai
and Jingpo minorities were the most affected
ethnic groups in 1989–95, Han Chinese over-
took these minorities in 1996 and up to 2006
accounted for around 60% of infections.
Changes in age distribution are also evi-
dent. Although on average more than 95% of
infected individuals have been aged 20–40,
HIV-1 prevalence has increased among the
30–59 group and decreased among the 20–29
group. This could be attributed to ageing of
infected individuals or to new infections of
relatively older age groups over time. Nonethe-
less, high prevalence in the 20–29 and younger
than 20 age groups suggests ongoing infection
within the young population.
HIV-1 in Yunnan has also spread to the
female population. Before 1996, most infected
individuals were male. However, from 1996–
2006, the proportion of HIV-1-infected women
gradually increased from 7.1% to 35%, and
the male to female ratio decreased from 13:1
With the dramatic changes in disease distribu-
tion, HIV-1 genetics in Yunnan have become
increasingly complex. The initial HIV-1 epi-
demic among intravenous drug users in Yun-
nan in 1989 was caused by a mixture of viruses
closely resembling European/North American
subtype B and Thai subtype B (B’)13. But by
1996, the B’ subtype began to dominate13,14.
During the same period, a second epidemic
took root among intravenous drug users in
Yunnan, with strains genetically related to
subtype C viruses from India15. Co-existence
of multiple subtypes led to the formation of
circulating recombinant forms (CRFs) of
HIV-1 — CRF07_BC and CRF08_BC among
intravenous drug users along drug trafficking
routes16 and CRF01_AE in Chinese sex work-
ers who had worked in Thailand17. In the mid-
1990s, viruses closely related to CRF01_AE
and CRF08_BC in Yunnan were identified
among intravenous drug users in Guangxi18.
Further novel recombinants arose in subse-
We compared over 500 nucleotide sequences
from Yunnan6,7 with those from other prov-
inces in China and neighbouring countries.
Comparing sequences from the HIV-1 gag
p17 with reference sequences from
the HIV-1 Database (www.hiv.lanl.
gov/content/index), we identified the
three main subtypes of HIV-1 found in
Yunnan. These subtypes are those clus-
tering closely with subtype C, CRF07_
BC, or CRF08_BC (53.0%); those with
CRF01_AE or CRF15_01B (40.5%);
and those with subtype B (6.5%).
Notably, more than 90% of infected
intravenous drug users had C/CRF07_
BC/CRF08_BC viruses, whereas 85.4%
of CRF01_AE/CRF15_01B infections
were acquired through sexual trans-
mission. Furthermore, sequences in
the C/CRF07_BC/CRF08_BC group
were found throughout Yunnan, while
those in the CRF01_AE/CRF15_01B
group were largely confined to prefec-
tures bordering Myanmar. Sequences
in the subtype B groups have only been
identified in the Dehong and Baoshan
prefectures in Yunnan.
The dominant C/CRF07_BC/
CRF08_BC viruses in Yunnan are
related to strains in Guangxi prov-
ince and distant Xinjiang province,
supporting the notion that HIV-1
has spread along known drug-traf-
ficking routes. In contrast, sequences
similar to CRF01_AE/CRF15_01B
have been largely confined to Yun-
nan and are closely related to strains from
Thailand, Myanmar and Vietnam. Subtype
B sequences from Yunnan are genetically
similar to those from former blood donors
in Henan and adjacent provinces, and can
be broadly classified into two major groups:
one with sequences similar to those from
Thailand and Myanmar, and the other with
sequences more similar to those in France
and the United States. These results are con-
sistent with the hypothesis that HIV-1 spread
from Yunnan to central China, and sug-
gest multiple introductions of HIV-1 from
foreign countries to Yunnan6.
Challenge and opportunity
Over the past 20 years, HIV-1 in Yunnan
has overcome preventive measures to spread
beyond high-risk populations. The dramatic
increase in sexual transmission has changed
the demographic profile of those infected. As
the epidemic continues to expand, the genetic
makeup of HIV-1 subtypes have become
increasingly complex, potentially posing
greater challenges to our efforts in antiretro-
viral treatment and vaccine development.
In light of the observed demographic
changes, HIV-1 prevention strategies must
focus more on stopping sexual transmission
of HIV-1 within high-risk groups and halt-
ing the spread to the general public. There are
urgent needs to scale up and integrate those
proven successful prevention programmes
such as condom promotion among female sex
workers; drug rehabilitation, needle exchange
Percentage of infection
Intravenous drug users
Female sex workers
Patients willing to be
Figure 2 | Changing trends. HIV-1 prevalence among various risk
groups in Yunnan between 1992 and 2006.
NATURE|Vol 455|2 October 2008
and methadone maintenance for intravenous Download full-text
drug users ; and free antiretroviral therapy for
There is an old Chinese saying: “When there
is a crisis, there is an opportunity.” Indeed, as
HIV-1 plagues certain high-risk groups in
China, there is still a window of opportunity
to prevent further spread to the general popu-
lation. The time to act is now.
1. Wu, Z., Sullivan, S. G., Wang, Y., Rotheram-Borus, M. J. &
Detels, R. Lancet 369, 679–690 (2007).
2. Wu, Z. Y., Liu, Z. Y. & Detels, R. Lancet 346, 61–62 (1995).
3. Kaufman, J. & Jing, J. Science 296, 2339–2340 (2002).
4. State Council AIDS Working Committee Office and UN
Theme Group on AIDS in China, A Joint Assessment of HIV/
AIDS Prevention, Treatment and Care in China (2007).
5. Gill, B., Huang, Y. & Lu, X. Demography of HIV/AIDS in China
Center for Strategic and International Studies (2007).
6. Zhang, L. et al. J. Virol. 78, 13591–13599 (2004).
7. Zhang, Y. et al. PLoS Med. 3, e443 (2006).
8. US Department of State Bureau for International Narcotics
and Law Enforcement Affairs. International Narcotics
Control Strategy Report Volume I Drug and Chemical Control
9. Chin, K.-L. & Zhang, S. US Department of Justice Report,
The Chinese Connection: Cross-border Drug Trafficking
between Myanmar and China (2007).
10. Zheng, X. et al. AIDS 8, 1141–1147 (1994).
11. Xiao, Y., Kristensen, S., Sun, J., Lu, L. & Vermund, S. H. Soc.
Sci. Med. 64, 665–675 (2007).
12. Parekh, B. S., Pau, C. P., Kennedy, M. S., Dobbs, T. L. &
McDougal, J. S. AIDS Res. Hum. Retroviruses 17, 137–146
13. Graf, M. et al. AIDS Res. Hum. Retroviruses 14, 285–288
14. Weniger, B. G., Takebe, Y., Ou, C. Y. & Yamazaki, S. AIDS
8, S13–S28 (1994).
15. Luo, C. C. et al. Lancet 345, 1051–1052 (1995).
16. Su, L. et al. J. Virol. 74, 11367–11376 (2000).
17. Cheng, H., Zhang, J., Capizzi, J., Young, N. L. & Mastro, T. D.
Lancet 344, 953–954 (1994).
18. Piyasirisilp, S. et al. J. Virol. 74, 11286–11295 (2000).
19. Yang, R. et al. J. Virol. 77, 685–695 (2003).
Acknowledgement This work is supported by
National Basic Research Program (also called
973 Program) of Chinese Ministry of Science and
Technology to L.Z. (2006CB504200) and by the
Tenth Five-year Key Technologies R&D Programme of
China:2004BA719A14-1, 2004BA719A14-2. We also
thank Mark Goldin for helpful suggestions.
Author information Correspondence should be
addressed to L.Z. (e-mail firstname.lastname@example.org
or email@example.com). L.L. and M.J. contributed
equally to this work.
Lin Lu1, Manhong Jia1, Yanling Ma1, Li Yang1, Zhiwei Chen2, David D. Ho3,4, Yan Jiang5* and Linqi Zhang4,6*
1Yunnan Center for Disease Control and Prevention, Yunnan, People’s Republic of China. 2AIDS Institute, The University of Hong Kong Li Ka Shing Faculty of Medicine,
Hong Kong SAR, People’s Republic of China. 3Aaron Diamond AIDS Research Center, The Rockefeller University, New York, USA. 4Comprehensive AIDS Research Center,
Tsinghua University, Beijing, People’s Republic of China. 5National AIDS Reference Laboratory, National Center for AIDS/STD Control and Prevention, Chinese Center for
Disease Control and Prevention, Beijing, People’s Republic of China. 6AIDS Research Center, State Key Laboratory for Molecular Virology and Genetic Engineering, Institute
of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China.
NATURE|Vol 455|2 October 2008