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Rapid dissemination of a novel B/C recombinant HIV-1 among injection drug users in southern China

2001; Lippincott Williams & Wilkins; Volume: 15; Issue: 4 Linguagem: Inglês

10.1097/00002030-200103090-00012

1473-5571

Xiao-Fang Yu, Wei Liu, Jie Chen, Wei Kong, Bindong Liu, Jin-ye Yang, Fuxiong Liang, Francine E. McCutchan, Sucheep Piyasirisilp, Shenghan Lai,

HIV/AIDS drug development and treatment

HIV infection among injection drug users (IDU) is a growing public health problem in many Asian countries including China [1]. IDU have been the primary risk group affected by HIV-1 in China since the first epidemic in 1989 [2]. A rapid increase of HIV-1 infection in China has been reported over the past few years [3,4]. By the end of 1999, a total of 18 143 HIV cases had been reported, and IDU accounted for more than two-thirds of all HIV infections [3,4]. It is estimated that there could be more than 500 000 HIV-infected individuals in China [3,4]. Although the largest number of accumulated HIV-positive cases is still found in Yunnan province, where the initial HIV-1 outbreak occurred in China, more than 50% of the new HIV-1 infections in China have occurred outside Yunnan province [3,4]. HIV infections in Sichuan (mid-west), Xinjiang (north-west), and Guangxi (south) provinces have increased dramatically in the past 3 years [3,4] (Fig. 1).Fig. 1.: Distribution pattern of HIV-1 subtypes in China and geographical locations of HIV surveillance sites in the Guangxi province of China. Arrows indicate potential drug trafficking routes from the heroin-producing regions in Myanmar and Laos (shaded area). The distributions of HIV-1 subtypes in Guangxi are shown next to each site. The major highway systems in Guangxi are shown as solid lines.Guangxi, a southern province of China that borders Vietnam in the south and Yunnan province in the west, is a major transit place for heroin trafficking from the 'Golden Triangle' opium-growing region of Laos and Burma [1,5]. Between 1996 and 1997, two geographically separated outbreaks of HIV infection among IDU were detected in Guangxi [5]. Based on full-length HIV-1 sequence analysis, it was clear that two different subtypes of HIV-1 were responsible for the separate outbreaks: a novel recombinant B/C was found in a city (Baise) bordering Yunnan province, whereas subtype E was found in a city (Pingxiang) bordering northern Vietnam [6]. Since the initial outbreaks of HIV infection in 1996 and 1997, HIV-positive cases have increased rapidly in Guangxi in recent years. Guangxi now has the third highest accumulated number of HIV-positive cases in China, following Yunnan and Xinjiang provinces. HIV outbreaks have been detected among drug users in several non-border regions including the capital city, Nanning, in Guangxi province. The majority of the HIV infections were associated with drug abuse, with a very low level of infection among other high-risk populations such as commercial sex workers, sexually transmitted disease patients, and long-distance truck drivers. Determination of the transmission pattern of HIV infection in Guangxi by molecular epidemiology should contribute to the design and implementation of effective intervention strategies targeted towards both IDU and other high-risk groups to reduce HIV-1 spread in China. Information about circulating HIV-1 subtypes in Guangxi may also be useful for vaccine development and evaluation. To determine the HIV-1 subtype(s) that are responsible for the recent outbreak of HIV infection in Tianyang, Tiandong, Binyang, and Nanning, we obtained HIV-1 env sequences (C2–V4 region) from 18 IDU. These sequences were compared with env sequences from Baise, Pingxiang, and representative subtype reference sequences (Fig. 2). The new HIV-1 env sequences from Tianyang (99TY021, 023, 024 and 027), Tiandong (98TD001–98TD008), Binyang (00BY004–00BY 006), and Nanning (99NN001, 004, and 005) belong to subtype C HIV-1. The new sequences from Guangxi were clustered together with the previously identified HIV-1 sequences from Baise (97CNGX-3–97CNGX-6). These sequences are less related to the env sequence of another B/C recombinant virus (C54) identified in Xinjiang [7], northwestern China.Fig. 2.: Neighbour-joining trees of new env and p24 sequences obtained from Guangxi. The reference sequences from HIV-1 subtypes A–H are described in the Human Retroviruses and AIDS 1996 compendium [8]. New HIV-1 env sequences (C2–V5) were obtained from 15 drug users from Tianyang (99TY021, 023, 024 and 027), Tiandong (98TD001–98TD008), Binyang (00BY004, 00BY005, and 00BY006), and Nanning (99NN001, 004, and 005). The p24 sequences (nucleotides 85–495) were obtained from nine drug users from Tianyang (99TY021, 023, and 024), Tiandong (98TD004 and 98TD005), Binyang (00BY004 and 00BY005), and Nanning (99NN001 and 004).Because HIV-1 env sequences from Tianyang, Tiangdong, Binyang, and Nanning are very similar to those from Baise, this raises the question of whether HIV-1 infection in Tianyang, Tiangdong, Binyang, and Nanning was caused by the circulating B/C recombinant HIV-1. HIV-1 sequences corresponding to p24 region (approximately 600 basepairs) were amplified from the peripheral blood mononuclear cell samples obtained from selected individuals whose env sequences had been determined. Because our previous analysis of the B/C recombinants from Baise indicated that the N-terminal region of p24 (nucleotides 48–495) was from the B subtype and the C-terminal region of p24 was from the C subtype of HIV-1 [6], we therefore compared the N-terminal p24 sequences from Guangxi with the reference sequences from various subtypes. All the N-terminal p24 sequences from Tianyang, Tiangdong, Binyang, and Nanning grouped tightly with those from Baise, with a bootstrap value of 100% (Fig. 2). They also grouped with p24 sequences from the B subtype of HIV-1, including RL42 from China [8], with a bootstrap value of 80%. On the other hand, the C-terminal region of the p24 sequences from Tianyang, Tiangdong, Binyang, and Nanning grouped clearly with subtype C HIV-1 sequences (data not shown). The fact that HIV-1 p24 sequences from Tianyang, Tiangdong, Binyang, and Nanning were nearly identical to those from Baise and that they shared the same breaking point between subtype B and subtype C sequences in p24 suggest that they had the same B/C recombination in the p24 region. Our study suggests that although subtype E was apparently introduced into Guangxi at the same time or even earlier than the B/C recombinant HIV-1 [5,6], the B/C recombinant HIV-1 epidemic is spreading to other regions whereas the subtype E epidemic remains geographically localized. Both Baise and Pingxiang have highway connections with the capital city, Nanning. Several explanations may account for the rapid spread of the B/C recombinant HIV-1. Both Baise and Pingxiang are along potential drug trafficking routes [5]. It is possible that drug trafficking is more active from Baise to Nanning than that from Pingxiang to Nanning. Alternatively, there may be more interaction among drug users from Baise and those from Nanning, Binyang, Tianyang, and Tiandong than among drug users from Pingxiang and Nanning. Our study suggests that the recent outbreaks of HIV infection in Guangxi were initiated with the B/C intersubtype recombinants originally observed in Baise. The rapid dissemination of the B/C recombinant HIV-1 in Guangxi may have important implications for HIV transmission as well as vaccine development and evaluation. Xiao-Fang Yua Wei Liuc Jie Chenc Wei Konga Bindong Liua Jinye Yangc Fuxiong Liangc Francine McCutchand Sucheep Piyasirisilpa Shenghan Laib