Distribution of HIV-1 genotypes in Guangdong
A total of 1205 plasma specimens were selected from diagnosed HIV-positive persons, which constitute 21.7% of the total reported HIV-1 cases in 2013 in Guangdong. Among the samples, 1021 were determined for the HIV-1 genotypes from the 1.1-kb gag and/or the 563-bp env regions (Table 1). 862 gag genotypes (71.5% of samples) and 900 env genotypes (74.7%) were acquired, and both gag and env genotypes were assessable for 741 samples (61.5%).
Nine major HIV-1 subtypes and circulating recombinant forms (CRF) in total were detected in this study. They included subtypes B, B′ (Thai B strain), C, G, CRF01_AE, CRF07_BC, CRF08_BC, CRF55_01B, and CRF59_01B (Fig. 1a and Additional file 2: Table S2). CRF01_AE (43.2%), CRF07_BC (26.3%), CRF55_01B (8.5%), and CRF08_BC (8.4%) were the predominant HIV-1 subtypes circulating in Guangdong (Fig. 1a). These four subtypes were responsible for 86.4% of reported HIV infections in Guangdong in 2013. Minor HIV-1 genotypes included CRF59_01B (1.7%), B (1.1%), B′(0.7%), C (0.9%), and G (0.3%). They were classified as “other” genotypes. The remaining 8.8% were discordant genotypes between gag and env fragments, and included CRF01/C (4.1%), CRF07/CRF01 (3.1%), B/CRF01 (0.6%), CRF01/B (0.5%), 0107/CRF01 (0.4%), and BC/C (0.04%) (Additional file 2: Table S2).
HIV-1 genotype distribution by risk group
As illustrated in Fig. 1b, sexual transmission including heterosexual and MSM was the primary risk factor in Guangdong, which accounted for 88.4% (61.9% for heterosexual and 26.5% for MSM) of HIV reported cases in 2013, followed by IDU including sexual plus IDU (11.1%) and mother to child transmission (MCT, 0.2%). About 0.2% of HIV cases resulted from unknown transmission routes.
CRF01_AE (50.5%), CRF07_BC (21.3%), CRF08_BC (9.0%), and CRF55_01B (8.5%) were the main HIV-1 subtypes circulating among heterosexuals, accounting for 89.3% of infections in this risk group, followed by discordant genotypes (4.9%) (Fig. 1a). The greatest genotype diversity was identified among heterosexuals, in which almost all the HIV-1 genotypes were detected, except B/CRF01. The main genotypes prevailing among MSM were CRF07_BC (34.2%), CRF01_AE (30.3%), and CRF55_01B (12.3%). Interestingly, CRF08_BC was not detected in MSM, while the discordant genotypes accounted for 19.6% of MSM infections, which was the highest ratio in all risk groups (Fig. 1a). Other genotypes in MSM were subtype B (1.8%), CRF59_01B (1.6%), and B′ (0.3%). Three main genotypes were detected in IDU, including CRF07_BC (36.5%), CRF01_AE (32.2%), and CRF08_BC (24.9%), followed by subtype C (1.3%) and discordant genotypes (5.1%). Only three HIV-1 genotypes, including CRF01_AE (75.0%), CRF08_BC (16.7%), and subtype C (8.3%), were detected among MCT.
HIV-1 genotype distribution by geographic region
According to the social-economic status, Guangdong could be classified into four regions: Pearl River Delta (PRD) region, eastern, western, and northern. The PRD region located in the central part of Guangdong has a prevalent Cantonese culture and is one of the most densely urbanized areas in the world, which includes the cities of Guangzhou, Shenzhen, Dongguan, Foshan, Jiangmen, Zhongshan, Huizhou, Zhaoqing, and Zhuhai. The eastern Guangdong is Teochew dialect-based and includes the four prefecture cities of Jieyang, Chaozhou, Shantou, and Shanwei. Northern Guangdong is dominated by mountains and includes four cities (Meizhou, Heyuan, Shaoguan, and Qingyuan). The Hakka dialects is prevalent in these cities. Western Guangdong is Cantonese culture based and includes the four cities of Zhanjiang, Maoming, Yangjiang, and Yunfu. As illustrated in Fig. 2, most HIV-1 cases in Guangdong were distributed in the PRD region (79.9%), followed by west (11.6%), north (5.4%), and east (3.1%) of Guangdong.
The estimated city-specific distributions of HIV-1 genotypes are presented in Fig. 2. In the PRD region, heterosexual (56.6%), MSM (31.8%), and IDU (11.6%) were the major risk groups. The PRD region comprised the highest genotype diversity, and almost all the genotypes, except BC/C, were identified in this region. CRF01_AE (37.7%), CRF07_BC (27.4%), CRF55_01B (10.3%), and discordant genotypes (10.4%) were the main genotype categories. Most of the cases of CRF55_01B (453 of 471, 96.2%) and discordant genotypes (459 of 485, 94.6%) were found in this region. Heterosexuals (60.9%) and MSM (39.1%) were the main risk groups for CRF55_01B, while MSM (62.3%) and heterosexuals (31.6%) were the main risk group for discordant genotypes.
In the western region, heterosexuals (82.7%) accounted for the majority of HIV-1 cases, followed by IDU (11.9%), MSM (4.2%), and MCT (1.3%). CRF01_AE (71.4%), CRF07_BC (18.8%), and CRF08_BC (7.0%) were the main prevailing HIV-1 strains, followed by CRF55_01B (0.6%), discordant genotypes (1.9%; 1.4% for CRF07/CRF01 and 0.5% for 0107/CRF01), and CRF59_01B (0.3%). Over 70% of HIV cases were infected with CRF01_AE in heterosexual (72.8%), MSM (74.1%), and MCT (75%) risk groups. The CRF01_AE composition ratio in the western region was the highest in all geographic regions, although the proportion of heterosexuals in the western region (82.7%) was less than that in the northern region (86.9%).
In the northern region, heterosexual (86.9%) was the predominant risk group, followed by IDU (6.7%), MSM (4.7%), and not available (NA, 1.3%). CRF01_AE (58.1%) and CRF07_BC (32.2%) were the main HIV-1 genotypes, followed by CRF08_BC (4.4%), CRF55_01B (2.0%), and discordant genotypes (2.7%; 1.3% for CRF07/CRF01, 1.0% for 0107/CRF01, and 0.3% for CRF01/C). Lower composition ratios for CRF01_AE were found in heterosexuals (60.6%), MSM (28.6%), and IDU (35%), while higher CRF07_BC ratios were found in those three risk groups.
In the eastern region, heterosexuals (79.4%) and MSM (13.5%) were the main risk groups, followed by IDU (1.8%) and NA (5.3%). CRF01_AE (55.9%), CRF07_BC (15.9%), and other genotypes (17.1%; 8.8% for subtype B, 5.3% for B′, and 2.9% for subtype C) were the main genotype categories in this region, followed by CRF55_01B (4.7%), CRF08_BC (2.9%), and discordant genotypes (3.5%; 1.2% for CRF07/CRF01, 1.2% for BC/C, 0.6% for CRF01/C, and 0.6% for 0107/CRF01). Among all geographic regions, the highest proportion of other genotypes category was observed in both heterosexuals (17.0%; 6.7% for subtype B, 6.7% for B′, and 3.7% for subtype C) and MSM (26.1%; all for subtype B) in the region. Of note, although the least number of HIV cases were reported in this region, there were 11 HIV-1 genotypes detected, which was the second highest number of genotypes.
Distribution of HIV-1 strains in Guangdong by city and risk group
The geographic distributions of the main HIV-1 genotype categories in Guangdong are illustrated in Fig. 3. CRF01_AE was detected in all 21 cities accounting for 43.2% of reported HIV infections in Guangdong in 2013, which accounted for the highest proportion of HIV genotypes among 18 cities, except for Foshan, Zhuhai, and Shaoguan. The majority (69.7%) of CRF01_AE was distributed in the seven cities of Shenzhen (18.7%), Guangzhou (16.9%), Dongguan (10.1%), Foshan (7.0%), Jiangmen (6.5%), Zhanjiang (5.7%), and Yunfu (5.0%). The estimated number of CRF01_AE cases in Zhanjiang was 43.6% higher than that in the neighboring city of Maoming. It is conceivable that Zhanjiang was another possible epicenter for CRF01_AE in Guangdong along with Shenzhen and Guangzhou in the PRD region. The major risk groups for CRF01_AE were heterosexuals (72.3%) and MSM (18.6%), followed by IDU (8.3%) (Fig. 1b).
CRF07_BC was also detected in all cities in Guangdong. The majority (83.5%) of CRF07_BC infections were observed in the PRD region, especially in the five cities of Shenzhen (26.7%), Guangzhou (18.7%), Foshan (12.7%), Dongguan (8.5%), and Jiangmen (7.4%). Heterosexuals (50.1%), MSM (34.5%), and IDU (14.2%) were the main risk groups for CRF07_BC (Fig. 1b). Similar to CRF01_AE, the estimated number of CRF07_BC in Zhanjiang was higher than its nearby cities.
CRF55_01B was identified in 15 of 21 cities; the exceptions of were Yangjiang, Yunfu, Heyuan, Meizhou, Jieyang, and Shanwei. Most of the CRF55_01B cases were detected in the PRD region (96.2%) primarily in Guangzhou (42.9%), Shenzhen (22.5%), Dongguan (15.1%), and Foshan (5.5%). The two risk factors for CRF55_01B infections were heterosexual (61.8%) and MSM (38.2%).
CRF08_BC was detected in 18 cities (not in Yangjiang, Yunfu, and Chaozhou). The majority (83.5%) of CRF08_BC infections were identified in the PRD region (86.3%) and the western region (9.8%), primarily in Guangzhou (29.9%), Shenzhen (24.1%), Foshan (14.3%), Dongguan (10.0%), and Maoming (5.2%). Heterosexuals (66.6%) and IDUs (32.3%) were the primary risk populations for CRF08_BC infections (Fig. 1b), and no CRF08_BC was identified in MSM population.
Discordant genotypes were detected in 14 cities. Most (94.6%) were distributed in the PRD region, especially in Guangzhou (48.2%), Shenzhen (20.4%), and Dongguan (18.4%). MSM (59.2%) and heterosexuals (34.4%) were the main risk factors for the discordant genotypes in Guangdong, followed by IDU (6.4%).
CRF59_01B, subtypes B and B′, and subtypes C and G accounted for 35.5, 24.0, 15.3, 18.7 and 6.5% of the other genotypes, respectively. Most CRF59_01B infections were identified in the PRD region (97.8%) including Foshan (32.3%), Guangzhou (18.3%), Shenzhen (16.1%), Jiangmen (10.8%), Dongguan (9.7%), Zhongshan (4.3%), Zhuhai (4.3%), and Huizhou (2.2%), as well as the Maoming (2.2%) in the western region. CRF59_01B circulated in heterosexual (75.3%) and MSM (24.7%) groups. Subtypes B and B′ were identified in the PRD region (76.2 and 72.5%, respectively), the eastern region (23.8 and 22.5%, respectively), and the northern region (5.0% for B′). Heterosexuals comprised 58.7% of people with strain B and 90% of those with strain B′, whereas 41.3% of B and 10% of B′ were MSM. Subtype C was identified mainly in the PRD region (89.8%), including Guangzhou (34.7%), Jiangmen (20.4%), Zhongshan (20.4%), Huizhou (10.2%), and Zhaoqing (4.1%). There were also C infections in the eastern region, including Shantou (8.2%) and Chaozhou (2.0%). Heterosexual (81.6%), IDU (16.3%), and MCT (2.0%) were the risk factors for C infections. Subtype G was identified only in Guangzhou, and the risk factor was heterosexual transmission.