Increased prevalence and stable clustering rate of HIV-1 transmitted drug resistance strains after 'treat-all' in a megacity of China.

OBJECTIVES: The 'treat-all' strategy was implemented in Shenzhen, China in 2016. The effect of this extensive treatment on transmitted drug resistance (TDR) of HIV is unclear. METHODS: TDR analysis was performed, based on the partial HIV-1 pol gene obtained from the newly reported HIV-1 positive cases from 2011 to 2019 in Shenzhen, China. The HIV-1 molecular transmission networks were inferred to analyse the spread of TDR. Logistic regression was used to identify the potential risk factors with TDR mutations (TDRMs) to cluster. RESULTS: A total of 12 320 partial pol sequences were included in this study. The prevalence of TDR was 2.95% (363/12 320), which increased from 2.57% to 3.52% after 'treat-all'. The TDR prevalence was increased in populations with the characteristics of CRF07_BC, being single, educated to junior college level and above, MSM and male. The sensitivities of viruses to six antiretroviral drugs were decreased. The clustering rate of TDRMs remained stable, and the sequences in the three drug resistance transmission clusters (DRTCs) were mainly found during 2011-16. CRF07_BC and CRF55_01B were the factors associated with TDRMs clustering in the networks. CONCLUSIONS: The 'treat-all' strategy might have contributed to a small increase in TDR, while most of the TDRMs were distributed sporadically, which implies that the 'treat-all' strategy is helpful for the control of TDR in high-risk populations.

Antibody response to the third dose of inactivated COVID-19 vaccine in people living with HIV (PLWH): A longitudinal cohort.

The immunogenicity induced by the third dose of inactivated coronavirus disease 2019 (COVID-19) vaccines in people living with HIV (PLWH) is unclear, and relevant literature is extremely scarce. It is important to add evidence on the humoral immune response induced by the third dose of inactivated COVID-19 vaccine in PLWH. We collected peripheral venous blood for spike receptor binding domain-protein specific immunoglobulin G (S-RBD-IgG) antibody tests at 28 days after the second dose (T1 ), 180 days after the second dose (T2 ) and 35 days after the third dose (T3 ) of inactivated COVID-19 vaccines in PLWH. The differences in S-RBD-IgG antibody levels and specific seroprevalence among T1 , T2 , and T3 time periods were analyzed, and the effects of age, vaccine brand, and CD4+ T cell count on the levels and specific seroprevalence of S-RBD-IgG antibody induced by the third dose in PLWH were examined. The third dose of inactivated COVID-19 vaccines induced strong S-RBD-IgG antibody responses in PLWH. The levels and specific seroprevalence of S-RBD-IgG antibody were significantly higher than those at 28 and 180 days after the second dose and were not affected by vaccine brand or CD4+ T cell count. Younger PLWH produced higher levels of S-RBD-IgG antibody. The third dose of inactivated COVID-19 vaccine showed good immunogenicity in PLWH. It is necessary to popularize the third dose in the PLWH population, especially PLWH who do not respond to two doses of inactivated COVID-19 vaccines. Meanwhile, the durability of the protection provided by the third dose in PLWH must be continuously monitored.

Estimating Changes in Population Size and Behavioral Characteristics in Men Who Have Sex With Men Between 2014 and 2019: Longitudinal Study.

BACKGROUND: Men who have sex with men (MSM) are at high risk for HIV infection. Accurate estimation of the population size and monitoring the risk sexual behavioral change of MSM is of great importance to develop targeted HIV prevention and interventions. OBJECTIVE: The goal of the research was accurate estimation of the population size and monitoring the risk sexual behavioral change of MSM. METHODS: Street interception investigation methods were conducted among males aged 16 years and older in selected sites in Shenzhen in 2014 and 2019. A population survey was used to estimate the population size of MSM. Logistic regression analysis was applied to evaluate the difference in behavioral characteristics in MSM from 2014 to 2019. RESULTS: In this study, we surveyed 10,170 participants in 2014, of whom 448 (4.41%, 95% CI 4.01%-4.80%) participants were men who have ever had sex with another man (MSMe) and 229 (2.25%, 95% CI 1.96%-2.54%) were men who had sex with another man in the previous 6 months (MSMa). A total of 10,226 participants were surveyed in 2019, of which 500 (4.90%, 95% CI 4.47%-5.31%) and 208 (2.03%, 95% CI 1.76%-2.31%) participants were MSMe and MSMa, respectively. The results showed that the population size of MSM who are active (MSMa) in Shenzhen was 155,469 (2.29%, 95% CI 2.28%-2.30%) in 2014 and 167,337 (2.05%, 95% CI 2.04%-2.06%) in 2019. It was estimated that there were about 12,005,445 (2.04%, 95% CI 2.04%-2.04%) MSMa in China in 2019. Compared with 2014, the MSMa in 2019 were more likely to seek sex partners through mobile phone apps and less likely to have male and female sex partners in addition to having inconsistent condom use and more than 6 sex partners in the previous 6 months. CONCLUSIONS: In Shenzhen, the proportion of MSMa among the general male population was lower in 2019 than in 2014, and the prevalence of HIV risk behavior was reduced in 2019. Although the preferred platform to find male sex partners among MSM has changed, intervention with high-HIV risk MSM could still help to reduce HIV risk behaviors among the whole MSM group. Because MSM prefer to seek sex partners through mobile phone apps, further study is needed to strengthen internet interventions with high-HIV risk MSM to curb the spread of HIV.

IgG Antibody Responses and Immune Persistence of Two Doses of BBIBP-CorV Vaccine or CoronaVac Vaccine in People Living with HIV (PLWH) in Shenzhen, China.

The purpose of this study was to preliminarily evaluate the immunogenicity and immune persistence of inactivated SARS-CoV-2 vaccines in PLWH in the real world. We collected blood samples from 132 PLWH aged 18−59 years who were vaccinated with two doses of BBIBP-CorV vaccine (Sinopharm) or CoronaVac vaccine (SinoVac) at 28 ± 7 days and 180 ± 20 days the after second dose, to detect the level of Spike receptor binding domain-protein specific IgG (S-RBD-IgG) by using chemiluminescence. We found that the BBIBP-CorV vaccine or the CoronaVac vaccine induced lower S-RBD-IgG antibody seropositivity rates and levels in PLWH than in healthy controls (HCs). The BBIBP-CorV vaccine or the CoronaVac vaccine induced lower humoral immune responses in PLWH, having lower CD4+T cell counts (<350 cells/µL) compared to PLWH, and having higher CD4+T cell counts (≥350 cells/µL) after a second dose of vaccination. The BBIBP-CorV vaccine or the CoronaVac vaccine induced lower S-RBD-IgG antibody levels in PLWH, having CD4+T cell counts ≥350 cells/µL compared to HCs. No negative effects were observed in terms of the CD4+T cell counts and HIV RNA viral load (VL) of PLWH after vaccination. Ninety-nine PLWH and eighty-three HCs completed a second blood collection for testing; we found a statistically significant decrease in the humoral immune response both in PLWH and HCs from 28 days to 180 days after a second dose of BBIBP-CorV vaccine or CoronaVac vaccine. The S-RBD-IgG antibody induced by the BBIBP-CorV vaccine or the CoronaVac vaccine declined faster in the PLWH population than in the healthy population, and two doses of the BBIBP-CorV vaccine or the CoronaVac vaccine may not be enough to provide PLWH with persistent immunity against SARS-CoV-2. It is necessary for PLWH to be prioritized for a third dose over the healthy population, but the immunogenicity of the third dose of the homologous or heterologous vaccine requires further study.

Use of HIV Post-Exposure Prophylaxis Among Men Who Have Sex With Men in Shenzhen, China: A Serial Cross-Sectional Study.

HIV postexposure prophylaxis (PEP) has been prescribed to non-occupational people in recent years, but the implementation of PEP in China is still unclear. This study sought to examine the PEP use rate and factors associated with PEP in Men who have sex with men (MSM). We recruited HIV-negative MSM through offline methods from 2018 to 2020 in Shenzhen, China. Overall, PEP use increased from 3.92% to 2018, 5.73% in 2019, and 10.29% in 2020. Among 2833 participants who reported their most recent questionnaire, factors associated with PEP use included residence in Shenzhen less than 1 year, sexual intercourse with women, preferred way of finding sexual partners in MSM venues, multiple sexual partners (≥ 2), condom use, lubricant use, viagra use, less use of rush popper, HIV-related services and interest in initiating Pre-exposure prophylaxis (PrEP). The implementation of the PEP plan should focus on the groups that may be at risk of HIV infection and their continued risky behaviours. For the inappropriate use of PEP, PEP publicity should guide MSM to choose regular hospitals and strengthen HIV testing before and after PEP.

Molecular surveillance of HIV-1 newly diagnosed infections in Shenzhen, China from 2011 to 2018.

OBJECTIVES: Shenzhen is suffering severe HIV epidemic. No systematic surveillance on high risk populations, HIV genetic diversity, transmitted drug resistance (TDR) and molecular transmission clusters (MTCs) have been reported yet. In this study, we described them based on newly diagnosed HIV positive cases from 2011 to 2018 in Shenzhen city, China. METHODS: Plasma samples of newly reported HIV positive cases in Shenzhen, China were collected from 2011 to 2018. The HIV pol gene was amplified and sequenced for subtyping, genetic characterization, TDR and phylogenetic analysis. Demographic and risk characteristics associated with transmitted drug resistance-associated mutations (TDRAMs) and MTCs were explored by using logistic regression analyses. RESULTS: 10,378 HIV pol sequences were successfully obtained from newly diagnosed patients with available background information. The most prevalent HIV-1 subtype was CRF07_BC (40.92%). CRF07_BC, CRF55_01B and URFs increased across years. Total TDR was 6.02% during 2011 to 2018. CRF01_AE, CRF08_BC, CRF55_01B and subtype B were more likely to be associated with TDRAMs than CRF07_BC. 4460 (42.98%) patients were infected with strains included in MTCs. Patients younger than 30 and over 50 years were more likely to cluster. CONCLUSIONS: The prevalence of HIV-1 drug resistance and molecular transmission clusters in Shenzhen should raise a high alert. Interventions targeting on patients with strains locating in MTCs should be considered to improve prevention effect in Shenzhen.

Independent epidemic patterns of HIV-1 CRF01_AE lineages driven by mobile population in Shenzhen, an immigrant city of China.

Shenzhen, a city with >12 million migrant population, may play a key role in the spread of human immunodeficiency virus (HIV)-1 in China. The transmission dynamics of CRF01_AE, a predominant subtype in Shenzhen, is a good model to characterize the impact of human mobility on HIV-1 epidemic locally and nationally. We used phylodynamic and phylogeographic methods to estimate the viral transmission dynamics and migration trajectory of variable lineages based on 1,423 CRF01_AE sequences in Shenzhen sampled between 2006 and 2015. Eleven lineages of CRF01_AE were detected in Shenzhen. Of those, four main lineages originated during the 1990s. Their basic viral reproduction number (R 0) ranged 1.96-3.92. The effective viral reproduction number (R e ) of two lineages prevalent among heterosexuals/people who inject drugs had reduced <1 at the end of sampling, and the main sources were the intra-provincial immigrants (72 per cent) for one and local residents of Shenzhen (91 per cent) for another. Within two lineages among men who have sex with men (MSM), R e had been above or close to 1 at the end of sampling, and the immigrants from Jiangxi/Shaanxi and Hubei as sources accounted for 93 per cent and 68 per cent of all viral migration events, respectively. Moreover, no obvious recipients were found throughout the viral migration history for any lineage. Our findings demonstrate that HIV epidemic is declining in Shenzhen, which coincided with the initiation of the interventions during the 2000s. However, the obvious differences of the epidemic patterns between lineages emphasize the importance of further targeting interventions and continued molecular tracing, focusing on high-risk transmission sources among MSM.

Recreational drug use and risk of HIV infection among men who have sex with men: A cross-sectional study in Shenzhen, China.

BACKGROUND: Recreational drug use has increased in recent years, especially among MSM, and has been found to be associated with higher risk of HIV infection. However, there is limited information about current recreational drug use among MSM in Shenzhen which is an international gateway city to China with a rapidly expanding MSM population. METHODS: A cross-sectional survey among MSM in Shenzhen was conducted and was used to collected information on demographics, sexual behavior and drug use via questionnaires. Serologic results on HIV and syphilis were obtained from laboratory assays. We performed logistic regression analysis to evaluate correlates with drug use. RESULTS: Among the 1935 MSM surveyed, 12.7% reported use of recreational drugs in the past six months. Rush poppers had become the most frequently used drug (10.6%). Risk factors associated with the use of recreational drugs included being unmarried, non-Han ethnicity, having high education level, seeking male sex partners via the internet, having multiple male sex partners, performing receptive role during anal sex, and having unprotected anal intercourse. Recreational drug use was significantly associated with higher risk of both HIV and syphilis infections (aOR:1.89, 95% CI:1.28-2.79; aOR:1.79, 95% CI:1.25-2.60, respectively). CONCLUSIONS: Recreational drug use is associated with increased risk of HIV and syphilis infections among MSM in Shenzhen. Rush poppers were the most popular recreational drug. This finding suggests the need for targeted prevention and behavioral intervention programs to control the recreational drug use, and to reduce HIV and other sexually transmitted diseases among MSM in Shenzhen and internationally.

The dynamics of the HIV epidemic among men who have sex with men (MSM) from 2005 to 2012 in Shenzhen, China.

HIV-1 epidemics among MSM are a major public health concern in China, especially in large cities. This study sought to better understand the dynamics of HIV molecular epidemiology among MSM in Shenzhen, a rapidly developing city with over 13.8 million people. HIV-1 pol sequences were obtained from 996 (53.5%) of 1862 HIV-infected MSM and 403(9.0%) of 4498 heterosexuals and injection drug users in Shenzhen, China from 2005-2012. Eight HIV-1 subtypes and some inter-subtype recombinants were identified among sampled MSM with CRF07_BC (39.1%) and CRF01_AE (35.1%) being the most predominant. From 2006 to 2012, the prevalence of CRF07_BC and CRF55_01B rapidly increased, while the prevalence of subtypes B and CRF01_AE gradually decreased. The genetic distances within CRF07_BC and CRF55_01B groups were significantly lower than within CRF01_AE and B groups. The vast majority (90.3%) of HIV-1 infected MSM in Shenzhen were migrants who came from 31 of the 34 provinces of China, and these migrants had significantly different HIV-1 subtype distributions from the local MSM. This study highlighted the importance of CRF07_BC and migrants in the changing HIV epidemic among MSM in China, and provides a molecular epidemiology framework for understanding how HIV-1 epidemics can change in large cities with diverse risk groups.

Determinants of recent HIV testing among male sex workers and other men who have sex with men in Shenzhen, China: a cross-sectional study.

We recruited 510 male sex workers (also referred as 'money boys' (MBs) and 533 other men who have sex with men (MSM) to investigate determinants of recent (last year) HIV testing in Shenzhen, China. Overall, 43% of MBs and 48% of other MSM reported having been tested for HIV in the last year. The most important determinant of testing among MBs was having multiple anal sex partners; among other MSM, the most important determinants were having a homosexual orientation and having a history of sexually transmissible infection. For MBs, education programs are needed to increase their awareness of actual HIV risk. For other MSM, destigmatising programs are needed.

Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naïve HIV-mono-infected and HIV/HCV-co-infected Chinese.

Human Immunodeficiency Virus (HIV) infection and the resultant Acquired Immunodeficiency Syndrome (AIDS) epidemic are major global health challenges; hepatitis C virus (HCV) co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27), a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

A comparison of HIV infection and related risk factors between money boys and noncommercial men who have sex with men in Shenzhen, China.

BACKGROUND: HIV transmission among men who have sex with men (MSM) has become an increasing concern in China. Money boys (MBs) are a subgroup of MSM who sell sex to men. Direct comparison of HIV prevalence and related risk factors between MB and noncommercial MSM (ncMSM) has rarely been done. This study was conducted to make the comparison. METHODS: Eight hundred fifty MBs and 801 ncMSM were parallel recruited in Shenzhen by time-location sampling. Their behavioral and serologic data on HIV and syphilis were collected and compared. Multiple logistic regression analysis was performed to evaluate the determinants for HIV risk in MBs and ncMSM, respectively. RESULTS: The prevalence of HIV was 4.5% in MBs and 7.0% in ncMSM. Although MBs tended to have more male partners than ncMSM, they were more likely to report a consistent condom use in male anal intercourse, especially in commercial sex. Noncommercial MSM were more likely to visit parks and saunas instead of bars, massage centers, recreational centers, and home-based venues. Syphilis infection and recruitment venue were associated with HIV infection in both MBs and ncMSM. Being from a hometown with a high HIV prevalence and without a male partner from Hong Kong were found to be risk factors for HIV infection in MBs, and early sexual debut was a risk factor in ncMSM. CONCLUSION: Money boys differed from ncMSM in the rate of HIV infection and some sexual characteristics and behaviors. Formatting separate interventions specifically targeting the 2 subgroups may be necessary.

[The influence of T lymphocyte activation on HIV-1 susceptibility of Han Chinese].

OBJECTIVE: To explore the influence of T lymphocyte activation on HIV-1 susceptibility of Han Chinese. METHODS: In 2008, 37 HIV-1 highly exposed persistently seronegative individuals (ESNs) and 101 healthy controls were screened from Shenzhen. Flow cytometer was used to assay the expression difference of HIV-1 infection related co-receptor, the difference between the two groups were analyzed by Mann-Whitney U statistics methods. RESULTS: T cell HLA-DR(+) CD4 T cells and HLA-DR(+) expression of ESNs (12.64 (5.94 - 21.90), 21.12 (10.74 - 30.21)) were all significantly lower than that of healthy controls (22.52 (7.91 - 58.60), 32.28 (14.72 - 67.82)) (P values all < 0.05). T cell CD45RA-RO(+), CCR5(+)CD4 expression of ESNs (58.68 (49.06 - 72.44), 21.93 (15.84 - 25.89)) were all significantly higher than that of healthy controls (53.17 (42.63 - 63.21), 16.14 (11.94 - 21.98)) (P values all < 0.05). T cell CXCR4(+)CD4 T cells expression of ESNs (93.67 (92.17 - 94.96)) was significantly lower than that of healthy controls (95.16 (92.99 - 96.77)) (P values all < 0.05). Healthy controls and ESNs could be divided into low expression group and high expression group according to HLA-DR(+)CD8 T cells bimodal distribution. A total of 89.2% (33/37) ESNs fell into HLA-DR + CD8 low expression group, and 58.4% (59/101) of the healthy controls located in low expression group (P < 0.05). CONCLUSION: To Han Chinese, the low activation status of T lymphocyte has significant correlation with HIV-1 low susceptibility.

A comparison of HIV infection and related risks among male sex workers in different venues in Shenzhen, China.

Different risks of HIV infection have been reported among different types of male sex workers (MSW). In order to compare the prevalence of HIV infection and related risk behaviors of MSW in different venues in Shenzhen, China, a time-location sampling survey was conducted in 2008. 5.1% of the 394 MSWs were tested positive for HIV, with 6.9% in those working in parks (PMSW), 11.3% in small family clubs (FMSW) and 1.7% in entertainment venues. PMSWs and FMSWs reported a higher proportion of self-identified homosexual/gay. Moreover, FMSWs reported a lower coverage of HIV-related education and services and were more likely to self-report coming from provinces with higher HIV prevalence. The results indicated that MSWs in small venues and parks were comparatively at higher risk of being infected and suggested that current HIV preventive intervention needs to be expanded to the small venues in Shenzhen.

HIV prevalence and related risk factors among male sex workers in Shenzhen, China: results from a time-location sampling survey.

BACKGROUND: HIV transmission among men who have sex with men has recently become a major concern in China. Little is known, however, about HIV transmission among male sex workers (MSW). This study aimed to investigate HIV infection prevalence and risk factors among MSW in Shenzhen, China. MATERIALS AND METHODS: Following formative research, a cross-sectional study was conducted using time-location sampling among MSW in Shenzhen, from April to July 2008. Behavioural and serological data on HIV and syphilis were collected. The risk factors for HIV infection were analysed using a logistic regression model. RESULTS: In total, 394 MSW were recruited for the survey. The prevalence of HIV and syphilis among these workers was 5.3% and 14.3%, respectively. Only a quarter of the MSW self-identified as homosexual. More than 70% had sex with both men and women. HIV-related knowledge levels were high regardless of HIV serostatus. Consistent condom use was low (37.1%) and varied by type of sexual partner. Factors including more non-commercial male partners, working in small home-based family clubs, being drunk before sexual intercourse, having a history of HIV tests, syphilis infection and a short period of residence in Shenzhen were associated with an increased risk of HIV infection. CONCLUSIONS: High-risk sexual practices were common among MSW regardless of their high level of HIV awareness. The working venues were associated with HIV infection and a recent test for HIV was a potential predictor of HIV infection. The time-location sampling method was found to be an appropriate way of recruiting MSW for this study, especially those without fixed working places.

[Molecular epidemiological survey on HIV-1 among the injecting drug users population in Shenzhen].

OBJECTIVE: To study the prevalent status of human immunodeficiency virus-1 (HIV-1) subtypes in IDU (injecting drug users) population in Shenzhen and to study their source of infection in order to predict the epidemic trend and evolution. METHODS: 166 HIV-1 positive plasma from the IDUs was collected from 1996 to 2008. HIV-1 env genes were amplified by nested-PCR from RNA. The C2-V3 regions (450 bp) of HIV-1 env were sequenced for analyses. Phylogenetic analyses were performed on the nucleotide sequence data. RESULTS: Among 166 samples, there were 6 HIV-1 strains including CRF01_AE, CRF08_BC, CRF07_BC 3 circulating recombinant forms (CRFs) and B', C, A1 3 subtypes. Data from the genotype analyses showed that 65.06% (108/166) were CRF01_AE, 19.88% (33/166) were CRF07_BC, 6.02% (10/166) were CRF08_BC, 7.23% (9/166) were subtype B', 0.60% (1/166) were subtype C and 1.20% (2/166) were subtype A1. Phylogenetic tree analysis showed that some of HIV-1 clusters defined in CRF01_AE, CRF07_BC and subtype B' in different time groups. Significant increase of gene distance in CRF01_AE and CRF07_BC strains in the three different periods. CONCLUSION: CRF01_AE and CRF07_BC were the major epidemic CRF strains among the IDU population in Shenzhen while the subtype B', C, A1 and CRF08_BC were also circulating in IDU population in this region. The variation of all different subtypes was increasing through these years.