Yiming Shao

Surface-Engineered Gold Nanorods: Promising DNA Vaccine Adjuvant for HIV-1 Treatment

With the intense international response to the AIDS pandemic, HIV vaccines have been extensively investigated but have failed due to issues of safety or efficacy in humans. Adjuvants for HIV/AIDS vaccines are under intense research but a rational design approach is still lacking. Nanomaterials represent an obvious opportunity in this field due to their unique physicochemical properties. Gold nanostructures are being actively studied as a promising and versatile platform for biomedical application. Herein, we report novel surface-engineered gold nanorods (NRs) used as promising DNA vaccine adjuvant for HIV treatment. We have exploited the effects of surface chemistry on the adjuvant activity of the gold nanorod by placing three kinds of molecules, that is, cetyltrimethylammonium bromide (CTAB), poly(diallydimethylammonium chloride) (PDDAC), and polyethyleneimine (PEI) on the surface of the nanorod. These PDDAC- or PEI-modified Au NRs can significantly promote cellular and humoral immunity as well as T cell proliferation through activating antigen-presenting cells if compared to naked HIV-1 Env plasmid DNA treatment in vivo. These findings have shed light on the rational design of low-toxic nanomaterials as a versatile platform for vaccine nanoadjuvants/delivery systems.

Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003–11) : a national observational cohort study

BACKGROUND On the basis of the results of the randomised clinical trial HPTN 052 and observational studies, WHO has recommended that antiretroviral therapy be offered to all HIV-infected individuals with uninfected partners of the opposite sex (serodiscordant couples) to reduce the risk of transmission. Whether or not such a public health approach is feasible and the outcomes are sustainable at a large scale and in a developing country setting has not previously been assessed. METHODS In this retrospective observational cohort study, we included treated and treatment-naive HIV-positive individuals with HIV-negative partners of the opposite sex who had been added to the national HIV epidemiology and treatment databases between Jan 1, 2003 and Dec 31, 2011. We analysed the annual rate of HIV infection in HIV-negative partners during follow-up, stratified by treatment status of the index partner. Cox proportional hazards analyses were done to examine factors related to HIV transmission. FINDINGS Based on data from 38,862 serodiscordant couples, with 101,295·1 person-years of follow-up for the seronegative partners, rates of HIV infection were 2·6 per 100 person-years (95% CI 2·4-2·8) among the 14,805 couples in the treatment-naive cohort (median baseline CD4 count for HIV-positive partners 441 cells per μl [IQR 314-590]) and 1·3 per 100 person-years (1·2-1·3) among the 24,057 couples in the treated cohort (median baseline CD4 count for HIV-positive partners 168 cells per μl [62-269]). We calculated a 26% relative reduction in HIV transmission (adjusted hazard ratio 0·74, 95% CI 0·65-0·84) in the treated cohort. The reduction in transmission was seen across almost all demographic subgroups and was significant in the first year (0·64, 0·54-0·76), and among couples in which the HIV-positive partner had been infected by blood or plasma transfusion (0·76, 0·59-0·99) or heterosexual intercourse (0·69, 0·56-0·84), but not among couples in which the HIV-positive partner was infected by injecting drugs (0·98, 0·71-1·36). INTERPRETATION Antiretroviral therapy for HIV-positive individuals in serodiscordant couples reduced HIV transmission across China, which suggests that the treatment-as-prevention approach is a feasible public health prevention strategy on a national scale in a developing country context. The durability and generalisability of such protection, however, needs to be further studied. FUNDING Chinese Governments 12th Five-Year Plan, the National Natural Science Foundation of China, and the Canadian International Development Research Centre.

Relationship between syphilis and HIV infections among men who have sex with men in Beijing, China.

Background: Little is known about risk of HIV and other STDs among men who have sex with men (MSM) in China. Objective: To survey the prevalence and risk factors of HIV and syphilis and evaluate correlation of two infections among MSM in the Chinese capital city. Methods: A community-based sample of 526 MSM was recruited in 2005 through Internet advertising, community outreach, and peer referring. Interviewer-administered interviews were conducted to collect information on demographics and sexual and other risk behaviors, and blood samples were collected to test for syphilis and HIV infections. Results: Seventeen (3.2%) participants were HIV seropositive and 59 (11.2%) syphilis seropositive. Sixty-four percent of participants were migrants who did not have Beijing residence. Forty percent had >10 lifetime male sex partners and 28.8% reported having ever had sex with women. Consistent condom use with primary male sex partners ranged from 21% to 24%, with nonprimary male sex partners from 35% to 42%, and with female partners around 33%. Illicit drug use was not common; only 2.5% reported using Ecstasy or ketamine in the past 6 months. Multivariate logistic regression analyses demonstrated that >10 lifetime male sex partners were independently associated with seropositivity of both syphilis (OR, 1.9; 95% CI, 1.1–3.4) and HIV (OR, 4.3; 95% CI, 1.4–13.6). In addition, HIV infection is significantly associated with syphilis seropositivity (OR, 3.8; 95% CI, 1.3–10.8). Conclusions: High mobility, multiple sexual partners, and high prevalence of unprotected sex behaviors and syphilis infection suggest a potential rapid spread of HIV in Chinese MSM.

Syphilis among female sex workers in southwestern China: potential for HIV transmission.

Objective: The objective of this study was to investigate the prevalence and risk factors of syphilis infection among female sex workers in a southwestern Chinese city along a drug trafficking route. Methods: From December 2004 to January 2005, 343 female sex workers (FSWs) were recruited through community outreach and peer referring. Confidential questionnaire interviews were administered to collect information on sexual and other sexually transmitted diseases/HIV risk behaviors. Cervical and blood samples were collected to test for syphilis and HIV antibodies and Neisseria gonorrhoeae infection; Condyloma acuminatum infection was diagnosed clinically. Results: Of 343 FSWs, 15.7% were infected with syphilis. The prevalence of HIV, gonorrhea, and C. acuminatum was 0.6%, 2.0%, and 1.5%, respectively. The subtype of 2 HIV-1 infections was both CRF 07BC. Nearly 10% of FSWs reported using illicit drugs. Consistent use, inconsistent use, and never use of condoms with commercial sex clients in the last month were reported by 53.9%, 38.5%, and 7.6% FSWs, respectively. Longer duration of sex work (odds ratio [OR] = 1.98; 95% confidence interval [CI] = 1.08–3.62), working at low-end establishments (OR = 2.03; 95% CI = 1.10–3.76), and if primary sex partners had sex with other women in the past 6 months (OR = 2.06; 95% CI = 1.08–3.91) were independently associated with syphilis infection. Conclusions: High prevalence of syphilis and overlapped unprotected commercial sex and drug using behaviors among FSWs along a drug-trafficking route may suggest a potential for rapid spread of HIV from injection drug users to FSWs and then to the general population and underscore the urgency of preventive interventions to break the bridge of FSWs for HIV/sexually transmitted disease spread.

The rapidly expanding CRF01_AE epidemic in China is driven by multiple lineages of HIV-1 viruses introduced in the 1990s.

Objectives:We sought to comprehensively analyze the origin, transmission patterns and sub-epidemic clusters of the HIV-1 CRF01_AE strains in China. Methods:Available HIV-1 CRF01_AE samples indentified in national molecular epidemiologic surveys were used to generate near full-length genome (NFLG) sequences. The new and globally available CRF01_AE NFLG sequences were subjected to phylogenetic and Bayesian molecular clock analyses, and combined with epidemiologic data to elucidate the history of CRF01_AE transmission in China. Results:We generated 75 new CRF01_AE NFLG sequences from various risk populations covering all major CRF01_AE epidemic regions in China. Seven distinct phylogenetic clusters of CRF01_AE were identified. Clusters 1, 2 and 3 were prevalent among heterosexuals and IDUs in southern and southwestern provinces. Clusters 4 and 5 were found primarily among MSM in major northern cities. Clusters 6 and 7 were only detected among heterosexuals in two southeast and southwest provinces. Molecular clock analysis indicated that all CRF01_AE clusters were introduced from Southeast Asia in the 1990s, coinciding with the peak of Thailands HIV epidemic and the initiation of Chinas free overseas travel policy for their citizens, which started with Thailand as the first destination country. Conclusion:Chinas HIV-1 epidemic of sexual transmissions, was initiated by multilineages of CRF01_AE strains, in contrast to the mono-lineage epidemic of B′ strain in former plasma donors and IDUs. Our study underscores the difficulty in controlling HIV-1 sexual transmission compared with parenteral transmission.

Incidence of HIV-1, syphilis, hepatitis B, and hepatitis C virus infections and predictors associated with retention in a 12-month follow-up study among men who have sex with men in Beijing, China.

Objective:To investigate the incidence of HIV-1, syphilis, hepatitis B virus (HBV), and hepatitis C virus (HCV) infections and predictors associated with retention in a 12-month follow-up study among men who have sex with men (MSM) in Beijing, China. Methods:A total of 507 eligible seronegative MSM were enrolled. Study participants were tested for HIV-1, syphilis, HBV, and HCV and counseled at the baseline, 6-month, and 12-month follow-up visits. The retention rates were analyzed as a function of demographic, behavioral, and recruitment variables. Results:Of the 507 participants, 86.2% (437) were retained in the cohort at the 12-month follow-up visit. The incidence rates were 2.6 per 100 person-years [95% confidence interval (CI): 1.1% to 4.1%] for HIV-1 infection, 16.9 per 100 person-years for syphilis (95% CI: 12.4% to 21.3%), 3.3 per 100 person-years for HBV (95% CI: 1.5% to 5.1%), and 0.2 per 100 person-years for HCV (95% CI: 0% to 0.7%). Higher education (adjusted odds ratio = 1.94, 95% CI: 1.03 to 3.66) and appearing at the 6-month follow-up visit (adjusted odds ratio = 26.15, 95% CI: 13.44 to 50.89) were significantly associated with 12-month retention. Conclusions:HIV, syphilis, and HBV incidence are high among MSM. Intensified intervention is needed urgently. Widespread screening for HIV, syphilis, HBV, and HCV in this group should be considered as measures for control.

Emerging HIV infections with distinct subtypes of HIV-1 infection among injection drug users from geographically separate locations in Guangxi province, China

Heroin users from Guangxi province, a southern province of China that borders Vietnam in the south and Yunnan province in China in the west, were studied for prevalence and risk factors for HIV-1 infection. Viral env sequences from HIV-1-positive individuals were also determined for subtypes of HIV-1. The overall HIV prevalence among 227 heroin users was 40%. Most had used drugs for < or = 3 years. Sharing of injection equipment and unprotected sex were significantly associated with HIV-1 infection. Subtypes C and E HIV-1 were detected in infected heroin users and were sharply segregated in two geographic locations: only subtype C was found in a border city with Yunnan province, whereas only subtype E was found in a city bordering northern Vietnam. HIV-1 strains within each subtype were remarkably homogenous, with a mean intersubject DNA distance of 2.32% for subtype E and 1.13% for subtype C, respectively. Phylogenetic analysis of C2-V5 region of Guangxi subtype E env sequences revealed significant clustering with subtype E sequences from southern Vietnam and Cambodia. These results suggest that HIV-1 infection among heroin users in Guangxi represents two emerging epidemics initiated from distinct sources: one from Vietnam and another from Yunnan province. Factors associated with HIV-1 infection were not restricted to injection practices. Unprotected sexual behaviors are likely to increase the probability of HIV transmission beyond this high-risk population. Designing and implementing effective intervention strategies targeted toward both injection drug use and high risk sexual behavior are urgently needed to further reduce HIV-1 spread in China.

A Peptide-Based Nanofibrous Hydrogel as a Promising DNA Nanovector for Optimizing the Efficacy of HIV Vaccine

This report shows that a nanovector composed of peptide-based nanofibrous hydrogel can condense DNA to result in strong immune responses against HIV. This nanovector can strongly activate both humoral and cellular immune responses to a balanced level rarely reported in previous studies, which is crucial for HIV prevention and therapy. In addition, this nanovector shows good biosafety in vitro and in vivo. Detailed characterizations show that the nanofibrous structure of the hydrogel is critical for the dramatically improved immune responses compared to existing materials. This peptide-based nanofibrous hydrogel shows great potential for efficacious HIV DNA vaccines and can be potentially used for delivering other vaccines and drugs.

Risk factors of HIV infection and prevalence of co-infections among men who have sex with men in Beijing, China.

Objectives:To investigate risk factors related to HIV infection and the prevalence of selected infections, especially sexually transmitted infections (STI) among men who have sex with men (MSM). Design:A cross-sectional study including questionnaire and blood sample collection. Methods:Between January 2005 and December 2006, 753 MSM were recruited through the voluntary counselling and testing (VCT) clinic at the Chaoyang District Centers for Disease Control and Prevention in Beijing. Sera samples were collected and tested for HIV, syphilis, Chlamydia trachomatis, Ureaplasma urealyticum, Toxoplasma gondii, and hepatitis C virus (HCV). Statistical analyses were performed to identify factors related to HIV and STI, as well as other co-infections. Results:The prevalence of HIV-1 infection among MSM attending the VCT clinic was 2.1%. Among all MSM, 7.0% had syphilis, 5.6% Chlamydia, 4.4% U. urealyticum, 2.5% T. gondii and 0.8% HCV (13.8% had one or more). Among HIV-negative MSM, 13.3% had one of these infections, whereas among HIV-positive MSM, 93.8% had serological evidence of one or more co-infections (P < 0.0001). Individuals with HIV infection were significantly more likely to have had more male sex partners or to report frequent receptive anal sex in the past 6 months. Conclusion:Serological evidence of infection with any of five STI or HIV-relevant conditions was far higher in HIV-infected than HIV-uninfected MSM. Co-infection in HIV-positive men was most frequent with syphilis. Our data suggest that strategies for HIV/AIDS and STI prevention and control among MSM should be synchronized.

Incidence of Hiv, hepatitis C and hepatitis B viruses among injection drug users in southwestern China: a 3-year follow-up study

Objective:To investigate the incidence rates of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among injection drug users (IDU) in a drug trafficking city in southwest China. Design:A prospective cohort study. Methods:A cohort of 333 HIV-seronegative IDU was followed for 36 months from November 2002 and evaluated every 6 months for seroconversions to HIV and HCV antibodies as well as hepatitis B surface antigen. Questionnaire interviews were conducted to collect information about risk behaviors. Results:Some 68.8% of subjects completed the last follow-up survey. A total of 14 HIV, 47 HCV and 51 HBV seroconversions were observed over the 36-month follow-up period, yielding average incidence rates of 2.3 per 100 person-years for HIV, 33.3 for HCV and 11.3 for HBV. Multivariate Poisson regression analyses showed that factors independently associated with HIV seroconversion were minority ethnicity and greater frequent sharing of needles or syringes in the past 3 months one or more times per week. Predictors of HCV seroconversion included being female, greater frequent drug use in the past 3 months seven or more times per week, and frequent sharing of needles or syringes in the past 3 months one or more times per week. Conclusion:Blood-borne infections continue to spread, but at lower rates with time among IDU in a southwestern Chinese city where intervention programmes have existed for a few years. Rigorous implementation of harm reduction programmes may have reduced seroconversion to blood-borne infections among targeted high-risk populations.