Huixin Liu

Emerging Trends of HIV Drug Resistance in Chinese HIV-Infected Patients Receiving First-Line Highly Active Antiretroviral Therapy: A Systematic Review and Meta-Analysis

BACKGROUND Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in AIDS-related morbidity and mortality through sustained suppression of human immunodeficiency virus (HIV) replication and reconstitution of the immune response. Settings like China that experienced rapid HAART rollout and relatively limited drug selection face considerable challenges in controlling HIV drug resistance (DR). METHODS We conducted a systematic review and meta-analysis to describe trends in emergent HIV DR to first-line HAART among Chinese HIV-infected patients, as reflected in the point prevalence of HIV DR at key points and fixed intervals after treatment initiation, using data from cohort studies and cross-sectional studies respectively. RESULTS Pooled prevalence of HIV DR from longitudinal cohorts studies was 10.79% (95% confidence interval [CI], 5.85%-19.07%) after 12 months of HAART and 80.58% (95% CI, 76.6%-84.02%) after 72 months of HAART. The HIV DR prevalence from cross-sectional studies was measured in treatment intervals; during the 0-12-month HAART treatment interval, the pooled prevalence of HIV DR was 11.1% (95% CI, 7.49%-16.14%), which increased to 22.92% at 61-72 months (95% CI, 9.45%-45.86%). Stratified analyses showed that patients receiving a didanosine-based regimen had higher HIV DR prevalence than those not taking didanosine (15.82% vs 4.97%). Patients infected through former plasma donation and those receiving AIDS treatment at village clinics had higher HIV DR prevalence than those infected through sexual transmission or treated at a county-level hospital. CONCLUSIONS Our findings indicate higher prevalence of HIV DR for patients with longer cumulative HAART exposure, highlighting important subgroups for future HIV DR surveillance and control.

Effectiveness of ART and condom use for prevention of sexual HIV transmission in serodiscordant couples: a systematic review and meta-analysis.

Background Consistent and correct condom use and suppressive antiretroviral therapy for the infected partner are two of the primary strategies recommended for prevention of heterosexual HIV transmission in serodiscordant couples today. The applied effectiveness of treatment as a prevention strategy in China is still under investigation, and much less is known about its effects in the presence of other prevention strategies such as consistent condom use. Methods We conducted a systematic search in PubMed and three Chinese language databases to identify relevant articles for the estimation of relative effectiveness of a) consistent condom use and b) ART use by index partners for preventing HIV transmission in serodiscordant couples. We also estimated the prevention effectiveness of ART stratified by condom use level and the prevention effectiveness of consistent condom use stratified by ART use level. Results Pooled results from the eleven eligible studies found a pooled HIV seroconversion incidence of 0.92 cases per 100 person years (PY) among HIV-negative spouses whose index partners were taking ART versus 2.45 cases per 100 PY in untreated couples. The IRR comparing seroconversion in couples where the index-partner was on ART versus not on ART was 0.47 (95%CI: 0.43, 0.52), while stratified by condom use, the IRR was 0.33(0.17,0.64). The IRR comparing incidence in couples reporting “consistent condom use” versus those reporting otherwise was 0.02(95%CI:0.01,0.04), after stratified by ART use level, the IRR was 0.01(95%CI: 0.00, 0.06). Conclusions ART use by index partners could reduce HIV transmission in serodiscordant couples, and the effectiveness of this prevention strategy could be further increased with consistent condom use.

A systematic review of cohort studies of the quality of life in HIV/AIDS patients after antiretroviral therapy

The aim of this paper was to review cohort studies that analyze changes in the quality of life of people living with HIV/AIDS. We searched the PubMed and EmBase databases from inception to December 2012 for primary cohort studies of the quality of life of people living with HIV/AIDS after combination antiretroviral therapy (cART). Two independent reviewers screened and selected published studies of quality of life that had been followed up for more than 12 weeks after the beginning of cART. Data from the papers were analyzed to identify common characteristics of the effects of cART on the quality of life of HIV/AIDS patients. Eight cohort studies were found: only four were assessed as high quality and four were assessed as moderate quality. None of the studies described patient selection. Six studies followed the patients for one year or more, and the other studies for less than 6 months. Seven studies reported quality of life had been improved after initiation of cART, and one study reported no change. Previous research suggested that cART improved the quality of life of AIDS patients for a limited time, so further research for longer periods is needed to confirm this outcome.

The prevalence of HIV-1 drug resistance among antiretroviral treatment naïve individuals in mainland China: a meta-analysis.

Background Surveillance of drug resistance in antiretroviral treatment-naïve patients in China is needed to ensure optimal treatment outcomes and control of the human immunodeficiency virus (HIV) epidemic. Methods A systematic literature search was conducted in English and Chinese through PubMed (English), China National Knowledge Infrastructure (Chinese), Chinese Biomedical Literature Database (Chinese), and Wanfang (Chinese). Random effects models were used to calculate the pooled prevalence of transmitted drug resistance and subgroup analyses examined prevalence estimates across time periods, study locations, and study populations. Results Analysis of data from 71 studies (47 in Chinese and 24 in English) yielded a pooled prevalence of transmitted HIV drug resistance to any antiretroviral drug class of 3.64% (95% confidence interval [CI]: 3.00%–4.32%). Rates were significantly high at initial stage of free ART program from 2003 to 2005 (5.18%, 95%CI: 3.13%–7.63%), and were much lower among studies conducted in 2006–2008 (3.02%, 95%CI: 2.03%–4.16%). A slight increase was observed again in the most recent study period from 2009 to 2012 (3.68%, 95%CI: 2.78%–4.69%). Subgroup analysis revealed highest prevalence levels of transmitted drug resistance in Beijing city, and Henan and Hubei provinces (above 5%), and although differences in prevalence rates among risk groups were negligible, men who have sex with men were unique in their relatively large portion of protease inhibitor resistance, a second-line drug of limited availability in China. Conclusions Overall prevalence of transmitted HIV drug resistance in China is classified as “low” by the World Health Organization. However regional and temporal variability suggest a more complex epidemic for which closer HIV drug resistance surveillance is needed. A nationwide HIV drug resistance surveillance system to monitor both treatment-experienced and treatment-naïve patients will be a cornerstone to ensure the effectiveness of treatment scale-up, particularly as China seeks to expand a national policy of antiretroviral treatment as prevention.

Treatment to Prevent HIV Transmission in Serodiscordant Couples in Henan, China, 2006 to 2012

BACKGROUND Antiretroviral therapy (ART) administered in clinical trial settings virtually eliminates the sexual transmission of human immunodeficiency virus (HIV) in serodiscordant couples, but effectiveness of treatment as prevention in the community is debated. Conflicting results from previous analyses in a Chinese cohort underscore the importance of determining effectiveness of ART delivered in resource limited settings. METHODS All available years of data (2006-2012) from local disease control records of HIV patients and their seronegative spouses in Henan Province, China, were analyzed using marginal structural Cox models to estimate the effect of ART in the initially infected partner his or her partners HIV seroconversion risk. RESULTS We observed 157 seroconversion events in 4916 serosdiscordant couples, for an incidence rate of 0.59 cases per 100 person-years (PY) (95% confidence interval [CI], .51-.70). Of these, 84 occurred after the index partner had initiated ART (0.43/100PY; 95% CI, .35-.53) and 73, whereas index partners were untreated (5.87/100 PY; 95% CI, 4.65-7.42). In a marginal structural Cox model weighted for confounding and censoring, the hazard ratio (HR) for HIV transmission was 0.52 (95% CI, .34-.82). ART efficacy varied significantly by time period; least effective in the early phase from 2006 to 2008 (HR, 0.68; 95% CI, .34-1.36) but far more protective from 2009 onward (HR, 0.33; 95% CI, .20-.55). CONCLUSIONS ART can provide HIV-infected persons in resource-limited setting substantial protection against sexual transmission. Effectiveness in the Henan cohort appears to have increased over time, suggesting that quality of care and service infrastructure may be integral to successful use of treatment for prevention.

A Novel Isothermal Assay of Borrelia burgdorferi by Recombinase Polymerase Amplification with Lateral Flow Detection

A novel isothermal detection for recombinase polymerase amplification with lateral flow (LF-RPA) was established for Borrelia burgdorferi (B. burgdorferi) detection in this study. This assay with high sensitivity and specificity can get a visible result without any additional equipment in 30 min. We designed a pair of primers according to recA gene of B. burgdorferi strains and a methodology evaluation was performed. The results showed that the RPA assay based on the recA gene was successfully applied in B. burgdorferi detection, and its specific amplification was only achieved from the genomic DNA of B. burgdorferi. The detection limit of the new assay was about 25 copies of the B. burgdorferi genomic DNA. Twenty Lyme borreliosis patients’ serum samples were detected by LF-RPA assay, real-time qPCR and nested-PCR. Results showed the LF-RPA assay is more effective than nested-PCR for its shorter reaction time and considerably higher detection rate. This method is of great value in clinical rapid detection for Lyme borreliosis. Using the RPA assay might be a megatrend for DNA detection in clinics and endemic regions.

Polymorphism of 41 kD Flagellin Gene and Its Human B-Cell Epitope in Borrelia burgdorferi Strains of China

The 41 kD flagellin of Borrelia burgdorferi (B. burgdorferi) is a major component of periplasmic flagellar filament core and a good candidate for serodiagnosis in early stage of Lyme disease. Here, we chose 89 B. burgdorferi strains in China, amplified the gene encoding the 41 kD flagellin, and compared the sequences. The results showed that genetic diversity presented in the 41 kD flagellin genes of all 89 strains among the four genotypes of B. burgdorferi, especially in the genotype of B. garinii. Some specific mutation sites for each genotype of the 41 kD flagellin genes were found, which could be used for genotyping B. burgdorferi strains in China. Human B-cell epitope analysis showed that thirteen of 15 nonsynonymous mutations occurred in the epitope region of 41 kD flagellin and thirty of 42 B-cell epitopes were altered due to all 13 nonsynonymous mutations in the epitope region, which may affect the function of the antigen. Nonsynonymous mutations and changed human B-cell epitopes exist in 41 kD flagellin of B. burgdorferi sensu lato strains; these changes should be considered in serodiagnosis of Lyme disease.

Genomic Characteristics of Chinese Borrelia burgdorferi Isolates

In China, B. burgdorferi, B.garinii, B. afzelii and B. yangtze sp. nov have been reported; B.garinii and B. afzelii are the main pathogenic genotypes. But until now only one Chinese strain was reported with whole genome sequence. In order to further understand the genomic characteristics and diversity of Chinese Borrelia strains, 5 isolates from China were sequenced and compared with the whole genome sequences of strains in other areas. The results showed a high degree of conservation within the linear chromosome of Chinese strains, whereas plasmid showed a much larger diversity according to the majority genomic information of plasmids. The genome sequences of the five Chinese strains were compared with the corresponding reference strains, respectively, according to the genospecies. Pairwise analysis demonstrates that there are only 70 SNPs between the genomes of CS4 and B31. However, there are many more SNPs between the genomes of QX-S13 and VS116, PD91 and PBi, FP1 and PKo, R9 and Pko, respectively. Gene comparison showed some important different genes. OspA was one of the important different genes. Comparative genomic studies have found that OspA gene sequences of PD91 and R9 had great differences compared with the sequence of B31. OspA gene sequence of R9 had a 96bp deletion; OspA gene of PD91 had two deletions: 9bp and 10 bp. To conclude, we showed the genomic characteristics of four genotype Chinese B. burgdorferi strains. The genomic sequence of B. yangtze sp. nov and differences from B. valaisiana were first reported. Comparative analysis of Chinese strains with the different Borrelia species from other areas will help us to understand evolution and pathogenesis of Chinese Borrelia burgdorferi strains.

Prediction of potential geographic distribution of Lyme disease in Qinghai province with Maximum Entropy model

OBJECTIVE To predict the potential geographic distribution of Lyme disease in Qinghai by using Maximum Entropy model (MaxEnt). METHODS The sero-diagnosis data of Lyme disease in 6 counties (Huzhu, Zeku, Tongde, Datong, Qilian and Xunhua) and the environmental and anthropogenic data including altitude, human footprint, normalized difference vegetation index (NDVI) and temperature in Qinghai province since 1990 were collected. By using the data of Huzhu Zeku and Tongde, the prediction of potential distribution of Lyme disease in Qinghai was conducted with MaxEnt. The prediction results were compared with the human sero-prevalence of Lyme disease in Datong, Qilian and Xunhua counties in Qinghai. RESULTS Three hot spots of Lyme disease were predicted in Qinghai, which were all in the east forest areas. Furthermore, the NDVI showed the most important role in the model prediction, followed by human footprint. Datong, Qilian and Xunhua counties were all in eastern Qinghai. Xunhua was in hot spot areaⅡ, Datong was close to the north of hot spot area Ⅲ, while Qilian with lowest sero-prevalence of Lyme disease was not in the hot spot areas. The data were well modeled in MaxEnt (Area Under Curve=0.980). CONCLUSIONS The actual distribution of Lyme disease in Qinghai was in consistent with the results of the model prediction. MaxEnt could be used in predicting the potential distribution patterns of Lyme disease. The distribution of vegetation and the range and intensity of human activity might be related with Lyme disease distribution.

Effects of patient load and travel distance on HIV transmission in rural China: Implications for treatment as prevention

Background Sustained viral suppression through ART reduces sexual HIV transmission risk, but may require routine access to reliable and effective medical care which may be difficult to obtain in resource constrained areas. We investigated the roles of patient load and travel distance to HIV care clinic on transmission risk in HIV serodiscordant couples in Henan Province, China. Methods Cox proportional hazard models were used to compare HIV transmission events across couples living near, medium, or farther distances from their assigned HIV care clinics, as well as those attending clinics where clinicians bore high versus low patient loads. Results Most (84·4%) of the 3695 serodiscordant couples lived within 10 kilometers of their assigned HIV clinic, and most (73·5%) attended clinics with patient-to-provider ratios of at least 100:1. In adjusted Cox models, attending clinics where clinicians bore average patient loads of 100 or more elevated HIV transmission risk (aHR, 1·50, 95% CI, 1·00–4·84), an effect amplified in village tier clinics (aHR = 1·55; 95% CI, 1·23–6·78). Travel distance was associated with HIV transmission only after stratification; traveling medium distances to village clinics (5-10km) increased transmission risk (aHR = 1·83, 95% CI, 1·04–3·21) whereas traveling longer distances to township or county level clinics lowered transmission risk (aHR = 0·10, 95% CI, 0·01–0·75). Conclusion Higher patient loads at HIV clinics was associated with risk of HIV transmission in our population, particularly at village level clinics. Farther travel distance had divergent effects based on clinic tier, suggesting unique mechanisms operating across levels of resource availability. The resource intensity of long-term HIV treatment may place significant strains on small rural clinics, for which investments in additional support staff or time-saving tools such as point-of-care laboratory testing may bring about impactful change in treatment outcomes.