Accelerated Screening of Alternative DNA Base-Organic Molecule-Base Architectures via Integrated Theory and Experiment.

Organic molecule-mediated noncanonical DNA self-assembly expands the standard DNA base-pairing alphabets. However, only a very limited number of small molecules have been recognized as mediators because of the tedious and complicated experiments like crystallization and microscopy imaging. Here we present an integrative screening protocol incorporating molecular dynamics (MD) for fast theoretical simulation and native polyacrylamide gel electrophoresis for convenient experimental validation. Melamine, the molecule that was confirmed mediating noncanonical DNA base-pairing, and 38 other candidate molecules were applied to demonstrate the feasibility of this protocol. We successfully identified seven stable noncanonical DNA duplex structures, and another eight novel structures with sub-stability. In addition, we discovered that hairpins at both ends can significantly stabilize the noncanonical DNA structures, providing a guideline to design small organic molecule-incorporated DNA structures. Such an efficient screening protocol will accelerate the design of alternative DNA-molecule architectures beyond Watson-Crick pairs. Considering the wide range of potential mediators, it will also facilitate applications such as noncovalent, highly dense loading of drug molecules in DNA-based delivery system and probe design for sensitive detection of certain molecules.

The immunogenicity of an HIV-1 gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy.

OBJECTIVE: The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART). DESIGN: AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4+ T-cell counts greater than 500 cells/µl, and nadir CD4+ T-cell counts greater than 350 cells/µl. METHODS: The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55Gag DNA vaccine at weeks 12 and 24 (arm A); full-length p55Gag DNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm c). The active and placebo vaccines were administered by intramuscular electroporation. RESULTS: There was a modest, but significantly greater increase in the number of conserved elements recognized by CD4+ and/or CD8+ T cells in arm A compared with arm C (P = 0.014). The percentage of participants with an increased number of conserved elements recognized by T cells was also highest in arm A (8/18, 44.4%) vs. arm C (0/10, 0.0%) (P = 0.025). There were no significant differences between treatment groups in the change in magnitude of responses to total conserved elements. CONCLUSION: A DNA-delivered HIV-1 Gag conserved element vaccine boosted by a combination of this vaccine with a full-length p55Gag DNA vaccine induced a new conserved element-directed cellular immune response in approximately half the treated PWH on ART.

Using molecular network analysis to understand current HIV-1 transmission characteristics in an inland area of Yunnan, China.

HIV-1 molecular surveillance provides a new approach to explore transmission risks and targeted interventions. From January to June 2021, 663 newly reported HIV-1 cases were recruited in Zhaotong City, Yunnan Province, China. The distribution characteristics of HIV-1 subtypes and HIV-1 molecular network were analysed. Of 542 successfully subtyped samples, 12 HIV-1 strains were identified. The main strains were CRF08_BC (47.0%, 255/542), CRF01_AE (17.0%, 92/542), CRF07_BC (17.0%, 92/542), URFs (8.7%, 47/542), and CRF85_BC (6.5%, 35/542). CRF08_BC was commonly detected among Zhaotong natives, illiterates, and non-farmers and was mostly detected in Zhaoyang County. CRF01_AE was frequently detected among married and homosexual individuals and mostly detected in Weixin and Zhenxiong counties. Among the 516 pol sequences, 187 (36.2%) were clustered. Zhaotong natives, individuals aged ≥60 years, and illiterate individuals were more likely to be found in the network. Assortativity analysis showed that individuals were more likely to be genetically associated when stratified by age, education level, occupation, and reporting area. The genetic diversity of HIV-1 reflects the complexity of local HIV epidemics. Molecular network analyses revealed the subpopulations to focus on and the characteristics of the risk networks. The results will help optimise local prevention and control strategies.

Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus.

BACKGROUND: Neurocognitive impairment (NCI) in people with HIV (PWH) on antiretroviral therapy (ART) is common and may result from persistent HIV replication in the central nervous system. METHODS: A5324 was a randomized, double-blind, placebo-controlled, 96-week trial of ART intensification with dolutegravir (DTG) + MVC, DTG + Placebo, or Dual - Placebo in PWH with plasma HIV RNA <50 copies/mL on ART and NCI. The primary outcome was the change on the normalized total z score (ie, the mean of individual NC test z scores) at week 48. RESULTS: Of 357 screened, 191 enrolled: 71% male, 51% Black race, 22% Hispanic ethnicity; mean age 52 years; mean CD4+ T-cells 681 cells/µL. Most (65%) had symptomatic HIV-associated NC disorder. Study drug was discontinued due to an adverse event in 15 (8%) and did not differ between arms (P = .17). Total z score, depressive symptoms, and daily functioning improved over time in all arms with no significant differences between them at week 48 or later. Adjusting for age, sex, race, study site, efavirenz use, or baseline z score did not alter the results. Body mass index modestly increased over 96 weeks (mean increase 0.32 kg/m2, P = .006) and did not differ between arms (P > .10). CONCLUSIONS: This is the largest, randomized, placebo-controlled trial of ART intensification for NCI in PWH. The findings do not support empiric ART intensification as a treatment for NCI in PWH on suppressive ART. They also do not support that DTG adversely affects cognition, mood, or weight.

Treatment duration of wrist-ankle acupuncture for relieving post-thyroidectomy pain: A randomized controlled trial.

BACKGROUND: Treatment duration of wrist-ankle acupuncture (WAA) is uncertain for post-thyroidectomy pain relief. OBJECTIVE: This study evaluated the effect of different WAA treatment duration on post-operative pain relief and other discomforts associated with thyroidectomy. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This randomized controlled trial was conducted at a single research site in Guangzhou, China. A total of 132 patients receiving thyroidectomy were randomly divided into the control group (sham WAA, 30 min) and three intervention groups (group 1: WAA, 30 min; group 2: WAA, 45 min; group 3: WAA, 60 min), with group allocation ratio of 1:1:1:1. Acupuncture was administered within 1 hour of leaving the operating room. OUTCOMES AND MEASURES: Primary outcome was patients' pain at the surgical site assessed by visual analogue scale (VAS) at the moment after acupuncture treatment (post-intervention). Secondary outcomes included the patients' pain VAS scores at 6, 12, 24, 48 and 72 h after the thyroidectomy, the 40-item Quality of Recovery (QoR-40) score, the grade of post-operative nausea and vomiting (PONV), and the use of additional analgesic therapy. RESULTS: The adjusted mean difference (AMD) in VAS scores from baseline to post-intervention in group 1 was -0.89 (95% confidence interval [CI], -1.02 to -0.76). The decrease in VAS score at post-intervention was statistically significant in group 1 compared to the control group (AMD, -0.43; 95% CI, -0.58 to -0.28; P < 0.001), and in groups 2 and 3 compared to group 1 (group 2 vs group 1: AMD, -0.65; 95% CI, -0.81 to -0.48; P < 0.001; group 3 vs group 1: AMD, -0.66; 95% CI, -0.86 to -0.47; P < 0.001). The VAS scores in the four groups converged beyond 24 h after the operation. Fewer patients in group 2 and group 3 experienced PONV in the first 24 h after operation. No statistical differences were measured in QoR-40 score and the number of patients with additional analgesic therapy. CONCLUSION: Compared with the 30 min intervention, WAA treatment with longer needle retention time (45 or 60 min) had an advantage in pain relief within 6 h after surgery. WAA's analgesic effect lasted for 6-12 h post-operatively. Please cite this article as: Han XR, Yue W, Chen HC, He W, Luo JH, Chen SX, Liu N, Yang M. Treatment duration of wrist-ankle acupuncture for relieving post-thyroidectomy pain: A randomized controlled trial. J Integr Med. 2023; 21(2): 168-175.

The bacterial communities in vagina of different Candida species-associated vulvovaginal candidiasis.

The incidence of vaginal infection caused by Candida species has considerably increased over the past two decades. Candida albicans is the main cause of vulvovaginal candidiasis (VVC); however, non-albicans Candida (NAC) species, such as Candida glabrata and Candida tropicalis, are now frequently identified in VVC patients. Although the vaginal microbiome (VMB) was well studied in Candida albicans-associated VVC patients, the fungal influence on bacterial communities of NAC species-associated VVC and potential microbial interplay contributing to VVC pathology remain elusive. We characterized VMB via Candida albicans and NAC species-associated VVC patients, as Candida albicans (CA, n = 16), Candida glabrata (CG, n = 16), Candida tropicalis (CT, n = 4), and recruiting healthy (CON, n = 20) women as references of dysbiosis and eubiosis. The bacterial diversity of the vagina in the CG group significantly declined. Further, all VVC patients have a higher abundance of Lactobacillus iners, especially for the CG group. Meanwhile, the predicted functions in all VVC are toned which may be associated with a disruption in the bacterial network. In conclusion, according to the taxonomic analysis, we found that the vaginal microbiome in C. glabrata-associated VVC women is different from that of other Candida species-associated VVC women, implying a different pathogenesis.

Mechanochemical treatment of hexachlorobenzene-contaminated soil with additives.

The use of mechanochemistry for the remediation of hexachlorobenzene (HCB)-contaminated soil was investigated. Additives such as alkaline materials, neutral materials, natural minerals, and solid waste were studied to explore their effect on the degradation of hexachlorobenzene in soil with single or combined addition by mechanochemical method. The best combination of materials were determined based on HCB destruction percentage by considering the impact on soil quality, the treatment cost, and the availability of additives. Scanning electron microscope (SEM) images and X-ray photoelectron spectrometer (XPS) analysis were conducted for the mechanism studies. The combination of albite and ferric oxide (Fe3O4) was found to achieve the best performance in the degradation of HCB with the destruction percentage from 74.3 to 92.5% after 2-h and 6-h reaction, respectively. The developed fracture structure and complex compositions of albite provided abundant reaction sites for mechanochemical degradation of HCB in soil.

HIV-1 pretreatment drug resistance and genetic transmission network in the southwest border region of China.

BACKGROUND: HIV drug resistance increased with the widespread use of antiretroviral drugs, and posed great threat to antiretroviral therapy (ART). Pu'er Prefecture, lying in the southwest of Yunnan Province, China, borders Myanmar, Laos and Vietnam, is also the area where AIDS was discovered earlier, however, in which there has been no information on HIV drug resistance. METHODS: A cross-sectional survey of pretreatment drug resistance (PDR) was conducted in Pu'er Prefecture in 2021. Partial pol gene sequences were obtained to analyze drug resistance and construct genetic transmission network. HIV drug resistance was analyzed using the Stanford University HIVdb algorithm. RESULTS: A total of 295 sequences were obtained, among which 11 HIV-1 strain types were detected and CRF08_BC (62.0%, 183/295) was the predominant one. Drug resistance mutations (DRMs) were detected in 42.4% (125/295) of the sequences. The prevalence of PDR to any antiretroviral drugs, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 10.8% (32/295), 9.5% (28/295), 1.0% (3/295) and 0.3% (1/295), respectively. The risk of PDR occurrence was higher among individuals with CRF01_AE strain types. HIV-1 molecular network was constructed, in which 56.0% (42/75) of links were transregional, and 54.7% (41/75) of links were associated with Lancang County. Among the sequences in the network, 36.8% (35/95) harbored DRMs, and 9.5% (9/95) were drug resistance strains. Furthermore, 8 clusters had shared DRM. CONCLUSION: The overall prevalence of PDR in this study was in a moderate level, but NNRTIs resistance was very approaching to the threshold of public response initiation. PDR was identified in the transmission network, and DRMs transmission was observed. These findings suggested that the consecutive PDR surveillance should be conducted in this region.

Using molecular network analysis to explore the characteristics of HIV-1 transmission in a China-Myanmar border area.

BACKGROUND: The China-Myanmar border area is considered a hot spot of active HIV-1 recombination in Southeast Asia. To better understand the characteristics of HIV-1 transmission in this area, a cross-sectional HIV-1 molecular epidemiological survey was conducted in Baoshan Prefecture of Yunnan Province. METHODS: In total, 708 newly reported HIV-1 cases in Baoshan Prefecture from 2019 to 2020 were included in this study. HIV-1 gag, pol and env genes were sequenced, and the spatial and demographic distributions of HIV-1 genotypes were analyzed. The characteristics of HIV-1 transmission were investigated using the HIV-1 molecular network method. RESULTS: In the 497 samples with genotyping results, 19 HIV-1 genotypes were found, with URFs being the predominant strains (30.2%, 150/497). The main circulating HIV-1 strains were mostly distributed in the northern area of Baoshan. URFs were more likely identified in Burmese individuals, intravenous drug users and those younger than 50 years old. CRF08_BC was more likely detected in farmers and those of Han ethnicity, CRF01_AE in the young and those of Han ethnicity, and CRF07_BC in the subpopulation with junior middle school education and higher. Moreover, CRF118_BC and CRF64_BC were more likely found in the subpopulation aged ≥40 years and ≥50 years, respectively. Among 480 individuals with pol sequence detection, 179 (37.3%) were grouped into 78 clusters, with Baoshan natives being more likely to be in the network. The proportion of the linked individuals showed significant differences when stratified by the regional origin, marital status, age and county of case reporting. In the molecular network, recent infections were more likely to occur among nonfarmers and individuals aged below 30 years. CONCLUSIONS: HIV-1 genetics has become complex in Baoshan. HIV-1 molecular network analysis provided transmission characteristics in the local area, and these findings provided information to prioritize transmission-reduction interventions.

Identifying potentially contaminated areas with MaxEnt model for petrochemical industry in China.

The presence of heavy metal and organic pollutants in wastewater effluents, flue gases, and even solid wastes from petrochemical industries renders improper discharges liable to posing threats to the ecological environment and human health. It is beneficial for pollution control to find out the regional distribution of contaminated sites. This study explored the relationship between the petrochemical contaminated areas and natural, socio-economic, and traffic factors. Ten indicators were selected as input variables, and the MaxEnt model was conducted to identify the potentially contaminated areas. Moreover, among these 10 variables, the factors that have the great impact on the results were determined according to the contribution of variables. The results showed that the MaxEnt model performed well with AUC of 0.981 ± 0.004, and 90% of the measured contaminated sites was located in areas with medium and high probability of contamination in the prediction results. The map of potentially contaminated areas indicated that the areas with high probability of contamination were distributed in Yangtze River Delta, Beijing, Tianjin, southern Guangdong, Fujian coastal areas, central Hubei and northeast Hunan, central Sichuan, and southwest Chongqing. The responses of variables presented that high probability of petrochemical contamination tended to appear in cities with developed economy, dense population, and convenient transportation. This study presents a novel way to identify the potentially contaminated areas for petrochemical sites and provides a theoretical basis to formulate future management strategies.

A Randomized Clinical Trial of Human Papillomavirus Test-and-Treat as Compared to Cytology-Based Screening for Prevention of Cervical Cancer Among Women With Human Immunodeficiency Virus: AIDS Clinical Trials Group Protocol A5282.

BACKGROUND: Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes. METHODS: Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion. RESULTS: In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13). CONCLUSIONS: HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs. CLINICAL TRIALS REGISTRATION: NCT01315363.

Human health risk identification of petrochemical sites based on extreme gradient boosting.

Petrochemical industry is a key industry of soil pollution, which presents great effects on human health and the ecological environment. It is of great significance to achieve rapid, economic and efficient health risk identification for petrochemical industry in China. In this work, an efficient method was developed based on extreme gradient boosting (XGBoost) algorithm for human health risk identification, which is different from the traditional health risk assessment with complicated procedures. In this methodology, an index system of 13 indicators was established from the perspective of "sources - pathways - receptors" for risk identification. The 10-fold cross validation was used to assess the generalization performance, and the accuracy, precision and recall were employed to evaluate the performance of the algorithms. Wilcoxon signed-rank test was conducted to analyze the differences between XGBoost and other models for statistical support. The results showed that XGBoost significantly presented a better performance for health risk identification over multilayer perceptron neural network with error backpropagation training (BPNN), support vector machine (SVM), gradient boosting decision tree (GBDT) and light gradient boosting machine (LightGBM), with an accuracy of 0.783. The most important features contributing to the risk identification were determined with the sequence of site location (in the industrial zone or not), site planning and production period. Great attention should be given to the petrochemical sites that are not located in the industrial zone with long production period and sensitive receptors in the health risk identification. This method has important reference significance for relevant departments to carry out soil contamination screening and health risk assessment of petrochemical sites.

Brief Report: No Differences Between Lopinavir/Ritonavir and Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy on Clearance of Plasmodium falciparum Subclinical Parasitemia in Adults Living With HIV Starting Treatment (A5297).

BACKGROUND: HIV protease inhibitors anti-Plasmodium falciparum activity in adults remains uncertain. METHODS: Adults with HIV CD4+ counts >200 cells/mm3 starting antiretroviral therapy (ART) with P. falciparum subclinical parasitemia (Pf SCP) were randomized 1:1 to (step 1) protease inhibitor lopinavir/ritonavir (LPV/r)-based (arm A) or nonnucleoside reverse transcriptase inhibitor (nNRTI)-based ART (arm B) for 15 days. In step 2, participants received nNRTI-based ART and trimethoprim/sulfamethoxazole prophylaxis for 15 days. P. falciparum SCP clearance was measured by polymerase chain reaction. The Fisher exact test [95% exact confidence interval (CI)] was used to compare proportions of P. falciparum SCP clearance (<10 parasites/µL on 3 occasions within 24 hours) between LPV/r and nNRTI arms at day 15. The Kaplan-Meier method and log-rank test were used to compare time-to-clearance. RESULTS: Fifty-two adults from Kenya, Malawi, and Uganda with a median age = 31 (Q1, Q3: 24-39) years, 33% women, with baseline median CD4+ counts of 324 (259-404) cells/mm3, median HIV-1 RNA viremia of 5.18 log10 copies/mL (4.60-5.71), and median estimated P. falciparum density of 454 parasites/µL (83-2219) enrolled in the study. Forty-nine (94%) participants completed the study. At day 15, there was no statistically significant difference in the proportions of P. falciparum SCP clearance between the LPV/r (23.1% clearance; 6 of the 26) and nNRTI (26.9% clearance; 7 of the 26) arms [between-arm difference 3.9% (95% CI, -21.1% to 28.4%; P = 1.00)]. No significant difference in time-to-clearance was observed between the arms (P = 0.80). CONCLUSIONS: In a small randomized study of adults starting ART with P. falciparum SCP, no statistically significant differences were seen between LPV/r- and nNRTI-based ART in P. falciparum SCP clearance after 15 days of treatment.

The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China.

HIV-1 drug resistance can compromise the effectiveness of antiretroviral therapy (ART). A survey of pretreatment HIV-1 drug resistance (PDR) was conducted in Lincang Prefecture of Yunnan Province. From 372 people living with HIV/AIDS initiating ART for the first time during 2017-2018, 322 pol sequences were obtained, of which 11 HIV-1 strain types were detected. CRF08_BC (70.2%, 226/322) was the predominant strain, followed by URF strains (10.6%, 34/322). Drug resistance mutations (DRMs) were detected among 34.2% (110/322) of the participants. E138A/G/K/R (14.3%, 46/322) and V179E/D/T (13.7%, 47/322) were the predominant DRMs. Specifically, E138 mutations commonly occurred in CRF08_BC (19.9%, 45/226). Among the DRMs detected, some independently conferred resistance, such as K65R (1.6%, 5/322), Y188C/F/L (0.9%, 3/322), K103N (0.6%, 2/322) and G190A (0.3%, 1/322), which conferred high-level resistance. The prevalence of PDR was 7.5% (95% CI: 4.6-10.3%) and the prevalence of non-nucleotide reverse transcriptase inhibitor (NNRTI) resistance was 5.0% (95% CI: 2.6-7.4%), which is below the threshold (⩾10%) of initiating a public health response. In conclusion, HIV-1 genetic diversity and an overall moderate level of PDR prevalence were found in western Yunnan. PDR surveillance should be continually performed to decide whether a public health response to NNRTI resistance should be initiated.

Oral Cytokine Levels Are More Linked to Levels of Plasma and Oral HIV-1 RNA Than to CD4+ T-Cell Counts in People With HIV.

BACKGROUND: We determined the levels of 11 soluble immune mediators in oral washings of AIDS Clinical Trials Group A5254 participants with varying degrees of plasma viremia and CD4 T-cell counts to characterize the mucosal immune response at different stages of HIV-1 infection. METHODS: A5254 was a multicenter, cross-sectional study in people with HIV (PWH) recruited into 4 strata based on CD4 count and levels of plasma viremia: stratum (St) A: CD4 ≤200 cells/mm3, HIV-1 RNA (viral load [VL]) >1000 cps/mL; St B: CD4 ≤200, VL ≤1000; St C: CD4 >200, VL >1000; St D: CD4 >200, VL ≤1000. Oral/throat washings were obtained from all participants. Soluble markers were tested in oral/throat washings using a multibead fluorescent platform and were compared across strata. Linear regression was used to determine the associations between cytokines and HIV-1 in plasma and oral fluid. RESULTS: St A participants had higher levels of interleukin (IL)-1ß, IL-6, IL-17, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) compared with St B and D (P = .02; P < .0001) but were not different from St C. IL-8, IL-10, and IL-12 were elevated in St A compared with the other 3 strata (P = .046; P < .0001). Linear regression demonstrated that oral HIV-1 levels were associated with IL-1ß, IL-6, IL-8, and TNFα production (R > .40; P < .001) when controlling for CD4 count and opportunistic infections. CONCLUSIONS: Our results show that high levels of oral HIV-1, rather than low CD4 counts, were linked to the production of oral immune mediators. Participants with AIDS and uncontrolled viremia demonstrated higher levels of pro- and anti-inflammatory soluble immune mediators compared with participants with lower HIV-1 RNA. The interplay of HIV-1 and these immune mediators could be important in the oral health of PWH.

Demographic characteristics and spatial clusters of recent HIV-1 infections among newly diagnosed HIV-1 cases in Yunnan, China, 2015.

BACKGROUND: The characteristics of recent HIV infections can provide the information about the dynamics of HIV transmission. Yunnan is one of the provinces hardest-hit by HIV-1 in China. To further understand the characteristics of the HIV-1 epidemic in Yunnan, we analyzed the prevalence of recent HIV-1 infections among newly diagnosed cases, identified the associated factors and explored the spatial distribution of recent HIV-1 infections. METHODS: Residual plasma samples from HIV-1 diagnostic tests were preserved. The associated information was collected from China HIV/AIDS case reporting system. Recent HIV-1 infections were estimated by combining the information about disease progression and BED- capture enzyme immunoassay (CEIA). The proportions of recent HIV-1 infections among newly diagnosed cases stratified by demographic characteristics were analyzed. The spatial clusters of recent HIV-1 infections were investigated by spatial scan statistics. RESULTS: Among 6119 HIV/AIDS cases were newly reported between January 2015 and June 2015 in Yunnan Province, 9.3% (570/6119) were estimated as recent infections. Female, aged below 25 years and homosexual contact were more associated with the higher proportion of recent HIV-1 infections. Among the different demographic sub-groups, men who have sex with men (MSM) aged < 25 years and ≥ 50 years had a higher chance of being diagnosed as recent infections, heterosexually infected men aged ≥25 years had a lower chance of being diagnosed as recent infections. In the sub-groups with different screening approaches, the highest proportion of recent infections (16.1%) was found among women diagnosed by testing during pregnancy and childbirth. In the sub-groups with different contact histories, the higher proportion of recent infections was found among the female cases having commercial heterosexual contacts (16.4%) and MSM (19.7%). The statistically significant spatial clusters of recent infections attributed to heterosexual contact, homosexual contact and intravenous drug injection were identified, respectively. CONCLUSIONS: The investigation of recent HIV infections among newly diagnosed cases supplements the routine HIV surveillance, and reveals the characteristics of ongoing HIV transmission. Our finding identified the potential sub-populations and geographic areas in need of services or improved interventions.

Spatial clusters of HIV-1 genotypes in a recently infected population in Yunnan, China.

BACKGROUND: As a gateway for HIV-1 in China, Yunnan has experienced dramatic changes in HIV-1 epidemics, during which HIV-1 genotypes have become complex. To track dynamic changes in HIV-1 genotypes, an HIV-1 molecular epidemiological study was implemented in the recently infected population in Yunnan. METHODS: From 6,357 HIV-1-positive samples diagnosed during the first half of 2015 in Yunnan, 586 samples were identified as recent infections with BED-capture enzyme immunoassay (CEIA) and were subjected to phylogenetic analyses. Spatial scanning analyses for the main HIV-1 genotypes were also performed. RESULTS: Among the 439 specimens successfully genotyped, more than ten genotypes were detected, including CRF08_BC (45.3%), CRF07_BC (19.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (11.4%), subtype C (2.1%), CRF85_BC (1.1%), CRF55_01B (0.9%), subtype B (0.5%), CRF64_BC (0.5%), CRF59_01B (0.2%), CRF83_cpx (0.2%) and CRF87_cpx (0.2%). Females, Chinese, heterosexual contact and intravenous drug injection were significantly associated with CRF08_BC infection; homosexual contact was significantly associated with CRF01_AE and CRF07_BC infection; males and non-Chinese had a higher risk of URF infection than females. Among all HIV-1 genotypes, the geographic coverage of CRF08_BC was the largest. For CRF08_BC, CRF07_BC, URFs and CRF01_AE, spatial clusters were detected. The two CRF08_BC clusters and one URF cluster were associated with heterosexual transmission, and two of CRF01_AE clusters were associated with homosexual transmission. Transmitted drug resistance (TDR)-associated mutations were detected in 2.4% of individuals. CONCLUSIONS: The diversity of HIV-1 genotypes increased in recent infections because of a long-term HIV-1 epidemic in Yunnan. The predominant HIV-1 strains showed distinct demographic characteristics and formed spatial clusters. These findings improved our understanding of the evolution of HIV-1 in Yunnan and provided information for further HIV-1 control and prevention.

Immune Correlates of Herpes Zoster in People Living with HIV on Effective Antiretroviral Therapy.

Herpes zoster (HZ) has high morbidity in people living with HIV (PLHIV). We investigated immunological factors that correlated with the development of HZ in PLHIV with controlled HIV replication on antiretroviral therapy (ART). PLHIV who developed HZ on ART (cases), with undetectable plasma HIV RNA, and CD4 counts ≥200 cells/µL were matched 1:1 to controls by CD4 count, age, gender, race, and duration of ART. Varicella-zoster virus (VZV)-specific T cells and circulating regulatory T cells (Treg) were measured by flow cytometry before and after HZ. Differences between cases and controls were assessed by paired t-tests and longitudinal changes by Wilcoxon signed rank test. HZ cases (N = 31) had higher CD4+FOXP3+CD25+% Treg before HZ compared with 31 controls. After VZV ex vivo restimulation, cases had lower T cell responses, including CD8+perforin+% cytotoxic T lymphocytes (CTLs), CD4+IL10+%, and CD4+TGFß+% compared with controls. Overall, Treg negatively correlated with VZV-specific Th1 responses. Moreover, Treg decreased over time on ART in HZ cases, VZV-CTLs were stable and did not increase even after HZ. Increased circulating Treg and decreased VZV-specific T cell immune responses were associated with the risk of HZ in PLHIV. The kinetics of Treg over time, but not of VZV-CTLs, paralleled the natural history of HZ, whose incidence decreases over time on effective ART.