Prevention and control of HIV/AIDS in China: lessons from the past three decades / 中华医学杂志(英文版)

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Disparity of human immunodeficiency virus incidence and drug resistance in college student, non-student youth and older men who have sex with men: a cross-sectional study from seven major cities of China / 中华医学杂志(英文版)

BACKGROUND@#Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM.@*METHODS@#We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤ 168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, <25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance.@*RESULTS@#Overall, 4,496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1,094 NSYM, and 2,837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100PY, 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100PY, and TDR prevalence were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age< 21-year-old, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (AOR: 2.5; 95% CI: 1.0-5.8).@*CONCLUSIONS@#College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.

Age-Related CD4+CD25+Foxp3+ Regulatory T-Cell Responses During Plasmodium berghei ANKA Infection in Mice Susceptible or Resistant to Cerebral Malaria

Different functions have been attributed to CD4+CD25+Foxp3+ regulatory T-cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg response and pro- and anti-inflammatory cytokines during infection with Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old) C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the middle-aged mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The levels of pro-inflammatory cytokines, such as TNF-alpha, in young CM-susceptible mice were markedly higher than in middle-aged CM-resistant mice. An increased absolute number of Tregs 3-5 days post-inoculation, co-occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant mice but not in young CM-susceptible mice. Our findings suggest that Treg proliferation might be associated with the suppression of excessive pro-inflammatory Th1 response during early malaria infection, leading to resistance to CM in the middle-aged mice, possibly in an IL-10-dependent manner.

Estimation of postmortem interval by detecting thickness of cornea using ultrasonic method / 法医学杂志

OBJECTIVE@#To explore the postmortem changes of cornea thickness measured by ultrasonic pachymetry.@*METHODS@#Eleven rabbits were randomly divided into two groups: one group with intact corneal epithelium and another group without intact corneal epithelium. In the later group, the corneal epithelium of the rabbit was scraped using mechanical elimination method. The corneal thickness was monitored continuously by ultrasonic pachymetry at several postmortem interval points in rabbits of the two groups. The changes of corneal thickness and postmortem interval were explored by relative regression analysis.@*RESULTS@#The thickness of the cornea showed a strong non-linear correlation with the postmortem interval in the group with intact corneal epithelium. The group with intact corneal epithelium showed the correlation coefficient 0.922 and the group without intact corneal epithelium showed the correlation coefficient 0.822, respectively.@*CONCLUSION@#The corneal thickness measured by ultrasonic pachymetry shows a potential value for estimating early postmortem interval. The intact corneal epithelium is a crucial factor for the measurement of cornea thickness by ultrasonic pachymetry.

Association of variations of NAb 2F5 and 4E10 epitopes and disease progression in Chinese antiretroviral treatment-naïve patients infected with HIV-1 clade B' / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Studies on human immunodeficiency virus type 1 (HIV-1) vaccines have recently focused on targeting the conserved neutralizing epitopes 2F5 and 4E10, and hence it is important to understand the extent of mutations in these two viral epitopes. Here, we investigated the amino acid mutations in epitopes of 2F5 (ELDKWA, HIV-1 HXB2 env 662 - 667 aa) and 4E10 (NWFDIT, HIV-1 HXB2 env 671 - 676 aa) in the membrane proximal-external region of gp41 from clade B' HIV-1-infected individuals living in Henan province, China. We also examined the frequency of a mutation and its relation to disease progression.</p><p><b>METHODS</b>A cohort of 54 treatment-naïve HIV-1-infected individuals was recruited in this study, and 16 individuals were selected for a short-term longitudinal study on sequence evolution. The HIV-1 env gp41 gene was amplified, cloned, and sequenced, and predicted amino acid sequences were aligned for analysis.</p><p><b>RESULTS</b>The mutations E662A and K665E on the 2F5 epitope and N671S and T676S on the 4E10 epitope were seen. Simultaneous RNA sequencing showed some discrepancies with proviral DNA sequences. In our longitudinal study, mutation levels of these two neutralizing epitopes were low but diverse and persistent. The frequencies of mutations within the 4E10 peptide NWFDIT in slow progressors were noticeably lower than those in AIDS patients (P < 0.05).</p><p><b>CONCLUSIONS</b>Antigenic variation of the neutralizing epitopes 2F5 and 4E10 is limited in subtype B' infection, and that 4E10 peptide mutation is correlated with disease progression. Monitoring epitope mutations will offer useful data for development of the candidate 2F5-like and 4E10-like antibodies to prevent and treat AIDS.</p>

The prevalence of hepatitis C virus (HCV) subtypes in Chinese HIV-1/HCV co-infected individuals / 中华流行病学杂志

Objective To better understand the prevalence and geographic distribution of genotypes/subtypes on HCV and the relationship between HCV genotypes/subtypes and HIV infection disease progression in the HIV-1/HCV co-infected individuals living in high HIV-1 prevalent areas in China. Methods 186 plasma samples were collected from HIV-1 seropositive individuals infected through paid blood donors (PBD), injecting drug users (IDUs) or sexual contact, living in most severely affected provinces, Henan, Yunnan, Xinjiang, Jilin and Liaoning provinces. Samples with HCV viral load >1000 cop/ml were amplified by RT-nested PCR, sequenced and phylogenetically analyzed for genotyping/subtyping of HCV. HIV-1, HCV viral loads and CD4 T lymphocytes were measured for all subjects. Results (1) HCV were identified as 1 a (1.7%), 1 b (39.9%), 2a (17.9%), 3a (10.4%), 3b (15.6%), 6a (1.2%), 6n (6.4%), and a newly unclassified subtype (7.5%). HCV 2a and lb subtypes predominated in PBD in Henan, 3a and 3b in IDUs in Xinjiang and Yunnan, and 6 genotype/subtypes in IDU in Yunnan. (2) There were no significant differences in CD4 T cell counts among the different HCV subtypes. (3) The viral load of HCV RNA in lb subtype was higher than that of non-1b subtype, however, no significant differences in HIV-1 viral loads and CD4 T cell counts were found between Ib and non-1b subtype. Both HIV and HCV viral loads were lower in 2a than non-2a subtype. Conclusion The prevalence of HCV genotype/subtype in HIV-1/FICV co-infected individuals was associated with geographic areas and transmission routes. HCV subtypes had no direct correlation with HIV infection disease progression.

Association of IL-7 with disease progression in Chinese HIV-1 seropositive individuals / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Elevated levels of interleukin-7 (IL-7) have been correlated with CD4(+) T cell depletion and the emergence of syncytium-inducing (SI) variants in human immunodeficiency virus type-1 (HIV-1) infection, and suggested as an indicator of acquired immunodeficiency syndrome (AIDS) disease progression. Therefore, we investigated the effects of IL-7 on disease progression and virus phenotype in Chinese HIV/AIDS patients.</p><p><b>METHODS</b>In a cross-sectional study of 71 untreated HIV-1 seropositive individuals and 12 healthy donors, plasma IL-7 levels were determined by an ultra sensitive enzyme-linked immunosorbent assay (ELISA), and its relations to CD4(+) T cells, CD8(+) T cells, plasma viral loads and HIV phenotypes were analyzed.</p><p><b>RESULTS</b>Significant higher IL-7 levels were found in Chinese HIV/AIDS patients [(3.33 +/- 3.60) pg/ml] than those of health controls [(1.2 +/- 0.81) pg/ml] (P < 0.05), and IL-7 levels were inversely associated with CD4(+) T cell counts (r = -0.497, P < 0.01). Furthermore, IL-7 levels were significant higher in patients with SI variants [(9.12 +/- 4.55) pg/ml] than those with non-syncytium-inducing variants [(1.50 +/- 2.69) pg/ml] (P < 0.01).</p><p><b>CONCLUSIONS</b>Increased IL-7 levels were found in Chinese HIV/AIDS patients and significantly associated with disease progression, thus increased IL-7 plasma levels may indicate disease progression.</p>

Activation and coreceptor expression of T lymphocytes induced by highly active antiretroviral therapy in Chinese HIV/AIDS patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>At the end of 2005, 650,000 people lived with human immunodeficiency virus type-1 (HIV-1) in China, of whom 75 000 were AIDS patients. Many AIDS patients received highly active antiretroviral therapy (HAART) supported by the "China CARES" program but the immune responses of HAART were seldom reported. This study investigated the effect of HAART on the activation and coreceptor expression of T lymphocytes in Chinese HIV/AIDS patients and evaluated its effect on immune reconstitution.</p><p><b>METHODS</b>Seventeen HIV/AIDS patients were enrolled and three-color-flow cytometry was used to detect the activation of HLA-DR CD38 and the coreceptor CCR5, CXCR4 expression on T lymphocytes in whole blood samples taken from the patients before and after 3- or 6-month HAART.</p><p><b>RESULTS</b>The activation percents of CD4(+), CD8(+) T lymphocytes were significantly higher before therapy than the normal controls (HLA-DR/CD4: 40.47 +/- 18.85 vs 11.54 +/- 4.10; CD38/CD4: 81.34 +/- 10.86 vs 53.34 +/- 11.44; HLA-DR/CD8: 63.94 +/- 12.71 vs 25.67 +/- 9.18; CD38/CD8: 86.56 +/- 11.41 vs 58.84 +/- 6.16, all P < 0.01). After 6-month combined antiretroviral treatment, the activation of T lymphocytes in HIV/AIDS patients was significantly decreased (HLA-DR/CD4: 28.31 +/- 13.48; CD38/CD4: 69.88 +/- 12.64; HLA-DR/CD8: 46.56 +/- 18.64; CD38/CD8: 70.17 +/- 14.54, all P < 0.01 compared with the pre-treatment values). Before the treatment, CCR5 expression on CD8(+) T lymphocytes was up-regulated while CXCR4 expression on CD8(+) T lymphocytes downregulated in HIV/AIDS patients compared with the normal controls (CD8/CCR5: 70.91 +/- 10.03 vs 52.70 +/- 7.68; CD8/CXCR4: 24.14 +/- 11.08 vs 50.05 +/- 11.68, all P < 0.01). After 6-month HAART, CCR5 expression on CD8(+) T lymphocytes significantly decreased (56.35 +/- 12.96, P < 0.01), while CXCR4 expression on CD8(+) T lymphocytes increased (36.95 +/- 9.96, P < 0.05) compared with the pre-treatment and the normal controls. A significant statistical relationship was observed between the expression of activation markers, CCR5 and the CD4(+) T lymphocyte counts after HAART (P < 0.05).</p><p><b>CONCLUSIONS</b>Reduced activation of T lymphocytes and a normalization of coreceptor expression were observed in Chinese HIV/AIDS patients after HAART. Immunity can be restored in HIV/AIDS patients receiving HAART.</p>

Variant genotyping of CCR2-64I, SDF1-3' A and CCR5Delta32 in HIV-1 infected Chinese long-term nonprogressors / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To investigate variant genotyping of CCR2-64I, SDF1-3'A and CCR5Delta32 in HIV-1 infected Chinese Long-term nonprogressors and to study their association with disease progression.</p><p><b>METHODS</b>The genotypes of CCR2-64I, SDF1-3'A and CCR5Delta32 were detected by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) assay in seventeen HIV-1 infected Chinese Long-term nonprogressors (LTNPs) and thirty-nine Chinese typical progressors (TPs).</p><p><b>RESULTS</b>The frequency of CCR2-64I and SDF1-3'A in LTNPs are 50% and 62.5%, higher than those (23.08% and 33.33%) in TPs. Only one heterozygous CCR5 mutant was detected in LTNPs, and no CCR5 mutant in TPs.</p><p><b>CONCLUSION</b>Variant genotyping of CCR2-64ISDF1-3'A and CCR5Delta32 may be protective factors for delaying disease progression in HIV-1 infected Chinese LTNPs.</p>

Resistance to HIV-1 infection of CD4 + T lymphocytes in vitro from chinese HIV-1 exposed seronegative individuals / 中国医学科学院学报

<p><b>OBJECTIVE</b>To determine the relative resistance to HIV-1 infection of CD4 + T lymphocytes in HIV-exposed seronegative individuals (ESNs) in China.</p><p><b>METHODS</b>HIV primary isolates were obtained from peripheral whole blood of HIV-infected persons. CD4 + T lymphocytes of Chinese ESNs were separated from peripheral blood mononuclear cells with magnetic cell sorting (MACS). The purified CD4 + T lymphocytes were cocultured with HIV primary isolates. The p24 level was detected and the culture medium was refreshed every 3 days within 2 weeks.</p><p><b>RESULTS</b>For M tropic HIV strains, p24 level was significantly lower in ESN group than in control group (P < 0.05); for some M tropic HIV strains, even no p24 replicated in ESN group. However, T tropic virus strains had no significant difference between these two groups (P > 0.05).</p><p><b>CONCLUSION</b>CD4 + T lymphocytes of Chinese ESNs may possess relative resistance to M tropic HIV strains, which may be one of the main influencing factors that result in ESN.</p>

Background study of HIV-1 drug resistant mutations in treatment-naive patients in liaoning province / 中国医学科学院学报

<p><b>OBJECTIVE</b>To collect background information on drug resistance mutations in treatment-naïve HIV-1 infected individuals in Liaoning Province.</p><p><b>METHODS</b>Samples from 91 antiretroviral therapy-naïve patients were collected. The entire protease gene and 1-290 amino acids of the reverse transcriptase gene were amplified by nested PCR from provirus DNA and sequenced. The results were analyzed with HIVdb-Drug Resistance Algorithm, and genotypic resistance mutations were determined to particular anti-HIV drugs.</p><p><b>RESULTS</b>Totally 91 sequences were obtained, 3 of which displayed M46I mutations in the protease gene. Minor resistance mutation rate to protease inhibitors was 100%, including types of L63P (60.4%), V77I (60.4%), M36I/V (31.9%), A71V/T (22.0%), L10I (8.8%), and K20R (6.6%). Only one sequence carried reverse transcriptase related resistance mutations M184I.</p><p><b>CONCLUSIONS</b>About 4.4% of HIV-1 infected individuals in Liaoning Province carried strains with drug resistance mutations. Most treatment-naïve HIV-1 infected individuals in Liaoning Province were sensitive to the currently available antiviral medicines, but antiviral treatment must be in accordance with the strict procedures to keep better adherence and avoid the prevalence of drug-resistant strains.</p>

Study on non-programmed process using dimethyl sulfoxide and hydroxyethyl starch as cryoprotectants in cryopreservation of cord blood hematopoietic cells / 中国实验血液学杂志

This study was aimed to search for effective cryoprotectants and freezing methods used in cord blood bank (CBB) for cryopreservation of cord blood hematopoietic stem cells. The non-programmed group using 8% final concentration of dimethyl sulfoxide (DMSO) and 5% final concentration hydroxyethyl starch (HES) (molecular weight 120,000) as protectants and group of conventional of programmed controller method using 10% DMSO only as cryoprotectant in cryopreservation of cord blood hematopoietic stem cells were compared. In each of the two groups, 15 cord blood units were used. In non-programmed group, cord blood units put in -80 degrees C refrigerator for 24 hours as a transitional step before deep-freezing in liquid nitrogen, when both of DMSO and HES had been added. The recoveries of the nuclear cells number, the yield of granulocyto-macrophage colony forming units (CFU-GM) and the cells viability in cord blood units before preservation and after thawing were tested for both methods. The results showed that no significant difference was found in above assays between two groups. The clinical application results also showed that hematopoietic engraftment rates after infusion were similar in both groups. It is concluded that the non-programmed method by -80 degrees C refrigerator as a transitional step and using the combined two protectants seems simple in operation and effective in clinical transplantation as well as the conventional programmed method.

Mutation of envelop protein V3 loop in HIV-1 epidemic in Liaoning province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the characteristics of human immunodeficiency virus (HIV-1) V3 loop amino acid mutations among HIV-1 infected people in Liaoning province.</p><p><b>METHODS</b>The whole blood samples of the HIV carriers and AIDS patients were collected in Liaoning province, China and were extracted PBMC genome DNA. HIV-1 V3 and flanking region sequences were amplified by nest-polymerase chain reaction (nest-PCR) with env specific primers: ED5/ED12 and ED31/ED33. Products were sequenced directly and sequences were aligned, translated and analyzed.</p><p><b>RESULTS</b>In AIDS group, some amino acid mutations at specific position of V3 loop: S to R at position 11, H to S, T and N at position 13, A to V at position 19, F to Y at position 20, Q or D to N at position 25 and 29, were found and all common mutations were associated with T tropic/SI phenotype. The frequency of such amino acid mutations in specific positions was higher in AIDS group than that of the asymptomatic infection group (P < 0.05). In addition, we found some unusual tetramer compositions on the tip of V3 loop: GQGR, APGR and RPGA, GLGR, RPGA in addition to some rare mutations, such as: N to H at position 5 and H to S, F at position 34.</p><p><b>CONCLUSION</b>The amino acid mutations on the V3 loop of HIV-1 epidemic in Liaoning province were in agreement with the results of subtype B, but we observed some rare mutations and unusual tetramer compositions on the tip of V3 loop.</p>