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Objective: To understand the survival of HIV/AIDS patients after receiving antiretroviral therapy for 10 year in Henan province and related factors. Methods: The database of national integrated management system of HIV/AIDS was used to collect the basic information and follow-up information of HIV/AIDS patients who received antiretroviral therapy between 2003 and 2005 in Henan province. Software SPSS 23.0 was used to analyze the patients' survival and related factors based on the life-table method and Cox proportional hazards model. Results: Among the 2 448 HIV/AIDS patients who started antiretroviral therapy during 2003-2005, the men accounted for 53.5 % , and women accounted for 46.5 % . Up to 70.1 % of the patients were aged 40-59 years and 95.5 % of the patients had blood borne infections. The patients were observed for 10 years after antiviral treatment, and 719 cases died from AIDS related diseases, with a mortality rate of 3.78/100 per year (719/19 010 per year). The cumulative survival rates of patients within 1-year, 3 years, 5 years and 10 years were 0.94, 0.86, 0.78, 0.69 respectively. Compared with the patients aged <40 years, the HR s of the patients aged 40-, 50-, 60- and ≥70 years were 1.417 (95 %CI : 0.903-2.222), 1.834 (95 %CI : 1.174-2.866), 2.422 (95 %CI : 1.539-3.810) and 3.424 (95 %CI : 2.053-5.709) respectively. Compared with patients with baseline CD(4+)T lymphocyte >350 unit/ul, the HR s of the patients with CD(4+)T lymphocyte <50 unit/μl, 50-199 unit/ul and 200-350 unit/ul were 7.105 (95 %CI : 5.449-9.264), 4.175 (95 %CI : 3.249-5.366) and 2.214 (95 %CI : 1.691-2.900) respectively. Compared with the women, the HR of the men was 1.480 (95 %CI : 1.273-1.172). Compared with the patients who received second line ART therapy, the HR of patients receiving no second line therapy was 11.923 (95 %CI : 9.410-15.104). Conclusions: The cumulative survival rate the HIV/AIDS patients after 10 years of antiretroviral therapy reached 0.69 in Henan. Male, old age, low basic CD(4+)T lymphocyte count and receiving no second line therapy were the risk factors for long-term survival of AIDS patients.

Objective: To explore the causes of secondary drug resistance among HIV infected persons who were receiving antiretroviral therapy in Shandong province, and provide evidence for the improvement of antiretroviral therapy strategy. Methods: A case-control study was designed with 1∶2 matching on case and control groups. Household and face-to-face interview were conducted in October, 2015. All the study subjects were screened from both the drug resistant database of antiretroviral therapy of Shandong provincial laboratory and national comprehensive HIV/AIDS database in Shandong. The sample size was estimated as 330 cases including 110 drug resistant and 220 non-drug resistant cases. Subjects were people living with HIV/AIDS (PLWHA) aged 15 or older and received antiretroviral therapy for more than 6 months with records of virus load (VL). Subjects who presented VL above 1 000 copies/ml would receive drug resistance testing. Subjects who were confirmed resistant to with secondary drug, were selected as case group, the rest subjects with non-secondary drug resistance would form the control group. EpiData 3.1 software and SPSS 22.0 software were used to establish a database. Related influencing factors were analyzed with non- conditional stepwise logistic regression model. Results: A total of 288 cases were enrolled, including 103 in the case and 185 cases in the control groups, with average age as (37.62±1.06) years and (37.90±0.74) years old, respectively. Most of them were male, married/cohabitant, with education level of junior/senior high school or below and under Han nationality. Results from the multivariate logistic regression model showed that ORs (95 %CI ) of receiving antiretroviral therapy for 1-3 years, or more than 3 years were equal to 8.80 (3.69-21.00), 3.00 (1.20-7.53), compared with receiving antiretroviral therapy less than one year, respectively. OR (95 %CI ) of Among the PLWHA that with missing rate above 25.0 % on medication, the OR appeared as 15.41(4.59-51.71), compared with not missing medication. OR (95 %CI ) among those who took the medicine themselves was 0.22 (0.07-0.74). Conclusions: Factors as duration of treatment, missing rate on medication and taking medicine by oneself were of influence on secondary drug resistance. Other factors as duration on antiretroviral therapy longer than 1 year, missing rate above 25.0 % on medication, were related to the risk on secondary drug resistance. However, if the medicine was taken by oneself, it served as a protective factor for secondary drug resistance. It is necessary to strengthen the intervention and health education programs related to antiretroviral therapy.

Objective: To investigate the progression and drug resistance of long-term non-progressors during three follow-up in Henan province., Methods: In May 2009, 26 cases of long-term non-progressors were recruited who infected HIV more than 10 years with blood collection and supply routes, did not receive anti-retroviral therapy, CD4(+)T lymphocyte count ≥350/μl and did not show typical symptoms of AIDS from Weishi, Shangcai, and Linying of Henan Province. Continuous follow-up were conducted three times since 2009 every two years with cohort analysis, the epidemiological information of infection routes, infection time and blood were collected, and 78 parts of 10 ml EDTA anticoagulated whole blood were collected. The changes of CD4 (+) T lymphocytes, viral load, and virus gene variety were characterized from 2009 to 2014. In-house methods were used to explore primary drug resistance of long-term non-progressors. Nonparametric Kruskal-Wallis test were used to compare CD4(+) T lymphocyte count and viral load changes during different follow-up times., Results: The average age and infection time of 26 cases were (48.51 ± 6.75) years, (13.42 ± 4.26) years, respectively. Three follow-up times, CD4(+) T lymphocyte count P50 (P25-P75) was 573.5 (487.4-789.8), 499.8 (403.5-635.7), and 418.8 (297.6-537.8)/μl (H=63.99,P<0.001), respectively. And natural logarithm of viral load P50 (P25-P75) were 3.93 (3.43-4.55), 4.29 (3.78-4.75), 4.50 (4.01-4.81) (H=3.19,P=0.355), respectively. Subtype and phylogenetic analysis of HIV showed that prevalent cases were B subtype, accounting for 88.5% (23/26), and three cases showed restructuring changes. Two cases appeared highly resistant of 18 infected patients whose viral load >1 000 copies/ml., Conclusion: The CD4(+)T lymphocyte had a declining trend, virus subtype recombinant changes in a few cases, and primary drug resistance was found of long-term non-progressors in Henan province.

Objective: To investigate the effect of Euphorbia fischeriana extract on latent HIV reactivation and the pathway involved in this process and discuss the value of Euphorbia fischeriana extract in eliminating HIV., Methods: Fresh tissues of Euphorbia fischeriana root were crushed into powder after quick freezing with liquid nitrogen and extracted with acetone followed by a three-day vacuum freeze-drying for dehydration of the extract. The extract (EFE) was separated using RP-C18 column with high-performance liquid chromatography (HPLC) and identified with mass spectrometry (MS). The activity of reactivated latent HIV was analyzed by fluorescence-activated cell sorting in a J-Lat 10.6 cell model treated with EFE (50 µg/mL) for 24 h, using TNF-α (10 ng/mL) as the positive control. The effect of a NF-κB pathway inhibitor (Bay 11-7082) on EFE activity was tested. The changes in P65 expression in the cell nuclei within 2 h and HIV protein p24 expression within 24 h were analyzed by Western blotting in cells treated with EFE., Results: EFE was obtained by one-step acetone extraction, and the concentration of prostratin in the extract was around 0.53 mmol/L. About 50% of the cells showed HIV reactivation after treatment with 50 µg/mL EFE for 24 h accompanied by a significantly increased p24 expression. The activity of EFE in reactivating latent HIV was inhibited by Bay 11-7082 in a concentration-dependent manner, and p65 accumulation was detected in the cell nuclei within 2 h., Conclusion: EFE we obtained contains the active compounds of prostratin and its analogues and shows a strong capacity to reactivate latent HIV through classical NF-κB pathway.

Objective: To estimate the prevalence of antiretroviral drug resistance in treatment-naive individuals with human immunodeficiency virus (HIV) in China., Methods: Five electronic databases [Chinese BioMedical Literature Database (CBM), Chinese Journal Full-text Database (CNKI), Chinese Science-Technology Journal Database (VIP), Wanfang Data, and PubMed] were searched for studies of HIV drug resistance in untreated individuals. Drug resistance data were abstracted then pooled using the random effect model. Subgroup analysis was done across sampling time, location, study population (mean age and infection status), and sample size., Results: Seventy-six studies were included for our meta-analysis (46 in Chinese, 30 in English). The pooled rates of drug resistance to total, to non-nucleoside reverse transcriptase inhibitor (NNRTI), to nucleoside reverse transcriptase inhibitor (NRTI), and to protease inhibitor (PI) were 4.7% (95%CI:4.0%-5.4%), 2.3% (95%CI:1.8%-2.8%), 1.8% (95%CI:1.3%-2.3%), and 1.4% (95%CI: 1.1%-1.8%), respectively. All the rates before 2007 were higher than those for 2008 or later. Meanwhile, significant differences were found in the sample areas (P<0.05), in which, the rates in South-central and Southwest were both higher than 5%. The difference was complex between mean age and infection status subgroup, and we found the total prevalence in the group under 25 years and the newly infected, and confirmed group was lower than in the others. For sample size, all the rates in the group under 100 samples were higher than in the others, and the difference was significant (P<0.05)., Conclusion: The prevalence of HIV primary drug resistance in China was 4.7%, which stayed low, but was also close to the line set by WHO. Enhanced surveillance for drug resistance is necessary in high epidemic areas including the South-central and Southwest China whose prevalence has crossed the line.

Highly active antiretroviral combination therapy significantly reduced the mortality, but in the high-speed copying, high genetic variation and drug selection pressure under the effect of the increasingly serious problem of drug resistance greatly weakened the role of HAART inhibit viral replication and reduce antiviral treatment. This paper reports the latest trends in HIV drug-resistance in order to develop anti-HIV drugs in clinical programs, research and development of new guidance anti-HIV-1 strategy to bring guidance.

Aptamers are capable of binding a wide range of biomolecular targets with high affinity and specificity. It has been widely developed for diagnostic and therapeutic purposes. Because of unique three dimensional structures and cell-membrane penetration, aptamers inhibit virus infection not only through binding specific target, such as the viral envelope, genomic site, enzyme, or other viral components, but also can be connected to each other or with siRNA jointly achieve antiviral activity. Taking human immunodeficiency virus and hepatitis C virus as examples, this paper reviewed the effects and mechanisms of aptamers on disturbing viral infection and replication steps. It may provide an insight to the development of aptamer-based new antiviral drugs.

Lignan compounds have a variety of pharmacological activities. The mechanism of anti-HIV lignans is through affecting a particular aspect of HIV replication cycle, thus inhibiting viral replication and infection. Lignan is divided into four categories based on different anti-HIV detection methods. In this paper, we summarize the advance in the study on anti-HIV lignan compounds in last two decades.

AIDS is a serious threat to the human health. Although highly active anti-retroviral therapy (HAART) has obviously prohibited the progress of AIDS, a yearly increasing problems of human immunodeficiency virus (HIV) drug resistance have arousing more attention, affecting the clinical efficacy of HAART, and even resulting in treatment failure. We are lack of exchangeable medicines, while the therapeutic course of AIDS treatment is longer. It is not feasible to monitor and detect the drug resistance of medicine takers by taking the exchangeable medicines as the outcome. Better indications have been obtained by combining the experiences for Chinese medicine and pharmacy (CMP) intervention and CMP's intervening HIV drug resistance by clinical trails. Based on retrospective studies on the HIV biological features, reasons for HIV drug resistance, the occurrence, the predisposing population, and the mutation sites, the authors addressed it is a good opportunity for CMP in intervening HIV drug resistance at present situation in China. Meanwhile, the authors also raised too much difficulties and challenges. We hope CMP's intervention can minimize and delay the generation of drug resistance to the utmost, solve key problems in HIV/AIDS prevention and control in China.

Objective: To survey the prevalence of drug resistant HIV in Zhejiang province in 2009-2011., Methods: WHO truncated sequential sampling technique was adopted annually by using 63, 62 and 57 samples of newly diagnosed as HIV positive and aged 16-25 years in Hangzhou, Ningbo and Wenzhou from 2009 to 2011, respectively. RNA was prepared and HIV pol region was amplified by RT-PCR and nested PCR. Pol genetic mutation associated with drug resistance was analyzed., Results: The success rates for sequence acquisition of the survey were 82.5% (52/63), 95.2% (59/62) and 94.7% (54/57) from year 2009 to 2011, respectively, and the main subtype was CRF01&#95;AE (68.5% (37/54)-71.2% (37/52)). A total of 4 surveillance drug-resistance mutation (SDRMs), 2 SDRMs and 2 SDRMs were found by analyzing the 47 sequences each year, sampled from year 2009 to 2010, respectively, indicating that the prevalence of drug resistant HIV stains was moderate in 2009, and low for the next two years (2010-2011). A total of 8 individuals with drug resistant HIV stains found in this study were all infected by sexual transmission, especially in homosexual transmission (6 cases), and the main subtype was CRF01&#95;AE (7 cases). SDRMs for protease inhibitor (PI), nucleotide HIV-reverse transcriptase inhibitor (NRTI) and non-NRTI (NNRTI) (L90M, T215S and Y188L) were all found in one case., Conclusion: The prevalence of drug resistant HIV stains in major areas with AIDS epidemic in Zhejiang province was low in 2009-2011.

Objective: To understand the prevalence and evolution of HIV drug-resistant strains in people who live with HIV/AIDS (PLWHA) during HIV antiretroviral therapy in Shandong province., Methods: Viral load testing was performed by using fluorescence real-time quantitative PCR (NucliSens EasyQ system) on 324 patients who were under HIV antiretroviral therapy (ART) over 1 year in Shandong province. HIV resistance testing was conducted on the samples with more than 1000 copies/ml by using genotypic resistance testing method established in our lab. We tested the samples from drug-resistant patients before and after treatment to analyze the evolution of HIV resistant strains., Results: The resistance rate for the patients under HIV ART over 1 year was 6.2% (20/324). The rate of drug-resistant mutation, but not resistant to ART was 0.6% (5/324). Nucleoside reverse transcriptase inhibitor (NRTIs) and non-NRTIs (NNRTIs) accounted for 93.1% (94/101) and protein inhibitors (PIs) accounted only 6.9% (7/101) of all mutations. M184V (48.0%, 12/25) and Y181C (32.0%, 8/25) were the most frequent mutations among 25 samples. Our research showed 20.0% (2/10) patients were resistant to primary ART and 1 patient was detected drug resistance in 6 months after ART treatment. HIV evolved from wild type to drug resistant virus, from low level to high level drug resistance, and from resistance to few to multiple drugs. In addition, interactions between mutations may influence the sensitivity of patients to other drug treatment., Conclusion: The prevalence of HIV drug-resistant strains in Shandong province is still at a low level, but its evolution is complex.

Betulinic acids are lupine-type pentacyclic triterpenoid saponins commonly found in some plants of Betulaceae family, especially in the bark of betula alba (birch). The potent anti-HIV and anti-tumor activities of betulinic acids have been greatly concerned. The natural betulinic acids include betulinic acid, 23-hydroxy betulinic acid, betulin and so on. Some investigations on the structural modifications of betulinic acids were carried out, and many derivatives with excellent biological activity have been obtained nowadays. In this paper, the research advances of the structural modification of betulinic acids, as well as their anti-HIV and anti-tumor activities are reviewed.

Anti-HIV drugs still remain as the dominant role in the treatment of acquired immunodeficiency syndrome (AIDS), because no vaccine was found till today. Owing to structural diversity, few side effects, and abundant resources, natural compounds from traditional Chinese medicines and medicinal plants have unique advantages and good potential in prevention and treatment of AIDS. Many researchers have made great efforts in the field of anti-HIV natural compounds, and have found some natural compounds from traditional Chinese medicines with potent anti-HIV activities. These compounds can be classified into the following categories: alkaloids, coumarins, lignans, flavonoids, terpenoids, tannins, polysaccharides, proteins and peptides, and polyphenols. However, most of these researches are performed in vitro, and most natural compounds show weak anti-HIV activities and indefinite acting targets. In the paper, we reviewed some natural compounds derived from traditional Chinese medicines with potent anti-HIV activities in recent years.

As the spreading of AIDS over the world, to research effective anti-HIV drugs is required. The review contains the process of discovering targets for anti-HIV especially entry/infuse, reverse transcriptase, protease and integrase, and describes the effective component of traditional Chinese drugs for these targets and the anti-HIV drugs being researched or used in clinic.

3',4'-Di-O-(S)-comphanoyl-(+)-cis-khellactone (DCK) is a synthetic khellactone ester that exhibits potent anti-HIV activity with a mechanism distinct from clinically used anti-HIV agents. Several series of DCK analoges have been synthesized and evaluated for inhibitory effects against HIV. This review article describes recent progress in the discovery, structural modification, and structure-activity relationship studies of potent anti-HIV DCK derivatives.

Objective: To study the CD8+ cell noncytotoxic antiviral response (CNAR) to HIV in nosocomial HIV infected individuals, and reveal the relationship between the CNAR and CD4+ cell count., Method: CD8+ cells from HIV-1 sero-positive individuals were separated by immunomagnetic beads and mixed with CD4+ cells at different CD8 CD4 cell input ratios (2:1, 1:1, 0.5:1 and 0.25:1). Reverse transcriptase (RT) activity of cocultured supernatant was tested and compared with negative control and the suppression rate of HIV-1 replication was measured., Result: The average CD8:CD4 cell input ratios to reach 80% suppression of HIV replication in the group with CD4 < 300/microl and CD4 > 300/microl were 2.4:1 and 1.3:1, respectively (P < 0.05)., Conclusion: CNAR activity in HIV infected individuals is associated with CD4+ cell count. The ability to suppress HIV replication in subjects with CD4 > 300 is stronger than those with CD4 < 300.

This paper summarized the recent 6 years' progress of anti-HIV compounds and traditional Chinese medicines by searching international network and reviewing the domestic and foreign literature. Traditional Chinese medicinal appeared to be a rich source of potentially useful materials for the treatment of human immunodeficiency virus infection. Some of them are much more potent in anti-HIV activity. And some components extracted from the herbs are even more tonic than the crude herb medicines. It has been proved that some active components such as alkaloids, proteins, flavonoids, quercetin, terpene, lignanoid are able to work on anti-HIV. People should pay more attention to the study of traditional Chinese medicine and the leading compounds on anti-HIV/AIDS in the clinic and in the laboratory. So searching for high efficacy and low toxicity anti-HIV drug from traditional Chinese medicine is an important and prospective research direction in the future.

Objective: To study the dynamic changes of T lymphocyte subsets of AIDS patients during more than 24 months of highly active antiretrovirus therapy (HAART) with successful suppression of HIV replication and different CD4 + T cell restoration., Methods: Totally 45 AIDS patients who had received HAART for more than 24 months were included. During HAART (including DO, M3, M6, M12, M18, and M24), the number of plasma HIV-1 RNA was measured quantitatively using the bDNA assay, and T lymphocyte subsets including CD3 + CD4 + cells, CD3 + CD8 + cells, naive CD4 + cells (CD4 + CD45RA + CD62L +), CD4 + CD28 + cells , and CD8 + CD38 + cells were detected with flow cytometer., Results: Among 45 patients, 24 patients (53.3%) whose plasma viral load decreased to less than 500 copies/ml at M6 and maintained to M24 were classified into three groups according to the CD4 + T cell count increments on M24 (compared with DO): group A (< 100/mm3), group B (100-200/mm3), and group C (> 200/mm3). After the initiation of HAART, T lymphocyte response, including CD4 + T cell counts, naive CD4 + cell counts, percentages of CD4 + CD28 + cells in these patients were improved gradually, while CD8 + CD38 + percentage decreased. The improvement of T lymphocyte response in group C was most remarkable even with highest plasma viral load and lowest CD4 T cell count on DO. Compared with group A and B, group C had significantly better improvement not only in the quantities of CD4 + T cell, but also in the CD28 + expression and naive CD4 + T cell populations., Conclusions: T lymphocyte response of AIDS patients can be effectively reconstituted by HAART. Different dynamics of CD4 + CD28 + and naive CD4 + populations may considerably contribute to the quantity and cellular function restoration of CD4 + T lymphocyte.

Thirty-three chinese medicinal herbs reputed by ancient chinese folklore to have anti-infective properties were extracted. The extracts and their compounds were tested for inhibitory activity against the human immunodeficiency virus RT in vitro. 8 of the 33 extracts were found to be active. Of these, MBAA9045 was studied in greater depth. We found that it was a noncompetitive inhibitor against HIV-RT. The concentration of MBAA9045 reducing HIV-RT activity by 50% (IC50) was 22 mumol/L. Chinese medicinal herbs appear to be a rich source of potentially useful materials for the treatment of human immunodeficiency virus infection.