Longitudinal impact of compliance with routine CD4 monitoring on all cause deaths among treated people with HIV in China.

Keeping adherence to the continuous and standardized CD4 follow-up monitoring service is of great significance to the control of disease progression and the reduction of avoidable mortality for HIV-infected patients. As non-communicable diseases (NCDs) have become main causes of deaths for people with HIV (PWH) in the era of combination antiretroviral therapy (cART), how and to what extent does adherence to routine CD4 monitoring differentially impact on AIDS-related versus NCDs-related deaths in low- and middle-income countries (LMIC) remains elucidated. A CD4 test index was developed by dividing the actual number of received CD4 tests by the theoretical number of CD4 tests that should have been performed according to national treatment guidelines during the study period, with an index value of 0.8-1.2 reflecting compliance. From 1989 to 2020, 14,571 adults were diagnosed with HIV infection in Dehong Prefecture of Yunnan province in Southwestern China, 6,683 (45.9%) PWH had died with the all-cause mortality of 550.13 per 10,000 person-years, including 3,250 (48.6%) AIDS-related deaths (267.53 per 10,000 person-years). Among patients on cART, the median CD4 test index was 1.0 (IQR 0.6-1.3), and 35.2% had a CD4 test index less than 0.8. Cox proportional hazards regression analysis indicated that PWH with CD4 test index at 0.8-1.2 were at the lowest risk of both AIDS-related (aHR = 0.06; 95%CI: 0.05-0.07) and NCDs-related (aHR = 0.13; 95%CI: 0.11-0.16)deaths. Adherence to routine CD4 monitoring is critical for reducing both AIDS-related and NCDs-related mortality of PWH. An appropriate (once or twice a year) rather than an unnecessarily higher frequency of routine CD4 testing could be most cost-effective in reducing mortality in LMIC.

Untargeted Plasma Metabolomics Reveals Extensive Metabolic Alterations Among Treatment-Naive Human Immunodeficiency Virus/Hepatitis C Virus Co-Infected Patients with Liver Disease Progression.

Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) may induce metabolic disorders and cause liver complications. Therefore, we aim to analyze the metabolite differences among treatment-naive HIV/HCV co-infected patients with versus without liver disease progression (LDP) and HIV mono-infected patients. A cross-sectional study was conducted in 65 HIV/HCV co-infected patients (22 with LDP and 43 without) and 65 HIV mono-infected patients in Dehong prefecture of Yunnan province, China. Plasma metabolomics were measured by gas chromatography-mass spectrometry (MS) and liquid chromatography-MS. Discrimination analysis, pathway enrichment analysis, generalized linear model with binomial distribution, and area under the receiver-operating characteristic curve (AUC) were conducted to identify bilateral differences in metabolites and pathways in different comparison groups. A total of 10,831 with 673 named and 10,158 unnamed metabolites were detected. Compared with HIV/HCV co-infected patients without LDP, phenylalanine, tyrosine, and tryptophan biosynthesis pathway with the increased level of tyrosine were significantly altered among HIV/HCV co-infected patients with LDP. Compared with HIV mono-infected patients, the decreased level of glutamine and increased levels of glutamic acid, arachidonic acid, and its derivatives were identified among HIV/HCV co-infected patients. Metabolite panels adjusted for baseline information had a higher accuracy than baseline model (without metabolite information) in distinguishing HIV/HCV co-infected patients with versus without LDP (AUC 0.951 vs. 0.849, p = .027) and HIV/HCV co-infected patients from HIV mono-infected patients (AUC 0.889 vs. 0.766, p < .001). A novel set of metabolites were found to discriminate HIV/HCV co-infected patients with versus without LDP, and from HIV mono-infected patients, which may have mechanistic and interventional implications.

Microbial translocation is associated with advanced liver fibrosis among people with HIV.

BACKGROUND: The prevalence of liver complications is increasing among people living with HIV, and microbial translocation (MT) might play a vital role. We conducted a prospective cohort study to evaluate the association between plasma biomarkers of MT and liver fibrosis (LF) among people living with HIV in southwest China. METHOD: A total of 665 people living with HIV were enrolled at baseline and had at least one follow-up visit during the 3-year study period. We calculated the Liver Fibrosis Index (FIB-4) to evaluate LF and measured plasma soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP) as surrogate biomarkers for MT. We used ordinal logistic regression to investigate correlates of LF at baseline and used a linear mixed model to examine the association between dynamic changes in MT biomarkers and LF. RESULTS: Of the participants, 61 (9.17%) had advanced LF (FIB-4 >3.25), and 193 (29.02%) had moderate LF (1.45 ≤ FIB-4 ≤ 3.25). Patients with advanced LF had higher plasma levels of sCD14 and LBP than those with moderate or no LF, both at baseline and at follow-up. The following factors were significantly associated with advanced LF: the highest quartile of LBP (adjusted odds ratio [aOR] = 1.69; 95% confidence interval [CI] 1.02~2.81), current intravenous drug use (aOR = 1.82; 95% CI 1.06~3.12), baseline CD4 <200 cells/µl (aOR = 3.25; 95% CI 2.13~4.95), hepatitis C virus coinfection (aOR = 2.52; 95% CI 1.41~4.51) and age >50 years (aOR = 32.66; 95% CI 15.89~66.36). LF progression (increasing FIB-4) was significantly associated with increasing sCD14 level (ß = 1.11; 95% CI 0.97~1.26; p < 0.001) with covariate adjustment. CONCLUSION: The significant relationship between MT and LF may reveal pathogenic mechanisms and potential intervention targets of liver complications among people living with HIV in China.

Location-Based LTE-M Uplink Power Control and Radio Resource Scheduling.

Long-Term Evolution for Metro (LTE-M) is adopted as the data communication system in urban rail transit to exchange bio-direction train-wayside information. Reliable data communication is essential in LTE-M systems for ensuring trains' operation safety and efficiency. However, the inter-cell inference problem exists in LTE results in throughput reduction, especially when trains are in the edge area of adjacent cells, and has negative effects on train operation. The uplink power control and radio resource scheduling scheme is studied in LTE-M system which differentiates from public cellular networks in user numbers and the availability of the trains' locations. Since the locations of the trains are available, the interferences from the neighbouring cells can be calculated, and a location based algorithm together with soft frequency reuse is designed. In addition, a proportional fair algorithm is taken to improve uplink radio resource scheduling considering the fairness to different train-wayside communication service requirements. Through simulation, the practicability of the proposed schemes in communication system of urban rail transit is verified in aspects of radio power control and data communication throughput.

Increase in HIV-1-transmitted drug resistance among ART-naïve youths at the China-Myanmar border during 2009 ~ 2017.

BACKGROUND: HIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART. METHODS: From 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool. RESULTS: The most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p = 0.013). CONCLUSIONS: The increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots.

Frequently Transmission and Close Relationship Among Immigrants in the China-Myanmar Border Region Indicated by Molecular Transmission Analysis From a Cross-Sectional Data.

Background: Accurate identification of molecular transmission clusters (MTCs) and understanding the dynamics of human immunodeficiency virus (HIV) transmission are necessary to develop targeted interventions to prevent HIV transmission. We evaluated the characteristics of antiretroviral therapy-naïve individuals who belonged to HIV-1 MTCs in the China-Myanmar border region to inform targeted effective HIV intervention. Methods: Phylogenetic analyses were undertaken on HIV-1 pol sequences to characterize subtypes or circulating recombinant forms and identify MTCs. MTCs were defined as those with 2 or more sequences having bootstrap support > 80% and a pairwise gene distance less than or equal to 0.03. Factors correlated with MTCs were evaluated using logistic regression analysis. The chi-square test was used to compare differences between Chinese and Burmese participants belonging to MTCs. Results: A total of 900 people had their pol gene successfully sequenced. Twenty-one MTCs were identified and included 110 individuals (12.2%). Individuals in MTCs were more likely to be Burmese [aOR = 2.24 (95% CI: 1.33, 3.79), P = 0.003], be younger [aOR = 0.34 (95% CI: 0.20, 0.58), P < 0.001 for age 26-50 vs. 25 years or younger], have a lower CD4 T cell count [aOR = 2.86 (95% CI: 1.34, 6.11), P = 0.007 for < 200 vs. 350 or greater], and have subtypes CRF07_BC or C [CRF07_BC: aOR = 7.88 (95% CI: 3.55, 17.52), P < 0.001; C: aOR = 2.38 (95% CI: 1.23, 4.62), P = 0.010 compared to CRF01_AE]. In MTCs, Burmese were younger (89.7 vs. 57.7% for age 25 years or younger), had a lower education level (41.0 vs. 8.5% for illiterate), were more likely to be infected through injection drug use (35.9 vs. 12.7%), and had a higher proportion of subtype BC (33.3 vs. 15.5%) and CRF01_AE (20.5 vs. 8.5%) compared to Chinese (P < 0.05 for all). Conclusion: Burmese participants were more likely to belong to MTCs, and most MTCs had both Burmese and Chinese participants. These data highlight the bidirectional transmission of HIV-1 frequently transmission and close relationship among immigrants in the China-Myanmar border region. Local health departments should pay more attention to HIV screening and intervention to immigrants Burmese with the characteristics of younger age, having lower CD4 T cell count and infected with HIV subtypes CRF07_ BC or C.

Plasma Inflammatory Biomarkers Associated with Advanced Liver Fibrosis in HIV-HCV-Coinfected Individuals.

BACKGROUND: HIV and HCV coinfection leads to accelerated liver fibrosis, in which microbial translocation and systemic inflammation might play important roles. OBJECTIVE: This study aimed to provide an extensive profile of the plasma microbial translocation and inflammation biomarkers associated with advanced liver fibrosis among HIV-HCV-coinfected patients. METHODS: This cross-sectional study recruited 343 HIV-HCV-coinfected patients on combination antiretroviral therapy (cART) from a rural prefecture of Yunnan province in Southwest China. The plasma concentrations of sCD14 and 27 cytokines and chemokines were assayed and compared against advanced or mild levels of liver fibrosis. RESULTS: Of the 343 HIV-HCV-coinfected patients, 188 (54.8%) had severe or advanced liver fibrosis (FIB-4 > 3.25). The patients with advanced liver fibrosis (FIB-4 > 3.25 vs. FIB-4 ≤ 3.25) had higher plasma levels of interleukin (IL)-1ß, IL-6, IL-7, IL-9, IL-12, IL-15, IL-17, granulocyte macrophage colony stimulating factor (GM-CSF), Interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), IL-4, IL-10, IL-13, fibroblast growth factor 2 (FGF-basic), and Monocyte chemoattractant protein-1 (MCP-1). Multivariable logistic regression models showed that advanced liver fibrosis was associated with an increased plasma level of IL-1ß, IL-6, IL-7, IL-12, IL-17, GM-CSF, IFN-γ, IL-4, IL-10, MCP-1, Eotaxin, and FGF-basic, with FGF-basic continuing to be positively and significantly associated with advanced liver fibrosis, after Bonferroni correction for multiple comparisons (adjusted odds ratio (aOR) = 1.92; 95%CI: 1.32-2.81; p = 0.001). Plasma sCD14 was also significantly associated with advanced liver fibrosis (aOR = 1.13; 95%CI: 1.01-1.30; p = 0.049). CONCLUSIONS: HIV-HCV-coinfected patients are living with a high prevalence of advanced liver fibrosis which coexists with a mixture of elevated plasma inflammation and microbial translocation biomarkers. The significant associations of advanced liver fibrosis with FGF-basic and sCD14 may reveal pathogenic mechanisms and potential clinical intervention targets for liver fibrosis in HCV-HIV coinfection.

Identifying major drivers of incident HIV infection using recent infection testing algorithms (RITAs) to precisely inform targeted prevention.

BACKGROUND: Recent infection testing algorithms (RITAs) incorporating clinical information with the HIV recency assay have been proven to accurately classify recent infection. However, little evidence exists on whether RITAs would help in precisely identifying major drivers of the ongoing HIV epidemic. METHODS: HIV recency test results and clinical information were collected from 1152 newly diagnosed HIV cases between 2015 and 2017 in Dehong prefecture of Yunnan province, and the efficacy of four different RITAs in identifying risk factors for new HIV infection was compared. RESULTS: RITA 1 uses the recency test only. RITA 2 and RITA 3 combine the recency test with CD4+ T cell count and viral load (VL), respectively. RITA 4 combines both CD4+ T cell count and VL. All RITAs identified the MSM group and young people between 15 and 24 years as risk factors for incident HIV infection. RITA 3 and RITA 4 further identified the Dai ethnic minority as a risk factor, which had not been identified before when only the HIV recency test was used. CONCLUSIONS: By comparing different RITAs, we determined that greater accuracy in classifying recent HIV infection could help elucidate major drivers impacting the ongoing epidemic and thus inform targeted interventions.

Fibrosis-4 index predicts mortality in HIV/HCV co-infected patients receiving combination antiretroviral therapy in rural China.

End-stage liver disease (ESLD) is among leading causes of death for people living with HIV and HCV. Little is known how liver fibrosis score predicts mortality in HIV/HCV co-infected population under combination antiretroviral therapy (cART). A retrospective cohort study of 691 HIV/HCV co-infected patients receiving cART in Yunnan, China from 2005 to 2016 was carried out to explore the association between Fibrosis-4 index (FIB-4) and all-cause mortality. Cox proportional hazard models were used to estimate the hazard ratios (HRs) for FIB-4 and covariates. After a median follow-up of 4.8 years with a total follow-up time of 3,696 person-years (PY), 131 deaths occurred and the all-cause mortality was 3.5 per 100 PY. The mortality was 2.9 (95% CI: 2.3-3.5)/100 PY for the FIB-4 ≤ 3.25 group and 5.8 (4.2-7.4)/100 PY for the FIB-4 > 3.25 group at baseline. People with FIB-4 changed from mild to advanced group showed HR of 1.81 (95% CI: 1.01-3.25) for death, and with FIB-4 sustaining advanced showed HR of 3.11 (1.75-5.54), both compared to those with FIB-4 remained mild, while lower risk of death was observed among married people (HR = 0.63, 95% CI: 0.41-0.99) compared to unmarried, among those with most recent CD4+ T cell counts between 200 and 350 cells/µL (0.50, 0.30-0.86) and > 350 cells/µL (0.25, 0.15-0.41) compared to CD4 under 200 cells/µL. Advanced and progressive liver fibrosis is a strong predictor of all-cause mortality in HIV/HCV co-infected patients under cART in China.

The Transmission and Evolution of HIV-1 Quasispecies within One Couple: a Follow-up Study based on Next-Generation Sequencing.

Next-generation sequencing (NGS) has been successfully used to trace HIV-1 infection. In this study, we investigated the transmission and evolution of HIV-1 quasispecies in a couple infected through heterosexual behavior. A heterosexual couple in which both partners were infected with HIV-1 was followed up for 54 months. Blood samples including whole-blood and plasma samples, were collected at various time points. After HIV-1 subtyping, NGS (Miseq platform) was used to sequence the env region of the HIV-1 quasispecies. Genetic distances were calculated, and phylogenetic trees were generated. We found both partners were infected with HIV-1 subtype circulating recombinant form (CRF), CRF65_cpx. The quasispecies distribution was relatively tightly clustered in the phylogenetic tree during early infection. Over time, the distribution of HIV-1 quasispecies gradually became more dispersed at 12th months, with a progressive increase in gene diversity. By 37th months, the sequences obtained for both partners formed different clusters in the phylogenetic tree. These results suggest that the HIV-1 contact tracing results generated by the Miseq platform may be more reliable than other conventional sequencing methods, which can provide important information about the transmission and evolution of HIV-1. Our findings may help to better target preventative interventions for promoting public health.

An alternative strategy to western blot as a confirmatory diagnostic test for HIV infection.

BACKGROUND: In China, western blot (WB) is the recommended procedure for the diagnosis of HIV infection. However, this technique is time consuming and labor intensive, and its complexity restricts wide application in resource-limited regions. OBJECTIVE: The aim of this study was to evaluate the efficacy of a dry blood spots (DBS)-urine paired enzyme-linked immunosorbent assay (ELISA) test, instead of WB, for HIV antibody detection. STUDY DESIGN: Plasma, DBS, and urine samples were collected from 1213 subjects from different populations. Two diagnostic testing strategies were conducted in parallel. The equivalence of the paired ELISA and WB strategies was assessed. RESULTS: A diagnosis of HIV was determined in 250 subjects according to the paired ELISA test, and in 249 according to the WB strategy. The discordant case was judged HIV-positive during follow-up. In total, 18 subjects were diagnosed with possible HIV using the paired ELISA test, among whom, 11 subjects tested negative with WB, and one was confirmed to be HIV-positive during follow-up. For the remaining 945 subjects, both strategies indicated a negative result. The kappa test indicated good conformity (kappa=0.954) between the two diagnostic strategies. CONCLUSION: The DBS-urine paired ELISA could be applied as an alternative to WB in HIV diagnosis, which would be valuable in resource-limited regions owing to the associated affordability and ease of use.

[Incidence and risk factors of HIV infection among sero-negative spouses of people living with HIV/AIDS in Dehong prefecture, Yunnan province].

OBJECTIVE: To study the incidence rate and risk factors of HIV infection among sero-negative spouses of people living with HIV/AIDS (HIV/AIDS) in Dehong prefecture, Yunnan province. METHODS: A prospective cohort study was conducted from February 2009 to December 2014 in Dehong prefecture, Yunnan province. Questionnaire survey and HIV related tests were carried out once a year. RESULTS: By the end of December 2014, 2 091 sero-negative spouses had been recruited, of whom 1 692 were followed-up for at least one time. RESULTS showed that 34 new HIV infections were identified within 5 494.52 person years of follow-up, for an overall incidence of 0.62 per 100 person years. HIV incidence rates appeared as 0.79 per 100 person years, 0.62 per 100 person years, 0.47 per 100 person years in 2009-2010, 2011-2012, 2013-2014, respectively. Data from the Cox proportional hazard regression model indicated that risk factors of HIV infection among sero-negative spouses of HIV/AIDS were: non-consistent condom use (HR=4.64, 95%CI: 1.89-11.40,P= 0.001), HIV/AIDS delayed antiviral retrovirus therapy (ART) for more than one year (HR=3.70, 95% CI: 1.44-9.49,P=0.007) after the HIV negative spouses were initially recruited, HIV/AIDS did not receive any ART (HR=3.62, 95% CI: 1.14-11.51,P=0.029). CONCLUSIONS: The incidence of HIV infection among sero-negative spouses in Dehong prefecture was relatively low. Publicity on consistent condom use program should be emphasized among sero-negative spouses of HIV/AIDS, together with the timely provision of ART to those HIV/AIDS.

Risk factors for incident HSV-2 infections among a prospective cohort of HIV-1-discordant couples in China.

OBJECTIVES: Identification of risk factors is essential for developing herpes simplex virus type 2 (HSV-2) prevention interventions that could also reduce HIV-1 transmission, particularly among HIV-1-discordant couples. METHODS: A prospective cohort study was conducted among HIV-1-discordant couples from June 2009 to March 2011 in Yunnan province, China. 413 HIV-1-infected partners and 517 HIV-1-uninfected partners who were HSV-2 seronegative or equivocal at enrolment and who had a study partner completing the baseline survey and HSV-2 testing were included in the analysis. RESULTS: HSV-2 incidence was 2.9 per 100 person-years (PY) for HIV-1-infected partners and 4.5 per 100 PY for HIV-1-uninfected partners. At least 36% of incident HSV-2 infections were from outside sexual partner. Among HIV-1-infected partners, multivariate analysis indicated that HSV-2 incidence was significantly higher among those with baseline equivocal HSV-2 result, having an initially HSV-2 seropositive or equivocal partner, reporting no sex with study partner and initiating antiretroviral therapy (ART) during follow-up. Among HIV-1-uninfected partners, multivariate analysis indicated that HSV-2 incidence was significantly higher among those having an initially HSV-2 seropositive partner and reporting sex with study partner ≥5 times/month, but was lower among those having a partner with baseline CD4(+) count ≥350 cells/µL. CONCLUSIONS: Our findings underscore the importance of developing prevention and intervention programmes to reduce HSV-2 transmission among this population. The relationship between ART initiation and HSV-2 seroconversion requires further investigation.

[Analysis on HIV-1 genetics and threshold of drug resistance in Dehong prefecture of Yunnan province in 2013].

OBJECTIVE: To study the HIV-1 genotypes and transmitted drug resistance (TDR) in Dehong prefecture of Yunnan province in 2013. METHODS: Referring to the guidelines for HIV drug resistance threshold survey (HIVDR-TS), 54 plasma samples of recently reported HIV-infected individuals, aged between 16 and 25 years, were collected in Dehong prefecture from January to August 2013. Genotyping of partial pol gene was performed by using reverse transcriptional PCR. HIV-1 genotype. Prevalent levels of HIV-1 drug resistance transmission were analyzed. RESULTS: Forty-eight plasma samples were successfully sequenced and analyzed. Among them, 45.8% were Chinese and the rest 54.2% were all Burmese. Based on pol sequences, identified HIV genotypes included subtype C (41.7%), URF (31.3%), CRF01_AE (12.5%), CRF07_BC (10.4%), CRF08_BC (2.1%) and subtype B (2.1%), C subtype appeared dominated in Chinese while URF was dominated in Burmese. One drug resistant mutation to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was detected in one sequence from Burmese. Based on the statistical method of HIVDR-TS, the prevalence of transmitted HIV-1 drug resistance was adjusted as < 5%. CONCLUSION: Diverse HIV-1 genotypes were found in this study, and the current HIV-1 drug resistant strains transmission was catalogued as at low prevalence level, in Dehong. To prevent the increase of the prevalence of transmitted HIV-1 drug resistance, standard treatment and scientific management for people living with HIV/AIDS should be strictly followed. Meanwhile, relevant surveillance, including drug resistance surveillance should also be performed among cross-border migrant population.

Illicit Heroin and Methamphetamine Use among Methadone Maintenance Treatment Patients in Dehong Prefecture of Yunnan Province, China.

OBJECTIVE: Methadone maintenance treatment (MMT) was introduced to China in 2004 to reduce the harm of injecting drug users (IDUs). However, little is known about continued drug use, especially methamphetamine (MAMP), among MMT patients. METHODS: A survey was conducted among patients attending five major MMT clinics in Dehong Prefecture in 2014 to investigate the heroin and MAMP use and their associated risk factors. Participants were administered with face-to-face interviews, and urine tests for morphine and MAMP. RESULTS: A total of 2,121 were eligible and participated in the study. Among them, 220 (10.4%) were only positive for morphine, 12.9% were only positive for MAMP, and 196 (9.2%) were positive for both morphine and MAMP. Compared with neither use of heroin nor MAMP during MMT, heroin use (not using MAMP) was associated with ethnicity, shorter duration of MMT, lower dose of methadone, and having had no more than two sex partners in the past year; MAMP use (not using heroin) was associated with ethnicity, longer duration of MMT, higher dose of methadone and being aged <30 years (vs. ≥50 years); use of both heroin and MAMP was associated with being Dai minority (vs. Han), a marital status of divorced or widowed, having used drugs for ≥10 years and shorter duration of MMT. CONCLUSION: These findings indicate the complexity in the treatment of heroin users and underscore the importance in prescribing appropriate methadone dosages in order to reduce both heroin and MAMP use.

[Analysis of follow-up and administration of HIV-infected Burmese in Dehong prefecture of Yunnan province].

OBJECTIVE: To compare follow-up and administration of HIV-infected local Chinese and Burmese in Dehong prefecture of Yunnan province, for scientific development of prevention and control measures. METHODS: 14 270 HIV-infected local Chinese and 5 436 HIV-infected Burmese reported from 1989 to December 31, 2013 in Dehong prefecture were recruited as the subjects of study, comparing the differences of follow-up and management, CD4⁺ T lymphocyte count tests and antiretroviral therapy (ART) between the two groups. RESULTS: The proportion of HIV-infected Burmese identified in Dehong prefecture was 27.6% (5 436/19 706) during 1989-2013. The number had been growing rapidly from 17.1% in 1989-2003, 12.4% in 2004 and 14.7% in 2005 to over 51.4% in 2012, hitting 59.4% in 2013 (trends χ² = 1 732.84, P < 0.000 1). The proportion of HIV-infected Burmese among case reports of various characteristics kept rising over the years. By the end of 2013, 8 095 HIV-infected local Dehong residents and 5 326 HIV-infected Burmese were still alive. 95.8% of them were under follow-up, 88.5% having CD4⁺ T lymphocyte count tests, and 78.3% under ART. Among the HIV-infected B urmese, only 19.2% of them were under follow-up, 13.0% having CD4⁺ T lymphocyte count tests, and 6.1% under ART, significantly lower than the local Dehong residents (P < 0.000 1). CONCLUSION: The proportion of follow-up and administration, CD4⁺ T lymphocyte count tests, and ART of HIV-infected Burmese was low in Dehong prefecture, Yunnan province, which called for more effective follow-up and administration measures.

Evaluation of PIMA point-of-care CD4 analyzer in Yunnan, China.

BACKGROUND: CD4 count is used to determine antiretroviral therapy (ART) eligibility. In China, flow cytometers are mostly located in urban areas with limited access by patients residing in remote areas. In an attempt to address this issue, we conducted a study to validate the performance of Alere PIMA point-of-care CD4 analyzer. METHODS: Venous and finger-prick blood specimens were collected from HIV-positive participants from two voluntary counseling and testing sites in Yunnan Province. Both venous and finger-prick blood specimens were tested with the PIMA analyzer. Venous blood specimens tested with the Becton Dickinson FACSCalibur were used as a reference. RESULTS: Venous specimens from 396 and finger-prick specimens from 387 persons were available for analysis. CD4 counts by PIMA correlated well with those from FACSCalibur with an R2 of 0.91 for venous blood and 0.81 for finger-prick blood. Compared to FACSCalibur, the PIMA analyzer yielded lower counts with a mean bias of - 47.0 cells/µl (limit of agreement, [LOA]: -204-110 cells/µl) for venous blood and -71.0 cells/µl (LOA: -295-153 cells/µl) for finger-prick blood. For a CD4 threshold of 350 cells/µl, the positive predictive value (PPV) of PIMA was 84.2% and 75.7% and the negative predictive value (NPV) was 97.6% and 95.8% for venous and finger-prick blood, respectively. For an ART threshold of 500 cells/µl, the corresponding PPV was 90.3% and 84.0% and NPV was 94.3% and 93.4%, respectively. CONCLUSIONS: CD4 counting using venous blood with PIMA analyzers is a feasible alternative to a large flow cytometer to determine ART eligibility.

[Study on HIV-1 related genetics and threshold on drug resistance in Dehong prefecture of Yunnan province in 2012].

OBJECTIVE: To study the HIV-1 genotypes and transmitted drug resistance (TDR) in Dehong prefecture of Yunnan province in 2012. METHODS: Referring to the guidelines for HIV drug resistance threshold survey (HIVDR-TS), 60 plasma samples of recently reported HIV-infected individuals between 16 and 25 years old were collected in Dehong prefecture from January to August 2012. Genotyping of partial pol gene was performed by using reverse transcriptional PCR. HIV-1 genotype and the prevalent levels of HIV-1 drug resistance transmission were analyzed. RESULTS: 52 plasma samples were successfully sequenced and analyzed. Among them, 59.6% were Chinese, and the rest (40.4%) were Burmese. Based on pol sequences, identified HIV genotypes would include unique recombinant forms (URFs, 38.5%), subtype C (34.6%), CRF01_AE (21.2%), CRF08_BC (3.8%), and subtype B (1.9%). One drug resistant mutation to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was detected in respective two sequences. Based on the statistical method of HIVDR-TS, the prevalence of transmitted HIV-1 drug resistance was adjusted as a moderate level (5%-15%). CONCLUSION: Diverse HIV-1 genotypes were found in this study, and the current HIV-1 drug resistant strains transmission was catalogued as moderate prevalence level in Dehong.

[Study on HIV viral load in plasma and drug resistance among AIDS patients receiving antiretroviral treatment in Dehong prefecture,Yunnan province].

OBJECTIVE: To understand HIV rival suppression and drug resistance (HIVDR) among AIDS patients who were receiving antiretroviral treatment (ART) in Dehong prefecture, Yunnan province. METHODS: All AIDS patients who were aged over 15 years and with experience more than six months on ART by the end of 2012 in Dehong prefecture, were enrolled to receive testing for HIV viral load in plasma and genetic mutations associated with HIVDR. RESULTS: A total of 4 390 AIDS patients were qualified for the study according to the selection criteria, of whom 3 964 (90.3%) finally participated in the study. Among them, 2 307(58.2%) had CD4(+) cell counts more than 350 cells/mm³. 3 169 (79.9%) patients showed undetectable plasma HIV viral load which was lower than the detection threshold. Those who had the following factors as:resided in Ruili city, being female, older than 45 years of age, married, heterosexually infected with HIV, having received ART more than 5 years, and CD4(+) cell counts >500 cells/mm³, were more likely to have undetectable plasma virus load, with the differences statistically significant. 402 (10.1%) patients had plasma viral load ≥ 1 000 copies/ml, of whom 353 (87.8%) were successfully amplified and examined for HIVDR. Among them, 198 (56.1% ) were identified to bear genetic mutations associated with HIVDR. Most mutations were related to the resistance to nucleotide reverse transcriptase inhibitors (NNRTIs) or non-nucleotide reverse transcriptase inhibitors (NNRTIs), with M184V and K103N most frequently seen. 12 patients (3.4%) were found to have mutations resistant to protease inhibitors (PI). Data from multiple logistic regression analysis indicated that the period of receiving ART and the initial ART regimen could both significantly predict the occurrence of HIV resistance. CONCLUSION: Viral suppression was highly achieved among ART-prescribed AIDS patients in Dehong prefecture,Yunnan province. However, among those who did not show effective viral suppression, the proportion of HIVDR was high, underscoring the needs for health education so as to improve the adherence to drugs as well as for improving testing for viral load and HIVDR among AIDS patients.