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1.  Association of Blood Biomarkers of Bone Turnover in HIV-1 Infected Individuals Receiving Anti-Retroviral Therapy (ART) 
Objective
To evaluate the association of bone turnover biomarkers with blood levels of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), osteocalcin (OC), tartrate-resistant acid phosphatase (TRAP), parathyroid hormone (PTH), and other blood markers in HIV-1 infected men receiving anti-retroviral therapy (ART). Advances in the treatment of HIV-1 infection have extended the life span of HIV-1 infected individuals. However, these advances may come at the price of metabolic side effects and bone disorders, including premature osteopenia, osteoporosis and osteonecrosis.
Methods
Analyses of Ostase BAP, osteocalcin, and TRAP in blood were measured in three groups of MACS participants: 35 HIV-1 infected men on ART (A); 35 HIV-1- infected men not on ART (B); and 34 HIV-1 uninfected men (C).
Results
The mean and standard deviation results for groups A, B, and C were 19.7 ± 6.56, 17.2 ± 3.96, and 16.9 ± 5.78 for ostase BAP; 7.9 ± 9.53, 8.5 ± 8.30, and 5.5 ± 1.65 for osteocalcin; and 3.9 ± 1.04, 3.1 ± 0.81, and 2.5 ± 0.59 for TRAP, respectively. Simple and multivariate analyses showed significant differences in mean TRAP and BAP concentrations between the three groups. In addition strong correlations between blood levels of Ostase BAP and TRAP (r=0.570, p=0.0004), and between blood levels of Ostase BAP and PTH (r=0.436, P=0.0098) for HIV-1 infected men on ART were observed.
Conclusion
New strategies for measurement of blood and urine biochemical markers of bone formation and resorption during bone turnover can be useful for clinical monitoring of treatment of HIV-1 infected patients. Recently developed methods for measuring serum levels of TRAP and Ostase BAP represent superior laboratory tools for assessing the hyperactivity of osteoclasts, osteoblasts and bone loss in HIV-1 infected individuals receiving ART. Measurements of TRAP and BAP as bone turnover biomarkers are economical and are important for monitoring bone metabolism during ART and the need for osteoporosis treatment.
doi:10.4172/2155-6113.1000360
PMCID: PMC4332849
Alkaline phosphatase; HIV infection; Osteocalcin; Osteoporosis; Parathyroid hormone; Tartrate-resistant acid phosphatase
2.  Factors Associated with Loss-to-Follow-Up during Behavioral Interventions and HIV Testing Cohort among Men Who Have Sex with Men in Nanjing, China 
PLoS ONE  2015;10(1):e115691.
Background
Behavioral interventions (BIs) remained the cornerstone of HIV prevention in resource-limited settings. One of the major concerns for such efforts is the loss-to-follow-up (LTFU) that threatens almost every HIV control program involving high-risk population groups.
Methods
To evaluate the factors associated with LTFU during BIs and HIV testing among men who have sex with men (MSM), 410 HIV sero-negatives MSM were recruited using respondent driven sampling (RDS) in Nanjing, China during 2008, they were further followed for 18 months. At baseline and each follow-up visits, each participant was counseled about various HIV risk-reductions BIs at a designated sexually transmitted infection (STI) clinic.
Results
Among 410 participants recruited at baseline, altogether 221 (53.9%) were LTFU at the 18-month follow-up visit. Overall, 46 participants were found to be positive for syphilis infection at baseline while 13 participants were HIV sero-converted during the follow-up period. Increasing age was less (Adjusted Odds Ratio(aOR) of 0.90, 95% confidence Interval (CI) 0.86–0.94) and official residency of provinces other than Nanjing (AOR of 2.49, 95%CI 1.32–4.71), lower level of education (AOR of 2.01, 95%CI 1.10–3.66) and small social network size (AOR of 1.75, 95%CI 1.09–2.80) were more likely to be associated with higher odds of LTFU.
Conclusion
To improve retention in the programs for HIV control, counseling and testing among MSM in Nanjing, focused intensified intervention targeting those who were more likely to be LTFU, especially the young, less educated, unofficial residents of Nanjing who had smaller social network size, might be helpful.
doi:10.1371/journal.pone.0115691
PMCID: PMC4283967  PMID: 25559678
3.  HIV Infection is associated with reduced pulmonary diffusing capacity 
Journal of acquired immune deficiency syndromes (1999)  2013;64(3):10.1097/QAI.0b013e3182a9215a.
Rationale:
Prior studies comparing abnormalities in pulmonary function between HIV-infected and HIV-uninfected persons in the current era are limited.
Objectives:
To determine the pattern and severity of impairment in pulmonary function in HIV-infected compared to HIV-uninfected individuals.
Methods:
Cross-sectional analysis of 300 HIV-infected and 289 HIV-uninfected men enrolled from 2009-2011 in two clinical centers of the Lung HIV Study. Participants completed pre- and post-bronchodilator spirometry, diffusing capacity (DLCO) measurement, and standardized questionnaires.
Results:
Most participants had normal airflow; 18% of HIV-infected and 16% of HIV-uninfected men had airflow obstruction. The mean percent predicted DLCO was 69% in HIV-infected vs. 76% in HIV-uninfected men (p<0.001). A moderately to severely reduced DLCO of ≤60% was observed in 30% of HIV-infected compared to 18% of HIV-uninfected men (p<0.001), despite the fact that 89% of those with HIV were on antiretroviral therapy. A reduced DLCO was significantly associated with HIV and CD4 cell count in linear regression adjusting for smoking and other confounders. The DLCO was lowest in HIV-infected men with CD4 cell counts <200 compared to those with CD4 cell counts ≥200 and to HIV-uninfected men. Respiratory symptoms of cough, phlegm and dyspnea were more prevalent in HIV-infected patients particularly those with abnormal pulmonary function compared to HIV-uninfected patients.
Conclusions:
HIV infection is an independent risk factor for reduced DLCO, particularly in individuals with a CD4 cell count below 200. Abnormalities in pulmonary function among HIV-infected patients manifest clinically with increased respiratory symptoms. Mechanisms accounting for the reduced DLCO require further evaluation.
doi:10.1097/QAI.0b013e3182a9215a
PMCID: PMC3845879  PMID: 23979001
Pulmonary function; FEV1; DLCO; gas exchange; COPD; HIV/AIDS
4.  Temporal stability of serum concentrations of cytokines and soluble receptors measured across two years in low-risk HIV seronegative men 
Background
Prospective cohort studies often quantify serum immune biomarkers at a single time point to determine risk of cancer and other chronic diseases that develop years later. Estimates of the within-person temporal stability of serum markers partly assess the utility of single biomarker measurements, and may have important implications for the design of prospective studies of chronic disease risk.
Methods
Using archived sera collected from 200 HIV-seronegative men at three visits spaced over approximately two years, concentrations of 14 biomarkers (ApoA1, sCD14, sgp130, sIL-6R, sIL-2Rα, sTNFR2, BAFF/BLyS, CXCL13, IFN-γ, IL-1β, IL-6, IL-8, IL-10, TNF-α) were measured in a single laboratory. Age-and ethnicity-adjusted intraclass correlation coefficients (ICC) were calculated for each biomarker, and mixed linear regression models were utilized to examine the influence of age, ethnicity, season, and study site on biomarker concentrations.
Results
Across all three study visits, most biomarkers had ICC values indicating fair to excellent within-person stability. ApoA1 (ICC=0.88)and TNF-α (ICC=0.87) showed the greatest stability; the ICC for IL-8 (ICC=0.33) was remarkably less stable. The ICCs were similar when calculated between pairs of consecutive visits. The covariables did not influence biomarker levels or their temporal stability. All biomarkers showed moderate to strong pairwise correlations across visits.
Conclusions
Serum concentrations of most evaluated immune biomarkers displayed acceptable to excellent within-person temporal reliability over a 2-year period. Further investigation may be required to clarify the stability of IL-8.
Impact
These findings lend support to using these serologic immune biomarkers in prospective studies investigating associations with chronic diseases.
doi:10.1158/1055-9965.EPI-13-0379
PMCID: PMC3829469  PMID: 23983237
Temporal stability; biomarkers; cytokines; soluble receptors; intraclass correlation coefficient
5.  TLR2 activated B cells are phenotypically similar to the abnormal circulating B cells seen preceding the diagnosis of AIDS related non-Hodgkin lymphoma (NHL) diagnosis 
Background
AIDS-related non-Hodgkin lymphoma (AIDS-NHL) is a common AIDS-defining cancer. Prior studies suggest that chronic B cell activation precedes AIDS-NHL diagnosis. Activation of B cells by multiple factors, including Toll-like receptor (TLR) signaling, leads to the expression of activation-induced cytidine deaminase (AID), a DNA mutating molecule that can contribute to oncogene translocations/mutations, leading to NHL. The goal of this study was to determine whether surface markers expressed on activated and/or germinal center (GC) B cells, and AID expression, were elevated on circulating B cells preceding AIDS-NHL, as well as to determine if TLR signaling contributes to this activated B cell phenotype.
Methods
Stored viable peripheral blood mononuclear cell (PBMC) specimens, obtained prior to AIDS-NHL diagnosis, were assessed by multi-color flow cytometry. Additionally, B cells isolated from PBMC were exposed to TLR ligands in vitro, after which B cell phenotype was assessed by flow cytometry.
Results
An elevated fraction of B cells expressing CD10, CD71, or CD86 was seen in those who went on to develop AIDS-NHL. AID expression was detected in some who developed AIDS-NHL, but not in HIV+ or HIV− controls. TLR2- stimulated purified B cells exhibited the activated B cell phenotype observed in HIV+ subjects prior to AIDS-NHL diagnosis.
Conclusions
These results indicate that an elevated fraction of B cells display an activated/GC phenotype in those HIV+ subjects who go on to develop AIDS-NHL, and suggest that TLR2-mediated activation may play a role in HIV infection-associated B cell activation, potentially contributing to the genesis of AIDS-NHL.
doi:10.1097/QAI.0b013e31829d4d50
PMCID: PMC3778065  PMID: 23722608
Immunophenotype; HIV; AIDS lymphoma; non-Hodgkin lymphoma; activation induced cytidine deaminase (AID); Toll-like receptor (TLR)
7.  Sexual Risk Behaviors among Club Drug Users in Shanghai, China: Prevalence and Correlates 
AIDS and behavior  2013;17(7):2439-2449.
We surveyed 276 club drug users in Shanghai, China. Overall, 43.8% reported ≥2 sex partners in the past 30 days, and 48.9% reported having sex with non-regular partners, 67.4% of whom had unprotected sex. Having ≥2 recent sex partners was associated with being 35 years or older, male, living with friends or others, introduced to club drug use by non-regular sex partners, using methamphetamine recently, self-identified as gay/lesbian or bisexual, had sexual debut before 20 years old, and recently had sex under the influence of drugs. Having unprotected sex with non-regular partners in the past 30 days was associated with lower education levels, having sex to obtain drugs, and lower levels of HIV/AIDS knowledge. Club drug users should be targeted for intervention programs. Future research needs to identify other protective and risk factors for sexual risk behaviors and design interventions to reduce club drug use and associated sexual risk behaviors.
doi:10.1007/s10461-012-0380-1
PMCID: PMC3624056  PMID: 23247360
club drugs; new-type drugs; methamphetamine; sexual risk behaviors; HIV; China
8.  Circumstances of initiation into new-type drug use among adults in Shanghai: Are there differences by types of first new-type drug used? 
Drug and alcohol dependence  2013;131(3):278-283.
Background
This study investigated circumstances of initiating new-type drug use among adult new-type drug users and differences among those who first used methamphetamine, ecstasy and ketamine.
Methods
A total of 276 participants were recruited, using respondent-driven sampling (RDS) from nine seeds recruited through NGOs, social workers and outreach workers in Shanghai, China.
Results
Methamphetamine was the most frequently reported first new-type drug used (37.1%), followed by ecstasy (35.6%) and ketamine (20.0%). 38.7% of participants initiated new-type drug use before the age of 21 years. 47.8% knew at initiation that club drugs can be harmful. Most were introduced to new-type drug use by friends, spouses or boy/girlfriends. The three most common reasons for initiation were curiosity, peer influence, and wishing to dull one’s emotions. Those first using methamphetamine were more likely to be female, have a monthly individual income less than 3000 Yuan (app $476), initiate use at 21 years or older and at private setting than those first using ecstasy and ketamine.
Conclusions
There is an urgent need for drug education efforts in China to raise awareness of the harms of new-type drugs, as well as to increase knowledge about the paradox of new-type drug effects. Drug prevention and intervention programs should be tailored to target populations and their social context.
doi:10.1016/j.drugalcdep.2012.12.019
PMCID: PMC3644522  PMID: 23312339
new-type drugs; initiation; methamphetamine; ecstasy; ketamine; China
9.  Factors Associated With Mortality of HIV-Positive Clients Receiving Methadone Maintenance Treatment in China 
The Journal of Infectious Diseases  2013;208(3):442-453.
Background. Little is known about mortality of opiate users attending methadone maintenance treatment (MMT) clinics. We sought to investigate mortality and its predictors among human immunodeficiency virus (HIV)–positive MMT clients.
Methods. Records of 306 786 clients enrolled in China's MMT program from 24 March 2004 to 30 April 2011 were abstracted. Mortality rates were calculated for all HIV-positive antiretroviral treatment (ART)–naive and ART-experienced clients. Risk factors were examined using stratified proportional hazard ratios (HRs).
Results. The observed mortality rate for all clients was 11.8/1000 person-years (PY, 95% confidence interval [CI], 11.5–12.1) and 57.2/1000 PY (CI, 54.9–59.4) for HIV-positive clients (n = 18 193). An increase in average methadone doses to >75 mg/day was associated with a 24% reduction in mortality (HR = 0.76, CI, .70–.82), a 48% reduction for ART-naive HIV-positive clients (HR = 0.52, CI, .42–.65), and a 47% reduction for ART-experienced HIV-positive clients (HR = 0.53, CI, .46–.62). Among ART-experienced clients, initiation of ART when the CD4+ T-cell count was >300 cells/mm3 (HR = 0.64, CI, .43–.94) was also associated with decreased risk of death.
Conclusions. We found high mortality rates among HIV-positive MMT clients, yet decreased risk of death, with earlier ART initiation and higher methadone doses. A higher daily methadone dose was associated with reduced mortality in both HIV-infected and HIV-uninfected clients, independent of ART.
doi:10.1093/infdis/jit163
PMCID: PMC3698997  PMID: 23592864
mortality; HIV; drug users; methadone maintenance treatment; China
10.  HIV/AIDS Patients’ Medical and Psychosocial Needs in the Era of HAART: A Cross-sectional Study among HIV/AIDS Patients Receiving HAART in Yunnan, China 
AIDS care  2012;25(7):915-925.
Background
Since the launch of China’s Free Antiretroviral Therapy (ART) Program in 2002, more than 100,000 HIV/AIDS patients have been treated with highly actively antiretroviral therapy (HAART). However, the current evaluation system for this program mainly focused on its medical outcomes. This study aims to evaluate the medical and psychosocial needs of HIV/AIDS patients after initiating HAART.
Methods
A cross-sectional study was conducted among 499 HIV/AIDS patients who were currently being treated with HAART in three designated hospitals in Luxi City, Yunnan Province. A questionnaire was used to collect information about participants’ demographic characteristics, perceived HIV-related stigma, physician-patient relationship, quality of life, family functioning, etc. Patients’ medical records in the National HIV Information System were linked with their questionnaire by their ART identification number.
Results
Patients on HAART who were infected with HIV through injection drug use and were current smokers typically had poorer physical health than other participants on HAART. Better financial status and better physician-patient relationship were associated with both physical and psychological well-being. Family awareness of the patient’s HIV status was negatively associated with the patient’s psychological well-being. Higher levels of perceived HIV-related stigma were associated with poorer psychological health and poorer family functioning.
Conclusion
This study emphasizes the importance of assuring a caring environment in China’s AIDS treatment program and re-enforces the need to combat the stigma encountered with health providers and the public.
doi:10.1080/09540121.2012.729804
PMCID: PMC3586758  PMID: 23061980
HIV/AIDS; HAART; Patient’s need
11.  Incident Hepatitis C Virus Infection in Men Who Have Sex With Men: A Prospective Cohort Analysis, 1984–2011 
In the United States, incident hepatitis C among men who have sex with men has been ongoing since at least 1984. Risk factors included unprotected receptive anal intercourse with multiple partners, HIV infection, and lower CD4 T-cell count among HIV-infected men.
Background Prospective characterization of hepatitis C virus (HCV) transmission in both human immunodeficiency virus (HIV)–infected and –uninfected men who have sex with men (MSM) over the entire HIV epidemic has not been comprehensively conducted.
Methods To determine the trends in and risk factors associated with incident HCV in MSM since 1984, 5310 HCV antibody (anti-HCV)–negative MSM in the Multicenter AIDS Cohort Study were prospectively followed during 1984–2011 for anti-HCV seroconversion.
Results During 55 343 person-years (PYs) of follow-up, there were 115 incident HCV infections (incidence rate, 2.08/1000 PYs) scattered throughout the study period. In a multivariable analysis with time-varying covariates, older age (incidence rate ratio [IRR], 1.40/10 years, P < .001), enrollment in the later (2001–2003) recruitment period (IRR, 3.80, P = .001), HIV infection (IRR, 5.98, P < .001), drinking >13 alcoholic drinks per week (IRR, 1.68, P < .001), hepatitis B surface antigen positivity (IRR, 1.68, P < .001), syphilis (IRR, 2.95, P < .001), and unprotected receptive anal intercourse with >1 male partner (IRR, 3.37, P < .001) were independently associated with incident HCV. Among HIV-infected subjects, every 100 cell/mm3 increase in CD4 count was associated with a 7% (P = .002) decrease in the HCV incidence rate up to a CD4 count of 500 cells/mm3, whereas there was no association with highly active antiretroviral therapy.
Conclusions The spread of HCV among both HIV-infected and -uninfected MSM in the United States has been ongoing since the beginning of the HIV epidemic. In HIV-infected men with <500 CD4+ T cells, the HCV incidence rate was inversely proportional to CD4 T-cell count.
doi:10.1093/cid/cit197
PMCID: PMC3669529  PMID: 23532480
incident HCV; sexual transmission; MSM
12.  Reducing STD/HIV stigmatizing attitudes through community popular opinion leaders in Chinese markets 
Human communication research  2012;38(4):379-405.
Reducing STDs and HIV/AIDS incidence requires campaigns designed to change knowledge, attitudes and practices of risky sexual behavior and its consequences. In China, a significant obstacle to such changes is the stigma associated with these diseases. Thus one campaign intervention strategy is to train credible community popular opinion leaders to discuss these issues in everyday social venues. This study tested the effectiveness of such an approach on reducing HIV/AIDS stigma, across two years, from a sample of over 4500 market vendors, in three conditions. Results showed an increasing growth in market communication about intervention messages, and concomitant declines in stigmatizing attitudes, across time, with the greatest changes in community popular opinion leaders, significant changes in intervention non-opinion leaders, and little change in the control markets.
doi:10.1111/j.1468-2958.2012.01436.x
PMCID: PMC4059367  PMID: 24944433
STD; HIV; communication campaign; public opinion leader; stigma; China; repeated measures
13.  Long-term predictive value of the Framingham Risk Score for Stroke in HIV-positive vs HIV-negative men 
Neurology  2013;81(24):2094-2102.
Objective:
To test the predictive accuracy of the Framingham Risk Score for Stroke (FRS-S) in HIV-infected (HIV+) vs HIV-uninfected (HIV−) men.
Methods:
The Multicenter AIDS Cohort Study (MACS) is an ongoing prospective study of HIV+ and HIV− men who have sex with men (MSM) enrolled in 4 US cities. We ascertained all reported stroke events during a recent 15-year timeframe (July 1, 1996 to June 30, 2011) among 3,945 participants (1,776 HIV+ and 2,169 HIV−). For those with strokes, FRS-S were calculated 10 years before the stroke event and assessed according to HIV status.
Results:
A total of 114 stroke events occurred, including 57 HIV+ and 37 HIV− participants with first-ever strokes and 19 fatal strokes. The incidence of first-ever stroke was 1.7/1,000 person-years among HIV− and 3.3/1,000 person-years among HIV+ participants. Among those with strokes, HIV+ participants were younger than HIV− participants (median age 51.3 vs 61.8 years, p < 0.0001). For these men with stroke, the average 10-year risk of stroke was higher for HIV− MSM (6.6% [range 3%–26%] vs 4.9% for HIV+ MSM [range 0%–15%], p < 0.04). Traditional risk factors for stroke were similar among the Framingham cohort and the MACS HIV+ and HIV− participants.
Conclusions:
FRS-S prediction was systematically different in HIV+ vs HIV− men with stroke events. The FRS-S underestimates the long-term risk of stroke in HIV+ men.
doi:10.1212/01.wnl.0000437296.97946.73
PMCID: PMC3863354  PMID: 24212385
14.  Baseline CD4 Cell Counts of Newly Diagnosed HIV Cases in China: 2006–2012 
PLoS ONE  2014;9(6):e96098.
Background
Late diagnosis of HIV infection is common. We aim to assess the proportion of newly diagnosed HIV cases receiving timely baseline CD4 count testing and the associated factors in China.
Methods
Data were extracted from the Chinese HIV/AIDS Comprehensive Response Information Management System. Adult patients over 15 years old who had been newly diagnosed with HIV infection in China between 2006 and 2012 were identified. The study cohort comprised individuals who had a measured baseline CD4 count.
Results
Among 388,496 newly identified HIV cases, the median baseline CD4 count was 294 cells/µl (IQR: 130–454), and over half (N = 130,442, 58.8%) were less than 350 cells/µl. The median baseline CD4 count increased from 221 (IQR: 63–410) in 2006 to 314 (IQR: 159–460) in 2012. A slight majority of patients (N = 221,980, 57.1%) received baseline CD4 count testing within 6 months of diagnosis. The proportion of individuals who received timely baseline CD4 count testing increased significantly from 20.0% in 2006 to 76.9% in 2012. Factors associated with failing to receiving timely CD4 count testing were: being male (OR: 1.17, 95% CI: 1.15–1.19), age 55 years or older (OR:1.03, 95% CI: 1.00–1.06), educational attainment of primary school education or below (OR: 1.30, 95% CI: 1.28–1.32), infection with HIV through injection drug use (OR: 2.07, 95% CI: 2.02–2.12) or sexual contact and injection drug use (OR: 1.87, 95% CI: 1.76–1.99), diagnosis in a hospital (OR: 1.91, 95% CI: 1.88–1.95) or in a detention center (OR: 1.75, 95% CI: 1.70–1.80), and employment as a migrant worker (OR:1.55, 95% CI:1.53–1.58).
Conclusion
The proportion of newly identified HIV patients receiving timely baseline CD4 testing has increased significantly in China from 2006–2012. Continued effort is needed for further promotion of early HIV diagnosis and timely baseline CD4 cell count testing.
doi:10.1371/journal.pone.0096098
PMCID: PMC4047021  PMID: 24901790
15.  Acute HIV-1 Seroconversion with an Unusual Plasma Biomarker Profile 
Clinical and Vaccine Immunology : CVI  2013;20(11):1774-1777.
An unusual case of acute primary HIV-1 infection in a man with a high plasma viral load, a 51-fold increase in C-reactive protein, and antibodies against only gp160 is described. Numerous serum cytokine concentrations were elevated during HIV-1 seroconversion.
doi:10.1128/CVI.00366-13
PMCID: PMC3837784  PMID: 24006141
16.  Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts 
Background
Several lung diseases are increasingly recognized as comorbidities with HIV; however, few data exist related to the spectrum of respiratory symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective of the study is to determine the impact of HIV on prevalence and incidence of respiratory disease in the current era of effective antiretroviral treatment.
Methods
A pulmonary-specific questionnaire was administered yearly for three years to participants in the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS). Adjusted prevalence ratios for respiratory symptoms, testing, or diagnoses and adjusted incidence rate ratios for diagnoses in HIV-infected compared to HIV-uninfected participants were determined. Risk factors for outcomes in HIV-infected individuals were modeled.
Results
Baseline pulmonary questionnaires were completed by 907 HIV-infected and 989 HIV-uninfected participants in the MACS cohort and by 1405 HIV-infected and 571 HIV-uninfected participants in the WIHS cohort. In MACS, dyspnea, cough, wheezing, sleep apnea, and incident chronic obstructive pulmonary disease (COPD) were more common in HIV-infected participants. In WIHS, wheezing and sleep apnea were more common in HIV-infected participants. Smoking (MACS and WIHS) and greater body mass index (WIHS) were associated with more respiratory symptoms and diagnoses. While sputum studies, bronchoscopies, and chest computed tomography scans were more likely to be performed in HIV-infected participants, pulmonary function tests were no more common in HIV-infected individuals. Respiratory symptoms in HIV-infected individuals were associated with history of pneumonia, cardiovascular disease, or use of HAART. A diagnosis of asthma or COPD was associated with previous pneumonia.
Conclusions
In these two cohorts, HIV is an independent risk factor for several respiratory symptoms and pulmonary diseases including COPD and sleep apnea. Despite a higher prevalence of chronic respiratory symptoms, testing for non-infectious respiratory diseases may be underutilized in the HIV-infected population.
doi:10.1186/1471-2466-14-75
PMCID: PMC4021087  PMID: 24884738
AIDS; HIV; Pulmonary disease; Chronic obstructive; Respiratory tract diseases; Sleep apnea syndromes
17.  Serum levels of the chemokine CXCL13, genetic variation in CXCL13 and its receptor CXCR5, and HIV-associated non-Hodgkin B cell lymphoma risk 
Background
CXCL13 and CXCR5 are a chemokine and receptor pair whose interaction is critical for naïve B cell trafficking and activation within germinal centers. We sought to determine whether CXCL13 levels are elevated prior to HIV-associated non-Hodgkin B-cell lymphoma (AIDS-NHL), and whether polymorphisms in CXCL13 or CXCR5 are associated with AIDS-NHL risk and CXCL13 levels in a large cohort of HIV-infected men.
Methods
CXCL13 levels were measured in sera from 179 AIDS-NHL cases and 179 controls at three time-points. TagSNPs in CXCL13 (n=16) and CXCR5 (n=11) were genotyped in 183 AIDS-NHL cases and 533 controls. Odds ratios (OR) and 95% confidence intervals (CIs) for the associations between one unit increase in log CXCL13 levels and AIDS-NHL, as well as tagSNP genotypes and AIDS-NHL, were computed using logistic regression. Mixed linear regression was used to estimate mean ratios (MR) for the association between tagSNPs and CXCL13 levels.
Results
CXCL13 levels were elevated >3 years (OR=3.24, 95% CI=1.90–5.54), 1–3 years (OR=3.39, 95% CI=1.94–5.94) and 0–1 year (OR=3.94, 95% CI=1.98–7.81) prior to an AIDS-NHL diagnosis. The minor allele of CXCL13 rs355689 was associated with reduced AIDS-NHL risk (ORTCvsTT=0.65; 95% CI=0.45–0.96) and reduced CXCL13 levels (MRCCvsTT=0.82, 95% CI=0.68–0.99). The minor allele of CXCR5 rs630923 was associated with increased CXCL13 levels (MRAAvsTT=2.40, 95% CI=1.43–4.50).
Conclusions
CXCL13 levels were elevated preceding an AIDS-NHL diagnosis, genetic variation in CXCL13 may contribute to AIDS-NHL risk, and CXCL13 levels may be associated with genetic variation in CXCL13 and CXCR5.
Impact
CXCL13 may serve as a biomarker for early AIDS-NHL detection.
doi:10.1158/1055-9965.EPI-12-1122
PMCID: PMC3703445  PMID: 23250934
Non-Hodgkin Lymphoma; HIV; CXCL13; CXCR5; chemokine
18.  Factors Affecting the Prevalence of Strongly and Weakly Carcinogenic and Lower-Risk Human Papillomaviruses in Anal Specimens in a Cohort of Men Who Have Sex with Men (MSM) 
PLoS ONE  2013;8(11):e79492.
Background
MSM are at higher risk for invasive anal cancer. Twelve human papillomaviruses (HPVs) cause cervical cancer in women (Group 1 high-risk HPVs (hrHPVs)) and 13 HPVs are probable/possible causes (Group 2 hrHPVs) of cervical malignancy. HPVs rarely associated with malignancy are classified as lower-risk HPVs (lrHPVs).
Materials and Methods
Dacron-swab anal-cytology specimens were collected from and data complete for 97% (1262/1296) of Multicenter AIDS Cohort Study (MACS) men tested for HPVs using the Linear Array assay. Multivariate Poisson regression analyses estimated adjusted prevalence ratios for Group 1/2 hrHPVs and lrHPVs, controlling for the effects of age, race, ethnicity, sexual partnerships, smoking; HIV-infection characteristics, treatment, and immune status among HIV-infected men.
Results
HIV-infected men showed 35–90% higher prevalence of Group 1/2 hrHPVs and lrHPVs than HIV-uninfected men, and higher prevalence of multi-Type, and multiple risk-group infections. CD4+ T-cell count was inversely associated with HPV Group 2 prevalence (p<0.0001). The number of receptive anal intercourse (RAI) partners reported in the 24 months preceding HPV testing predicted higher prevalence of Group 1/2 hrHPVs. Men reporting ≥30 lifetime male sex partners before their first MACS visit and men reporting ≥1 RAI partners during the 24 months before HPV testing showed 17–24% and 13–17% higher prevalence of lrHPVs (p-values ≤0.05). Men reporting smoking between MACS visit 1 and 24 months before HPV testing showed 1.2-fold higher prevalence of Group 2 hrHPVs (p = 0.03). Both complete adherence to CART (p = 0.02) and HIV load <50 copies/mL (p = 0.04) were protective for Group 1 hrHPVs among HIV-infected men.
Conclusions
HIV-infected men more often show multi-type and multi-group HPV infections HIV-uninfected men. Long-term mutual monogamy and smoking cessation, generally, and CART-adherence that promotes (HIV) viremia control and prevents immunosuppression, specifically among HIV-infected MSM, are important prevention strategies for HPV infections that are relevant to anal cancer.
doi:10.1371/journal.pone.0079492
PMCID: PMC3835810  PMID: 24278140
19.  Feasibility of Recruiting a Diverse Sample of Men Who Have Sex with Men: Observation from Nanjing, China 
PLoS ONE  2013;8(11):e77645.
Background
Respondent-driven-sampling (RDS) has well been recognized as a method for sampling from most hard-to-reach populations like commercial sex workers, drug users and men who have sex with men. However the feasibility of this sampling strategy in terms of recruiting a diverse spectrum of these hidden populations has not been understood well yet in developing countries.
Methods
In a cross sectional study in Nanjing city of Jiangsu province of China, 430 MSM were recruited including 9 seeds in 14 weeks of study period using RDS. Information regarding socio-demographic characteristics and sexual risk behavior were collected and testing was done for HIV and syphilis. Duration, completion, participant characteristics and the equilibrium of key factors were used for assessing feasibility of RDS. Homophily of key variables, socio-demographic distribution and social network size were used as the indicators of diversity.
Results
In the study sample, adjusted HIV and syphilis prevalence were 6.6% and 14.6% respectively. Majority (96.3%) of the participants were recruited by members of their own social network. Although there was a tendency for recruitment within the same self-identified group (homosexuals recruited 60.0% homosexuals), considerable cross-group recruitment (bisexuals recruited 52.3% homosexuals) was also seen. Homophily of the self-identified sexual orientations was 0.111 for homosexuals. Upon completion of the recruitment process, participant characteristics and the equilibrium of key factors indicated that RDS was feasible for sampling MSM in Nanjing. Participants recruited by RDS were found to be diverse after assessing the homophily of key variables in successive waves of recruitment, the proportion of characteristics after reaching equilibrium and the social network size. The observed design effects were nearly the same or even better than the theoretical design effect of 2.
Conclusion
RDS was found to be an efficient and feasible sampling method for recruiting a diverse sample of MSM in a reasonable time.
doi:10.1371/journal.pone.0077645
PMCID: PMC3828322  PMID: 24244280
20.  Labor force participation and health-related quality of life in HIV-positive men who have sex with men: The Multicenter AIDS Cohort Study 
AIDS and behavior  2012;16(8):2350-2360.
Too many people with HIV have left the job market permanently and those with reduced work capacity have been unable to keep their jobs. There is a need to examine the health effects of labor force participation in people with HIV. This study presents longitudinal data from 1,415 HIV-positive men who have sex with men taking part in the Multicenter AIDS Cohort Study. Generalized Estimating Equations show that employment is associated with better physical and mental health quality of life and suggests that there may be an adaptation process to the experience of unemployment. Post-hoc analyses also suggest that people who are more physically vulnerable may undergo steeper health declines due to job loss than those who are generally healthier. However, this may also be the result of a selection effect whereby poor physical health contributes to unemployment. Policies that promote labor force participation may not only increase employment rates but also improve the health of people living with HIV.
doi:10.1007/s10461-012-0257-3
PMCID: PMC3575137  PMID: 22814570
21.  Value of a Quality Assessment Program in Optimizing Cryopreservation of Peripheral Blood Mononuclear Cells in a Multicenter Study 
Cryopreservation of peripheral blood mononuclear cells (PBMC) allows assays of cellular function and phenotype to be performed in batches at a later time on PBMC at a central laboratory to minimize assay variability. The Multicenter AIDS Cohort Study (MACS) is an ongoing prospective study of the natural and treated history of human immunodeficiency virus (HIV) infection that stores cryopreserved PBMC from participants two times a year at four study sites. In order to ensure consistent recovery of viable PBMC after cryopreservation, a quality assessment program was implemented and conducted in the MACS over a 6-year period. Every 4 months, recently cryopreserved PBMC from HIV-1-infected and HIV-1-uninfected participants at each MACS site were thawed and evaluated. The median recoveries of viable PBMC for HIV-1-infected and -uninfected participants were 80% and 83%, respectively. Thawed PBMC from both HIV-1-infected and -uninfected participants mounted a strong proliferative response to phytohemagglutinin, with median stimulation indices of 84 and 120, respectively. Expression of the lymphocyte surface markers CD3, CD4, and CD8 by thawed PBMC was virtually identical to what was observed on cells measured in real time using whole blood from the same participants. Furthermore, despite overall excellent performance of the four participating laboratories, problems were identified that intermittently compromised the quality of cryopreserved PBMC, which could be corrected and monitored for improvement over time. Ongoing quality assessment helps laboratories improve protocols and performance on a real-time basis to ensure optimal cryopreservation of PBMC for future studies.
doi:10.1128/CVI.00693-12
PMCID: PMC3623420  PMID: 23408528
22.  Job stress and hypertension in younger software professionals in India 
Background:
We report the results of a moderately large study (1071) to study the prevalence of hypertension among software professionals in the Indian subcontinent employed at 27 different companies in Bangalore. The focus of our study is on the age gradient of hypertension prevalence and exploring the association of workplace psychosocial predictors of hypertension.
Materials and Methods:
We used mixed methods sampling strategy, the first stage of which involved stratified sampling to select the clusters of software companies in Bangalore and the second stage involved selecting individual companies through purposive sampling. Job stress questionnaire was self-administered to collect information on job stress and blood pressure classification is done based on 7 th report of Joint National Commission.
Results:
The prevalence of hypertension among Information Technology/Information Technology Enabled Services professionals was 31% and pre-hypertension was 45.7%. The prevalence of stage-1 hypertension in the age group of 19-25 years was 18% and 23% in 26-30 years group while the prevalence of stage-2 hypertension in the age group of 19-25 years was 5% and 3% in 26-30 years group. The results indicate that dimensions of workplace autonomy and workplace environment are associated with hypertension.
Conclusions:
Hypertension affects the young urban Indians a decade earlier compared to available evidence. Furthermore, there is an association of autonomy and work-environment with hypertension. This signifies further exploration of underlying endocrine mechanisms.
Funding:
The funding UCLA International Research and Training Program and the Public Health Foundation of India provided the funding for this study.
Results:
The study was supported through Fogarty/UCLA International Research and Training Program (Grant Number: D43 TW000013) and the Public Health Foundation of India
doi:10.4103/0019-5278.130848
PMCID: PMC4035605  PMID: 24872668
Hypertension in India; hypertension in young urban subjects; job stress
23.  Herpes simplex virus type 2 (HSV-2) as a coronary atherosclerosis risk factor in HIV-infected men: Multicenter AIDS Cohort Study 
Atherosclerosis  2012;223(2):433-436.
We assessed associations of herpes simplex virus types 1 and 2 (HSV-1 and -2), cytomegalovirus (CMV), and human herpesvirus 8 (HHV-8) infection with subclinical coronary atherosclerosis in 291 HIV-infected men in the Multicenter AIDS Cohort Study. Coronary artery calcium (CAC) was measured by non-contrast coronary CT imaging. Markers for herpesviruses infection were measured in frozen specimens collected 10-12 years prior to case identification. Multivariable logistic regression models and ordinal logistic regression models were performed. HSV-2 seropositivity was associated with coronary atherosclerosis (adjusted odds ratio [AOR] =4.12, 95% confidence interval [CI] =1.58-10.85) after adjustment for age, race/ethnicity, cardiovascular risk factors, and HIV infection related factors. Infection with a greater number of herpesviruses was associated with elevated CAC levels (AOR=1.58, 95% CI=1.06-2.36). Our findings suggest HSV-2 may be a risk factor for subclinical coronary atherosclerosis in HIV-infected men. Infection with multiple herpesviruses may contribute to the increased burden of atherosclerosis.
doi:10.1016/j.atherosclerosis.2012.03.002
PMCID: PMC3392500  PMID: 22472456
herpesvirus; HSV-2; atherosclerosis; HIV-1/AIDS; risk factors
24.  HIV Risk-Reduction Counseling and Testing on Behavior Change of MSM 
PLoS ONE  2013;8(7):e69740.
HIV and AIDS incidence in China is high among men who have sex with men (MSM) and ours was one of few studies in China to evaluate the role of HIV risk reduction counseling and testing. Respondent-driven sampling (RDS) was used to recruit 430 MSM. Participants were followed up at 6, 12 and 18 months to evaluate behavioral changes after counseling to reduce risk behaviors. At baseline, HIV prevalence was 4.7%, whereas HIV incidence was 5.2 per 100 person-years. The incidence was 3.8 during six to 12 months, and 1.1 during 12 to 18 months. During the study period, the reported unprotected anal intercourse (UAI) significantly decreased from 60.9% to 42.9%. The proportion of participants who had one or no partner significantly increased from 40.9% to 48.0%. The study also found that some risk behaviors decreased between baseline and 12 months, followed by a slight increase between 12 and 18 months. Reductions in UAI can be achieved through counseling and testing, but may wane over time. Future programs should consider HIV risk-reduction counseling and testing for interventions in MSM in China.
doi:10.1371/journal.pone.0069740
PMCID: PMC3726787  PMID: 23922787
25.  Color-Coded Audio Computer-Assisted Self-Interviews (C-ACASI) for Poorly Educated Men and Women in a Semi-rural Area of South India: “Good, Scary and Thrilling” 
AIDS and behavior  2013;17(6):2260-2268.
It is challenging to collect accurate and complete data on sensitive issues such as sexual behaviors. Our objective was to explore experience and perceptions regarding the use of a locally programmed color-coded audio computer-assisted self interview (C-ACASI) system among men and women in a semi-rural setting in south India. We conducted a mixed-methods cross-sectional survey using semi-structured interviews among 89 truck drivers and 101 truck driver wives who had participated earlier in the C-ACASI survey across a predominantly rural district in Tamil Nadu. To assess the color-coded format used, descriptive quantitative analysis was coupled with thematic content analysis of qualitative data. Only 10 % of participants had ever used a computer before. Nearly 75 % did not report any problem in using C-ACASI. The length of the C-ACASI survey was acceptable to 98 % of participants. Overall, 87 % of wives and 73 % of truck drivers stated that C-ACASI was user-friendly and felt comfortable in responding to the sensitive questions. Nearly all (97 %) participants reported that using C-ACASI encouraged them to respond honestly compared to face-to-face personal interviews. Both the drivers and wives expressed that C-ACASI provided confidentiality, privacy, anonymity, and an easy mechanism for responding truthfully to potentially embarrassing questions about their personal sexual relationships. It is feasible and acceptable to use C-ACASI for collecting sensitive data from poorly computer-literate, non-English-speaking, predominantly rural populations of women and men. Our findings support the implementation of effective and culturally sensitive C-ACASI for data collection, albeit with additional validation.
doi:10.1007/s10461-013-0414-3
PMCID: PMC3711697  PMID: 23361948
Color-coded ACASI; Computer interview; Sensitive questions; Acceptability; Rural India

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