Jennifer M. McGoogan

Antiretroviral Therapy Reduces HIV Transmission in Discordant Couples in Rural Yunnan, China

Background Although HIV treatment as prevention (TasP) via early antiretroviral therapy (ART) has proven to reduce transmissions among HIV-serodiscordant couples, its full implementation in developing countries remains a challenge. In this study, we determine whether Chinas current HIV treatment program prevents new HIV infections among discordant couples in rural China. Methods A prospective, longitudinal cohort study was conducted from June 2009 to March 2011, in rural Yunnan. A total of 1,618 HIV-discordant couples were eligible, 1,101 were enrolled, and 813 were followed for an average of 1.4 person-years (PY). Routine ART was prescribed to HIV-positive spouses according to eligibility (CD4<350 cells/µl). Seroconversion was used to determine HIV incidence. Results A total of 17 seroconversions were documented within 1,127 PY of follow-up, for an overall incidence of 1.5 per 100 PY. Epidemiological and genetic evidence confirmed that all 17 seroconverters were infected via marital secondary sexual transmission. Having an ART-experienced HIV-positive partner was associated with a lower rate of seroconvertion compared with having an ART-naïve HIV-positive partner (0.8 per 100 PY vs. 2.4 per 100 PY, HR = 0.34, 95%CI = 0.12–0.97, p = 0.0436). While we found that ART successfully suppressed plasma viral load to <400 copies/ml in the majority of cases (85.0% vs. 19.5%, p<0.0001 at baseline), we did document five seroconversions among ART-experienced subgroup. Conclusions ART is associated with a 66% reduction in HIV incidence among discordant couples in our sample, demonstrating the effectiveness of Chinas HIV treatment program at preventing new infections, and providing support for earlier ART initiation and TasP implementation in this region.

High Prevalence of HIV-1 Intersubtype B′/C Recombinants among Injecting Drug Users in Dehong, China

Objective To examine the distribution of HIV-1 genotypes among injecting drug users (IDUs) from Dehong, Yunnan province. Materials and Methods Blood samples from a total of 95 HIV-positive IDUs were retrospectively analyzed. Samples were collected between 2005 and 2009 from four cities in Dehong prefecture, western Yunnan province, the geographical origin of the HIV epidemic in China. HIV-1 gag, partial pol, vpr-env fragment, half-genome, or near-full-length sequences were analyzed to determine the HIV-1 genotypes of each subject. Results were compared with findings from past studies of IDUs in Dehong and in neighboring Myanmar. Results We observed a high prevalence of B′/C recombinants (82.4%) among IDUs in Dehong, the structural profiles of which do not match those previously reported in Dehong or in Myanmar. Furthermore, statistically significant differences in geographical and temporal distributions of HIV-1 genotypes were characterized by a predominance of HIV-1 B′/C recombinant forms among older subjects(p = 0.034), subjects from Longchuan district (p = 0.022), and subjects diagnosed between 2000 and 2004 (p = 0.004). Conclusions The increasing prevalence of multiple, new B′/C recombinant forms suggest that HIV-1 intersubtype recombination is substantial and ongoing in western Yunnan. This reflects the high-risk behavior of IDUs in this region and argues the need for stronger monitoring and prevention measures in Dehong and other high-prevalence areas around China.

Mortality and Treatment Outcomes of China's National Pediatric Antiretroviral Therapy Program

BACKGROUND The aim of this study was to describe 3-year mortality rates, associated risk factors, and long-term clinical outcomes of children enrolled in Chinas national free pediatric antiretroviral therapy (ART) program. METHODS Records were abstracted from the national human immunodeficiency virus (HIV)/AIDS case reporting and national pediatric ART databases for all HIV-positive children ≤15 years old who initiated ART prior to December 2010. Mortality risk factors over 3 years of follow-up were examined using Cox proportional hazards regression models. Life tables were used to determine survival rate over time. Longitudinal plots of CD4(+) T-cell percentage (CD4%), hemoglobin level, weight-for-age z (WAZ) score, and height-for-age z (HAZ) score were created using generalized estimating equation models. RESULTS Among the 1818 children included in our cohort, 93 deaths were recorded in 4022 child-years (CY) of observed time for an overall mortality rate of 2.31 per 100 CY (95% confidence interval [CI], 1.75-2.78). The strongest factor associated with mortality was baseline WAZ score <-2 (adjusted hazard ratio [HR] = 9.1; 95% CI, 2.5-33.2), followed by World Health Organization stage III or IV disease (adjusted HR = 2.4; 95% CI, 1.1-5.2), and hemoglobin <90 g/L (adjusted HR = 2.2; 95% CI, 1.2-3.9). CD4%, hemoglobin level, WAZ score, and HAZ score increased over time. CONCLUSIONS Our finding that 94% of children engaged in this program are still alive and of improved health after 3 years of treatment demonstrates that Chinas national pediatric ART program is effective. This program needs to be expanded to better meet treatment demands, and efforts to identify HIV-positive children earlier must be prioritized.

Factors Associated With Mortality of HIV-Positive Clients Receiving Methadone Maintenance Treatment in China

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 Chinas 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/mm(3) (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.

Factors associated with depression and anxiety among patients attending community-based methadone maintenance treatment in China

AIM To estimate the prevalence of, and identify factors associated with, depression and anxiety among community-based methadone maintenance treatment (MMT) clients in China. DESIGN A cross-sectional survey. SETTING Nine MMT clinics, three each from three Chinese provinces (Yunnan, Anhui and Jiangsu) between October 2008 and February 2009. PARTICIPANTS A total of 1301 MMT clients. MEASUREMENTS A questionnaire, including the Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS), and on-site urine drug testing. FINDINGS The prevalence of depression (SDS score≥53) and anxiety (SAS score≥50) in our sample was 38.3% [95% confidence interval (CI)=35.7, 40.9] and 18.4% (95% CI=16.3, 20.5), respectively, with 14.2% (95% CI=12.3, 16.1) displaying symptoms of both. Sample prevalence rates for depression [mean=49.69, standard deviation (SD)=10.34] and anxiety (mean=40.98, SD=10.66) were higher than the national average for each (t(0.05/2, 1300)=19.2, P<0.001 and t(0.05/2, 1300)=8.0, P<0.001, respectively). Employing multi-level modelling techniques, gender (P=0.03) and employment status (P<0.001) were found to be associated significantly with depression in a single-level model; however, in a multi-level mixed model, only employment status (P<0.001) was associated with depression. Gender (P=0.03), education level (P=0.02), marital status (P=0.04), employment status (P<0.001), positive urine drug test results (P=0.02) and daily methadone dose (P<0.001) were found to be associated significantly with anxiety in a single-level model, while only employment status (P<0.01) and positive results for the urine drug test (P=0.04) were associated with anxiety in a multi-level mixed model. CONCLUSIONS A considerable proportion of methadone maintenance treatment clients in China have experienced depression and anxiety during treatment. There is a need to provide tailored mental health interventions for this high-risk population.

Sexual dysfunction improved in heroin-dependent men after methadone maintenance treatment in Tianjin, China.

Objective To investigate whether methadone maintenance treatment (MMT) is correlated with sexual dysfunction in heroin-dependent men and to determine the prevalence and risk factors of sexual dysfunction among men on MMT. Methods The study included a retrospective survey and a cross-sectional survey which contained interviews of 293 men who are currently engaged in MMT. The results of the two surveys were compared. For a subset of 43 participants, radioimmunoassay was additionally conducted using retrospective and prospective blood samples to test the levels of plasma testosterone and luteinizing hormone. Other study evaluations were the International Index of Erectile Function (IIEF-15), and Self-rating Depression Scale. Results Sexual dysfunction in all five IIEF-15 domains (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction) was strongly associated with long-term use of heroin. A decrease in the severity of sexual dysfunction was associated with MMT initiation. Erectile dysfunction, lack of sexual desire, inability to orgasm, and lack of intercourse satisfaction were significantly correlated with increasing age of the participants. Methadone dose and duration of methadone treatment were not found to be associated with sexual dysfunction. The level of plasma testosterone significantly declined during methadone treatment, but results from multivariate analysis indicated low levels of testosterone were not the main cause of sexual dysfunction. No correlation between reported depression status and sexual function was found. Conclusions While high levels of sexual dysfunction were reported by heroin-dependent men in our study before and after MMT initiation, MMT appears to be correlated with improved sexual function in the population of the study.

Mortality among methadone maintenance clients in China: a six-year cohort study.

Objective To assess the overall mortality of methadone maintenance treatment (MMT) clients in China and its associated factors. Methods A total of 1,511 MMT clients, all of whom enrolled in Chinas first eight MMT clinics between March and December 2004, were included in this cohort study and followed for approximately six years, until June 2010. Mortality and its predictors were examined using Cox proportional hazards regression models. Results A total of 154 deaths were observed within 5,391 person-years (PY) of follow-up for an all-cause mortality rate of 28.6 per 1,000 PY. The leading causes of death were drug overdose (33.8%), HIV/AIDS-unrelated disease (21.4%), and HIV/AIDS (16.9%). The all-cause mortality rate of clients engaged in MMT for one year or less was roughly three times that of clients who stayed in MMT for four years or more (14.0 vs. 4.6, p<0.0001), HIV-positive subjects was nearly four times mortality rate than that of HIV-negative individuals (28.1 vs.6.8, p<0.0001). ART-naive HIV-positive subjects had approximately two times higher mortality rate than those receiving ART (31.2 vs. 17.3, <0.0001). After adjusting for confounding variables, we found that being male (HR = 1.63, CI: 1.03–2.57, p = 0.0355) and being HIV-positive (HR = 5.16, CI: 3.70–7.10, p<0.0001) were both associated with higher risk of death whereas increased durations of methadone treatment were associated with a lower risk of death (HR = 0.26, CI: 0.18–0.38, p<0.0001 for two to three years, HR = 0.08, CI: 0.05–0.14, p<0.0001 for four or more years). Conclusion Overall mortality was high among MMT clients in China. Specific interventions aimed at decreasing mortality among MMT clients are needed. Our study supports the need for keeping client at MMT longer and for expanding ART coverage and suggests the potential benefits of integrated MMT and ART services for drug users in China.

Needle and syringe exchange programmes and prevalence of HIV infection among intravenous drug users in China.

AIM To examine the association between needle and syringe exchange programme (NSEP) participation and human immunodeficiency virus (HIV) infection among intravenous drug users (IDUs) in China. DESIGN Cross-sectional survey study design. SETTING Six counties with active NSEP were selected from each of the seven provinces with active NSEP sampled, resulting in a sample of 42 counties in China. PARTICIPANTS Subjects were aged more than 18 years and had injected drugs in the past month before the survey, but were excluded if they were currently enrolled in methadone maintenance treatment in order to avoid mixed effects. MEASUREMENTS HIV prevalence was the primary measure. Odds ratios (ORs), 95% confidence intervals (CIs) and P-values were calculated to evaluate associations between HIV infection and NSEP participation. FINDINGS A total of 3494 IDUs were interviewed, of whom 1928 (55.2%) were NSEP attendees (meaning they had attended NSEP at least once in their life-time). The unadjusted HIV prevalence was 13.9% among NSEP attendees and 16.5% among NSEP non-attendees (meaning IDUs who had never used NSEP services). After adjusting for potential confounders and taking into account the variation between counties, NSEP non-attendees were 1.67 times more likely to be HIV-positive compared to NSEP attendees (OR=1.67, CI=1.19-2.32, P=0.0031). CONCLUSIONS Participation in needle and syringe exchange programmes was associated with a substantially lower risk of HIV infection among intravenous drug users in China. Needle and syringe exchange programmes should be expanded to include those who are needle and syringe exchange programme non-attendees.

Referring heroin users from compulsory detoxification centers to community methadone maintenance treatment: a comparison of three models

BackgroundBoth compulsory detoxification treatment and community-based methadone maintenance treatment (MMT) exist for heroin addicts in China. We aim to examine the effectiveness of three intervention models for referring heroin addicts released from compulsory detoxification centers to community methadone maintenance treatment (MMT) clinics in Dehong prefecture, Yunnan province, China.MethodsUsing a quasi-experimental study design, three different referral models were assigned to four detoxification centers. Heroin addicts were enrolled based on their fulfillment to eligibility criteria and provision of informed consent. Two months prior to their release, information on demographic characteristics, history of heroin use, and prior participation in intervention programs was collected via a survey, and blood samples were obtained for HIV testing. All subjects were followed for six months after release from detoxification centers. Multi-level logistic regression analysis was used to examine factors predicting successful referrals to MMT clinics.ResultsOf the 226 participants who were released and followed, 9.7% were successfully referred to MMT(16.2% of HIV-positive participants and 7.0% of HIV-negative participants). A higher proportion of successful referrals was observed among participants who received both referral cards and MMT treatment while still in detoxification centers (25.8%) as compared to those who received both referral cards and police-assisted MMT enrollment (5.4%) and those who received referral cards only (0%). Furthermore, those who received referral cards and MMT treatment while still in detoxification had increased odds of successful referral to an MMT clinic (adjusted OR = 1.2, CI = 1.1-1.3). Having participated in an MMT program prior to detention (OR = 1.5, CI = 1.3-1.6) was the only baseline covariate associated with increased odds of successful referral.ConclusionFindings suggest that providing MMT within detoxification centers promotes successful referral of heroin addicts to community-based MMT upon their release.

The Human Immunodeficiency Virus Care Continuum in China: 1985–2015

Background Human immunodeficiency virus (HIV) care continuum attrition is a major global public health challenge. Few studies have examined this problem in resource-limited settings. We aimed to assess cumulative, current, and historical achievement along Chinas HIV continuum of care. Methods A nationwide, serial cross-sectional study of all individuals with HIV infection diagnosed in China between 1 January 1985 and 31 December 2015 was conducted using data from Chinas HIV/AIDS information systems. Biennial estimates of the number of persons living with HIV were also used. We defined 7 steps in HIV care continuum as infected (estimated), diagnosed, linked, retained, enrolled, receiving antiretroviral therapy (ART), and virally suppressed. Cumulative, 30-year performance, and biennial performance during the most recent 10 years were examined. Results A total of 573529 persons diagnosed with HIV infection were included. Cumulatively, 94% were linked, 88% were retained, 73% were enrolled, 67% were receiving ART, and 44% were suppressed. Greatest attrition was observed for adolescents, minorities, and those who reported injecting drug use as their route of infection. Improvement was observed from 2005 to 2015. As of the end of 2015, 68% among those infected were diagnosed, 67% among diagnosed were receiving ART, and 65% among those receiving ART were virally suppressed. After adjusting for those without viral load testing, the proportion suppressed increased to 89%. Conclusions Despite dramatic improvements, China faces serious challenges in achieving the Joint United Nations Programme on HIV/AIDS 90-90-90 targets, because of substantial attrition along its continuum of HIV care.