Lingjie Liao

Impact of HIV drug resistance on virologic and immunologic failure and mortality in a cohort of patients on antiretroviral therapy in China.

Objectives:To study the dynamics of HIV drug resistance (HIVDR) and its association with virologic and immunologic failure as well as mortality among patients on combination antiretroviral therapy (cART) in China. Design:We recruited 365 patients on cART in two rural Chinese counties in 2003–2004 and followed them every 6 months until May 2010. Methods:Virologic failure, HIVDR, immunologic failure and death were documented. We used Kaplan–Meier and the proportional hazards models to identify the timing of the events, and risk factors for mortality. Results:At the end of study, patients had been followed for 1974.3 person-years, a median of 6.1 years. HIVDR mutations were found in 235 (64.4%) patients and 75 died (20.5%, 3.8/100 person-years). Median time from cART to detection of virologic failure was 17.5 months, to HIVDR 36.6 months and to immunologic failure 55.2 months (≈18-month median interval between each adverse milestone). Being male, having a baseline CD4+ cell count of less than 50 cells/&mgr;l and HIVDR were associated with higher mortality. Patients who developed HIVDR in the first year of treatment had higher mortality than those developing HIVDR later (adjusted hazard ratio 1.90, 95% confidence interval 1.01–3.48). Conclusion:HIVDR was common and was associated with higher mortality among Chinese patients on cART, particular when HIVDR was detected early in therapy. Our study reinforces the importance of improving patient adherence to cART in order to delay the emergence of HIVDR and obviate the need to switch to costly second-line drug regimens too early.

HIV Drug Resistance and Its Impact on Antiretroviral Therapy in Chinese HIV-Infected Patients

Background Highly active antiretroviral therapy (HAART) has significantly decreased mortality among Chinese HIV patients. However, emerging HIV drug resistance (HIVDR) poses a growing threat to the long-term success and durability of HAART. Methods Three cross-sectional surveys were conducted across the country from 2004 to 2006, respectively. Patients completed a questionnaire and provided blood for CD4 cell count, HIV viral load (VL), and HIV resistance genotyping. Factors associated with HIVDR were identified by logistic regression. Results 3667 unique patients were included across the three surveys. Among 2826 treatment-experienced patients, median duration of treatment was 17.4 (IQR 8.6–28.4) months and HIVDR was identified in 543 (19.2%). Factors significantly associated with HIVDR included ART drug distribution location, CD4 cell count, initial HAART regimen, self-reported medication adherence, and province. Conclusions Virologic failure increased over time on therapy but a significant proportion of patients in failure had no resistance mutations identified, suggesting that treatment adherence is suboptimal and must be emphasized. Due to the significantly higher risk of HIVDR in certain provinces, additional steps to reduce HIVDR should be taken.

Surveys of Transmitted HIV Drug Resistance in 7 Geographic Regions in China, 2008–2009

In 2003, antiretroviral therapy became available free of charge in Chinas public health sector. During 2008 and 2009, 10 surveys to classify transmitted human immunodeficiency virus drug resistance (HIVDR) were conducted in 7 regions in 5 provinces (autonomous regions and municipalities) according to World Health Organization guidance. In 2008, transmitted HIVDR was classified as low (<5%) to nucleoside reverse-transcriptase inhibitors, nonnucleoside reverse-transcriptase inhibitors, and protease inhibitors in 6 surveys performed in 6 regions. In 2009, 3 of 4 surveys showed low rates of transmitted HIVDR to all drug classes, and 1 survey showed moderate (5%-15%) rates of transmitted protease inhibitor resistance. In China, routine surveillance of transmitted HIVDR should continue and be expanded to other regions of the country.

Virologic outcomes of first-line HAART and associated factors among Chinese patients with HIV in three sentinel antiretroviral treatment sites

Objective  To evaluate HIV drug resistance (HIVDR) among Chinese patients with HIV receiving first‐line highly active antiretroviral therapy (HAART).

Incidence and associated factors of HIV drug resistance in Chinese HIV-infected patients receiving antiretroviral treatment.

Background A critical indicator of the future success of highly active antiretroviral therapy (HAART) is the incidence of HIV drug resistance, which has not been studied in China on the national scale. Methods HIV drug resistance baseline survey was conducted in the eight provinces with the largest numbers of patients on HAART in 2009, and a prospective cohort study with 12-month follow-up was completed in 2010. Patients completed an interviewer-administrated questionnaire and provided blood for CD4+ T-lymphocyte count (CD4 count), HIV viral load (VL), and HIV drug resistance genotyping. Factors associated with incidence of HIVDR were identified by Cox regression analysis. Results The overall prevalence of HIV RNA ≥1000 copies/ml and HIVDR at baseline was 12.4% and 5.6%, respectively. Incidence of HIVDR in the one year follow-up was 3.5 per 100 person years. Independently associated factors were started treatment with a didanosine-based regimen, received care at township hospital or village clinic, low baseline CD4 counts, and high baseline VL. Conclusions The incidence of HIVDR in China was higher than that of some developed countries. China urgently needs to provide comprehensive education and training to doctors at village clinics and township hospitals to improve quality community-based care and treatment.

Trends of HIV subtypes and phylogenetic dynamics among young men who have sex with men in China, 2009–2014

To investigate the origins of HIV transmission and phylogenetic dynamics among men who have sex with men (MSM), a total of 1205 newly diagnosed HIV-infected 16–25 year-olds were recruited in 13 provinces across China between 2009 and 2014. Based on phylogenetic analyses of partial pol sequences, HIV-1 subtypes including CRF01_AE (45.3%), CRF07_BC (37.8%), subtype B (6.1%), and B’ (3.7%), as well as some other recombinants (7.1%) were identified. In addition to two distinct CRF01_AE clusters [cluster 4 (33.7%, 406/1205) and cluster 5 (7.1%, 85/1205)], we identified a new CRF07_BC cluster (cluster 1) (36.0%, 434/1205), which entered Chinese MSMs in 2004, and had been rapidly spreading since about 2004, which indicating the third wave of the HIV epidemic among the population. Moreover, two new clusters of CRF_01B recombinants were found in this study. The complexities of HIV subtypes and recombinants strongly supports the necessity for a comprehensive study about risk behaviors and their relationship with increasing HIV epidemic subtypes among the MSM group. Implementation and evaluation of comprehensive harm reduction strategies in Chinese MSM are urgently needed.

HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China

Objective To explore HIV virological failure and drug resistance among injecting drug users (IDUs) receiving first-line antiretroviral treatment (ART) in China. Design A series of cross-sectional surveys from 2003 to 2012 from the Chinese National HIV Drug Resistance (HIVDR) Surveillance and Monitoring Network. Setting China. Participants Data were analysed by the Chinese National (HIVDR) Surveillance and Monitoring Network from 2003 to 2012. Demographic, ART and laboratory data (CD4+ cell count, viral load and drug resistance) were included. Factors associated with virological failure were identified by logistic regression analysis. Results 929 of the 8556 individuals in the Chinese HIVDR database were IDUs receiving first-line ART. For these 929 IDUs, the median duration of treatment was 14 months (IQR 6.0–17.8). 193 of the 929 IDUs (20.8%) experienced virological failure (HIV viral load ≥1000 copies/mL). The prevalence of HIVDR among patients with virological failure was 38.9% (68/175). The proportion of patients with drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTIs), nucleoside reverse transcriptase inhibitor (NRTIs) and protease inhibitors (PIs) was 52.9%, 76.5% and 4.4%, respectively. Factors independently associated with virological failure include: ethnic minorities, junior high school education or less, farmers, self-reported missing doses in the past month, CD4 cell count at survey from 200 to 349 cells/mm3 or from 0 to 199 cells/mm3, and residence of Guangxi and Yunnan provinces. Conclusions The proportion of virological failure was high among IDUs receiving first-line ART in China. However, better treatment outcomes were observed in Guangxi and Yunnan, which indicates the importance of ART education and adherence to intervention, especially for patients who are farmers, minorities or have a poor educational background.

Virological outcomes and drug resistance in Chinese patients after 12 months of 3TC-based first-line antiretroviral treatment, 2011-2012.

Objective To determine the prevalence of virological failure and HIV drug resistance among Chinese patients one year after initiating lamivudine-based first-line antiretroviral treatment. Methods A prospective cohort study with follow-up at 12 months was conducted in four urban sentinel sites in China. Antiretroviral naive patients ≥18 years old were recruited. Blood samples were collected for testing CD4 cell count, viral load, and (for samples with HIV-1 RNA ≥1000 copies/ml) genotyping of drug resistance. Results A total of 513 patients were enrolled in this cohort, of whom 448 (87.3%) were retained at 12 months. The median final CD4 cell count was 313 cells/mm3, which increased from 192 cells/mm3 at baseline (P<0.0001). Of the 448 remaining subjects, 394 (87.9%) had successful virological suppression (HIV RNA <1000 copies/ml). Among 54 samples with viral load ≥1000 copies/ml, 40 were successfully genotyped, and 11 were found with detectable HIV drug resistance mutations. Of these, the proportions of drug resistance to NNRTIs, NRTIs and PIs were 100%, 81.8% and 0%, respectively. Injecting drug use (AOR = 0.40, 95% CI: 0.19,0.84; P = 0.0154), CD4 count at baseline ≥350 cells/mm3 (AOR = 0.32, 95% CI: 0.14,0.72; P = 0.0056), and missed doses in the past month (AOR = 0.30, 95% CI: 0.15,0.60; P = 0.0006) were significantly negatively associated with HIV RNA <1000 copies/ml. Conclusions Our study demonstrates effective virological and immunological outcomes at 12 months among these who initiated first-line ART treatment. However, patients infected through drug injection, who missed doses, or with higher CD4 count at baseline are at increased risk for poor virological response.

The sexually driven epidemic in youths in China’s southwestern border region was caused by dynamic emerging multiple recombinant HIV-1 strains

Dehong prefecture, Yunnan province on China’s southwestern border was the gateway of the country’s AIDS epidemic. Studies on HIV-1 molecular epidemiology will provide key information on virus transmission dynamics and help to inform HIV prevention strategies. HIV-1 infected youths (age 16–25 years) diagnosed in the continuous 3 months in 2009 to 2012 were enrolled. By means of phylogenetic and statistical analyses, It was showed that two thirds (133/205) of youths in Dehong, of which 74.1% were infected sexually, were infected by uncharacterized recombinant HIV-1 strains. Among them about 59.4% (79/131) were unique recombinant forms (URFs) and 40.6% (54/131) formed 11 transmission clusters, termed potential circulating recombinant forms (pCRFs). The emergence of recombinants was statistically significant related with people of low education, residents outside the capital city of Dehong and being Myanmar residents. It was the first report with ongoing HIV-1 recombinant strains in a sexually driven epidemic area in China. Great efforts should be put on reducing multiple risk exposures behavior in local young people, containing the spread of pCRFs to other regions, and preventing the URFs from evolving into future CRFs. Collaborative prevention across border is needed to better control the local AIDS epidemic.

Efficacy and HIV drug resistance profile of second-line ART among patients having received long-term first-line regimens in rural China.

Antiretroviral therapy has significantly expanded and an increased proportion of patients have switched to second-line regimens in China. We describe the outcomes of second-line therapy among patients having received long-term first-line ART. A prospective follow-up study was conducted in rural areas in China. We compared the virological, immunological outcomes and genotypic drug resistance (DR) profiles before and after regimen switches. A total of 303 patients were enrolled, 283 (93.4%) were retained at 12 months. Of 90 participants with HIV-RNA ≥ 1000 copies/ml before switch, the proportion of viral load (VL) ≥ 1000 copies/ml at 6 and 12 months was 49.4% and 43.9%, respectively. Of 213 patients with HIV-RNA < 1000 copies/ml before switch, the proportion of VL ≥ 1000 copies/ml at 6 and 12 months was 4.8% and 6.5%, respectively. The rates of drug resistance to NNRTIs, NRTIs, PIs decreased from 65.5%, 53.3%, and 1.1% before regimen switch to 26.8%, 18.3%, and 0% at 12 months, respectively. DDI-based initial ART regimens and missing doses in past month were associated with HIV RNA ≥ 1000 copies/ml at 12 months. The results showed that patients having received long-term first-line ART and experiencing virological failure had good virological outcomes after switching to second-line treatment in China.