Yanling Li

CRF01_AE subtype is associated with X4 tropism and fast HIV progression in Chinese patients infected through sexual transmission.

Background:The molecular epidemiology of the HIV-1 CRF01_AE subtype as a risk factor for fast HIV-1 progression remains poorly understood. Methods:We analyzed HIV-1 tropism by utilizing samples from 201 treatment-naive patients in our multicenter cohort (12 research centers in different provinces of China). Tropism was determined by V3 loop sequencing. Data from 235 treatment-naive patients infected sexually (including aforementioned 201 patients) in this cohort with date of estimated seroconversion (EDS) were retrospectively evaluated. Median time from EDS to AIDS was analyzed by Kaplan–Meier curves. Hazard ratios were determined by Cox proportional model. Results:CRF01_AE subtype was predominant (46.0%), especially in the MSM group. Further analysis revealed that the proportion of X4 tropism was higher in the CRF01_AE subtype (45.5%) than in others (C/CRF07_BC/CRF08_BC, 4.3%; B, 6.1%; Pu200a<0.001). CRF01_AE subtype was associated with faster progression from EDS to AIDS (4.8 vs. 6.4 years, Pu200a=u200a0.018) compared with non-CRF01_AE subtypes. In a multivariate model, the adjusted hazard ratio (aHR) of CRF01_AE was 1.42 (95% confidence interval, CI 0.99–2.03, Pu200a=u200a0.057), independent of HIV-1 viral load; it was also associated with fast progression to advanced immunodeficiency (aHR, 1.81, 95% CI 1.03–3.18, Pu200a=u200a0.038). Conclusion:CRF01_AE, a predominant HIV-1 subtype in Chinese HIV-1 sexually infected patients, tends to be associated with fast progression to AIDS and advanced immunodeficiency, which might be ascribed to high proportion of X4 tropism. Further investigation of these risk factors may have significant implications to clinical practice and policy-making.

Prevalence of hepatitis B and C viruses in HIV-positive patients in China: a cross-sectional study.

Liver disease related to hepatitis B (HBV) and hepatitis C (HCV) may temper the success of antiretroviral therapy (ART) in China. Limited data exist on their prevalence in HIV‐positive Chinese. A multi‐centre, cross‐sectional study was carried out to determine the prevalence and disease characteristics of HBV and HCV co‐infection in HIV‐positive patients across 12 provinces.

Comparison of genotypic resistance mutations in treatment-naive HIV type 1-infected patients in Korea and China.

Seventy-six treatment-naive human immunodeficiency virus (HIV)-1-infected patients were recruited from Korea and China to evaluate transmitted drug resistance (TDR). Although no major TDR was observed within the study population, some resistance-associated mutations in the reverse transcriptase region were observed (V118I 9.2%, V179D 7.9%). The frequencies of resistance-associated mutations in NNRTI (V179D) and PI minor mutations were higher in Korean patients compared with Chinese patients (13.6% vs. 0%, 45.5% vs. 12.5%, p < 0.05). Although unique clustering was observed in phylogenetic analyses according to geographic sources, cautious monitoring is recommended due to increasing TDR reports in this area where the population shares close geographic and cultural aspects.

Combination Antiretroviral Therapy Is Associated With Reduction in Liver Fibrosis Scores in HIV-1-Infected Subjects.

Abstract HIV increases the risk of liver disease as do two common coinfections, hepatitis B and C viruses (HBV and HCV). However, whether combination antiretroviral therapy (cART) reverses or exacerbates hepatic fibrosis remains unclear. This was an observational retrospective study. cART-naïve HIV-infected subjects without a history of substance abuse (including alcohol) had liver disease stage determined by aspartate aminotransferase-to-platelet ratio indices (APRIs) and fibrosis-4 (FIB-4) before and 24 and 48 weeks after cART. All the data were retrieved from previously established cohorts. Values before and after cART were compared using Wilcoxon test for paired samples. Regression analyses were used to determine factors associated with moderate-to-severe liver disease. Of the 1105 HIV-infected subjects, 120 were HBV coinfected and 64 were HCV coinfected. About 20% of HIV monoinfected participants had APRI and FIB-4 scores consistent with moderate-to-significant fibrosis compared to ∼36% of HIV–HBV coinfected and 67% to 77% of HIV–HCV coinfected participants. In adjusted analyses compared with HIV monoinfection, HBV coinfection was associated with 1.18-fold higher APRI (Pu200a<u200a0.001) and a 1.12-fold higher FIB-4 (Pu200a=u200a0.007) prior to cART; while HCV coinfection was associated with 1.94-fold higher APRI (Pu200a<u200a0.001) and a 1.43-fold higher FIB-4 (Pu200a<u200a0.001). After 48 weeks of cART, both fibrosis scores decreased in all subjects; however, HCV coinfection was still associated with higher fibrosis scores at week 48 compared to HIV monoinfection. cART was associated with improvement in hepatic fibrosis scores in the majority of HIV-hepatitis coinfected and HIV-monoinfected Chinese participants.

HIV-1 subtype B/B' and baseline drug resistance mutation are associated with virologic failure: a multicenter cohort study in China.

Background:Distribution of HIV-1 subtypes, transmitted drug resistance (TDR)/drug resistance mutation (DRM), and their impact on response to combination antiretroviral therapy remain poorly understood in China. Methods:We analyzed data from our multicenter cohort study with 444 antiretroviral-naive participants recruited between 2008 and 2010. HIV-1 subtype and tropism were determined by V3 sequencing, and TDR/DRM was determined by Pol sequencing. Virologic and immunologic responses were monitored over 96 weeks of follow-up. The initial combination antiretroviral therapy regimen for all patients was nevirapine + lamivudine + zidovudine or stavudine. Analysis 1 included patients who finished 96 weeks of follow-up (n = 379), and analysis 2 included all 444 patients. Results:Subtype B/B′ was associated with higher prevalence of TDR/DRM to nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors. Median time to HIV-1 suppression was 18 weeks in all 3 subtype groups. In Cox proportional models for viral suppression, neither viral tropism nor HIV-1 subtypes had any impact on viral suppression; however, subtypes CRF01_AE and C/CRF07_BC/CRF08_BC were associated with lower risk of virologic failure compared with subtype B/B′, with adjusted hazard ratio of 0.11 (P = 0.032) and 0.06 (P = 0.036), respectively in analysis 1, 0.42 (P = 0.047) and 0.22 (P = 0.008), respectively in analysis 2. This association was attenuated by adding DRM profiles to multivariate regression models. Neither subtype nor HIV-1 tropism affected immunologic response. Conclusions:HIV-1 subtype tended to be associated with virologic but not immunologic response; this effect could be ascribed to baseline DRM.

Prospective Echocardiographic Assessment of Cardiac Structure and Function in Chinese Persons Living With HIV

BACKGROUNDnPersons living with human immunodeficiency virus (HIV) are at increased risk of developing cardiovascular disease. Few studies have focused on echocardiographic abnormalities in this population.nnnMETHODSnChina AIDS Clinical Trial 0810 is a prospective, multicenter cohort study of persons living with HIV (PLWH). We performed an echocardiography substudy of 325 PLWH. We examined the prevalence of left ventricular systolic dysfunction (LVSD), diastolic dysfunction (DD), pulmonary arterial hypertension (PAH), and increased left ventricular mass (ILVM) in antiretroviral therapy (ART)-naive PLWH at baseline and week 48 after initiation of ART.nnnRESULTSnCompared with age- and sex-matched healthy controls, PLWH had a higher prevalence of DD (16.5% vs 7.2%, P < .027) and a marginally significant higher prevalence of LVSD (7.3% vs 2.1%, P = .056). The increase in the prevalence of DD from baseline to week 48 in PLWH was marginally significant (P = .056). No significant difference was observed in the prevalence of LVSD, PAH, or ILVM at baseline and week 48 in PLWH. In logistic regression analysis of all participants, age was significantly associated with LVSD; HIV infection, age, and hypertension were associated with DD whereas HIV infection and hypertension were associated with ILVM at baseline. Logistic regression analysis of PLWH showed that only age was significantly associated with LVSD and DD.nnnCONCLUSIONSnThe prevalence of echocardiographic abnormalities was significantly higher in ART-naive PLWH than in controls. HIV infection was significantly associated with cardiac abnormalities. No significant change in echocardiographic abnormalities was observed after 48 weeks of ART. Longer-term prospective studies are warranted.

Lamivudine Monotherapy-Based cART Is Efficacious for HBV Treatment in HIV/HBV Coinfection When Baseline HBV DNA <20,000 IU/mL.

Background:Although combination antiretroviral therapy (cART) including tenofovir (TDF)+lamivudine (3TC) or emtricitabine (FTC) is recommended for treatment of HIV/HBV coinfected patients, TDF is unavailable in some resource-limited areas. Some data suggest that 3TC monotherapy-based cART may be effective in patients with low pretreatment HBV DNA. Methods:Prospective study of 151 Chinese HIV/HBV coinfected subjects of whom 60 received 3TC-based cART and 91 received TDF+3TC-based cART. Factors associated with HBV DNA suppression at 24 and 48 weeks, including anti-HBV drugs, baseline HBV DNA, and baseline CD4 cell count, were evaluated overall and stratified by baseline HBV DNA using Poisson regression with a robust error variance. Results:Baseline HBV DNA ≥20,000 IU/mL was present in 48.3% and 44.0% of subjects in the 3TC and TDF groups, respectively (P = 0.60). After 48 weeks of treatment, HBV DNA suppression rates were similar between these 2 groups (96.8% vs. 98.0% for 3TC and TDF+3TC, P > 0.999) in subjects with baseline HBV DNA <20,000 IU/mL; whereas in those with baseline HBV DNA ≥20,000 IU/mL, TDF+3TC was associated with higher suppression rates (34.5% vs. 72.5% in 3TC and TDF+3TC groups, respectively, P = 0.002). In stratified multivariate regression, TDF use (RR 1.98, P = 0.010) and baseline HBV DNA (per 1 log increase in International Units Per Milliliter, RR 0.74, P < 0.001) were associated with HBV DNA suppression only when baseline HBV DNA ≥20,000 IU/mL. Conclusion:This study suggests that 3TC monotherapy-based cART is efficacious for HBV treatment through 48 weeks in HIV/HBV coinfection when baseline HBV DNA <20,000 IU/mL. Studies with long-term follow-up are warranted to determine if this finding persists.

The interaction of CD4 T-cell count and nevirapine hepatotoxicity in China: A change in national treatment guidelines may be warranted

Objectives:Nevirapine (NVP), a still widely used nonnucleoside reverse transcriptase inhibitor, can cause severe hepatotoxicity. Previous studies suggest that CD4 cell counts more than 250 cells per microliter in women and more than 400 cells per microliter in men are risk factors for NVP-related hepatotoxicity. These studies have informed Chinese national treatment guidelines. We evaluate whether current Chinese guidelines for NVP use are appropriate. Methods:Longitudinal data were pooled from 2 clinical trials between 2005 and 2009 across mainland China. Five hundred sixty-six antiretroviral therapy–naive Chinese patients were given NVP-containing antiretroviral therapy for 24 weeks. Hepatotoxicity was defined as alanine aminotransferase, aspartate transaminase, or total bilirubin level greater than 1.25 times the upper limit of normal range. Severe hepatotoxicity was defined as greater than 5 times the upper limit of normal range. Results:One hundred ninety-seven (36.1%) patients developed hepatotoxicity during treatment, including 42 (7.7%) patients with severe hepatotoxicity. CD4 cell count more than 250 cells per microliter was an independent predictor for hepatotoxicity both in men [relative risk = 1.22 (95% confidence interval: 1.04 to 1.44)] and in women [relative risk = 1.72 (95% confidence interval: 1.20 to 2.46)]. Severe hepatotoxicity was also more common among all persons with CD4 >250 cells per microliter. Conclusions:Hepatotoxicity was a common adverse effect of NVP among men and women with CD4 >250 cells per microliter. Chinese treatment guidelines should be considered to reflect this risk.

Relationship between HIV infection, antiretroviral therapy, inflammatory markers and cerebrovascular endothelial function among adults in urban China.

Background: Cerebrovascular risk is increased in people living with HIV infection compared with age-matched uninfected individuals. Cerebrovascular endothelial dysfunction related to antiretroviral therapy (ART) and inflammation may contribute to higher stroke risk in HIV infection. Methods: We compared cerebral vasoreactivity—a measure of cerebrovascular endothelial function assessed by the breath-holding index (BHI) using transcranial Doppler ultrasound—between virologically suppressed Chinese HIV-infected individuals followed in an HIV clinic in Beijing, China, and uninfected controls. We constructed mixed-effects models to evaluate the association of HIV, ART, and inflammatory markers with cerebral vasoreactivity. Results: In an unadjusted model, HIV infection was associated with a trend toward lower cerebral vasoreactivity (BHI 1.08 versus 1.26, P = 0.079). In multivariable analyses, cholesterol modified the association between HIV infection and cerebral vasoreactivity (P = 0.015 for interaction). At a lower total cholesterol of 4.15 mmol/L, HIV was associated with lower cerebral vasoreactivity (BHI −0.28, P = 0.019), whereas at a cholesterol of 5.15 mmol/L, the reduction in cerebral vasoreactivity associated with HIV was no longer statistically significant (BHI −0.05, P = 0.64). Among HIV-infected individuals, use of lopinavir/ritonavir compared with efavirenz was associated with lower cerebral vasoreactivity (BHI −0.24, P = 0.040). We did not find a significant association between inflammatory markers and cerebral vasoreactivity. Conclusions: Cerebrovascular endothelial dysfunction associated with HIV infection may be most relevant for individuals with less traditional vascular risk, such as those with lower cholesterol. Further study of the impact of ART on cerebrovascular endothelial function is warranted to aid with ART selection in individuals at high cerebrovascular risk.

Multicenter cohort study of diabetes mellitus and impaired fasting glucose in HIV-infected patients in China.

Background:As life expectancy increases, HIV-infected patients are facing a wide array of metabolic complications, including diabetes mellitus (DM) and impaired fasting glucose (IFG). However, little is known about the incidence of and risk factors for glycemic disorders in Chinese HIV-infected patients. Methods:Longitudinal data were pooled from a multicenter clinical trial of combination antiretroviral regimens between 2009 and 2010 across Mainland China. DM was defined as fasting glucose level ≥7.0 mmol/L and IFG as between 5.6 and 6.9 mmol/L on 2 separate measurements. We calculated the incidence densities of DM and IFG. Risk factors for DM and IFG were also identified. Results:Four hundred fifteen patients contributed 457.35 person-years of follow-up. The incidence densities of DM and IFG were 2.62 and 35.64 per 100 person-years, respectively. In a multivariate analysis, advanced age [adjusted hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.01 to 1.04], hepatitis B virus coinfection (adjusted HR: 1.59, 95% CI: 1.06 to 2.38), and baseline fasting glucose (adjusted HR: 1.28, 95% CI: 1.00 to 1.63) were associated with DM and IFG. Conclusions:A high incidence of DM and IFG was detected in Chinese HIV-infected patients receiving combination antiretroviral therapy. Clinicians should be aware of the potential for an increased risk of glycemic disorders in Chinese HIV-infected patients, particularly those of advanced age, with hepatitis B virus coinfection or high baseline fasting glucose.