Yijia Li

Introduction: 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.Methods: HIV‐positive ART‐naïve patients were recruited from two parent cohorts established during November 2008–January 2010 and August 2012–September 2014. Hepatitis B surface antigen (HBsAg), hepatitis B e antigen and HCV antibody (anti‐HCV) status were retrieved from parent databases at the visit prior to ART initiation. HBV DNA was then determined in HBsAg+ patients. HCV RNA was quantified in anti‐HCV+ patients. Aspartate aminotransferase‐to‐platelet ratio index (APRI) and the fibrosis‐4 (FIB4) were calculated. Chi‐square test, Kruskal–Wallis test and logistic regression were used for statistical analysis, as appropriate.Results: Of 1944 HIV‐positive patients, 186 (9.5%) were HIV–HBV co‐infected and 161 (8.3%) were HIV–HCV co‐infected. The highest HIV–HBV prevalence (14.5%) was in Eastern China while the highest HIV–HCV prevalence was in the Central region (28.2%). HIV–HBV patients had lower median CD4 + T cell count (205 cells/μL) than either HIV monoinfected (242 cells/μL, P=0.01) or HIV–HCV patients (274 cells/μL, P=0.001). Moderate‐to‐significant liver disease was present in >65% of the HIV–HCV, ~35% of the HIV–HBV and ~20% of the HIV monoinfected patients. Independent associations with moderate‐to‐significant liver disease based on APRI included HBV (Odds ratio, OR 2.37, P < 0.001), HCV (OR 9.64, P<0.001), CD4 count≤200 cells/μL (OR 2.55, P<0.001) and age ≥30 years (OR 1.80, P=0.001).Conclusions: HBV and HCV prevalence is high in HIV‐positive Chinese and differs by geographic region. HBV and HCV co‐infection and HIV monoinfection are risks for moderate‐to‐significant liver disease. Only HIV–HBV is associated with greater HIV‐related immunosuppression. Incorporating screening and management of hepatitis virus infections into Chinese HIV programmes is needed.

In China, HIV-1-infected patients typically receive antiretroviral therapy (ART) that includes lamivudine (3TC) as a reverse-transcriptase inhibitor (RTI) (ART-3TC). Previous studies from certain developed countries have shown that, in ART-3TC, 3TC-resistant HBV progressively emerges at an annual rate of 15–20% in patients coinfected with HIV-1 and HBV. This scenario in China warrants investigation because >10% of all HIV-infected patients in China are HBV carriers. We measured the occurrence of 3TC-resistant HBV during ART-3TC for HIV-HBV coinfection and also tested the effect of tenofovir disoproxil fumarate (TDF) used as an additional RTI (ART-3TC/TDF) in a cohort study in China. We obtained 200 plasma samples collected from 50 Chinese patients coinfected with HIV-1 and HBV (positive for hepatitis B surface antigen) and examined them for the prevalence of 3TC-resistant HBV by directly sequencing PCR products that covered the HBV reverse-transcriptase gene. We divided the patients into ART-3TC and ART-3TC/TDF groups and compared the efficacy of treatment and incidence of drug-resistance mutation between the groups. HIV RNA and HBV DNA loads drastically decreased in both ART-3TC and ART-3TC/TDF groups. In the ART-3TC group, HBV breakthrough or insufficient suppression of HBV DNA loads was observed in 20% (10/50) of the patients after 96-week treatment, and 8 of these patients harbored 3TC-resistant mutants. By contrast, neither HBV breakthrough nor treatment failure was recorded in the ART-3TC/TDF group. All of the 3TC-resistant HBV mutants emerged from the cases in which HBV DNA loads were high at baseline. Our results clearly demonstrated that ART-3TC is associated with the emergence of 3TC-resistant HBV in patients coinfected with HIV-1 and HBV and that ART-3TC/TDF reduces HBV DNA loads to an undetectable level. These findings support the use of TDF-based treatment regimens for patients coinfected with HIV-1 and HBV.

Tenofovir (TDF) and ritonavir-boosted lopinavir (LPV/r) were not introduced to China as second-line medications until 2009. The efficacy and safety of TDF/3TC/LPV/r based second-line regimen have not been evaluated in Chinese HIV patients who failed first-line regimens. This was a multicenter cohort study recruiting patients from Beijing, Shanghai, Guangdong, and Henan provinces between November 2008 and January 2010. Eighty HIV infected patients failing first-line regimens with serum creatinine lower than 1.5 times the upper limit of normal received TDF+ lamivudine (3TC)+ LPV/r were followed up for 120 weeks. CD4 cell count, viral load, and estimated glomerular filtration rate (eGFR) were monitored at each visit. At baseline, 31.2% and 48.8% of patients had moderate/high-level resistance to TDF and 3TC, respectively; while 2.5% of patients had only low-level resistance to LPV/r. During 120 weeks of follow-up, virological suppression rate reached over 70% (2 at baseline to 95.6 ml/min/1.73m² at week 24 and then recovered after week 96. This study for the first time demonstrated that TDF+ 3TC+ LPV/r was efficacious as second-line regimen with acceptable nephrotoxicity profiles in patients who failed zidovudine or stavudine based first-line regimens in China. ClinicalTrials.gov NCT00872417

Methods: We performed a cross-sectional study of Chinese adult ART-naïve HIV-infected patients from September 2005 through August 2014. Socio-demographic variables and laboratory results including platelets, CD4+ cell count, and viral load were obtained from medical records. Factors and outcomes associated with thrombocytopenia were assessed using logistic regression. Results: A total of 1730 adult ART-naïve HIV-infected patients was included. The mean age was 38 years. The prevalence of thrombocytopenia was 4.5%. There were significant differences in the prevalence of thrombocytopenia between patients 350 cells/mm3 (2.8%) compared with patients with CD4+ counts of 50–199 cells/mm3 (7.1%) (P = 0.002 and P = 0.005, respectively). The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab) seropositivity (10.2% for HCV-Ab positive vs. 3.9% for HCV-Ab negative, P = 0.001). We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection: Blood transmission (10.7%) versus men who have sex with men (3.9%) (P = 0.002) and versus heterosexual transmission (3.9%) (P = 0.001). In binary logistic regression analyses, age ≥50 years, HCV-Ab positivity and having a CD4+ cell count of 50–199 cells/mm3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]: 1.167, 5.281, P = 0.018), 2.091 (95% CI: 1.078, 4.055, P = 0.029) and 2.259 (95% CI: 1.028, 4.962, P = 0.042), respectively. Conclusions: Thrombocytopenia is not common among adult ART-naïve HIV-infected patients in China. Older age (age over 50 years), HCV-Ab positivity and lower CD4+ cell count are associated with an increased risk of thrombocytopenia. Therefore, early diagnosis and treatment of thrombocytopenia in these patients are necessary....

The molecular epidemiology of the HIV-1 CRF01_AE subtype as a risk factor for fast HIV-1 progression remains poorly understood. 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. 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%; P <0.001). CRF01_AE subtype was associated with faster progression from EDS to AIDS (4.8 vs. 6.4 years, P = 0.018) 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, P = 0.057), 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, P = 0.038). 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.

Background: An zidovudine (AZT)-substitution regimen containing 24-week stavudine (d4T) followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resourcelimited settings. However, evidence is scarce. This study aims to assess the efficacy and safety of AZT-substitution regimen, aiming to find a regimen with better efficacy, less adverse events, and more affordability in resource-limited settings. Methods: This prospective, multicenter study enrolled 499 (190 on d4T regimen, 172 on AZT regimen, and 137 on AZTsubstitution regimen) HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011. Lamivudine (3TC) and either nevirapine (NVP) or efavirenz (EFV) were the other two drugs in the antiretroviral regimens. Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96. Results: In terms of hematological adverse effects, AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group. In comparison with AZT-substitution group, AZT group was associated with higher risk of developing anemia (adjusted hazard ratio (aHR) for anemia ≥ grade II, 8.44, 95% CI 1.81–39.46) and neutropenia (aHR for neutropenia ≥ grade II, 1.86, 95% CI 1.19–2.93). The prevalence of lipodystrophy in d4T group was 19.5%, while that in AZT-substitution group was zero. As to antiretroviral efficacy, these three groups showed no differences. Conclusion: AZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.

Background: The aim of this study was to investigate the impact of a tenofovir disoproxil fumarate (TDF) plus ritonavir-boosted protease inhibitor (PI/r) regimen on renal function in Chinese HIV-infected patients. Methods: Seventy-five HIV-1 infected patients failing first-line antiretroviral therapy (ART) comprised the TDF+PI/r group. Seventy-five HIV-1 infected patients matched for gender, age, and renal function made up the control. All subjects completed follow-up visits over 48 weeks. CD4 cell count, plasma HIV-1 viral load, and urine protein level were assessed at the trial start (baseline, week 0) and at week 48. The serum creatinine and estimated glomerular filtration rate (eGFR) were monitored at each follow-up point. Change in eGFR from baseline to week 48 was also compared. Results: Compared to control, the TDF+PI/r group exhibited higher levels of serum creatinine (79 vs. 69.7 μmol/L, P2, P=0.009) at the end of week 48. Patients treated with TDF+PI/r showed greater decline in eGFR than control (−8.8 vs. 6.4ml/min/1.73m², PP<0.001). Conclusions: We found that a TDF+PI/r based ART regimen resulted in greater renal function decline over 48 weeks. Therefore, renal function should be monitored especially when TDF is used in combination with PI/r. Trial registration: ClinicalTrials.gov identifier: NCT00872417

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