Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong, China.

BACKGROUND: Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. METHODS: Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). CONCLUSIONS: Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

Persistently low CD4 cell counts are associated with hepatic events in HCV/HIV coinfected patients: data from the national free antiretroviral treatment program of China.

BACKGROUND: Chronic liver disease has emerged as a leading cause of non-acquired immune deficiency syndrome (AIDS)-related mortality in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients. The relationship between CD4 cell count and HIV-related opportunistic infections and tumors has been well characterized; however, it is unclear whether CD4 cell count is associated with HCV-related hepatic events. METHODS: This observational cohort study enrolled HCV/HIV-coinfected patients from the National Free Antiretroviral Treatment Program of China from 2004 to 2019 in Guangzhou. The primary outcome was a composite of hepatic events, including cirrhosis complications, hepatocellular carcinoma (HCC), and liver-related mortality. Kaplan-Meier survival and multivariate logistic regression analyses were performed. RESULTS: Among the 793 patients, 43 developed hepatic events during a median follow-up of 6.7 years, including 35 cirrhosis complications, 13 HCC cases, and 14 cases of liver-related mortality. The 5-year and 10-year cumulative incidences of hepatic events were 4.2% and 9.3%, respectively. Patients who developed hepatic events had a less satisfactory increase in CD4 cell count, lower peak CD4 (354.5 cells/µL vs. 560.0 cells/µL, P < 0.001), and lower percentage of peak CD4 > 500 cells/µL (30.2% vs. 60.7%, P < 0.001) after the initiation of antiretroviral therapy (ART) than those who did not. The cumulative incidences of hepatic events were higher in patients with lower peak CD4 levels with adjusted odds ratios of 3.96 (95% confidence interval [CI]: 1.51-10.40), 2.25 (95% CI: 0.87-5.86), and 0.98 (95% CI: 0.35-2.74) for patients with peak CD4 at <200 cells/µL, 200-350 cells/µL, and 351 to 500 cells/µL, respectively, relative to those with peak CD4 > 500 cells/µL. Peak CD4 was negatively associated with the risk of hepatic events in a dose-response manner ( P -value for trend = 0.004). CONCLUSION: Persistently low CD4 cell counts after ART are independently associated with a high risk of hepatic events in HCV/HIV-coinfected patients, highlighting the important role of immune reconstitution in improving liver outcomes.

HIV-infected patients rarely develop invasive fungal diseases under good immune reconstitution after ART regardless high prevalence of pathogenic filamentous fungi carriage in nasopharynx/oropharynx.

Purpose: We aimed to investigate the prevalence and risk factors of filamentous fungi (FF) carriage in human immunodeficiency virus (HIV)-infected patients in Guangdong province, along with its subsequent incidence of invasive fungal disease (IFD). Methods: Seven hundred and sixteen HIV-infected individuals from the outpatient clinic and 293 sex-matched healthy controls were recruited prospectively from May 1 to August 31, 2017. Fungi were isolated from oropharyngeal and nasopharyngeal swabs, then identified by morphological and molecular biological techniques. Logistic regression analysis was used to identify risk factors of pathogenic FF carriage. Pathogenic FF carriers were followed up through the end of 2019. Results: Of the 716 included HIV-infected patients, 602 (84.1%) were male, the median age was 34 (27-42) years, and the median CD4+ count was 385 (254-542) cells/µl. Pathogenic FF were isolated in 119 (16.6%) cases with HIV infection and 40 (13.7%) healthy controls. Mucorales were found in 3 HIV-infected individuals and Talaromyces marneffei in 2 HIV-infected individuals, but not in healthy controls. History of cured opportunistic infections (OIs; OR, 1.97; 95% CI, 1.23-3.13, p = 0.004), and smoking (OR, 1.55; 95%CI, 1.03-2.32, p = 0.035) were independent risk factors of pathogenic FF carriage in HIV-infected individuals. A total of 119 pathogenic FF carriers with HIV infection were followed. During follow-up, 119 (100%) cases received antiretroviral therapy (ART) for at least 28 months, 107 (90%) cases had CD4+ counts>200 cells/µl, and none developed IFD. Discussion: Pathogenic FF carriage is common in HIV-infected individuals but may not develop IFD in those who achieved immune reconstitution. Smoking and cured OIs history increase the risk of pathogenic FF carriage. Smoking abstinence and ART adherence are especially important for these patients.

[The therapeutic effects of highly active anti-retroviral therapy in 74 treatment-naive patients with AIDS in China].

OBJECTIVE: To evaluate the therapeutic effect of highly active anti-retroviral therapy (HAART) in treatment-naïve Chinese patients with AIDS, to provide evidences for standardizing HAART. METHODS: Seventy-four treatment-naive AIDS patients were initiated with HAART and followed up regularly for 3 years. The clinical and laboratory data, side effects and drug resistance were observed and analyzed during the follow-up period. RESULTS: Of the 74 patients, 46 were males and 28 were females, with the average age being 42 years. The mean HIV viral load was (2.2 ± 2.0) × 10(5) copies/ml and the baseline mean CD(4)(+)T lymphocyte count was (62 ± 71) cells/µl before treatment. After treatment for 3, 6, 12, 18, 24, 30 and 36 months, the percentage of undetectable HIV viral road (less than 50 copies/ml) was 71.6%, 83.8%, 75.7%, 77.0%, 82.4%, 81.1% and 79.7% respectively, and CD(4)(+)T lymphocyte count ascended to (167 ± 105), (177 ± 129), (238 ± 137), (290 ± 158), (304 ± 191), (331 ± 175) and (352 ± 202) cells/µl. The increase in amplitude of CD(4)(+)T lymphocyte count in different periods examined was different, with the period of 0-3 months post-treatment demonstrating the most obvious augmentation (P < 0.01). The most common adverse reactions were liver function injury (52/74, 70.3%), hyperlipemia (52/74, 70.3%), hematopoietic inhibition of the bone marrow (33/74, 44.6%), peripheral neuritis (32/74, 43.2%) and lipoatrophy (26/74, 35.1%). Clinical drug resistance were found in nine patients and HIV gene mutations were detected in these patients. CONCLUSIONS: Chinese treatment-naive AIDS patients have achieved good virological and immunological response to generic-drug-predominant HAART regimes with low drug resistance, but relatively more side effects.