Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong, China / 中华医学杂志(英文版)

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.

Risk factors associated with low-level viremia in human immunodeficiency virus/acquired immunodeficiency syndrome patients after anti-retroviral therapy / 中华传染病杂志

Objective:To investigate the risk factors of low-level viremia (LLV) among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients after combined anti-retroviral therapy (ART), and to provide evidence for reducing the risk of LLV.Methods:It was a cross-sectional observation study that enrolled HIV/AIDS patients with LLV (plasma HIV-1 RNA was 50 to 1 000 copies/mL) receiving ART over one year (LLV group) from January 2019 to December 2020 in Guangzhou Eighth People′s Hospital, Guangzhou Medical University. Contemporaneous patients with ART over one year and successful viral suppression (plasma HIV-1 RNA<50 copies/mL) were randomly selected as the control group (suppression group) with a ratio of 1∶2.5, and the risk factors for LLV were analyzed by unconditional logistic regression.Results:A total of 128 and 297 patients were enrolled in LLV group and the suppression group, respectively.ART durations were 3.62(1.83, 4.89) years and 4.91(2.90, 5.88) years, respectively. Multivariate logistic regression analysis showed that the risk factors associated with LLV included the age of initial ART treatment above 50 years old (odds ratio ( OR)=1.82, 95% confidence interval ( CI) 1.01 to 3.26, P=0.046), the baseline HIV-1 RNA over 1×10 5 copies/mL ( OR=2.18, 95% CI 1.30 to 3.68, P=0.003), using the simplified initial ART regimen ( OR=1.82, 95% CI 1.02 to 3.26, P=0.044), missing medication more than three times per year ( OR=2.49, 95% CI 1.55 to 4.01, P<0.001) and changing regimen during ART ( OR=1.90, 95% CI 1.14 to 3.14, P=0.013), while the duration of ART longer than five years could reduce the risk of LLV ( OR=0.37, 95% CI 0.22 to 0.64, P<0.001). In patients with simplified initial ART regimen, the baseline CD4 + T lymphocyte count of whom with LLV was lower than that of whom with viral suppression, and the difference was statistically significant (94.00 (24.00, 281.00)/μL vs 375.00 (310.00, 435.00)/μL, Z=-2.60, P<0.001). Conclusions:The occurrence of LLV is related to the age of initial ART treatment, the baseline HIV-1 RNA, the initial ART regimen, the medication adherence and the change of ART regimen during ART. Strategies may be beneficial to reducing the risk of LLV for HIV/AIDS patients, such as initiating ART as soon as possible, using simplified regimen as initial regimen with caution in patients with low baseline CD4 + T lymphocyte counts, strengthening compliance education, avoiding unnecessary ART regimen changes.

The therapeutic effects of highly active anti-retroviral therapy in 74 treatment-naive patients with AIDS in China / 中华内科杂志

Objective To evaluate the therapeutic effect of highly active anti-retroviral therapy (HAART) in treatment-na(i)ve 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 ) × 105 copies/ml and the baseline mean CD4+ 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 CD4+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 CD4+ 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-drugpredominant HAART regimes with low drug resistance, but relatively more side effects.

Pathogens and drug resistance of pulmonary infection in AIDS patients / 中华内科杂志

Objective To study the pathogens and drug resistance profiles of pulmonary infection in patients with AIDS. Methods The pathogens and their drug susceptibility of pulmonary infection diagnosed by fibrobronchescopy-induced brunchoalveolar lavage fluid (BAI.F) culture and/or transbronchial biopsy in 116 AIDS cases were analyzed. Results Monopathogenic infection in lungs were detected in 18 cases(15.5%) and mixed infection in 98 cases ( 84.5%). Of the 116 cases, bacteria were present in 91 patients, fungi in 62, tubercle bacillus in 49, pneumocystis jiroveci in 29, and cytomegalovirus in 11.Ninety-five bacterial strains were isolated from BALF, mainly including Streptococci (34), coagulase negative Staphylococcus (20), Klebsiella pneumoniae (10) and Escherichia (7). The isolated bacteria were resistant to β-lactam, macrolides, quinolones and aminoglycosides, of which were 14 methicillin-resistant Streptococci (MRS) strains and 12 extended spectrum β-lactamases (ESBL) strains. Sixty-eight fungal strains were isolated, including 36 Candida mycodermas, 19 Penicilliums, 6 Aspergilli and 5 Mold fungi;they were sensitive to amphotericin B but resistant to fluconazol (5.6% -50. 0% ) and itraconazole( 10. 5%-60. 0% ). Conclusion Pneumonia in AIDS patients are usually caused by multiple pathogens,predominantly consisting of multiresistant bacteria and fungi. Therefore, antibiotics should be rationally chosen according to drug susceptibility test.