BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

BACKGROUND: Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting. METHODS: A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch. RESULTS: One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable. CONCLUSIONS The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.
Adenine/therapeutic use* ; Adult ; Alanine ; Alkynes ; Anti-HIV Agents/adverse effects* ; Benzoxazines ; Central Nervous System ; Cobicistat/therapeutic use* ; Cyclopropanes ; Drug Combinations ; Emtricitabine/therapeutic use* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Prospective Studies ; Quality of Life ; Quinolones ; Sleep Quality ; Tenofovir/analogs & derivatives*

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.
Adult ; Anti-HIV Agents/adverse effects* ; Antiretroviral Therapy, Highly Active ; China ; Drug Therapy, Combination ; HIV Infections/drug therapy* ; HIV-1 ; Humans ; Maleimides ; Peptides ; Ritonavir/therapeutic use* ; Treatment Outcome ; Viral Load

BACKGROUND: Lipid abnormalities are prevalent among people living with human immunodeficiency virus (HIV) (PLWH) and contribute to increasing risk of cardiovascular events. This study aims to investigate the incidence of dyslipidemia and its risk factors in PLWH after receiving different first-line free antiretroviral regimens. METHODS: PLWH who sought care at the Third People's Hospital of Shenzhen from January 2014 to December 2018 were included, and the baseline characteristics and clinical data during the follow-up were collected, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The risk factors of dyslipidemia after antiretroviral therapy were analyzed with the generalized estimating equation model. RESULTS: Among the 7623 PLWH included, the mean levels of TC, HDL-C and LDL-C were 4.23 ± 0.85 mmol/L, 1.27 ± 0.29 mmol/L and 2.54 ± 0.65 mmol/L, respectively, and the median TG was 1.17 (IQR: 0.85-1.68) mmol/L. Compared with that in PLWH receiving tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + ritonavir-boosted lopinavir (LPV/r), zidovudine (AZT) + 3TC + efavirenz (EFV), and AZT + 3TC + LPV/r, the incidence of dyslipidemia was lower in PLWH receiving TDF + 3TC + EFV. In multivariate analysis, we found that the risks of elevations of TG, TC, and LDL-C were higher with TDF + 3TC + LPV/r (TG: odds ratio [OR] = 2.82, 95% confidence interval [CI]: 2.55-3.11, P < 0.001; TC: OR = 1.24, 95% CI: 1.14-1.35, P < 0.001; LDL: OR = 1.06, 95% CI: 1.00-1.12, P = 0.041), AZT + 3TC + EFV (TG: OR = 1.41, 95% CI: 1.28-1.55, P < 0.001; TC: OR = 1.43, 95% CI: 1.31-1.56, P < 0.001; LDL: OR = 1.18, 95% CI: 1.12-1.25, P < 0.001), and AZT + 3TC + LPV/r (TG: OR = 3.08, 95% CI: 2.65-3.59, P < 0.001; TC: OR = 2.40, 95% CI: 1.96-2.94, P < 0.001; LDL: OR = 1.52, 95% CI: 1.37-1.69, P < 0.001) than with TDF + 3TC + EFV, while treatment with TDF + 3TC + LPV/r was less likely to restore HDL-C levels compared with TDF + 3TC + EFV (OR = 0.95, 95% CI: 0.92-0.97, P < 0.001). In addition to antiretroviral regimens, antiretroviral therapy duration, older age, overweight, obesity and other traditional factors were also important risk factors for dyslipidemia. CONCLUSION The incidence of dyslipidemia varies with different antiretroviral regimens, with TDF + 3TC + EFV having lower risk for dyslipidemia than the other first-line free antiretroviral regimens in China.
Aged ; Anti-HIV Agents/adverse effects* ; China/epidemiology* ; Dyslipidemias/epidemiology* ; HIV ; HIV Infections/drug therapy* ; Humans ; Lamivudine/therapeutic use* ; Lipids ; Risk Factors

BACKGROUNDTenofovir disoproxil (TDF) is a promising salvage therapy for patients with chronic hepatitis B (CHB) who failed regimens of other nucleoside analogues (NAs). In this study, we aimed to investigate the clinical efficacy and safety of TDF monotherapy in Chinese CHB patients with genotypic resistance.

METHODSA total of 33 CHB patients who had failed treatment with other NAs and had genotypic resistance were switched to TDF monotherapy for 48 weeks. Patients' demographic data (age, sex, history of hepatitis B virus [HBV] therapy), laboratory testing results (hepatitis B e antigen [HBeAg] status, HBV DNA levels, alanine aminotransferase [ALT] levels, serum creatinine, urinary protein, genotypic assay), clinical symptoms, and liver color ultrasound examinations were collected for evaluation at day 0 (baseline) and the 12th, 24th, 36th, and 48th weeks after initiating treatment. Statistical analyses were carried out using rank sum test or rank correlation.

RESULTSWith regard to efficacy, the study found that all patients who switched to TDF monotherapy had undetectable HBV DNA levels after 48 weeks. In addition, patients with lower baseline HBV DNA levels realized earlier virological undetectability (rs = 0.39, P = 0.030). ALT levels were normal in 30 of 33 patients (91%). HBeAg negative conversion occurred in 7 of 25 patients (28%), among whom HBeAg seroconversion (12%) and HBeAg seroclearance (16%) occurred. The time of complete virological response was significantly affected by the number of resistance loci (rs = 0.36, P = 0.040). Concerning safety, the study found that no adverse events were observed during the 48 weeks.

CONCLUSIONTDF monotherapy is an effective and safe salvage treatment for CHB patients who are resistant to other NAs.

Adult ; Anti-HIV Agents ; adverse effects ; therapeutic use ; DNA, Viral ; genetics ; Drug Resistance, Viral ; Female ; Genotype ; Hepatitis B virus ; drug effects ; pathogenicity ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Tenofovir ; adverse effects ; therapeutic use

BACKGROUNDAn 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 resource-limited 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.

METHODSThis prospective, multicenter study enrolled 499 (190 on d4T regimen, 172 on AZT regimen, and 137 on AZT-substitution 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.

RESULTSIn 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.

CONCLUSIONAZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.

Adult ; Anti-HIV Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; HIV Infections ; drug therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stavudine ; administration & dosage ; adverse effects ; therapeutic use ; Zidovudine ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUNDIn the era of highly active antiretroviral therapy (HAART), the use of antiretrovirals as post-exposure prophylaxis (PEP) was the most important strategy for preventing occupational exposure to blood or fluids containing human immunodeficiency virus (HIV). The objective of this study was to retrospectively evaluate the tolerability, safety, and side effects of a HAART regimen containing three antiretroviral drugs, consisting of zidovudine, lamivudine, and lopinavir/ritonavir, in healthcare personnel (HCP) who experienced occupational exposure to HIV.

METHODSThe tolerability, safety, and side effects in 26 HCPs who experienced PEP and in 27 HIV/AIDS patients with HAART regimen, AZT+3TC+Lpv/r, were evaluated between January 2010 and December 2012.

RESULTSThe most frequent clinical side effect was fatigue (in 23 cases, 88.5%), and gastroenterological symptoms were the second most common side effects in HCP with PEP. Liver dysfunction was found in 10 cases (38.5%), while drug rash was found in 18 cases (69.2%) after PEP. The prevalence of side effects in HCPs who experienced PEP was higher than that in HIV/AIDS patients P < 0.05. One nurse (3.8%) experienced severe gastrointestinal symptoms, which led to withdrawal of PEP. No HIV infection was found during 6-month follow-up period.

CONCLUSIONHCPs who received occupational PEP with triple-drug regimen, AZT+3TC+Lpv/r, experienced different side effects, and the tolerability and safety of PEP regimen were good in this cohort.

Adult ; Anti-HIV Agents ; adverse effects ; therapeutic use ; Antiretroviral Therapy, Highly Active ; adverse effects ; Female ; HIV Infections ; drug therapy ; prevention & control ; Humans ; Lamivudine ; adverse effects ; therapeutic use ; Lopinavir ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Post-Exposure Prophylaxis ; Retrospective Studies ; Ritonavir ; adverse effects ; therapeutic use ; Zidovudine ; adverse effects ; therapeutic use

Current international anti-HIV drug efficacy evaluation criteria including CD4 cell count and viral load. Antiviral therapy has good effect in suppressing viral load, although there are many limitations. More and more researchers began to focus on Chinese medicine. A large number of clinical practice shows that Chinese herbal medicine is good at improving patient immune function, reducing symptoms and improving quality of life, but the efficacy of inhibiting viral load was not obvious, clinical manifestation, immunological and virological indicators index inconsistency how to explain? This article from the perspective of theory and literature review, pointing out the similarities and differences of efficacy action points of Chinese and Western medicine treatment of AIDS from three aspects, including immune function, viral load and symptoms to explore the relevance of them. This paper proposed that immune function improvement and viral load change is not a direct inverse relationship (ie, improve immunity, the virus must fall); immunity improve followed by symptom relief and improved quality of life is more common to be seen; long-term improvement of immune function may follow by stable virus or gradual decline; the analysis still need to be testified in large sample, prolonged clinical observation in the future.
Acquired Immunodeficiency Syndrome ; immunology ; therapy ; virology ; Animals ; Anti-HIV Agents ; adverse effects ; pharmacology ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; adverse effects ; methods

Low bone mineral density (BMD) is common in HIV-infected patients. We aimed to describe the prevalence of low BMD and risk factors in Korean HIV-infected patients and to assess the effects of antiretroviral therapy (ART) on BMD. We retrospectively evaluated 224 HIV infected-patients. The prevalence of osteopenia and osteoporosis were 41.5% and 12.9%. These were much higher in 53 patients aged 50 yr and older (52.8% and 34.0%). Older age, lower body mass index, and ART > 3 months were independent risk factors for low BMD. Osteoporosis was more prevalent in patients on the abacavir-based regimen for < 1 yr than > or = 1 yr; however, it was more prevalent in patients on the zidovudine-based regimen for > or = 1 yr than < 1 yr (P = 0.017). Osteoporosis in patients on the abacavir-based regimen was more common in the spine than in the femur (P = 0.01). Given such a high prevalence of low BMD, close monitoring of BMD for HIV-infected patients on ART is required. The different prevalence of osteoporosis over time and affected areas between two regimens suggest they may play roles in different mechanisms in bone loss.
Adult ; Anti-HIV Agents/adverse effects/*therapeutic use ; Asian Continental Ancestry Group ; Body Mass Index ; *Bone Density ; Bone Diseases, Metabolic/*epidemiology/etiology ; Dideoxynucleosides/adverse effects/*therapeutic use ; Female ; HIV Infections/*drug therapy/epidemiology/pathology ; Humans ; Male ; Middle Aged ; Odds Ratio ; Osteoporosis/*epidemiology/etiology ; Prevalence ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Zidovudine/adverse effects/*therapeutic use

A retrospective study was conducted to determine the mortality, causes and risk factors for death among HIV-infected patients receiving antiretroviral therapy (ART) in Korea. The outcomes were determined by time periods, during the first year of ART and during 1-5 yr after ART initiation, respectively. Patients lost to follow-up were traced to ascertain survival status. Among 327 patients initiating ART during 1998-2006, 68 patients (20.8%) died during 5-yr follow-up periods. Mortality rate per 100 person-years was 8.69 (95% confidence interval, 5.68-12.73) during the first year of ART, which was higher than 4.13 (95% confidence interval, 2.98-5.59) during 1-5 yr after ART. Tuberculosis was the most common cause of death in both periods (30.8% within the first year of ART and 16.7% during 1-5 yr after ART). During the first year of ART, clinical category B and C at ART initiation, and underlying malignancy were significant risk factors for mortality. Between 1 and 5 yr after ART initiation, CD4 cell count < or = 50 cells/microL at ART initiation, hepatitis B virus co-infection, and visit constancy < or = 50% were significant risk factors for death. This suggests that different strategies to reduce mortality according to the time period after ART initiation are needed.
Anti-Retroviral Agents/*adverse effects/*therapeutic use ; Antiretroviral Therapy, Highly Active/adverse effects ; CD4 Lymphocyte Count ; Cause of Death ; Coinfection ; Female ; HIV Infections/*drug therapy/*mortality/virology ; Humans ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Treatment Outcome