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

Nucleoside reverse transcriptase inhibitors (NRTIs), which are used for the treatment of human immunodeficiency virus (HIV) infection have been associated with a wide spectrum of clinical manifestations, including hepatic steatosis, lipodystrophy, myopathy, and lactic acidosis. Such adverse effects are postulated to result from the inhibition of mitochondrial DNA gamma polymerase, which causes the depletion of mitochondrial DNA and eventual the disruption of oxidative phosphorylation. Although cases of severe decompensated lactic acidosis are rare, this syndrome is associated with a high mortality rate. We report upon the first Korean case, of severe lactic acidosis in an acquired immunodeficiency syndrome (AIDS) patient receiving stavudine, an anti-HIV drug.
Acidosis, Lactic/*chemically induced ; Acquired Immunodeficiency Syndrome/*drug therapy ; Adult ; Anti-HIV Agents/*adverse effects/therapeutic use ; Female ; Human ; Sodium Bicarbonate/therapeutic use ; Stavudine/*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

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

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

As the severity of the HIV epidemic in China grew, National Free Antiretroviral Treatment (ART) Program was announced since 2003. Even though there still were many difficulties, China had obtained great achievements in fighting against HIV. Over 52 000 adult patients had received first-line HAART thus far and the mortality of AIDS in China decreased significantly. This paper presents an overview of the HIV/AIDS epidemic in China; the status of national free ART program, the difficulties suffered and the achievements made since the initiation of program and the challenges ahead for continued progress for China. This paper also provides suggestions to overcome these challenges.
Anti-Retroviral Agents ; adverse effects ; therapeutic use ; China ; epidemiology ; HIV Infections ; drug therapy ; epidemiology ; Humans ; Lipodystrophy ; chemically induced

OBJECTIVETo clinically study the antiviral effects of lamivudine and entecavir on patients with early-to-mid stage Hepatitis B related acute on chronic liver failure (HBV-ACLF). METHODS; A prospective, randomized, open and parallel controlled clinical trial was designed to observe the antiviral effects of nucleoside analogues on patients with early-to-mid stage HBV-ACLF. Three groups were set for controlled study, i. e. basic treatment group, lamivudine plus basic treatment group and entecavir plus basic treatment group.

RESULTSOne month after treatment, the improvement rates of lamivudine group and entecavir group were 58.85% and 59.15% respectively, significantly higher than that of basic treatment group which was 34.84% (Chi(2) = 9.8323, P = 0.043). By the end of six months, the cumulative survival rates of patients with the antiviral treatments, i.e., lamivudine, entecavir, were 65.8%, 60.1%, significantly higher than that (42%) without the antiviral treatment (P = 0.045, P = 0.04 respectively). The cumulative survival rate in patients with a MELD score < 30 was higher than that with a MELD score over 30 (Chi(2) = 3.920, P = 0.048). For the patients with pretreatment HBV DNA > or = 10(7), the cumulative survival rate in patients with entecavir treatments group was higher than that of patients in basic treatment group (Chi(2) = 5. 014 P= 0.025). According to the Ordinal Regression analysis, antiviral therapy by using either lamivudine or entecavia could significantly increase the improvement rate of patients with early-to-mid stage HBV-ACLF. But severe complications, including hepatorenal syndrome, electrolyte imbalance and hepatic encephalopathy, medical history of liver cirrhosis, and pretreatment HBV DNA > or = 10(7) had significant impacts on prognosis of this group patients.

CONCLUSIONSAntiviral therapy by using either lamivudine or entecavia could significantly increase the survival rate of patients with early-to-mid stage HBV-ACLF.

Anti-HIV Agents ; adverse effects ; therapeutic use ; Disease Susceptibility ; End Stage Liver Disease ; chemically induced ; Guanine ; adverse effects ; analogs & derivatives ; therapeutic use ; Humans ; Lamivudine ; adverse effects ; therapeutic use ; Prognosis

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

In the two decades since AZT was first approved for clinical use in 1987, 24 additional antiretroviral agents have been approved. They include 7 nucleoside analogs, a nucleotide analog and 4 non-nucleoside reverse transcriptase inhibitors, 10 protease inhibitors, 2 entry inhibitors and an integrase inhibitor. More than 20 investigational agents are currently being studied in clinical trials. Highly active antiretroviral therapy (HAART), which involves a combination of anti-HIV-1 drugs, is extremely effective in suppressing HIV-1 replication and increasing CD4+ number and results in substantial reductions in HIV-1-related morbidity and mortality. In last 20 years, much has been learned about resistance to antiretroviral drugs, drug interactions and metabolic complications of antiviral drug use. Drugs are now selected on the basis of resistance tests and on the risk of specific drug complications in individual patients. As a result, decisions about the therapy of HIV/AIDS have become personalized and are made on a patient-by-patient basis. With appropriate medical management, a person with HIV-1 now has the possibility of a nearly normal life expectancy.
Anti-HIV Agents ; adverse effects ; pharmacology ; therapeutic use ; Antiretroviral Therapy, Highly Active ; Cyclohexanes ; chemistry ; pharmacology ; therapeutic use ; Drug Resistance, Viral ; HIV Envelope Protein gp41 ; chemistry ; therapeutic use ; HIV Fusion Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Infections ; drug therapy ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Protease Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Reverse Transcriptase ; chemistry ; pharmacology ; therapeutic use ; HIV-1 ; drug effects ; physiology ; Humans ; Molecular Structure ; Peptide Fragments ; chemistry ; therapeutic use ; Pyrrolidinones ; chemistry ; pharmacology ; therapeutic use ; Raltegravir Potassium ; Saquinavir ; chemistry ; pharmacology ; therapeutic use ; Triazoles ; chemistry ; pharmacology ; therapeutic use ; Virus Replication ; drug effects ; Zidovudine ; chemistry ; pharmacology ; therapeutic use

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